Podcasts about cardiac mri

CardioNerds (Drs. Daniel Ambinder and Eunice Dugan) join Dr. Namrita Ashokprabhu, Dr. Yulith Roca Alvarez, and Dr. Mehmet Yildiz from The Christ Hospital. Expert commentary by Dr. Odayme Quesada. Audio editing by CardioNerds intern, Christiana Dangas. This episode highlights the pivotal role of cardiac MRI and functional testing in uncovering coronary vasospasm as an underlying cause of MINOCA. Cardiac MRI is crucial in evaluating myocardial infarction with nonobstructive coronary arteries (MINOCA) and diagnosing myocarditis, but findings must be interpreted within clinical context. A 58-year-old man with hypertension, hyperlipidemia, diabetes, a family history of cardiovascular disease, and smoking history presented with sudden chest pain, non-ST-elevation on EKG, and elevated troponin I (0.64 µg/L). Cardiac angiography revealed nonobstructive coronary disease, including a 40% stenosis in the LAD, consistent with MINOCA. Eight weeks later, another event (troponin I 1.18 µg/L) led to cardiac MRI findings suggesting myocarditis. Further history revealed episodic chest pain and coronary vasospasm, confirmed by coronary functional angiography showing severe vasoconstriction, resolved with nitroglycerin. Management included calcium channel blockers and long-acting nitrates, reducing symptoms. Coronary vasospasm is a frequent MINOCA cause and can mimic myocarditis on CMRI. Invasive coronary functional testing, including acetylcholine provocation testing, is indicated in suspicious cases.  US Cardiology Review is now the official journal of CardioNerds! Submit your manuscript here. CardioNerds Case Reports PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Notes - Coronary Vasospasm What are the potential underlying causes of MINOCA (Myocardial Infarction with Non-Obstructive Coronary Arteries)?  Plaque Rupture: Plaque disruption, which includes plaque rupture, erosion, and calcified nodules, occurs as lipids accumulate in coronary arteries, leading to inflammation, necrosis, fibrosis, and calcification. Plaque rupture exposes the plaque to the lumen, causing thrombosis and thromboembolism, while plaque erosion results from thrombus formation without rupture and is more common in women and smokers. Intravascular imaging, such as IVUS and OCT, can detect plaque rupture and erosion, with studies showing plaque disruption as a frequent cause of MINOCA, particularly in women, though the true prevalence may be underestimated due to limited imaging coverage.  Coronary Vasospasm: Coronary vasospasm is characterized by nitrate-responsive chest pain, transient ischemic EKG changes, and >90% vasoconstriction during provocative testing with acetylcholine or ergonovine, due to hyper-reactivity in vascular smooth muscle. It is a common cause of MINOCA, with approximately half of MINOCA patients testing positive in provocative tests, and Asians are at a significantly higher risk than Whites. Smoking is a known risk factor for vasospasm. In contrast, traditional risk factors like sex, hypertension, and diabetes do not increase the risk, and vasospasm is associated with a 2.5–13% long-term risk of major adverse cardiovascular events (MACE).  Spontaneous Coronary Artery Dissection: Spontaneous coronary artery dissection (SCAD) involves the formation of a false lumen in epicardial coronary arteries without atherosclerosis, caused by either an inside-out tear or outside-in intramural hemorrhage. SCAD is classified into four types based on angiographic features, with coronary angiography being the primary diagnostic tool. However, in uncertain cases, advanced imaging like IVUS or OCT may be used cautiously. While the true prevalence is unclear due to missed diagnoses, SCAD is more common in women and is considered a cause of MINOCA when i...

Julien Dreyfus, MD, PhD, JACC: Case Reports Associate Editor, is joined by author Khalid Shakfeh, MD, discussing this study from Shakfeh et al presented at ACC.25 and published in JACC: Case Reports. A 56 year old man with chronic chest pain syndrome presented with sudden onset of weakness. Evaluation for a stroke revealed a large mass in the right atrium measuring approximately 2.2 x 2.0 cm immediately above the tricuspid valve annulus and adjacent to the atrio-ventricular groove on TTE. Cardiac MRI ruled out intracardiac mass, but rather demonstrated an RCA fusiform aneurysm. Coronary CTA characterized this as two fusiform RCA aneurysms. A LHC confirmed this. Giant coronary aneurysms appearing as a large space-occupying intracavitary cardiac mass are rarely diagnosed. Escalating multimodal imaging is essential for accurate diagnosis and surgical planning. Kawasaki disease can have a late presentation and should be considered in the differential diagnosis of coronary aneurysms. A multimodal imaging approach is essential for accurate diagnosis and management of giant coronary aneurysms.

CardioNerds (Dr. Rick Ferraro and Dr. Dan Ambinder) join Dr. Sri Mandava, Dr. David Meister, and Dr. Marissa Donatelle from the Columbia University Division of Cardiology at Mount Sinai Medical Center in Miami. Expert commentary is provided by Dr. Pranav Venkataraman.   They discuss the following case involving a patient with cardiac sarcoidosis presenting as STEMI:  A 57-year-old man with a history of hyperlipidemia presented with sudden onset chest pain. On admission, he was vitally stable with a normal cardiorespiratory exam but appeared in acute distress and was diffusely diaphoretic. His ECG revealed sinus rhythm, a right bundle branch block (RBBB), and ST elevation in the inferior-posterior leads. He was promptly taken for emergent cardiac catheterization, which identified a complete thrombotic occlusion of the mid-left circumflex artery (LCX) and large obtuse marginal (OM) branch, with no underlying coronary atherosclerotic disease. Aspiration thrombectomy and percutaneous coronary intervention (PCI) were performed, with one drug-eluting stent placed. An echocardiogram showed a left ventricular ejection fraction (EF) of 31%, hypokinesis of the inferior, lateral, and apical regions, and an apical left ventricular thrombus. The patient was started on triple therapy. A hypercoagulable workup was negative. A cardiac MRI was obtained to further evaluate non-ischemic cardiomyopathy. In conjunction with a subsequent CT chest, the results raised suspicion for cardiac sarcoidosis with systemic involvement. In view of a reduced EF and significant late-gadolinium enhancement, electrophysiology was consulted to evaluate for ICD candidacy. A decision was made to delay ICD implantation until a definitive diagnosis of cardiac sarcoidosis could be established by tissue biopsy. The patient was started on HF-GDMT and discharged with a LifeVest. Close outpatient follow-up with cardiology and electrophysiology was arranged.  US Cardiology Review is now the official journal of CardioNerds! Submit your manuscript here. CardioNerds Case Reports PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Pearls - Cardiac Sarcoidosis Presenting as STEMI Cardiac sarcoidosis can present with a variety of symptoms, including arrhythmias, heart block, heart failure, or sudden cardiac death. Symptoms can be subtle or mimic other cardiac conditions.  Conduction abnormalities, particularly AV block or ventricular arrhythmias, are common and may be the initial indication of cardiac involvement with sarcoidosis.  The additive value of Echocardiography, FDG-PET, and cardiac MR is indispensable in the diagnostic workup of suspected cardiac sarcoidosis.  Specific role of MRI/PET: Both cardiac MRI and FDG-PET provide a complementary role in the diagnosis of cardiac sarcoidosis. Cardiac MRI is an effective diagnostic screening tool with fairly high sensitivity but is limited by its inability to decipher inflammatory (“active” disease) versus fibrotic myocardium. FDG-PT helps to make this discrimination, refine the diagnosis, and guide clinical management. Ultimately, these studies are most useful when interpreted in the context of other clinical information.  Primary prevention of sudden cardiac death in cardiac sarcoidosis focuses on risk stratification, with ICD placement for high-risk patients. For patients awaiting definitive diagnosis, a LifeVest may be used as a temporary measure to protect from sudden arrhythmic events until an ICD is placed.  Notes - Cardiac Sarcoidosis Presenting as STEMI 1. Is STEMI always a result of coronary artery disease?  By definition, a STEMI is an acute S-T segment elevation myocardial infarction. This occurs when there is occlusion of a major coronary artery, which results in transmural ischemia and damage,

This week we step back in time 3 years ago to review an important cardiac MRI report on Fontan geometry and hemodynamics as measured by computational fluid dynamic analysis. How do factors like Fontan geometry or 'power loss' relate to quality of life for the Fontan young adult patient? How do these data inform imaging in the operating room during these palliations? We speak with the first author of this work, Associate Professor of Pediatrics at U. Penn, Dr. Laura Mercer-Rosa about this important and intriguing work. https://doi.org/10.1016/j.athoracsur.2022.01.017

In this episode, Dr. Valentin Fuster discusses a groundbreaking study on cardiac MRI predictors of arrhythmic sudden cardiac events in patients with Fontan circulation, highlighting key risk factors for these life-threatening incidents. The study, part of the multi-center FORCE registry, reveals significant findings, including the impact of clinical status and ventricular function, while emphasizing the importance of large-scale research in improving outcomes for single ventricle patients.

CardioNerds (Dr. Dan Ambinder and Dr. Rick Ferraro) join Dr. Mansi Oberoi and Dr. Mohan Gudiwada from the University of Nebraska Medical Center discuss a case of constrictive pericarditis. Expert commentary is provided by Dr. Adam Burdorf, who serves as the Program Director for the Cardiovascular Medicine Fellowship at the University of Nebraska Medical Center. The case discussed involves a 76-year-old woman with a history of monoclonal gammopathy of undetermined significance, chronic obstructive pulmonary disease, type 2 diabetes mellitus, and squamous cell carcinoma was admitted to the hospital for worsening shortness of breath, swelling in lower extremities, hyponatremia, and urinary tract infection. CT chest to evaluate for pulmonary embolism showed incidental pericardial calcifications; the heart failure team was consulted for the management of her decompensated heart failure. Echo images were nondiagnostic. Subsequent invasive hemodynamic monitoring showed elevated right and left-sided filling pressures, diastolic equalization of LV and RV pressures, and positive RV square root sign with ventricular interdependence. Cardiac MRI showed septal flattening on deep inspiration and septal bounce, suggestive of interventricular dependence. After a heart team discussion and with shared-decision making the patient opted for medical management owing to her comorbidities and frailty. Enjoy this 2024 JACC State-of-the-Art Review to learn more about pericardial diseases and best practices for pericardiectomy (Al-Kazac et al., JACC 2024) US Cardiology Review is now the official journal of CardioNerds! Submit your manuscript here. CardioNerds Case Reports PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Case Media - Constrictive Pericarditis Echo: Left Ventricular ejection fraction = 55-60%. Unclear septal motion in the setting of atrial fibrillation MRI: Diastolic septal flattening with deep inspiration as well as a septal bounce suggestive of interventricular dependence and constrictive physiology  References Garcia, M. Constrictive Pericarditis Versus Restrictive Cardiomyopathy. Journal of the American College of Cardiology, vol. 67, no. 17, 2016, pp. 2061–2076. Pathophysiology and Diagnosis of Constrictive Pericarditis. American College of Cardiology, 2017. Geske, J., Anavekar, N., Nishimura, R., et al. Differentiation of Constriction and Restriction: Complex Cardiovascular Hemodynamics. Journal of the American College of Cardiology, vol. 68, no. 21, 2016, pp. 2329–2347. Constrictive Pericarditis. ScienceDirect. Constrictive Pericarditis. Journal of the American College of Cardiology, vol. 83, no. 12, 2024, pp. 1500-1512.

N Engl J Med 2020;382:1395-407 - ISCHEMIAN Engl J Med 2020;382:1608-16 - ISCHEMIA-CKDBackground: The COURAGE trial, published in 2007, represented a major reversal in cardiovascular medicine. In patients with stable CAD an initial strategy of revascularization plus medical therapy did not reduce the chance of dying or having a heart attack compared to an initial strategy of medical therapy alone. Prior to these results, patients with stable CAD were routinely managed with an initial invasive approach and the field of cardiology was intensely focused on finding coronary blockages and “fixing” them in symptomatic and asymptomatic patients alike. Thus, it's not surprising that following results from COURAGE, the practice continued to be vigorously defended and applied routinely in the management of patients with stable CAD.The first major attempt to reverse the results of COURAGE came from the FAME 2 trial, published in 2012, which tested the hypothesis that patients with stable CAD and an abnormal fractional flow reserve (FFR) in the cath lab would do better with an initial invasive strategy compared to medical therapy alone. The trial was stopped early for efficacy but the positive results were driven entirely by revascularization during follow up - not death or heart attack. The trial was criticized for being stopped inappropriately without providing an answer to whether an early invasive strategy improved hard endpoints compared to initial medical therapy alone. The concepts of “faith healing” and “subtraction anxiety” are useful for understanding the results and limitations of the FAME 2 trial.The ISCHEMIA trial which began enrolling patients in 2012 sought to overcome limitations of COURAGE and FAME. The investigative aim of the study was to test the hypothesis that in patients with stable CAD and moderate to severe ischemia on provocative testing, an initial invasive strategy reduced a composite of major cardiac events compared to initial medical therapy alone. The ISCHEMIA-CKD trial was performed in conjunction with the ISCHEMIA Research Group to address an important knowledge gap in managing patients with CAD. Patients with advanced chronic kidney disease (CKD) experience a higher rate of cardiac events than their counterparts without CKD; however, they are also at a higher risk of procedural complications. The standard of care at the time was generally to manage a patient with stable CAD and CKD like any other patient with CAD despite the fact that such patients were historically excluded from participation in clinical trials and thus, there was really no data from clinical trials to guide decision making.The ISCHEMIA-CKD investigators sought to test the hypothesis that in patients with advanced CKD and stable CAD and moderate to severe ischemia on stress testing, an initial invasive strategy reduced death or MI compared to initial medical therapy alone.Cardiology Trial's Substack is a reader-supported publication. To receive new posts and support our work, consider becoming a free or paid subscriber.Patients: For the ISCHEMIA trial, eligible patients had to be at least 21 years of age or older with at least moderate ischemia on a qualifying stress test based on the following criteria:* Nuclear perfusion with SPECT or PET with >/= 10% ischemic myocardium* Echocardiography with >/= 3/16 segments with stress-induced severe hypokinesis or akinesis* Cardiac MRI with >/= 10% ischemic myocardium on perfusion imaging and/or >/= 3/16 segments with stress-induced severe hypokinesis or akinesis on wall motion assessment* Exercise treadmill test without imaging that met all 4 following criteria* clinical history of typical angina or typical angina during the stress test* absence of resting ST depression > 1.0 mm or confounders that render exercise EKG non-interpretable (LBBB, LVH with repolarization, pacemaker, etc.)* exercise-induced horizontal or downsloping ST depression >/= 1.5 mm in 2 leads or >/= 2.0 mm in any lead or ST elevation >/= 1.0 mm in a non-infarct territory* either of the following:* workload at which ST segment criteria are met is NOT to exceed completion of stage 2 of a standard Bruce protocol or 7 METS if a non-Bruce protocol is used* ST segment criteria are met at

Commentary by Dr. Valentin Fuster

Bill Faulkner is joined by Dr Robert Biederman, and Ron Williams to discuss advances in Cardiac MRI CE Credit Coming Soon This MR iCast episode is supported by Bracco Diagnostics Inc. through an unrestricted educational grant.  

Full article: https://www.ajronline.org/doi/10.2214/AJR.23.30272  Peter Gunderman, MD discusses a recent AJR study that finds that a free-breathing accelerated cine sequence with deep learning reconstruction is just as accurate as standard breath-hold SSFP sequences in estimating left ventricular measurements. An accurate free-breathing cine sequence could benefit patients who have difficulty holding their breath and decrease scanning times, but there are limitations to the study that may hinder wider adoption.

Case Discussion 107 Answer: SCD risk and CMR in HCM

CardioNerds (Dr. Amit Goyal) join Dr. Anureet Malhotra, Dr. John Fritzlen, and Dr. Tarun Dalia from the University of Kansas School of Medicine for some of Kansas City's famous barbeque. They discuss a case of Hydroxychloroquine induced cardiomyopathy. Notes were drafted by Dr. Anureet Malhotra, Dr. John Fritzlen, and Dr. Tarun Dalia. Expert commentary was provided by Dr. Pradeep Mammen. The episode audio was edited by Dr. Akiva Rosenzveig. Drug-induced cardiomyopathy remains an important and under-recognized etiology of cardiomyopathy and heart failure. Hydroxychloroquine is a disease-modifying antirheumatic drug used for various rheumatological conditions, and its long-term use is well-known to have toxic effects on cardiac muscle cells. Multiple cardiac manifestations of these drugs have been identified, the most prominent being electrophysiological disturbances. In this episode, we discuss a biopsy-proven case of hydroxychloroquine-induced cardiotoxicity with detailed histopathological and imaging findings. We develop a roadmap for the diagnosis of hydroxychloroquine-induced cardiomyopathy and discuss the various differentials of drug-induced cardiomyopathy. We highlight the importance of clinical monitoring and early consideration of drug-induced toxicities as a culprit for heart failure. US Cardiology Review is now the official journal of CardioNerds! Submit your manuscript here. CardioNerds Case Reports PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Case Media - Hydroxychloroquine induced cardiomyopathy Pearls - Hydroxychloroquine induced cardiomyopathy Continued decline in left ventricular systolic function despite appropriate guideline directed medical therapy should prompt a thorough evaluation for unrecognized etiologies and warrants an early referral to advanced heart failure specialists. Transthoracic echocardiogram is a valuable non-invasive screening tool for suspected pulmonary hypertension, but right heart catheterization is required for definitive diagnosis. Cardiac MRI can be used for better characterization of myocardial tissue and can aid in the evaluation of patients with non-ischemic cardiomyopathy. Hydroxychloroquine (HCQ) is a commonly used DMARD that remains an underrecognized etiology of cardiomyopathy and heart failure. In addition to ophthalmological screening, annual ECG, as well as echocardiography screening for patients on long-term HCQ therapy, should be considered in patients at risk for cardiovascular toxicity, including those with pre-existing cardiovascular disease, older age, female sex, longer duration of therapy, and renal impairment. Management of hydroxychloroquine-associated cardiomyopathy consists of discontinuing hydroxychloroquine and standard guideline-directed medical therapy for heart failure.  HCQ cardiomyopathy may persist despite medical therapy, and advanced therapy options may have to be considered in those with refractory heart failure. Show Notes - Hydroxychloroquine induced cardiomyopathy What are the various cardiotoxic effects of hydroxychloroquine (HCQ) and the mechanism of HCQ-mediated cardiomyopathy? One of the most frequently prescribed disease-modifying antirheumatic drugs (DMARDs), HCQ is an immunomodulatory and anti-inflammatory agent that remains an integral part of treatment for a myriad of rheumatological conditions. Its efficacy is linked to inhibiting lysosomal antigen processing, MHC-II antigen presentation, and TLR functions.8 The known cardiac manifestations of HCQ-induced toxicity include conduction abnormalities, ventricular hypertrophy, hypokinesia, and lastly, cardiomyopathy. Conduction Abnormalities - by binding to and inhibiting the human ether-à-go-go-related gene (hERG) voltage-gated potassium channel,

CardioNerds cofounder Dr. Amit Goyal and cardiology fellows from the Cleveland Clinic (Drs. Alejandro Duran Crane, Gary Parizher, and Simrat Kaur) discuss the following case: A 61-year-old man presented with symptoms of heart failure and left ventricular hypertrophy. He was given a diagnosis of obstructive hypertrophic cardiomyopathy. He eventually underwent septal myectomy, mitral valve replacement, aortic aneurysm repair, and aortic valve replacement with findings of Fabry's disease on surgical pathology. The case discussion focuses on the differential diagnosis for LVH and covers Fabry disease as an HCM mimic. Expert commentary was provided by Dr. Angelika Ewrin. The episode audio was edited by student Dr. Diane Masket. US Cardiology Review is now the official journal of CardioNerds! Submit your manuscript here. CardioNerds Case Reports PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Case Media - An Unusual Cause of Hypertrophic Cardiomyopathy – Cleveland Clinic Pearls - An Unusual Cause of Hypertrophic Cardiomyopathy – Cleveland Clinic Left ventricular hypertrophy is a cardiac manifestation of several different systemic and cardiac processes, and its etiology should be clarified to avoid missed diagnosis and treatment opportunities. Fabry disease is a rare, X-linked inherited disease that can present cardiac and extra-cardiac manifestations, the former of which include hypertrophic cardiomyopathy, conduction defects, coronary artery disease, conduction abnormalities, arrhythmias, and heart failure.  The diagnosis of Fabry disease includes measurement of alpha-galactosidase enzyme activity as well as genetic testing to evaluate for pathogenic variants or variants of unknown significance in the GLA gene. Family members of patients diagnosed with Fabry disease should be screened based on the inheritance pattern.   Multimodality imaging can be helpful in the diagnosis of Fabry disease. Echocardiography can show left ventricular hypertrophy (LVH), reduced global strain, aortic and mitral valve thickening, and aortic root dilation with associated mild to moderate aortic regurgitation. Cardiac MRI can show hypertrophy of papillary muscles, mid-wall late gadolinium enhancement and low-native T1 signal.   The treatment of Fabry disease involves a multi-disciplinary approach with geneticists, nephrologists, cardiologists, nephrologists, and primary care doctors. Enzyme replacement therapy can delay the progression of cardiac disease.    Show Notes - An Unusual Cause of Hypertrophic Cardiomyopathy – Cleveland Clinic What are the causes of left ventricular hypertrophy? LVH is extremely common. It is present in 15-20% of the general population, and is more common in Black individuals, the elderly, obese or hypertensive individuals, with most cases being secondary to hypertension and aortic valve stenosis. In general terms, it is helpful to divide the causes of LVH into three main groups: high afterload states, obstruction to LV ejection, and intrinsic myocardial problems. Increased afterload states include both primary and secondary hypertension and renal artery stenosis. Mechanical obstruction includes aortic stenosis, subaortic stenosis, and coarctation of the aorta. Lastly, several intrinsic problems of the myocardium can cause LV hypertrophy, such as athletic heart with physiological LVH, hypertrophic cardiomyopathy with or without outflow obstruction, and infiltrative or storage diseases such as cardiac amyloidosis, Fabry's disease, or Danon disease, among others.  How does Fabry disease present? Fabry disease is present in all races and is an X-linked lysosomal storage disorder caused by pathogenic variants in the GLA gene that result in reduced alpha-galactosidase enzyme activity,

A patient with severe dyspnea, a patient with potential heart block, and a young patient with chest pain. How does cardiac magnetic resonance imaging (CMR) answer the clinical question? Credit available for this activity expires: 8/29/24 Earn Credit / Learning Objectives & Disclosures: https://www.medscape.org/viewarticle/995793?ecd=bdc_podcast_libsyn_mscpedu  

Meet Dr. Jason Johnson, Associate Chief of Pediatric Cardiology and Director of Cardiac MRI at Le Bonheur Children's Hospital!

In this episode, CardioNerds co-founder Amit Goyal joins Dr. Iva Minga, Dr. Kevin Lee, and Dr. Juan Pablo Salazar Adum from the University of Chicago - Northshore in Evanston, IL to discuss a case of primary cardiac diffuse large B-cell lymphoma. The ECPR for this episode is provided by Dr. Amit Pursnani (Advanced Cardiac Imaging, Fellowship program director, NorthShore University HealthSystem). Audio editing by CardioNerds Academy Intern, Dr. Akiva Rosenzveig. Case synopsis: A 77-year-old man with no significant medical history presents to the emergency department with progressive shortness of breath for 1 week. He reports an unintentional 15-pound weight loss in the prior month as well as constipation and abdominal/flank pain. On examination he was found to be tachycardic with a regular rhythm and further evaluation with a chest X-ray and chest CT scan demonstrated a large pericardial effusion. This was further investigated with an urgent echocardiogram that revealed a large pericardial effusion with a large mass attached to the pericardial side of the RV free wall, as well as signs of early cardiac tamponade. A pericardiocentesis was performed and 550mL of bloody fluid was withdrawn. The fluid was sent for laboratory analysis and cytology. A cardiac MRI demonstrated a large invasive mass in the pericardium and RV wall consistent with cardiac lymphoma. Cytology confirmed diffuse large B-cell lymphoma. Subsequent CT and PET scans did not find any other site of malignancy, giving the patient a diagnosis of primary cardiac diffuse large B-cell lymphoma. The patient underwent R-CHOP chemotherapy and was followed closely with repeat cardiac MRI and PET scans which demonstrated resolution of the cardiac mass at his one-year surveillance follow-up. This case was published in US Cardiology Review, the official journal of CardioNerds. To learn more, access the case report article here. CardioNerds is collaborating with Radcliffe Cardiology and US Cardiology Review journal (USC) for a ‘call for cases', with the intention to co-publish high impact cardiovascular case reports, subject to double-blind peer review. Case Reports that are accepted in USC journal and published as the version of record (VOR), will also be indexed in Scopus and the Directory of Open Access Journals (DOAJ). CardioNerds Case Reports PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Pearls - A Mystery Mass in the Heart - Cardiac Lymphoma The most common cause of malignant cardiac masses is metastasis. Primary cardiac tumors are rare. Cardiac tumors are separated into 2 categories: benign and malignant. They are often differentiated based on their location and their degree of tissue invasion. Multimodality imaging is essential in the diagnosis, management, and surveillance of cardiac masses. A multidisciplinary team approach is invaluable for management of patients with cardiac tumors. Show Notes - A Mystery Mass in the Heart - Cardiac Lymphoma 1. What is the clinical presentation of cardiac masses? Cardiac masses can have a variable presentation. They can present with arrhythmias, angina, heart failure symptoms, or pericardial effusion. Patients can also be asymptomatic; the masses can be found incidentally on cardiac or chest imagining. 2. What is the differential diagnosis for cardiac masses? Cardiac masses are separated into benign and malignant. The most common malignant cardiac masses are metastases from a distant source. The location of the mass is important in narrowing the differential. 3. What imaging modalities are used to diagnose cardiac masses? Multimodality imaging is needed to describe the mass in detail and guide diagnosis. An echocardiogram is usually the first imaging modality. Cardiac MRI is a great modality that allows for the...

A heart MRI is a painless, safe and noninvasive way for your healthcare provider to see detailed pictures of your heart. Cardiac MRI images show the parts of your heart and any damage to specific areas and also show how well your heart's chambers and valves are working. Cardiac MRI is often a necessary diagnostic test for patients with cardiac implantable electronic devices (CIED) but challenging due to patient safety concerns and poor image quality. Drs. Callahan and Wilkoff talk with Dr. Deborah Kwon, Director of Cardiac MRI at Cleveland Clinic about cardiac MRI safety and image optimization.

CardioNerds (Amit Goyal and Daniel Ambinder), ACHD series co-chairs Dr. Dan Clark and Dr. Josh Saef, and ACHD FIT lead Dr. J.D. Serfas (Duke University) and Cardiology Fellow Dr. Victoria Thomas (Vanderbilt University) join ACHD experts Dr. Jamil Aboulhosn (Professor of Medicine at UCLA and the director of the Ahmanson/UCLA Adult Congenital Heart Disease Center) and Dr. Joanna Ghobrial, Medical and Interventional Director of the Adult Congenital Heart Disease Center at Cleveland Clinic. They discuss common ACHD pathologies that benefit from interventional cardiology procedures such as transcatheter pulmonic valve replacement (TPVR) and share new advancements in transcatheter approaches to correct sinus venosus defects. They end with a brief discussion on how to become an adult cardiology interventionalist that performs ACHD interventions. Episode notes were drafted by Dr. Victoria Thomas. Audio editing by CardioNerds Academy Intern, student doctor Akiva Rosenzveig.  The CardioNerds Adult Congenital Heart Disease (ACHD) series provides a comprehensive curriculum to dive deep into the labyrinthine world of congenital heart disease with the aim of empowering every CardioNerd to help improve the lives of people living with congenital heart disease. This series is multi-institutional collaborative project made possible by contributions of stellar fellow leads and expert faculty from several programs, led by series co-chairs, Dr. Josh Saef, Dr. Agnes Koczo, and Dr. Dan Clark. The CardioNerds Adult Congenital Heart Disease Series is developed in collaboration with the Adult Congenital Heart Association, The CHiP Network, and Heart University. See more Disclosures: None CardioNerds Adult Congenital Heart Disease PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Pearls - ACHD: Interventional Cardiology The ductus arteriosus, which is formed from the distal portion of the left sixth arch, is key to fetal circulation because it allows blood to bypass Transcatheter pulmonic valve replacement (TPVR) is a treatment for many ACHD patients that can spare them repeat sternotomies. This is important as many ACHD patients hava already undergone multiple surgeries in their childhood.   Before any ACHD cardiology intervention, appropriate imaging (TEE, TTE, Cardiac MRI, Cardiac CTA, and/or 3D printing) is imperative to understanding the relevant anatomy and hemodynamics to guide procedural indication and planning.    As with other structural interventions, consider a SENTINEL device (cerebral embolic protection system) to provide embolic protection in procedures that could lead to debris/embolic dislodgement when appropriate. Sinus venosus defects can be repaired via a transcatheter approach with a covered stent in the superior vena cava (SVC).   Consider using 3D printing or 3D digital imaging when preparing for complex ACHD interventions.    Notes- ACHD: Interventional Cardiology 1. When considering a patient for TPVR there are 3 types of landing zones for pulmonic valves in ACHD patients:    Pulmonary conduits or homografts. These are typically seen in patients with TOF or prior Ross or Rastelli procedure. These may be calcified and stenotic and so pre-dilatation is often needed before valve replacement.   Bioprosthetic Valves. (Valve in Valve TPVR) Native outflow tract 2. What are some of the more severe complications to consider when talking to an ACHD patient about a TPVR?   Coronary artery compression Conduit rupture Vessel injury (including the pulmonary bed) Valve embolization Endocarditis 3. What are some of the hemodynamic measurements one would want to pay attention to in a patient with a Fontan heart?    You will see higher CVPs in patients with a Fontan palliation.

CardioNerds (Amit Goyal and Daniel Ambinder), ACHD series co-chairs Dr. Dan Clark and Dr. Josh Saef, and ACHD FIT lead Dr. J.D. Serfas (Duke University) and Cardiology Fellow Dr. Victoria Thomas (Vanderbilt University) join ACHD experts Dr. Jamil Aboulhosn (Professor of Medicine at UCLA and the director of the Ahmanson/UCLA Adult Congenital Heart Disease Center) and Dr. Joanna Ghobrial, Medical and Interventional Director of the Adult Congenital Heart Disease Center at Cleveland Clinic. They discuss common ACHD pathologies that benefit from interventional procedures such as transcatheter pulmonic valve replacement (TPVR) and share new advancements in transcatheter approaches to correct sinus venosus defects. They end with a brief discussion on how to become an adult cardiology interventionalist that performs ACHD interventions. Episode notes were drafted by Dr. Victoria Thomas. Audio editing by CardioNerds Academy Intern, student doctor Akiva Rosenzveig.  The CardioNerds Adult Congenital Heart Disease (ACHD) series provides a comprehensive curriculum to dive deep into the labyrinthine world of congenital heart disease with the aim of empowering every CardioNerd to help improve the lives of people living with congenital heart disease. This series is multi-institutional collaborative project made possible by contributions of stellar fellow leads and expert faculty from several programs, led by series co-chairs, Dr. Josh Saef, Dr. Agnes Koczo, and Dr. Dan Clark. The CardioNerds Adult Congenital Heart Disease Series is developed in collaboration with the Adult Congenital Heart Association, The CHiP Network, and Heart University. See more Disclosures: None CardioNerds Adult Congenital Heart Disease PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Pearls - ACHD: Interventional Cardiology The ductus arteriosus, which is formed from the distal portion of the left sixth arch, is key to fetal circulation because it allows blood to bypass Transcatheter pulmonic valve replacement (TPVR) is a treatment for many ACHD patients that can spare them repeat sternotomies. This is important as many ACHD patients hava already undergone multiple surgeries in their childhood.   Before any ACHD cardiology intervention, appropriate imaging (TEE, TTE, Cardiac MRI, Cardiac CTA, and/or 3D printing) is imperative to understanding the relevant anatomy and hemodynamics to guide procedural indication and planning.    As with other structural interventions, consider a SENTINEL device (cerebral embolic protection system) to provide embolic protection in procedures that could lead to debris/embolic dislodgement when appropriate. Sinus venosus defects can be repaired via a transcatheter approach with a covered stent in the superior vena cava (SVC).   Consider using 3D printing or 3D digital imaging when preparing for complex ACHD interventions.    Notes- ACHD: Interventional Cardiology 1. When considering a patient for TPVR there are 3 types of landing zones for pulmonic valves in ACHD patients:    Pulmonary conduits or homografts. These are typically seen in patients with TOF or prior Ross or Rastelli procedure. These may be calcified and stenotic and so pre-dilatation is often needed before valve replacement.   Bioprosthetic Valves. (Valve in Valve TPVR) Native outflow tract 2. What are some of the more severe complications to consider when talking to an ACHD patient about a TPVR?   Coronary artery compression Conduit rupture Vessel injury (including the pulmonary bed) Valve embolization Endocarditis 3. What are some of the hemodynamic measurements one would want to pay attention to in a patient with a Fontan heart?    You will see higher CVPs in patients with a Fontan palliation.

Dr. Shaimaa Fadl reviews cardiac MR features of hereditary cardiomyopathy; and the role of MRI in risk stratification, treatment, and prognostication Cardiac MRI of Hereditary Cardiomyopathy. Fadl et al. RadioGraphics 2022; 42:625–643.

Dr. Miranda Bijvoet and Dr. Casper Mihl join host Dr. Praveen Ranganath to discuss a compelling systematic review on the atrial fibrosis through the lens of cardiac MRI, electroanatomic mapping, and histopathology. Correlation between Cardiac MRI and Voltage Mapping in Evaluating Atrial Fibrosis. Bijvoet et al. Radiology: Cardiothoracic Imaging 2022; 4(5):e220061.

This week, please join author Sean Pokorney and Associate Editor Shinya Goto as they discuss the article "Apixaban for Patients With Atrial Fibrillation on Hemodialysis: A Multicenter Randomized Controlled Trial." Dr Carolyn Lam:               Welcome to Circulation on the Run, your weekly podcast summary and Backstage Pass of the journal and its editors. We're your cohost. I'm Dr. Carolyn Lam, Associate Editor from the National Heart Center and Duke National University of Singapore. Dr Greg Hundley:            And I'm Dr. Greg Hundley, Associate Editor, Director of the Pauley Heart Center at VCU Health in Richmond, Virginia. Carolyn, this week's feature, very interesting topic. In patients that have end stage renal disease that require dialysis, questions emerged should we anticoagulate them to prevent stroke, but of course, there's a risk of excess bleeding. Well, this feature discussion today is a study comparing apixaban and warfarin for anticoagulation in exactly this patient population. But before we get to those results, how about we grab a cup of coffee and go through some of the other articles in the issue? Would you like to go first? Dr Carolyn Lam:               Absolutely, Greg. So my first paper is a pre-specified analysis of the Paradise MI trial and knowing you'll likely ask me what that was about, Greg, at least to summarize for everyone, the Paradise MI trial compared sacubitril/valsartan with ramipril and its effect on reducing heart failure events after an MI in more than 5,600 patients with an acute myocardial infarction complicated by LV systolic dysfunction, pulmonary congestion, or both. Now in today's paper, what Dr. Mehran and colleagues found was that among patients with a recent AMI and LV systolic dysfunction, heart failure are both, sacubitril/valsartan decreased the risk of coronary related events by 14% as compared with ramipril over a median follow-up of 22 months. The reduction in coronary events occurred with a favorable safety profile. Dr Greg Hundley:            Wow, Carolyn, very interesting. Another indication perhaps for sacubitril/valsartan, especially relative to ACE inhibitors. So what does this mean for us clinically? Dr Carolyn Lam:               Well, the results really cause us to consider if in addition to antiplatelets and lipid lowering therapies, sacubitril/valsartan may be explored as a potential agent to mitigate the residual risk in survivors of AMI. Of course, dedicated studies are necessary to confirm this finding and elucidate its mechanism. Dr Greg Hundley:            Oh, very nice, Carolyn. Well, my first paper comes to us from the World of Preclinical Science and Carolyn, this study evaluated the scavenger receptors stabilin-1 and stabilin-2, proteins that are preferentially expressed by liver sinusoidal endothelial cells. Now, they mediate the clearance of circulating plasma molecules controlling distant organ homeostasis. And studies suggest that stabilin-1 and stabilin-2 may impact atherosclerosis. So in this study, the investigative team led by Professor Cyrill Géraud from the University Medical Center and Medical Faculty in Mannheim, Heidelberg comprehensively studied how targeting stabilin-1 and stabilin-2 affects atherosclerosis. Dr Carolyn Lam:               Huh. All right, nicely explained. And so what did they find, Greg? Dr Greg Hundley:            Right, Carolyn. So inhibition of evolutionary conserved class H scavenger receptors, stabilin-1 and stabilin-2, reduced aortic plaque burden in preclinical models and athero protection was mediated likely through down regulation on transcriptional factor ERG1 in monocytes by multifaceted plasma protein changes. And then finally, Carolyn transforming growth factor beta induced periostin, reelin, and they are novel ligands of stabilin-1 and stabilin-2 and are implicated in the development of atherosclerosis. Dr Carolyn Lam:               Okay. Wow. Could you give us a take home message, please Greg? Dr Greg Hundley:            Right. Carolyn, I knew you had asked me this. So here we go. Monoclonal, anti-stabilin-1 and anti-stabilin-2 antibodies provide a novel approach for the future treatment of atherosclerosis. And in the future, perhaps the plasma proteome composition may serve as a predictive factor, biomarker or surrogate parameter for cardiovascular disease in patients. Dr Carolyn Lam:               Wow. Thanks Greg. My next paper is a true story of discovery. Now I could ask you what you know about the condition hypertension with brachydactyly type E... Greg, I love that expression. I wouldn't be able to answer that too. So let me tell you the story. So hypertension with brachydactyly type E is an autosomal dominant Mendelian disease resembling essential hypertension. Untreated patients die of stroke by the age of 50 years. Now, these authors had previously demonstrated a gain of function phosphodiesterase 3A gene mutations that caused the condition by increasing peripheral vascular resistance. They studied a large family with the condition earlier and were puzzled that cardiac hypertrophy and heart failure did not occur despite the decades of hypertension. And so they hypothesized that in the heart, this phosphodiesterase 3A or PDE3A mutations could be protective. Isn't that neat? And so corresponding authors, Doctors Bader, Klussmann, Bähring and Hübner, all from the Max Delbruck Center for Molecular Medicine in Berlin, Germany. So they studied new patients as well as CRISPR-Cas9 engineered rat models of this condition of hypertension with brachydactyly type E. And they comprehensively phenotyped all of them with the human induced pluripotent stem cells carrying these PDE3A mutations as well. So analyzing all of this from cells to new patients to CRISPR-Cas9 models. Dr Greg Hundley:            Wow, Carolyn, what an interesting story. So what did they find? Dr Carolyn Lam:               So while in vascular smooth muscle, the PDE3A mutations caused hypertension, in the hearts, they conferred protection against hypertension-induced cardiac damage, hypertrophy and heart failure. The mechanism involved long-term adaptations of mRNA and protein expression as well as calcium cycling. Non-selective PDE3A inhibition was a final short term option in heart failure treatment to increase cardiac cyclic AMP and improve contractility. So the data argued that mimicking the effect of PDE3A mutations in the heart rather than non-selective PDE3 inhibition was cardioprotective in the long term. And these findings could indeed facilitate the search for new treatments to prevent hypertension-induced cardiac damage. This is discussed in a really lovely editorial by Dr. Chiong, Houslay, and Lavandero. Dr Greg Hundley:            Very nice, Carolyn. Wow. What another... we have such great articles from the World of Preclinical Science. Beautiful description as well. Well, we have some other articles in the issue, particularly from the Mailbag. And we have a Research Letter from Professor Thiagarajan entitled “Yield of Cardiac MRI in a pre-participation cohort of Young Asian males with T-Wave inversion.” Dr Carolyn Lam:               Interesting. There's an exchange of letters between Dr. Xu and Huang regarding the article associations of dietary cholesterol, serum cholesterol and egg consumption with overall and cause-specific mortality with a systematic review and updated meta-analysis. There is a Perspective piece by Dr. Marcus on Smart watch detected atrial fibrillation, the value in positive predictive value. Isn't that interesting? And now onto that very, very important question of anticoagulation in patients with kidney disease. Can't wait. Let's go, shall we? Dr Greg Hundley:            You bet. Carolyn. Welcome listeners to our December 6th feature discussion. And we have with us today Dr. Sean Pokorney from Duke University in Durham, North Carolina, and our associate editor, Dr. Shinya Goto from Tokai University in Isehara, Japan. Welcome gentlemen. Well, Sean, we're going to start with you. Can you describe for us some of the background information that went into the preparation of your study and what was the hypothesis that you wanted to address? Dr. Sean Pokorney:         Yeah, absolutely. Thanks for having me to discuss the renal AF trial. And so I would say that the background information to the study was that we know that atrial fibrillation is an incredibly common condition in patients with chronic kidney disease. And the decision of anticoagulation in patients with end-stage kidney disease, on hemodialysis is really quite complex because these patients are at high risk for stroke and they're at high risk for bleeding. There are concerns with warfarin around calcific uremic arteriolopathy or calciphylaxis and there have been some data including from the original Aristotle trial that apixaban was even more favorable in terms of bleeding reduction relative to warfarin in patients with more advanced chronic kidney disease. Although patients with creatinine clearance less than 25 were excluded from Aristotle and really all patients with endstage kidney disease on hemodialysis have been excluded from all trials of atrial fibrillation in the past. And so we really wanted to evaluate the safety of apixaban versus warfarin in patients with end-stage kidney disease, on hemodialysis. And the hypothesis was that apixaban was going to be non-inferior to warfarin with respect to safety in terms of major or clinically relevant, non-major bleeding in these patients with atrial fibrillation and end stage kidney disease on hemodialysis. Dr Greg Hundley:            Thanks so much, Sean. And you've mentioned the renal AF trial. So could you describe for us, for your, I guess, substudy, what was the study population? Who did you include and describe for us also your study design? Dr. Sean Pokorney:         Yeah, absolutely. So the trial included patients who had end-stage kidney disease, and/or on hemodialysis, as well as having concomitant atrial fibrillation. And the patients had to have a CHA-VASc score greater than equal to two. All of the patients had to be on hemodialysis for at least three months. So these were chronic hemodialysis patients. And the study design was an open label randomized trial that was 1:1 randomization between apixaban and warfarin with blinded outcome evaluation. And again, the primary endpoint of the study was major or clinically relevant non-major bleeding based on ISTH definitions. And there were secondary endpoints looking at stroke, systemic embolism, death, medication adherence, and I think a really important sub-study looking at PK data. And the goal was to have 50 patients where we included PK data that was going to more represent what chronic apixaban dosing data would look like in these patients with end-stage kidney disease on hemodialysis. And originally the goal of the trial was to include over 700 patients. Originally we were trying to include 762 patients based on our initial power calculations to achieve true non-inferiority. Unfortunately, the trial enrollment was low and so the trial was ultimately stopped prematurely at 154 patients, although we were able to include the original targeted 50 patients in the PK substudy. The dosing that we used in the renal AF trial was 5 mg of apixaban twice daily unless patients had a second dose-reduction criteria in addition to chronic kidney disease. So the fact that they had end-stage kidney disease and were on hemodialysis counted as one dose reduction criteria and patients that were under 60 kilograms or less were 80 years of age or older, who had then a second dose-reduction criteria were treated with the 2.5 mg twice daily dosage. And this was important to note because this is different than the dosage that was used in the AXADIA-AFNET trial. Dr Greg Hundley:            Very nice. And so Sean, what did you find? Dr. Sean Pokorney:         Yeah. So again, a lot of this data is really exploratory because of the limited sample size, we weren't really able to definitively conclude anything about the major or clinically relevant non-major bleeding rates. I would say that some of the key findings that we saw was that there were high rates of major or clinically relevant non-major bleeding in both arms of the trial and one year bleeding event rates were 25% in the warfarin arm and 31% in the apixaban arm. And again, there was no statistically significant difference, although again, this is really exploratory. I would say that some of the other interesting findings that we saw was that there were very low rates of ischemic and hemorrhagic stroke in this patient population. Again, there were 82 patients randomized to apixaban, 72 patients randomized to warfarin. And there was a difference in the randomization because of the stratification by site that was performed with the randomization. And so within the 82 patients that were randomized to apixaban, the patients, there was one ischemic stroke and one hemorrhagic stroke. There were no hemorrhagic strokes in the warfarin population and two ischemic strokes. Another key finding was the high rates of mortality in this patient population. So 26% of the apixaban patients experienced a mortality event, 18% in the warfarin arm. So again, the mortality rates in these patient populations were extremely high. I would also emphasize some of the data from the PK analysis. So we looked at the PK analysis in two different ways. For the patients that were treated with the 5 mg dose of apixaban, the PK data showed that there was consistent overlap in the steady state concentration at one month compared to patients in the Aristotle trial that had really mild to moderate, moderate to severe and severe chronic kidney disease. And so there was a consistent overlap in those steady state concentrations between the end-stage kidney disease population on hemodialysis and the chronic kidney disease population who benefited from a apixaban in the Aristotle trial. Similarly, in the 2.5 mg apixaban dose, the patient who had a second dose reduction criteria in addition to chronic kidney disease, those patients had consistent steady state concentrations of apixaban relative to patients with mild to severe chronic kidney disease. Dr Greg Hundley:            Very nice. Well thank you so much, Sean. And listeners, now we're going to turn to our associate editor, Dr. Shinya Goto. Shinya, can you, sort of, highlight for us some of the interesting findings that you see from these study results that Sean just presented? Dr. Shinya Goto:              Thank you, Greg. Thank you, Sean for your wonderful summary of your study. We had a great discussion with an editor for this paper. As Sean pointed out, this is a kind of underpowered trial or just terminated early, hypothesis was not tested in the trial. But this population of patient clearly needs a real-world clinical trial, patient with atrial fibrillation, end-stage kidney disease, on hemodialysis; things a clinician could do. In some country, nephology society defined warfarin contraindicated in this population. As Sean pointed out, whether the development of this trial include this high-risk population patient. So we had a discussion whether the underpowered trial provided something or nothing may be better than something just provided here. Our consensus finally reached was, this limited trial still provide something like, you have to make a decision to use the anticoagulation. I mean, that the apixaban might be still used due to the PK data. That is the kind of interesting point of this trial. Dr Greg Hundley:            Very nice Shinya. Well, Sean, turning back to you and Shinya with that nice lead in really, Sean, what do you think is the next study that needs to be performed in this sphere of research? Dr. Sean Pokorney:         Yeah, absolutely. I think this is a challenging patient population to study. And again, our trial, the renal AF trial stopped early. Unfortunately, the AXADIA-AFNET 8 study also stopped early, which was also looking at apixaban versus warfarin outside the US and Europe. And so again, it is a challenging patient population to study. But again, I also think it's a really important population to study because one of the main unanswered questions in this population is whether or not they should receive anticoagulation. And so I think that ultimately more work and additional studies trying to determine whether or not these patients truly benefit from anticoagulation or stroke prevention, I think is really one of the critical directions that we need to take the field in. Dr Greg Hundley:            And Shinya, do you have anything to add? Dr. Shinya Goto:              Well, I fully agree with Sean. I mean, this is a very challenging area and still raising the question whether anticoagulation is necessary or not by your study. Maybe next generation oral anticoagulant such as Factor XI inhibitor that is more elevated to contact pathway may be beneficial. So we really need a good clinical study in this very important and known answered area. Dr Greg Hundley:            Very nice. Well listeners, we want to thank Dr. Dr. Sean Pokorney from Duke University in Durham, North Carolina and our own associate editor, Dr. Shinya Goto from Tokai University in Japan for bringing us the results of this randomized open-label trial of apixaban versus warfarin in patients with chronic kidney disease on hemodialysis, revealing high rates of bleeding in both groups, but due to low enrollment, was unable to identify its non-inferiority endpoint. It's important to note, however, as both our author and editorialists have identified further research is really needed in this area to really examine the efficacy of anticoagulation for stroke prevention in this high-risk patient population. Well, on behalf of Carolyn and myself, we want to wish you a great week and we will catch you next week On The Run. Dr. Greg Hundley:           This program is copyright of the American Heart Association 2022. The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more, please visit ahajournals.org.

This week we review a recent cardiac MRI report on Fontan geometry and hemodynamics as measured by computational fluid dynamic analysis. How do factors like Fontan geometry or 'power loss' relate to quality of life for the Fontan young adult patient? How do these data inform imaging in the operating room during these palliations? We speak with the first author of this work, Associate Professor of Pediatrics at U. Penn, Dr. Laura Mercer-Rosa about this important and intriguing work. https://doi.org/10.1016/j.athoracsur.2022.01.017

Dr. Linda Chu discusses the clinical impact of cardiac MRI T1 and T2 maps in patients with suspected cardiomyopathy with Dr. William Warnica and Dr. Kate Hanneman. Clinical Impact of Cardiac MRI T1 and T2 Parametric Mapping in Patients with Suspected Cardiomyopathy. Warnica et al. Radiology 2022; 305:319–326.

How much does colonoscopy actually reduce the risk of colorectal cancer? Find out about this and more in today's PV Roundup podcast.

Dr. Linda Chu discusses the validation of artificial intelligence cardiac MRI measurements and relationship to heart catherization and mortality prediction with Dr. Samer Alabed and Dr. Andrew Swift. Validation of Artificial Intelligence Cardiac MRI Measurements: Relationship to Heart Catheterization and Mortality Prediction. Alabed et al. Radiology 2022; 305:68–79.  

MRI (magnetic resonance imaging) tests are incredibly helpful to aid in diagnosis. Dr. Deborah Kwon, Director of Cardiac MRI at Cleveland Clinic speaks with Dr. Christopher Nguyen, PhD, Director of MRI Research in the Advanced Imaging and Simulation Center for MRI, about the future and advancements in cardiac MRI.

MRI (magnetic resonance imaging) tests are an incredibly helpful test for your care team to learn about your heart. Dr. Deborah Kwon, Director of Cardiac MRI at Cleveland Clinic talks with Christopher Nguyen, PhD, Director of MRI Research in the Advanced Imaging and Simulation Center for MRI, about the benefits of cardiac MRI and how they are working together improve this technology and the patient experience.

In this #Back2basicsPodcast, We have invited Dr. Asaad Akbar Khan graduated with distinction from King Edward Medical College, Lahore. He completed his Internal Medicine residency training at University College Hospital Galway (Ireland). He went on to receive accredited General Cardiology training(CCST) from the Royal College of Physicians, Ireland. During the course of his training, he successfully acquired MRCP(Ireland) and MRCP(UK) qualifications. He then moved to Boston, USA where he received advanced fellowship training in Cardiac Imaging (advanced echocardiography, Cardiac CT, Cardiac MRI) from Massachusetts General Hospital, Harvard Medical School, U.S followed by Fellowships in Interventional Cardiology & Structural Heart Diseases from Mount Sinai Hospital, New York, USA.

CardioNerds (Amit Goyal and Daniel Ambinder) join Dr. Sonu Abraham (Cardiology fellow, Lahey Hospital and Medical Center), Dr. Amitoj Singh (Internal Medicine Resident, Lahey Hospital and Medical Center), Dr. Ahmed Ghoneem (Internal Medicine Resident, Lahey Hospital and Medical Center, CardioNerds Academy Chief) and Dr. Aanika Balaji (Internal Medicine Resident, Johns Hopkins) for a scrumptious meal on the Boston Harbor as they discuss a case of a young woman with metastatic melanoma on immune checkpoint inhibitors presenting with dyspnea. The presentation, risk factors, work up and management of patients with immune checkpoint inhibitor induced myocarditis are described. The E-CPR segment is provided by Dr. Sarju Ganatra, the founding director of the cardio-oncology program at Lahey Clinic.  CardioNerds Clinical Trialist Dr. Carrie Mahurin (University of Vermont Medical Center) is introduced at the beginning of the episode. A 41-year-old woman presented with mild dyspnea on exertion and non-productive cough. She had a history of Hashimoto thyroiditis, nodular thyroid s/p resection on levothyroxine, and metastatic melanoma on immune checkpoint inhibitor therapy with ipilimumab and nivolumab. She also had a history of obesity and underwent gastric bypass surgery several years prior. Though she lost weight after the surgery, she regained a significant amount and was 244 lbs with a BMI of 42. Her exam findings were remarkable for tachycardia, bilateral pulmonary rales, elevated JVP, and symmetric pedal edema. Investigations revealed a mild troponin elevation, non-specific EKG changes, and TTE with severely reduced left ventricular function (EF 15%) and a low GLS. Cardiac MRI showed patchy delayed myocardial enhancement in a non-ischemic distribution with marked global hypokinesis and EF of 11%. Endomyocardial biopsy confirmed the diagnosis of immune checkpoint inhibitor (ICI) associated myocarditis. The ICI therapy was discontinued and she was treated with high dose intravenous corticosteroids followed by a prolonged oral steroid taper with clinical improvement and complete recovery of left ventricular function. Jump to: Case media - Case teaching - References CardioNerds Case Reports PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Case Media - immune checkpoint inhibitor myocarditis Episode Schematics & Teaching CardioNerds Myocarditis, updated 1.20.21 Pearls - immune checkpoint inhibitor myocarditis ICI-associated myocarditis has a high mortality rate necessitating a high degree of clinical suspicion. When in doubt, check it out! The initial 4 diagnostic pillars include EKG, troponin, BNP and TTE. Cardiac MRI and endomyocardial biopsy help to confirm the diagnosis.Left ventricular function is normal in 50% of these patients with ICI-associated myocarditis, so the ejection fraction is not a sensitive test for ruling this out.Endomyocardial biopsy should be considered in patients with a high clinical suspicion but negative or ambiguous non-invasive imaging.Early initiation of corticosteroids within 24 hours of presentation is associated with better outcomes.ICIs should be discontinued indefinitely in those with Grade 3 or 4 disease. Notes - immune checkpoint inhibitor myocarditis 1. Immune checkpoint inhibitors – What are they and why should we as cardiologists know about them? Immune checkpoint inhibitors (ICI) boost the host immune response against tumor cells by inhibiting the intrinsic brakes of the immune response.There are currently 7 FDA approved drugs in this group: one CTLA-4-blocking antibody called ipilimumab; three PD-1-blocking antibodies [nivolumab, pembrolizumab, and cemiplimab]; and three PD-L1-blocking antibodies [atezolizumab, avelumab, and durvalumab].Like a car,

This week, please join author Enrico Ammirati and Guest Editor Stephane Heymans as they discuss the article "Prevalence, Characteristics, and Outcomes of COVID-19–Associated Acute Myocarditis." Dr. Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the Journal and its editors. We're your co-host. I'm Dr. Carolyn Lam, Associate Editor from the National Heart Center and Duke National University of Singapore.  Dr. Greg Hundley: And I'm Dr. Greg Hundley, Associate Editor, Director of the Pauley Heart Center at VCU Health in Richmond, Virginia. Well, Carolyn, this week's feature on this April 12, we are going to review COVID-19–associated acute myocarditis, looking at the prevalence and the outcomes. But before we get to that feature discussion, how about we grab a cup of coffee and discuss some of the other articles in the issue, and maybe there could be a quiz in there somewhere. Dr. Carolyn Lam: Oh, yikes.  Dr. Greg Hundley: But before we get to that quiz, Carolyn, would you like to go first? Dr. Carolyn Lam: I would, and we're starting with a topic that we rarely talk about, it's about neurodevelopmental impairment. We know that it's common in children with congenital heart disease, yet postnatal variables explain only 30% of the variance in outcomes. To explore whether the antecedence for neuro development disabilities might begin in utero, these authors, led by Dr. Rollins from Boston Children's Hospital and Harvard Medical School, analyzed whether fetal brain volume predicted subsequent neuro development outcome in children with congenital heart disease. To do this, the authors studied fetuses with isolated congenital heart disease and social demographically comparable healthy controlled fetuses, all undergoing fetal brain MRI and two year neurodevelopmental evaluation.  Dr. Greg Hundley: Ah, Carolyn, wonderful, interesting article that we're taking on here in Circulation. What did this group find? Dr. Carolyn Lam: In children with congenital heart disease, a smaller total brain volume on fetal MRI correlated with worse neurodevelopmental outcome at two years of age, across all domains of development and adaptive function. A predictive model, including total brain volume, along with sociodemographic and medical data, accounted for up to 45% of the variance in neurodevelopmental outcome within the congenital heart disease group. Fetal brain volume was the most consistent predictor of outcomes across neurodevelopmental domains compared with other sociodemographic and medical or surgical variables.  Dr. Greg Hundley: Very nice, Carolyn. Well, my first paper comes to us from the world of preclinical science. Okay, Carolyn, we're going to start it with the infamous Carolyn's quiz. Here we go. Dr. Carolyn Lam: Wait a minute, we should put a rule here, no quizzes on preclinical basic science, especially stuff we can't pronounce.  Dr. Greg Hundley: Ah, yes, but seems to me, there's a heart failure expert on the team. Always remember, you can phone a friend because we have our wonderful Augie Rivera, our production manager, who is available and you can call on him at any time. Okay, here's the quiz, is Cam Kinase II helpful to cure or harmful to exacerbate heart disease? Dr. Carolyn Lam: Oh goodness, Greg. Okay. Cam Kinase II, I know it's Calcium-calmodulin Kinase II. I know there are different isoforms, and I'm cheating here a bit because last week we talked about targeting CaM Kinase II in heart disease. I'm going to guess harmful, I'm going to guess dealing with something with calcium overload, but I'm sure there's more to the story.  Dr. Greg Hundley: Carolyn, getting onto to the article, cardiac ischemia-reperfusion injury really has emerged as an important therapeutic target for ischemic heart disease, the leading cause, as we know, of morbidity and mortality worldwide. Currently, there is no effective therapy for reducing ischemia-reperfusion injury. Calcium II Calmodulin dependent Kinase II, or CaM Kinase II plays, a pivotal role in the pathogenesis of severe heart conditions, including ischemia-reperfusion injury. Therefore, pharmacological inhibition of CaM Kinase II could be an important strategy in the protection against myocardial damage and cardiac diseases. But to date, however, there is no drug targeting CaM Kinase II for the clinical therapy of heart disease. Furthermore, currently, there is no selective inhibitor of CaM Kinase II Delta, the major CaM Kinase II isoform, in the heart. Dr. Carolyn Lam: Wow. What did the authors do?  Dr. Greg Hundley: Okay, Carolyn. A small molecule kinase inhibitor library, and a high throughput screening system for kinase activity of CaM Kinase II Delta9, the most abundant CaM Kinase II Delta splice variant in the human heart, were used to screen for CaM Kinase II Delta inhibitors. Using cultured neonatal rat ventricular myocytes and human embryonic stem cell derived cardiomyocytes, as well as in vivo mouse models, in conjunction with myocardial injury induced by ischemia-reperfusion or hypoxia-reoxygenation and CaM Kinase II Delta9 over expression, this team, led by Professor Yan Zhang, from Peking University, sought to investigate the protection of Hesperidin against cardiomyocyte death and cardiac diseases. Dr. Carolyn Lam: Oh, wow. Please tell us, so what happened?  Dr. Greg Hundley: Right, Carolyn. Several important findings. First, Hesperidin, the Aurora B kinase inhibitor, with antitumor activity in vitro directly bound to CaM Kinase II Delta and specifically blocked its activation in an ATP competitive manner. Second, Carolyn, functionally, Hesperidin ameliorated both ischemia-reperfusion and over express CaM Kinase II Delta9 induced cardiomyocyte death, myocardial damage, and heart failure in both rodents and human embryonic stem cell derived cardiomyocytes. And then, finally, Carolyn, in an in vivo BALB/C nude mouse model, with xenografted tumors of human cancer cells, Hesperidin delayed tumor growth without inducing cardiomyocyte death or cardiac injury. Dr. Carolyn Lam: Wow. Goodness, Greg, that's impressive. Okay, what's the take home message?  Dr. Greg Hundley: Well, Carolyn, these results suggest that Hesperidin is a specific small molecule inhibitor of CaM Kinase II Delta with dual functions of cardioprotective and antitumor effects. These findings not only suggests that Hesperidin is a promising leading compound for clinical therapy of cardiac ischemia-reperfusion injury, and heart failure, but also could provide a strategy for the joint therapy of cancer and cardiovascular disease caused by anti-cancer treatment. Dr. Carolyn Lam: Wow, Greg, that is an amazing summary. Thank you. Well, for my last paper, I'd like to tell you about a study in which authors led by Dr. Lubo Zhang from Loma Linda University in California, and the colleagues, tested the hypothesis that microRNA-210 protects the heart from myocardial ischemia-reperfusion injury by controlling mitochondrial bio energetics and reactive oxygen species flux. Myocardial infarction in an acute setting of ischemia-reperfusion was examined via comparing loss versus gain of function experiments in microRNA-210 deficient and wall type mice.  Dr. Greg Hundley: Ah, Carolyn, another really interesting paper from the world of preclinical science. What were the results here? Dr. Carolyn Lam: MicroRNA-210 deficiency induced an ischemic sensitive phenotype and exaggerated acute myocardial infarction and cardiac dysfunction after MI in males in a gender dependent pattern in a murine model of myocardial infarction. The study identified a novel mechanism of MicroRNA-210 targeting mitochondrial glycerol-3-phosphate dehydrogenase in controlling mitochondrial energy metabolism, and reactive oxygen species flux, and improving cardiac function in the setting of acute ischemic-reperfusion injury. Thus, the present findings reveal new insights into the mechanisms and therapeutic targets for treatment of ischemic heart disease.  Dr. Greg Hundley: Oh, beautiful descriptions, Carolyn. Well, my next papers come from the mail bag, and there is a great Research Letter from Professor Downing entitled “Critical Illness Among Patients Hospitalized With Acute COVID-19 With and Without Congenital Heart Defects.” Carolyn, there's a second Research Letter from Professor Zhao entitled “Dual Genetic Lineage Tracing Reveals Capillary to Artery Formation in the Adult Heart.” Dr. Carolyn Lam: Nice. There's also an On My Mind paper by Dr. Mintz on “Prioritizing Quad Therapy and the Path Forward in Guideline-Directed Medical Therapy for Patients with Heart Failure with Reduced Ejection Fraction.” Cool, Greg, thank you. Now, let's go to our feature discussion, shall we?  Dr. Greg Hundley: You bet. To learn more about the prevalence and outcomes in COVID-19–associated acute myocarditis. Dr. Carolyn Lam: Acute myocarditis is thought to be a rare cardiovascular complication of COVID-19, or is it? Well, we have minimal data available in case reports, but really not a large scale study until today's issue and today's feature paper, which really aims to look at the prevalence, baseline characteristics, in hospital management and outcomes for patients with COVID-19–associated acute myocarditis. Dr. Carolyn Lam: I'm so pleased to have the first author with us, Dr. Enrico Ammirati from Niguarda Hospital in Milano, Italy, as well as our guest editor, Dr. Stephane Heymans from Maastricht University Medical Center in The Netherlands. Welcome, gentlemen. Enrico, thank you, thank you, thank you for this very important study. Could you please tell us what you did and what you found? Dr. Enrico Ammirati: Carolyn, it's a pleasure to be here with you and Stephane. We performed, let's say, large study on myocarditis associated with the COVID-19. That is a multicenter study, including 23 centers in the United States and in Europe. The senior author is Professor Marco [Metra], from Brasia, and the co first author is Dr. Laura Lupi, again, from Brasia. What we have done was to better characterize the prevalence of in-hospital myocarditis among the patients hospitalized with the COVID-19 diagnosis. Dr. Enrico Ammirati: And then, we tried to describe the outcome and the clinical characteristic at presentation. First of all, we define the myocarditis as a definitive or probable. That was based on the presence of cardiac magnetic resonance imaging consistent with myocarditis plus increase in troponin plus presence of symptoms that are compatible with an acute myocarditis. Alternatively, the patients must have a positive endomyocardial biopsy. Dr. Enrico Ammirati: The first result was that among more than 56,000 patients hospitalized in these hospitals, the rough prevalence of myocarditis was around 2.4 among 1000 hospitalized patients. The second main message was that the prognosis, we divided the population, we spitted the population in two groups. Patients with an ongoing and concurrent pneumonia and patient with myocarditis, but without evidence on CT of pneumonia. What we have found it was that among 57% of cases of COVID patients, you can have a myocarditis without pneumonia. So this is an interesting and new finding, and we compare the clinical characteristic of this patient comparing with the patient with the pneumonia. And we found that generally patient with pneumonia were older comparing with the patient with the isolated myocarditis and the prognosis of patients was worse comparing with the patient with just myocarditis. Dr. Enrico Ammirati: The outcome was around, overall, the outcome of this population that had median age of 38 year was an incidence of 6% of death. And if we look at the patient with the concurrent pneumonia, the outcome was worse. Then we have other findings that are of potential interest. And that is, for instance, that in 55% of patients, corticosteroids were used, and that is consistent with the idea that corticosteroids can work in this setting. We have also data on the presence of such Coronavirus, two in the heart, in patient that undergo vital search. And it was just in 21% of cases that underwent genome research in the myocardium. So I would say that these are the main findings of this research. Dr. Carolyn Lam: Oh, wow. First of all, heartfelt congratulations more than fifth, almost 57,000 hospitalized patients with COVID-19 and 23 hospitals across us and Europe. Stefan, you really appreciate that you served as guest editor here. Could you tell us some of your initial reactions, put the findings in context, perhaps? Dr. Stephane Heymans: Yes, yes. For sure. Enrico, indeed, I would like to concur with this congratulations on this beautiful study. It's a lot of work to collect this data and also to try to distinguish myocarditis from all other possible cause of cardiac injury. When I first saw this data, I think, oh, how difficult should be to make a diagnosis of myocarditis. And, of course, increased troponins are often seen in those COVID-19 hospitalized patients. Cardiac MRI is quite a specific for any non-ischemic myopathy. Yeah, I was wondering, so are these cardiac MRI images suggestive of acute myocarditis, but a really specific, sensitive enough to make a definite accurate diagnosis of COVID 19 related myocarditis, or could also be severe illness related to COVID-19 sepsis of pneumonia, give similar images on cardiac MRI? Dr. Enrico Ammirati: Stephane, this is a very good point. We haven't studied so in detail the cardiac injury in patients with the viral pneumonia, with the other viruses, so we cannot say that this kind of cardiac involvement is specific for such Coronavirus too. But what I can say is that this population is a population of highly likely acute myocarditis because if you look at simple clinical characteristics, and you can find that the median age is 38 years. This is the first reassuring a clinical characteristic because if we compare with the age of the population, of the laboratory registry of acute myocarditis we published in 2018 in Circulation, the media age was 36. Dr. Enrico Ammirati: Then, another point in support of our finding is that in the end, we have both present of edema and positive LG in patients with consistent myocarditis on magnetic resonance imaging. So, I know that probably edema can be associated with either other form of myocardial injury that are not necessary so specific for myocarditis. But if you look at troponin increase in this population, the median increase was 55 folds above the upper reference limit, so it was not just a small increase. It was a huge increase in troponin.   Dr. Enrico Ammirati: Specifically, in patients that were above 45 years, we have a confirmation that was no coronary artery disease associated, to assure the readers that likely these are myocarditis. But as you said, we cannot be 100% sure about that. And you mentioned an important point, we cannot say that, also, in other form of viral disease, we can have a myocardial injury that can be very similar to myocarditis. Dr. Stephane Heymans: Yes. Thank you so much for your clear answer. It just underscores how sick a COVID-19 can make you because the numbers you're getting is two [in] 1000, you would say, okay, that's a small number, but still, there's so many more patients with a cardiac injury related to COVID-19. Indeed, to put it into context, so common viral myocarditis occurs in one to 10, 100,000, so the COVID-19 related myocarditis is up to 100 times more with your numbers. And of course, the common viral myocarditis, it's at the same age, similar age around 36, means a young, relatively young age. Dr. Stephane Heymans: Indeed, this COVID-19 is probably a trigger in immune and maybe genetic susceptible, young persons had to get myocarditis upon COVID-19 disease. Whereas, the COVID-19 vaccination related myocarditis, which is getting much more media attention, at least, previous months, only occurs in one to five in 100,000 people. And those patients are completely recover and transplant free. Survival is over 99%. To put it in context, it's still quite severe at this COVID-19 related myocarditis. Dr. Carolyn Lam: Thank you so much. Stephane. Dr. Enrico Ammirati: Can I add some comments? First of all, we have to say that these patients that died with myocarditis associated with the COVID-19, died to complication related to ECMO. For instance, we had a patient with a brain hemorrhage, and we had one patient who had a complication related septic shock. So, myocarditis can be something on top of a severe disease. We have a condition that is as background that is quite severe, and we a further complication related to myocarditis, so what we have seen is that, generally, even comparing with the previous Lombardy Registry I referred before the outcome of this patient was worse. Of course, it's very difficult to compare studies that have been performed in different centers during a different time period. But, of course, if you think that most of viral myocarditis are secondary to cold or flu, so the background condition is really mild. Dr. Enrico Ammirati: The main focus is the myocarditis. While in this patient, we have a subpopulation where you have in a great proportion of them, a severe myocarditis associated with a pneumonia. So you have the double component and that can explain why this patient had a worse outcome. Referring to them, vaccination, my thought is that for the first time we have a large vaccine campaign in this range of age, between 15 and 30 years or 35 years, that is the population at higher risk for myocarditis, where we do not generally perform large campaign for vaccination.   Dr. Enrico Ammirati: In the end, it can be that we have seen more myocarditis related to vaccination because it was the first time that we vaccinate this kind of population. We have seen something similar with a smallpox vaccination in the military population. And that's the case because for other reason, that are not really related to the health reason, we vaccinated a high-risk population for myocarditis by itself. And we found that smallpox is more associated with myocarditis. Probably, there are, as you said, genetics per count that can explain in some patients an increase risk of myocarditis, but that can be possible that is there is also hormonal or epigenetics phenomena that can explain the higher risk in this population for myocarditis, both for COVID related or for vaccine related. Dr. Stephane Heymans: Ah, yeah. Enrico, could you remind me, was this incident of prevalence of COVID-19 myocarditis more prevalent in male patients compared to female when correcting for the background numbers? Dr. Enrico Ammirati: In our population, the main population was exactly was about 60%. There was just a slight increase in the number of cases in the male population, but it was not such a large prevalence as you expect in, let's say, uncomplicated myocarditis, where you can find an 80% of male prevalence or in vaccine. Dr. Stephane Heymans: Indeed. In the common or the vaccine related myocarditis, it's mainly young male, hetero sex, hormonal factors are being involved, so probably, as you say, these COVID-19 patients have a change in their immune background. And some of those, might some of those also have already background cardiomyopathy or myocarditis, maybe cardiomyopathy, that was not known yet. And then with the COVID-19 might have developed a clinical myocarditis/cardiomyopathy. Dr. Enrico Ammirati: When we look at the endostolic diameter of the left ventricle, I can say that the diameter was in the normal range, so that can support the idea that generate this patient did not have a previous dilated cardiomyopathy, but I cannot say that this patient had a known dilated cardiomyopathy before this event. Dr. Carolyn Lam: You know, once in a while, Augie, I get to do some of these interviews, and it just takes off on its own. And I love it. And there's nothing I need to do except to sit and listen, and to be grateful that you are publishing this and having such a lovely discussion on this podcast. Thank you, both of you. And, if I could, just very quickly, do you have any take home clinical messages now, from what you've seen, for someone who may be managing one of these COVID-19 patients and suspecting anything? Dr. Enrico Ammirati: Can I add that, in the end, what I can, say based on this research, is that likely myocarditis associated with COVID-19 is worse compared with myocarditis associated to vaccine. So even if we see that probably the prevalence is, again, high year with COVID-19, but the most important point is that it's even worse with myocarditis is associated with COVID-19 comparing with the vaccine, so please get the vaccination. Dr. Carolyn Lam: Thank you. And you've been listening to Circulation on the Run. From Greg and I, thank you for joining us today. I'm sure you're so grateful, and have learned so much, as I have. And don't forget to tune in again, next week. Dr. Greg Hundley: This program is copyright of the American Heart Association, 2022. The opinions expressed by speakers in this podcast are their own, and not necessarily those of the editors or of the American Heart Association. For more, please visit ahajournals.org.

Is COVID-19-related diabetes temporary? Find out about this and more in today's PV Roundup podcast.

This week we delve into the coronavirus pandemic and specifically the multisystem inflammatory syndrome in children (MIS-C) following COVID-19 infection. When there was significant initial cardiac involvement seen in the setting of MIS-C, what findings are common in the CMR of patients 6+ months later? How common is delayed enhancement seen and how does this compare with findings seen in other myocarditis patients? Who should be referred for a CMR following MIS-C? Dr. David Barris, 2nd year cardiology fellow at Mount Sinai Kravis Children's Heart Center in NYC and the first author of this week's work, provides the answers this week. DOI: 10.1016/j.jpeds.2021.10.009

Listen NowDr. Steve Muyskens, Medical Director, Cardiac MRI, 3-D aPPROaCH Lab, Cook Children's, takes us into the world of 3D heart printing. It’s a fascinating journey into how this advancing technology can take the guess work out of pediatric heart surgery, helping more young patients can thrive into adulthood. Dr. Steve Muyskens Related InformationCook Children's 3D aPPROaCH LabCardiac Magnetic Resonance ImagingCook Children's Cardiothoracic Surgery programCook Children's Endowed Chair ProgramCook Children's Heart Center Transcript 00:00:02 Host: Hello and welcome to Cook Children's Doc Talk. Today we welcome Dr. Steve Muyskens, medical director of the Cardiac MRI program here at Cook Children's in Fort Worth, Texas. Dr. Muyskens, is an endowed chair supporting the expansion of our CMRI program and its diagnostic uses. He has since established the three-dimensional lab for the planning and printing of congenital heart disease, which uses advanced technology to support presurgical planning and family education for patients with complex heart conditions. He is our expert on this subject. So thank you for being with us today, Dr. Muyskens/ 00:00:36 Dr. Muyskens: Thank you very much for the invitation. 00:00:38 Host: So what exactly is a 3D model? And what is the process for creating that model? 00:00:44 Dr. Muyskens So I think the important part is to kind of start with the patient. There are conditions with varying degrees of complexity that our current diagnostic modalities fall short in some manner. So those patients have long been difficult to manage. We started realizing that we can use technology like 3D printing and virtual 3D animation to help us better understand their condition. So when we identify that patient, whether it be an older patient who has already had some surgeries, or a newborn who has a very complex heart, who we're hoping to do an initial palliation, or surgical repair on, the first thing we decide is, what is the best modality to obtain the information that we would need to then use that technology. The two most commonly used technologies would be MRI, or cardiac CT. You can use rotational angiography in the cath lab, but that's much less commonly used. Once we have that selection made, the data is obtained by us obtaining a typical CT scan or a typical cardiac MRI. But then that data, which is in a raw form called DICOM. DICOM data is then moved to specialized software. And from there, I take that data, and we segment it is the term we use, basically manipulate that data and create a virtual model, essentially, from that information. That model can then be viewed either in the virtual space, so on a typical computer that you would flip around, but then again, you're still only in two dimensions you're looking at in a screen. So then typically, we move on to a 3D printing of that data. So the typical segmentation portion, or manipulation of the data, can vary from anywhere to two to 24 hours of time, depending on the complexity of the model. An

Ischaemic v Non-ischamic Cardiac MRI and various Cardiomyopathies

Ilkay Oksuz is an Assistant Professor in Computer Engineering Department of Istanbul Technical University. He leads the Predictive Intelligence and Medical Imaging (PIMI) Lab. He talks about his research on machine learning for medical image quality assessment with a particular focus towards Cardiac Magnetic Resonance Imaging.

Wende Gibbs, MD, Podcast Associate Editor of RadioGraphics, discusses two articles from the January-February 2021 issue of RadioGraphics. 00:00-00:22-Introduction by Dr. Wende Gibbs 01:02-15:29 - Multimodality Approach to Imaging Ovarian Neoplasms with Pathologic Correlation. Taylor et al. RadioGraphics 2021; 41:289–315.  15:30-24:17 - Cardiac MRI in Patients with Acute Chest Pain. Broncano et al. RadioGraphics 2021; 41:8–31.

Kristie Janabajal, imaging director with Temecula Valley Hospital, explains cardiac MRIs.

CardioNerds (Amit Goyal & Daniel Ambinder) join Virginia Commonwealth University (VCU) cardiology fellows (Ajay Pillai, Amar Doshi, and Anna Tomdio) for a delicious skillet breakfast and amazing day in Richmond, VA! They discuss a fascinating case of a patient with Wolff-Parkinson-White (WPW) and hypertrophic cardiomyopathy (HCM). Dr. Keyur Shah provides the E-CPR and program director Dr. Gautham Kalahasty provides a message for applicants. Episode notes were developed by Johns Hopkins internal medicine resident Colin Blumenthal with mentorship from University of Maryland cardiology fellow Karan Desai. Jump to: Patient summary - Case media - Case teaching - References Episode graphic by Dr. Carine Hamo The CardioNerds Cardiology Case Reports series shines light on the hidden curriculum of medical storytelling. We learn together while discussing fascinating cases in this fun, engaging, and educational format. Each episode ends with an “Expert CardioNerd Perspectives & Review” (E-CPR) for a nuanced teaching from a content expert. We truly believe that hearing about a patient is the singular theme that unifies everyone at every level, from the student to the professor emeritus. We are teaming up with the ACC FIT Section to use the #CNCR episodes to showcase CV education across the country in the era of virtual recruitment. As part of the recruitment series, each episode features fellows from a given program discussing and teaching about an interesting case as well as sharing what makes their hearts flutter about their fellowship training. The case discussion is followed by both an E-CPR segment and a message from the program director. CardioNerds Case Reports PageCardioNerds Episode PageCardioNerds AcademySubscribe to our newsletter- The HeartbeatSupport our educational mission by becoming a Patron!Cardiology Programs Twitter Group created by Dr. Nosheen Reza Patient Summary A man in his mid-60s presented to the ED after an episode of unwitnessed syncope while drinking. Patient had suddenly passed out from a seated position with no prodrome or post-ictal state. He had episodes like this in the past, which were thought to be seizures, but otherwise PMHx only notable for alcohol use disorder. He denied any FH of SCD or syncope. In the ED, exam was unremarkable. Labs notable for mild thrombocytopenia, mild hyponatremia with AKI, 2:1 AST/ALT ratio, elevated NT-proBNP, and a very high lactate that rapidly corrected with fluids. EKG was notable for sinus tachycardia, short PR interval, wide QRS, and delta waves consistent with Wolff-Parkinson-White (WPW) pattern. Echo showed preserved LVEF, thickened LV septum (1.6 cm) and posterior wall (1.3 cm) concerning for hypertrophic cardiomyopathy (HCM). No outflow tract gradient was noted at rest or with stress, and the strain pattern demonstrated apical sparing. Evaluation for cardiac amyloid, including plasma cell dyscrasia and PYP scan, was negative. Cardiac MRI confirmed severely thickened LV inferior and inferolateral walls at 1.7 cm with no LVOT obstruction. 25% of the myocardium demonstrated patchy LGE.   Due to concern for WPW syndrome, the patient underwent an EP study. This revealed a malignant septal accessory pathway that was successfully ablated with resolution of the WPW EKG features. Given large LGE burden in setting of HCM, patient underwent placement of primary prevention ICD. Genetic testing for PRKAG2 mutation is pending given comorbid WPW and HCM.  Case Media ABCDEFClick to Enlarge A. CXR: Slightly increased interstitial markings in the lung bases, an elevated right hemidiaphragm. No acute airspace disease or pulmonary edemaB. ECG: Sinus tachycardia rate 120bpm, PR interval 80ms, QRS 130ms, WPW pattern.  Arruda algorithm localizes to posterior septum.C. CMR:  Myocardium nulls before blood pool.D. CMR:  Delayed gadolinium enhancementE. Follow up ECG: NSR 78, repolarization abnormalities.  T wave memory inferior leads.F.

Full article: https://www.ajronline.org/doi/abs/10.2214/AJR.20.23903  Transthoracic echocardiography (TTE) is the standard of care in cardiac imaging for patients with suspected cardioembolic stroke. In this podcast, Amber Liles, MD discusses how cardiac MRI and cardiac CT angiography perform in comparison to TTE in terms of prediction of stroke recurrence.

Happy Women in Medicine Month! We’re celebrating by talking with super doc Dr. Kamala Tamirisa, a cardiologist super specialist in Cardiac Electrophysiology & Advanced Cardiac Imaging at Texas Cardiac Arrhythmia. She completed her training in Internal Medicine and served as Chief Resident at St. Louis University in Missouri. After she completed General Cardiology, Cardiac Electrophysiology, and Cardiac MRI fellowships at the University of Michigan. She then joined a large cardiology group (ProMedica Physicians Cardiology) in Ohio where she serves as the Director of The University of Toledo.   She talks about her journey into medicine, which started with her father walking into her classroom trying to get her to stop studying medicine. Kamala and Donnica discuss how even though everyone is tired of talking about politics, politics plays a crucial role in our healthcare system. Kamala talks about her personal experience of working with patients who refuse to wear a mask during the pandemic. If Kamala could make one big change in the health care system, she would take away the insurance companies she has to fight with to get her patients the care they need. They discuss RBG’s legacy and the best way for the Supreme Court to move forward to give women the best fighting chance for fair healthcare.

athlete heart covid https://www.the-scientist.com/news-opinion/college-athletes-experienced-heart-damage-after-covid-19-study-67929 titiles like- “Images of the players’ hearts showed signs of inflammation consistent with myocarditis, a rare but potentially fatal condition.” “two dozen of Ohio State University players using cardiac magnetic resonance (CMR), they found evidence of myocarditis in 15 percent, while a further 30 percent had cellular damage or swelling “ The Ny york times said- https://www.nytimes.com/2020/09/16/well/move/is-coronavirus-affecting-the-hearts-of-college-athletes.html Is Coronavirus Affecting the Hearts of College Athletes? “In a new study of 26 college athletes who tested positive for coronavirus, four later showed signs of inflammation in their heart muscles.” and my favorite-- CNN says https://www.cnn.com/2020/09/14/health/covid-heart-inflammation-athletes-study/index.html Covid-19 study suggests to screen recovering athletes for heart inflammation before they return to play “As athletes recover from Covid-19, taking images of their hearts to screen for inflammation may help doctors determine when it could be safe to get back in the game, new research suggests.” Now lets look at this paper and see if this paper says what you think it says or at least does it say what the Big Ten thinks it says!! In the press release for the big ten return to football they say “The Big Ten Council of Presidents and Chancellors (COP/C) adopted significant medical protocols including daily antigen testing, enhanced cardiac screening and an enhanced data-driven approach when making decisions about practice/competition. “ they go on to say “All COVID-19 positive student-athletes will have to undergo comprehensive cardiac testing to include labs and biomarkers, ECG, Echocardiogram and a Cardiac MRI.” The thing I find funny is they say things like ‘data-driven approach but then say things like ‘a positive athlete can not return for a minimum of 21 days’ and athletes must get a cardiac MRI along with a bunch of other non evidence based and non data driven recommendations. BUT this podcast is about the cardiac MRI in athletes so let's look at that paper and why it is dead fricken wrong!! This is a perfect example of why school presidents should play doctor and realistically speaking, I as a doctor don’t want to be a school president. https://jamanetwork.com/journals/jamacardiology/fullarticle/2770645?guestAccessKey=ad3c4563-167f-452a-917f-7bfe15663b06&utm_source=For_The_Media&utm_medium=referral&utm_campaign=ftm_links&utm_content=tfl&utm_term=091120 The paper that has created this cardiac MRI craze is titled - Cardiovascular Magnetic Resonance Findings in Competitive Athletes Recovering From COVID-19 Infection it was in jama cardiology on sept 11 and they researchers at ohio state did CMR imaging in 26 competitive college athletes who previously had been diagnosed with COVID19. and they found “Four athletes (15%; all male individuals) had CMR findings consistent with myocarditis and Pericardial effusion was present in 2 athletes with CMR evidence of myocarditis.” the authors conclusions, “Cardiac magnetic resonance imaging has the potential to identify a high-risk cohort for adverse outcomes and may, importantly, risk stratify athletes for safe participation because CMR mapping techniques have a high negative predictive value to rule out myocarditis.4” they go on to say “cardiac magnetic resonance imaging evidence of myocardial inflammation has been associated with poor outcomes, including myocardial dysfunction and mortality.6 “ this sounds terrible!!! I will give you a second to grab a drink and sit down because I think in the next several minutes you will be both relieved and frustrated about what this article really says. music this was first released by anish koka on twitter but she was spot on and this sort of information needs widespread dissemination. As I said there were 26 athletes but out of those 12 had mild symptoms DURING the infection and 14 were asymptomatic during the infection. None of these pts had chest pain or required hospitalization not even a slightly elevated troponin from demand ischemia during their infection was reported and per the paper, “There were no diagnostic ST/T wave changes on electrocardiogram, and ventricular volumes and function were within the normal range” now the current return to play protocol is all expert opinion but in the article is cited as 2-week not activity and if asymptomatic then no diagnostic cardiac testing but if symptomatic then an electrocardiogram and transthoracic echocardiogram. The authors want you to look at this and say hey we might need to add CMRI lots look at their logic “Cardiac magnetic resonance imaging has the potential to identify a high-risk cohort for adverse outcomes and may, importantly, risk stratify athletes for safe participation because CMR mapping techniques have a high negative predictive value to rule out myocarditis.4” https://www.sciencedirect.com/science/article/pii/S0735109718388430?via%3Dihub and they site Cardiovascular Magnetic Resonance in Nonischemic Myocardial Inflammation: Expert Recommendations which the opening line says “This Journal of American College Cardiology Scientific Expert Panel provides consensus recommendations for an update of the cardiovascular magnetic resonance (CMR) diagnostic criteria for myocardial inflammation in patients with suspected acute or active myocardial inflammation” This is the first fault--remember these were healthy athlets THAT DID NOT HAVE SUSPECTED ACUTE OR ACTIVE MYOCARDIAL INFLMMATION!! you cant say well this test does really good at detecting a specific illness in this population so it must do a could job at detecting it in every population. That it like say well antibiotics work well to make people feel better when they have bacterial infections so they must work to make patients with cancer feel better. NO NO NO next they said, “Cardiac magnetic resonance imaging evidence of myocardial inflammation has been associated with poor outcomes, including myocardial dysfunction and mortality.6 “ and this comes from a paper titled “Prognostic value of cardiac magnetic resonance tissue characterization in risk stratifying patients with suspected myocarditis.” WITH SUSPECTED MYOCARDITIS!! this study was 670 patients who had CLINICALLY SUSPECTED myocarditis who then got a CMRI. just to get in to that study you had to have one of the following 1) acute chest pain syndromes with symptom onset

CardioNerds (Amit Goyal & Daniel Ambinder) join Northwestern University cardiology fellows (Sarah Hale, Sarah Chuzi, and Graham Lohrmann) for burgers and a great case by the Chicago River! They discuss a fascinating case of arrhythmogenic desmoplakin cardiomyopathy. Dr. Lisa Wilsbacher provides the E-CPR and program director Dr. Benjamin Freed provides a message for applicants.  Episode notes were developed by Johns Hopkins internal medicine resident Richard Ferraro with mentorship from University of Maryland cardiology fellow Karan Desai.  Jump to: Patient summary - Case figures & media - Case teaching - References - Production team Episode graphic by Dr. Carine Hamo The CardioNerds Cardiology Case Reports series shines light on the hidden curriculum of medical storytelling. We learn together while discussing fascinating cases in this fun, engaging, and educational format. Each episode ends with an “Expert CardioNerd Perspectives & Review” (E-CPR) for a nuanced teaching from a content expert. We truly believe that hearing about a patient is the singular theme that unifies everyone at every level, from the student to the professor emeritus. We are teaming up with the ACC FIT Section to use the #CNCR episodes to showcase CV education across the country in the era of virtual recruitment. As part of the recruitment series, each episode features fellows from a given program discussing and teaching about an interesting case as well as sharing what makes their hearts flutter about their fellowship training. The case discussion is followed by both an E-CPR segment and a message from the program director. CardioNerds Case Reports PageCardioNerds Episode PageCardioNerds AcademySubscribe to our newsletter- The HeartbeatSupport our educational mission by becoming a Patron!Cardiology Programs Twitter Group created by Dr. Nosheen Reza Patient Summary A male in his early 40s presented for second opinion regarding multiple ICD shocks. 10 years prior he was diagnosed with a "weak heart," thought secondary to a viral illness and a dual-chamber ICD was placed at that time. He noted shocks occurring for the first time 5 years prior, at which time amiodarone was started. They recurred two years prior, when he was diagnosed with paroxysmal atrial fibrillation. Finally, he was hospitalized one month before presentation with multiple ICD shocks and was found to have high defibrillation thresholds (DFTs) and amiodarone was stopped. He  then presented for a second opinion from the Northwestern CardioNerds!  The patient had been doing well on GDMT and had NYHA Class I symptoms (Enjoy Ep #13 - Approach to GDMT). He did note a family history of a cousin with "cardiac issues" and did not know his father's family history. Physical exam demonstrated bradycardia and ECG demonstrated an a-paced, v-sensed rhythm at 50 bpm. TTE demonstrated a moderately dilated LV with LVEF 30%, globally reduced LV function and multiple wall motion abnormalities without a vascular distribution.  PET-CT was performed which showed diffuse uptake and high-intensity signal at the inferolateral and basal anterior walls. Cardiac MRI showed diffuse circumferential epicardial delayed enhancement with associated diffuse, enhancing thickening of the pericardium favoring inflammatory versus fibrotic process. Patient was initially diagnosed with cardiac sarcoid and started on prednisone and weekly methotrexate.   On return of genetic testing, patient found to have a pathogenic variant for desmoplakin gene, and it was felt his cardiomyopathy was secondary to desmoplakin Left Dominant Arrhythmogenic Cardiomyopathy (LDAC, or left-dominant ARVC) presenting with inflammatory myocardial injury. On follow up the patient remained listed for transplant, and DFTs improved off amiodarone.   Case Media CXRECGCardiac MRIPET CT (Cardiac Sarcoid Protocol)Click to Enlarge Episode Schematics & Teaching Created by Dr.

Dr. Kamala Tamirisa is a clinical cardiac electrophysiologist at Texas Cardiac Arrhythmia, In Dallas Texas. Dr. Tamirisa completed her training in Internal Medicine and served as Chief Resident at St. Louis University. She then went on to complete her General Cardiology, Cardiac Electrophysiology, and Cardiac MRI fellowships at the University of Michigan, Ann Arbor, Michigan. In this podcast you’ll hear about Dr. Tamirisa’s unique take on how to become a leader in the field of medicine, her fascinating hobbies and how she uses them to decompress after a long day at work, you’ll hear her explain how the heart works in very simple terms, and the direction in which her field is moving. Her twitter handle is @KTamirisaMD. You can see her full bio at: https://tcaheart.com/dr-kamala-tamirisa/ White Coat Story is a podcast series for school students to gain first-person insights into the practice of medicine, and what it takes to get there.

What exactly is a cardiac MRI, and what should you expect if your doctor has ordered one? Dr. David Fieno, cardiologist at Shelby Baptist Medical Center, as well as Dr. Alain Bouchard and Dr. Mustafa Ahmed break down the benefits and drawbacks of this technology as well as what patients will most likely experience at their cardiac MRI scan.About the Team Dr. Alain Bouchard is a clinical cardiologist at Cardiology Specialists of Birmingham, AL. He is a native of Quebec, Canada and trained in Internal Medicine at McGill University in Montreal. He continued as a Research Fellow at the Montreal Heart Institute. He did a clinical cardiology fellowship at the University of California in San Francisco. He joined the faculty at the University of Alabama Birmingham from 1986 to 1990. He worked at CardiologyPC and Baptist Medical Center at Princeton from 1990-2019. He is now part of the Cardiology Specialists of Birmingham at St. Vincent’s Health System, Ascension. Dr. Mustafa Ahmed is a Structural Heart Specialist, Interventional Cardiologist and Scientist, and is the director of the Structural Heart Disease Program at UAB. He is a leading performer of minimally invasive heart procedures, including the Mitraclip procedure. He is credited with several first of their kind procedures and internationally recognized in areas including valvular and surgical heart disease and POTS. He was born in Nottingham, England, and went to medical school at the Victoria University of Manchester. He took postgraduate positions at the Manchester Royal Infirmary, then the Queens Medical Center. Dr Ahmed moved to Birmingham, AL, where he was the first person selected for the Physician Scientist Training Program with specialization in cardiology and interventional cardiology. Dr. Philip Johnson is originally from Selma, AL. Philip began his studies at Vanderbilt University in Nashville, TN, where he double majored in Biomedical and Electrical Engineering. After a year in the “real world” working for his father as a machine design engineer, he went to graduate school at UAB in Birmingham, AL, where he completed a Masters and PhD in Biomedical Engineering before becoming a research assistant professor in Biomedical Engineering. After a short stint in academics, he continued his education at UAB in Medical School, Internal Medicine Residency, and is currently a cardiology fellow in training with a special interest in cardiac electrophysiology. Medical DisclaimerThe contents of the MyHeart.net podcast, including as textual content, graphical content, images, and any other content contained in the Podcast (“Content”) are purely for informational purposes. The Content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read or heard on the Podcast! If you think you may have a medical emergency, call your doctor or 911 immediately. MyHeart.net does not recommend or endorse any specific tests, physicians, products, procedures, opinions, or other information that may be mentioned on the Podcast. Reliance on any information provided by MyHeart.net, MyHeart.net employees, others appearing on the Podcast at the invitation of MyHeart.net, or other visitors to the Podcast is solely at your own risk. The Podcast and the Content are provided on an “as is” basis.

The Cleveland Clinic Director of Cardiac MRI, Dr. Deborah Kwon, discusses the principles and clinical applications of cardiac MRI, taking us from the protons to the bedside with a series of illustrative cases. CardioNerds hosts Amit Goyal, Daniel Ambinder, and Carine Hamo are joined by Dr. Nicole Pristera (Cleveland Clinic cardiology fellow). Flutter moment by student doctor Arooma Shahid. On the CardioNerds Myocarditis page you will find podcast episodes, infographic, youtube videos, references, tweetorials and guest experts & contributors, flutter stars and so much more. Take me to the Myocarditis Series PageTake me to the Episode Topics PageCheck out Amit Goyal’s Myocarditis Tweetorial Links in this episode: Mental Filter: Matters of the Heart: Part 1Mental Filter: Matters of the Heart: Part 2Cardiac Imaging Agorà Dr. Debbie Kwon attended medical school at the University of Michigan and internal medicine residency at the University of Pennsylvania. She completed her general cardiology and cardiovascular imaging fellowships at the Cleveland Clinic. She is the Director of Cardiac MRI At the Cleveland Clinic and serves as the Core Lab MRI director for the Pulmonary Vascular Disease Phenomics (PVDOMICS) multicenter National institution of Health (NIH) Study. Dr. Nicole Pristera is a cardiology fellow at the Cleveland Clinic.  She earned her medical degree at Case Western Reserve University and completed her internal medicine residency training at Duke University. Her clinical interests include interventional cardiology and cardiac critical care. Outside of the hospital, she enjoys traveling, hiking, and learning foreign languages. Episode Outline What should we know about the common sequences for cardiac MRI?We all learn about the risks of NSF.  How much of these risks are a reality and when should we truly avoid gadolinium exposure?What are some challenges to MRI: Time of scanningPatient tolerability: breath holding, claustrophobia, lying flatNo patient monitorFerromagnetic devices (especially CIEDs) Artifacts (lead) CostWhat types of information about the heart can we obtain with a CMR?Anatomic: 0.5 x 0.5 x 0.5mm spatial resolutionChamber dimensions, volumes, mass, anomalies (LV aneurysm, hypertrophy)Aortic DissectionCardiac Tumors and Thrombi Congenital defects FunctionalCine images: EF, systolic wall thickening, wall motionMyocardial tagging → strain (infarct/scar)Measurement of blood flow velocity across the cardiac valves and the great vessels: regurg, stenosis, shunts, angioTissue characterization: gadolinium enhancementPerfusion (stress, rest)ViabilityScar (LGE)EdemaIron The role for Cardiac MRI in particular cases discussed with Dr. Kwon CAD: A 45 year old G1P1 woman with prior preeclampsia and anterior STEMI s/p LAD PCI 3 years ago is being seen for chest pain. TTE shows LVEF 45% with mid-apical anterior hypokinesis and apical aneurysm. How does CMR help delineate ischemic heart disease (perfusion, viability, chambers)  Pericarditis: her stress MRI shows an anteroapical perfusion defect and apical aneurysm with mural thrombus, with corresponding LGE. On further review, her chest pain is sharp, pleuritic, and worsens with recumbency. EKG on follow-up shows diffuse ST elevations and PR depressions except for in aVR which shows ST depression and PR elevation. ESR and CRP are moderately elevated.  ARVC: A 35 year old female athlete who is admitted after VF arrest that occurred during a tennis match. Thankfully she received immediate bystander CPR with early defibrillation and prompt ROSC. She has had prior syncope during training and an uncle died suddenly at age 40. Resting EKG shows an incomplete right bundle, right precordial TWIs, and epsilon waves in V1-V3.  On tele she’s had multiple runs of NSVT of LBBB morphology. Echocardiogram shows RV dilation. A heart failure consult is considering EMBx but requests a CMR beforehand.

In this episode, we discuss Cardiac MR with a Cardiologist (Dr. Marcotte) and a Radiologist (Dr. Jokerst). We cover various topics starting with the basics of what Cardiac MRI is used for, important sequences, 1.5T 3T comparison, what pathologies are better evaluated on MR vs other modalities, the purpose of Contrast, and all the ways CMR help with treatment and better outcomes for the patient. Thanks for joining us here in Zone 3.

A lot of us started our journey in healthcare 3D printing accidentally. Listen to this ice-breaker style interview with Dr. Shafkat Anwar, Pediatric Cardiology Director of Cardiac MRI, as well as Co-Founder and Co-Director of the UCSF Center for Advanced 3D+ Technologies (CA3D+). Hear his story on how 3D+ Technologies beyond 3D printing is helping patients (and their families) fighting against congenital heart disease and how UCSF 3D+ Lab is combating against the ongoing pandemic. His full written interview can be found here.   He will be speaking at "Point of Care" panel at the upcoming 3DHEALS2020 in June, 2020.Dr. Shafkat Anwar (Twitter: @ShafkatAnwar) is a pediatric cardiologist with a specialty in non-invasive cardiac imaging, including echocardiography and cardiac magnetic resonance imaging (MRI). He is the Pediatric Cardiology Director of Cardiac MRI, as well as Co-Founder and Co-Director of the UCSF Center for Advanced 3D+ Technologies (CA3D+). He is a founding member and the inaugural Chair of the Advanced 3D+ Visualization Special Interest Group in the Society for Cardiovascular Magnetic Resonance. He is a consultant at Printerprezz, a medical start-up in Fremont, CA utilizing additive and other advanced manufacturing technologies to develop the next generation of medical devices.  At Printerprezz. Dr. Anwar serves as the Senior Vice President of Medical Innovations. Dr. Anwar completed his internship and residency in Pediatrics at Children's National Medical Center, as well as a research fellowship at the National Institutes of Health. He completed fellowships in Pediatric Cardiology and Cardiac Imaging at Cleveland Clinic and Children's Hospital of Philadelphia. Prior to joining UCSF, Dr. Anwar was the Cardiology Director of Cardiac MRI at Washington University in St. Louis, St. Louis Children's Hospital.  At Wash. U. Dr. Anwar co-founded and co-directed the Center for 3D Printing, a multi-disciplinary 3D printing center. He will be speaking at "Point of Care" panel at the upcoming 3DHEALS2020 in June, 2020.Support the show (https://www.paypal.com/cgi-bin/webscr?cmd=_s-xclick&hosted_button_id=STF9STPYVE2GG&source=url)

David A. Bluemke, MD, PhD, Editor of Radiology discusses four research articles from the September 2019 issue of Radiology. ARTICLES DISCUSSED –Summary of Safety Considerations of 7-T MRI in Clinical Practice. Radiology 2019; 292:509–518. Summary of Summary of Left Atrial Fibrosis Assessed with Cardiac MRI in Patients with Paroxysmal and Those with Persistent Atrial Fibrillation. Radiology 2019; 292:575–582. Summary of Summary of Kidney Injury after Intravenous versus Intra-arterial Contrast Agent in Patients Suspected of Having Coronary Artery Disease: A Randomized Trial. Radiology 2019; 292:664–672. Summary of Iodine-based Dual-Energy CT of Traumatic Hemorrhagic Contusions: Relationship to In-Hospital Mortality and Short-term Outcome. Radiology 2019; 292:730–738.

Expand your idea of ischemic heart disease to include non-obstructive patterns, which as our guest, Dr Noel Bairey Merz, a clinical investigative cardiologist whose multiple roles include Director of the Barbra Streisand Women’s Heart Center and the Preventive Cardiac Center at the Smidt Cedars-Sinai Heart Institute, shares with us, is incredibly common, especially in women.  Learn to recognize these women and treat according to guidelines, preventing unnecessary IHD mortality in our female (and some male) patients. We review a variety of non-obstructive pathologies and the best techniques to evaluate them. Full show notes available at http://thecurbsiders.com/podcast. Join our mailing list and receive a PDF copy of our show notes every Monday. Rate us on iTunes, recommend a guest or topic and give feedback at thecurbsiders@gmail.com. Credits Written and produced by: Shreya Trivedi MD, Molly Heublein MD Hosts: Paul Williams MD, FACP; Shreya Trivedi MD; Molly Heublein MD Edited by: Matthew Watto MD, FACP; Emi Okamoto MD Graphics by: Hannah Abrams Guest: Dr. C Noel Bairey Merz MD, FACC, FAHA Curbsiders' Schwag! We’ve got the perfect father’s day gift for every internal medicine nerd. The Curbsiders have opened our own online shop. Get your Curbsiders t-shirts, hoodies, stickers, and coffee mugs. Help support the show and gain instant bragging rights. Note: All purchases come with admitting privileges at Kashlak Memorial Hospital! Time Stamps 00:00 Intro, disclaimer and guest bio 04:36 Guest one-liner; Advice for success in research and clinical practice 07:07 A case of shortness of breath and chest tightness; Why the paradigm of obstructive coronary artery disease is flawed. 12:04 Why is there a sex difference in ischemic heart disease? 14:52 How to recognize ischemic heart disease in women; Are certain symptoms more likely in women; Categorizing angina 20:13 Who needs stress testing?; Screening for ischemic heart disease in women 24:52 How guidelines make good doctors great doctors 27:00 Diagnosis of NSTEMI in a woman without obstructive coronary disease 29:33 Medical therapy for non-obstructive ischemic heart disease 33:18 Additional testing: Cardiac MRI for myocarditis; perfusion reserve testing; CT coronary angiograms 35:48 How current non-invasive techniques fail to identify microvascular ischemic heart disease in women 39:10 Antianginal therapy 41:40 HFpEF in women 47:10 Weight loss for paroxysmal atrial fibrillation 48:45 New nomenclature for ischemic heart disease 50:18 Take home points 52:40 Outro

Dr. Deborah Kwon Director of MRI in the Miller Family Heart & Vascular Institute at Cleveland Clinic answers questions about cardiac MRI: what is the best use? When should contrast be ordered? What is the latest research involving cardiac MRI? And - what clinicians should know about ordering MRI.

Dr. Deborah Kwon Director of MRI in the Miller Family Heart & Vascular Institute at Cleveland Clinic answers common questions about cardiac MRI: What is it used for? Is it safe after surgery or if you have a device implanted? What does conditionally safe mean? Is MRI safe after heart valve surgery? How long does an MRI take? What if I am claustrophobic? Who should not have an MRI? And – how do you get your results?

Dr. Paul Wang:           Welcome to the monthly podcast On the Beat for Circulation Arrhythmia and Electrophysiology. I'm Dr Paul Wang, editor-in-chief, with some of the key highlights for this month's issue. We'll also hear from Dr. Suraj Kapa reporting on new research from the latest journal articles in the field.                                                 In our first article, Barry Maron associates report on the long term clinical course of hypertrophic cardiomyopathy patients following ICD therapy for ventricular arrhythmias. They studied a cohort of 486 high-risk hypertrophic cardiomyopathy patients with ICDs from eight international centers. Of these 486 patients over 6.4 years, 94 patients or 19% experienced appropriate ICD interventions, terminating VT or VF. Of the 94 patients receiving appropriate ICD therapy, 87 were asymptomatic or only mildly symptomatic at the time of appropriate ICD interventions. Of these 87 patients, 74 or 85% remained in classes one or two without significant change in clinical status of the subsequent 5.9 years up to 22 years. Among the 94 patients, there was one sudden death in three patients who died from non arrhythmic hypertrophic cardiomyopathy related processes. Post ICD intervention, freedom from hypertrophic cardiomyopathy, mortality was 100% at one year, 97% at five years, and 92% at 10 years, distinctly lower than the risk of ischemic or non ischemic cardiomyopathy in ICD trials.                                                 Hypertrophic cardiomyopathy patients with ICDs interventions reported the heightened anxiety and expectation of future shocks. However, they did not affect general psychological well-being or quality of life. The authors concluded that in hypertrophic cardiomyopathy, unlike ischemic heart disease, prevention of sudden death with ICD therapies unassociated with a significant increase in cardiovascular morbidity and mortality, nor transformation into heart failure deterioration, ICD therapy does not substantially impair overall psychological and physical well-being. In our next article, Abdulla Damluji and associates examined the cost of hospitalizations for cardiac arrest using the US nationwide inpatient sample from 2003 to 2012. Using the log transformation of inflation adjusted costs the authors examined 1,387,396 patients who were hospitalized after cardiac arrest. They had a mean age of 66 years. Inpatient procedures included coronary angiography in 15%, PCI in 7%, intra-aortic balloon pump in 4.4%, therapeutic hypothermia in 1.1%, and mechanical circulatory support in 0.1% of patients.                                                 Notably the rates of therapeutic hypothermia increased from 0 in 2003 to 2.7 in 2012, p less than 0.001. Both hospital charges inflation adjusted costs linear increased over time. In a multi-variant analysis predictors of inflation adjusted costs included large hospitals size, urban teaching hospital, and length of stay. Among co-morbidities, atrial fibrillation or fluid and electrolytes imbalance were the most common associated with cost. The authors found that during the period between 2003 and 2012 post cardiac arrest, hospitalizations had a steady rise and associated healthcare costs likely related to increase length of stay, medical procedures and systems of care.                                                 In our next paper, Peter Huntjens and associates examined intrinsic interventricular dyssynchrony as a predictor of human dynamic response to cardiac resynchronization. The authors use a cardiovascular computational model CircAdapt to characterize the isolated effect of intrinsic interventricular or intraventricular activation on resynchronization therapy response that is the change in LV dP/dt max. The simulated change in LV dP to dt max had a range of 1.3 to 26.5% increased considerably with increasing inter ventricular dyssynchrony. In contrast, the isolated effect of intra ventricular dyssynchrony was limited with the change in the LV dP/dt max range and the left ventricle from 12.3 to 18.3% in the right ventricle from 14 to 15.7%.                                                 Secondly, electrocardiographic imaging derived activation characteristics of 51 CRT candidates were used to create individual models of ventricular activation in CircAdapt. The model predicted change in LV dP/dt max was close to the actual value in left bundle branch block patients with 2.7% difference between measured and simulated when only intrinsic interventricular dyssynchrony was personalized. Among non left bundle branch block patients a change in LV dP/dt max was systematically over predicted by CircAdapt with a 9.2% difference between measured and simulated. Adding intra ventricular activation to the model did not improve the accuracy of response prediction. The authors found that computer revealed intrinsic interventricular dyssynchrony is the dominant component of the electrical substrate driving the response to CRT.                                                 In the next paper Kenji Kuroki and associates examined the use of voltage limit adjustment of substrate mapping and fast Fourier transform analysis of local ventricular bipolar electrograms during sinus rhythm to predict VT isthmuses. They performed these studies and nine post infarction patients who underwent catheter ablation for total of 13 monomorphic ventricular tachycardias. Relatively higher voltage areas on electroanatomical map or defined as high voltage channels, which were further classified as full or partial if the entire or more than 30% of the high voltage channel was detectable. 12 full high voltage channels were identified in seven of nine patients. Relatively higher fast Fourier transform areas were defined as high frequency channels, which were located on seven of 12 full high voltage channels. Five VT isthmuses or 71% were included in the seven full high voltage channels positive in high frequency channel positive sites.                                                 While no VT isthmuses were found in five full high voltage channel positive but high frequency channel negative sites, high frequency channels were identical to 9 out of 16 partial high voltage channels. Eight VT isthmuses or 89% were included in nine partial high voltage channel positive in high frequency channel positive sites, whereas no VTs isthmuses were found in the seven partial high voltage channel positive and high frequency channel negative sites.                                                 All high voltage channel positive in high-frequency channel positive sites predicted VT isthmus with a sensitivity of 100% and specificity of 80%. The authors concluded that based on this small series that combined use of voltage, limited adjustment and fast Fourier transform analysis may be useful method to detect VT isthmuses.                                                 In the next study, John Whitaker and associates examined the use of lesion index, LSI index, a proprietary algorithm combining contact force, radio-frequency application duration, and RF current. Cardiac CT was used to assess atrial tissue thickness. Ablation lines two to three per animal were created in the right atrium in seven mini pigs with point lesions using 25 watts of energy. Two weeks after the ablation, serial sections of targeted atrial tissue or examine histologically to identify gaps and transmural ablation. LSI guidelines had a lower incidence of histological gaps. Four gaps in the 69 catheter moved or 5.8% compared to ablation using LSI plus two millimeter lines in which there is seven gaps in 33 catheter moves or 21.2% and using LSI plus four millimeter lines in which there are 15 gaps in 23 moves or 65.2% p less than 0.0. The change in LSI was calculated retrospectively is a distance between two adjacent lesions above the mean LSI of the two lesions. Changing LSI values of 1.5 or less were associated with no gaps in transmural ablation.                                                 The authors concluded that in this mod of chronic atrial ablation delivery of uninterrupted transmural linear lesions may be facilitated using LSI to guide catheter movement. When change in LSI between adjacent legions is 1.5 millimeters or lower, no gaps in atrial linear lesions should be expected.                                                 In our next paper, Matthew Bennett and associate examined whether their response to antitachycardia pacing in patients with ICD could further discriminate ventricular from super ventricular arrhythmias in patients receiving ATP in the RAFT trial. The RAFT trial randomized 1,798 patients with New York Heart Association class two or three heart failure, left ventricular ejection fraction less than or equal to 30%, in QRS duration 120 millisecond or greater, to an ICD plus or a minus cardiac resynchronization. Beginning with 10,916 ATP attempts for 8,150 tachycardia episodes in 924 patients, the author's excluded tachycardias where ATP terminated the episode or were the specific etiology tachycardia was uncertain. In this study, they analyzed 3,676 ATP attempts delivered to 2,046 tachycardia episodes in 541 patients. The authors found that a shorter difference between the post pacing interval is PPI minus TCL, was more likely to be associated with VT than SVT, mean of 138.1 milliseconds for VT and 277.4 milliseconds for SVT p, less than 0.001. A PPI minus TCL value of less than or equal to 300 milliseconds had a sensitivity in 97.4% and a specificity of 28.3% for VT.                                                 The authors concluded that specifically the PPI minus TCL following antitachycardia pacing may help distinguish ventricular from supraventricular arrhythmias.                                                 In the next study, Shailee Shah and Amr Barakat and associates examined the outcomes after repeat AF ablation. The authors examined 137 patients out of a total of 10,378 patients undergoing Afib ablation who had had initial long-term success defined from recurrent arrhythmias for greater than 36 months off anti-arrhythmic drugs in subsequent underwent repeat ablation for recurrent atrial fibrillation. The median arrhythmia free period that define long-term success was 52 months. In redo-ablations reconnection of at least one of the pulmonary veins was found in 111 or 81% of patients. Additional non PV ablations were performed in 127 or 92.7% of patients. After a mean follow-up of 17 months, 103 patients or 75% were arrhythmia-free, 79 off anti-arrhythmics, and 24 on arrhythmics. The authors found that repeat ablations with re-isolation to the point of veins and modifying the atrial substrate had a good success rate.                                                 In the next article Qiongling Wang and associates hypothesized that genetic inhibition of CaMKII oxidation in a mouse model of Duchenne muscular dystrophy can alleviate abnormal calcium homeostasis thus preventing ventricular arrhythmias. The authors tested whether the selective loss of oxidation of the CaMKII effects ventricular arrhythmias in the mouse model of Duchenne muscular dystrophy. Genetic inhibition of ox-CaM kinase II by knocking replacement of the regulatory domain methionines with valines, which we'll call MMVV, prevented ventricular tachycardia in the mdx mice. Confocal calcium imaging of ventricular myocytes, isolated from the mdx MMVV mice revealed normalization of intra-calcium release events compared to myocytes from the mdx mice. Abnormal action potentials as assessed by optical mapping mdx were also alleviated by genetic inhibition of ox-CaMK II. Knockout of the NADPH oxidase regulatory sub-unit P 47 Fox normalized elevated ox-CaMK II, repaired intracellular calcium hemostasis and rescued inducible ventricular arrhythmias in the mdx mice. The authors concluded that inhibition of ROS or ox-CaMK II protects against pro-arrhythmic intracellular calcium handling, preventing ventricular arrhythmias in a mouse model of Duchenne muscular dystrophy.                                                 In the next article, Kyohei Marume and Teruo Noguchi and associates examined whether the combination of QRS duration of 120 milliseconds or greater in late gadolinium enhancement is a precise prognostic indicator for the primary endpoint of all cause death and a composite of sudden cardiac death or aborted sudden cardiac death in 531 patients with dilated cardiomyopathy. They also analyzed the association between the combination of late gadolinium enhancement and increased QRS duration in these end points among patients with a class one indication for implantable defibrillator. The author's divided study patients in three groups according to late gadolinium enhancement in QRS duration. Two negative indices that is late gadolinium enhancement negative and narrow QRS, one positive index with either late gadolinium enhancement positive or wide QRS or two positive indices late gadolinium positive and wide QRS and followed them for 3.8 years. Multiple variable Cox regression analysis identified to positive indices as significant predictors of all cause death. A hazard ratio of 4.29 p equals 0.026. Among the 317 patients with a class one indication for ICD, the five year event rate of sudden cardiac death or aborted sudden cardiac death was lowest in the two negative indices groups, 1.4%. With propensity score matching cohorts the two negative indices group had a significant lower event rate of sudden cardiac death or aborted sudden cardiac death than to two other groups hazard ratio 0.2, p equals 0.046.                                                 The authors concluded that the combination of late gadolinium enhancement in wide QRS provides additional prognostic stratification compared to late gadolinium enhancement status alone.                                                 In the next study, Matthew Sulkin and associates examined whether a novel local impedance measurement on an ablation catheter identifies catheter tissue coupling and is predictive of lesion formation. The author's first studied explanted hearts, 10 swine, and then in vivo 10 swine, using an investigational electro anatomical mapping system that measures impedance from an ablation catheter with mini electrodes incorporated into the distal electrode. Rhythmia and Intellanav, Boston Scientific.                                                 Explanted tissue was placed in a warmed 37 degree celsius saline bath mounted on a scale, and the local impedance was measured 15 millimeters away from the tissue to five millimeters of catheter tissue compression at multiple catheter angles. Lesions were created for 31 and 50 watts from 5 to 45 seconds for an N of 70. During in vivo valuation of the local impedance measurements of the myocardium 90 and blood pool 30 were guided by intracardiac ultrasound while operators were blinded to the local impedance data. Lesions were created with 31 and 50 watts for 45 seconds in the ventricle with an n of 72. The local impedance of myocardium, which was 119.7 ohms, was significantly greater than in blood pool 67.6 ohms the p of less than 0.01. Models that incorporate local impedance drop to predict lesion size had better performance that models incorporate force time integral r squared of 0.75 versus r squared of 0.54 and generator impedance drop r squared of 0.2 versus r squared of 0.58. Steam pops displayed a significantly higher starting local impedance and a larger change in local impedance compared to successful RF applications, p less than 0.01.                                                 The authors concluded that local impedance recorded for miniature electrodes provides a valuable measure of catheter tissue coupling and the change in local impedance is predictive of lesion formation during RF ablation.                                                 In the next paper, Boaz Avitall and associates found that the rising impedance recorded from a ring electrode placed two millimeters from the cryoballoon signifies ice formation covering the balloon surface and indicates ice expansion. The authors studied 12 canines in a total of 57 pulmonary veins, which were targeted for isolation. Two cryoapplications were delivered per vein with a minimum of 90 and a maximum 180 second duration. Cryoapplications was terminated upon reaching a 500 ohm change from baseline. Animals recovered 38 plus or minus six days post procedure, and the veins were assessed electrically for isolation. Heart tissue was histological examined. Extra cardiac structures were examined for damage. Pulmonary vein isolation was achieved in 100% of veins if the impedance reached 500 ohms in 90 to 180 seconds. When the final impedance was between 200 and 500 ohms within 180 seconds of freeze time, pulmonary vein isolation was achieved in 86.8%. For impedance of less than 200 ohms pulmonary vein isolation was achieved in 14%. No extra cardiac damage was recorded. The authors found that impedance rise of 500 ohms at less than 90 seconds with a freeze time of 90 seconds resulted in 100% pulmonary vein isolation.                                                 In our final papers Sally-Ann Clur and associates examined left ventricular isovolumetric relaxation time as the potential diagnostic marker for fetal Long QT Syndrome. Left ventricular isovolumetric contraction time, ejection time, left ventricular isovolumetric relaxation time, cycle length, and fetal heart rate were measured using pulse doppler wave forms in fetuses. Time intervals were expressed as percentage of cycle length, and the left ventricular myocardium performance index was calculated. Single measurements were stratified and compared between Long QT Syndrome fetuses and controls. Receiver operator curves were reformed for fetal heart rate in normalized left ventricular isovolumetric relaxation time. A linear mixed effect model including multiple measurements was used to analyze fetal heart rate, the left ventricular iso volume metric relaxation time, and the left ventricular myocardial performance index. There were 33 Long QT fetuses in 469 controls. In Long QT fetuses the left ventricular isovolumetric relaxation time was prolonged in all groups, p less than 0.001, as was the left ventricular isovolumetric relaxation time.                                                 The best cutoff to diagnose Long QT syndrome was the normalized left ventricular isovolumetric relaxation time greater than equal to 11.3 at less than or equal to 20 weeks, giving a sensitivity in 92% and a specificity of 70%. Simultaneous analysis of the normalized left ventricular isovolumetric relaxation time and fetal heart rate improved the sensitivity and specificity of Long QT Syndrome, AUC of 0.96. The normalized left ventricular isovolumetric relaxation time, the left ventricular myocardial performance index, and fetal heart rate trends differed significantly between Long QT Syndrome fetuses and controls throughout gestation.                                                 The authors concluded that left ventricular volumetric relaxation time is Prolonged QT fetuses. Findings of a prolonged normalize left ventricular isovolumetric relaxation time, and sinus bradycardia can improve the prenatal detection of fetal Long QT Syndrome.                                                 That's it for this month, but keep listening. Suraj Kapa will be surveying all journals for the latest topics of interest in our field. Remember to download the podcasts On the Beat. Take it away Suraj. Suraj Kapa:                          Thank you, Paul and welcome back to On the Beat were we will be summarizing hard-hitting articles across the entire electrophysiologic literature. Today we'll be starting within the realm of atrial fibrillation where we're review an article within the realm of anticoagulation and stroke prevention. Quon et al. published in last month's issue of JACC cardiac electrophysiology on anticoagulant use and risk of ischemic stroke and bleeding in patients with secondary atrial fibrillation. It is well known that use of anticoagulation in atrial fibrillation can reduce overall thromboembolic outcomes. However, its role in secondary atrial fibrillation is unclear. Thus, the authors sought to evaluate the effects anticoagulant use on stroke and bleeding risk. Amongst those where atrial fibrillation occurred in the setting of acute coronary syndrome, pulmonary disease, or sepsis. Amongst around 2300 patients evaluated retrospectively there was no evidence of a lower incidence of ischemic stroke among those treated with anticoagulants compared to those who are not.                                                 However, anticoagulation was associated with a higher risk of bleeding in those with new onset AF associated with acute pulmonary disease. The authors suggest as a result that there is unclear overall benefit for long-term anticoagulation in patients with presumed secondary atrial fibrillation. The difficulty in assessing this is how to define secondary atrial fibrillation. However, in many studies patients who developed in the setting of acute illness still had a high risk of developing quote unquote clinically significant AF in long-term follow-up. However, this was not necessarily absolute as many patients not necessarily develop AF that could be considered clinically significant. Thus, the clinical question that arises is: how long should we treat a patient with anticoagulation when they have presumed secondary atrial fibrillation. These data seem to suggest that there may be no net overall benefits. In other words, all-comers with secondary atrial fibrillation should not necessarily be forever treated with anti-coagulation. However, this slightly requires clinical trials to evaluate further.                                                 Next we delve into the realm of cardiac mapping and ablation where we view an article by Gaita et al. entitled 'Very long-term outcome following transcatheter ablation of atrial fibrillation. Are results maintained after 10 years of follow-up?', published in Europace last month. While pulmonary vein isolation is a widely accepted approach for treatment of atrial fibrillation, most reported studies review outcomes in terms of freedom of AF over a relatively short time period, generally two to five years. However longer term follow up is inconsistently reported. Gaita et al. sought to review 10 year outcomes amongst 255 patients undergoing ablation in a single center. They noted 52% remainder arrhythmia-free amongst a mixed cohort of both paroxysmal and persistent patients while 10% progressed to permanent atrial fiBrillation. They found that absence of increases in blood pressure, BMI, and fasting glucose was protective against an arrhythmia recurrence.                                                 These findings suggest that in a relatively small cohort of patients limited to a single center that even long-term outcomes after pulmonary vein isolation are generally quite good, exceeding 50%. However, future freedom from atrial fibrillation is heavily tied to control of other risk factors. In other words, if a patient is going to have poor control of diabetes, blood pressure, or gain weight, the benefit of their pulmonary vein isolation over long-term follow-up is likely less. These data thus highlight both the potential long-term benefit of PVI, but also the importance of counseling patients regarding the need for continued management and control of future and existing risk factors.                                                 Staying within the realm of atrial fibrillation we next review an article by Weng et al. entitled 'Genetic Predisposition, Clinical Risk Factor Burden, and Lifetime Risk of Atrial Fibrillation' published in last month's issue of circulation. The probability of detecting atrial fibrillation in patients based on clinical factors and genetic risk is unknown. Weng et al. sought to clarify whether a combination of clinical and polygenic risk scores could be used to predict risk of developing atrial fibrillation over long-term followup in the Framingham Heart Study. Amongst 4,600 individuals, 580 developed incident atrial fibrillation and had an overall lifetime risk of developing atrial fibrillation of 37%. Those are the lowest risk tertile based on clinical risk factor burden and genetic predisposition had a lifetime risk of 22% versus 48% in the highest. Furthermore, a lower clinical risk factor burden was associated with delayed atrial fibrillation onset. In order to identify patients with atrial fibrillation, before negative sequelae such as stroke occur, patient and physician understanding of risk and monitoring needs is necessary. The fact is that it will be great to identify every single patient who has atrial fibrillation before they have a negative sequela of that atrial fibrillation such as ischemic stroke.                                                 However, performing continuous monitoring of all patients with potential negative sequelae of atrial fibrillation is extraordinarily difficult. The reason is it's excessively costly. We cannot monitor the entire population irrespective of whatever the risk factors are. However, if we're able to identify the highest risk cohorts early on before the atrial fibrillation onsets, this may offer opportunities for use of newer cheaper monitors. The work by Weng et al. suggests one such possible approach combines clinical and polygenic risk scores. Actionability of these data, however, remains to be seen and further validation other cohorts is necessary to clarify generalized ability.                                                 The next article we review is published in last month's issue of the Journal of American College of Cardiology by Lopes at al. entitled 'Digoxin and Mortality in Patients With Atrial Fibrillation. Lopes et al. sought to evaluate the impact of the Digoxin on mortality in patients with atrial fibrillation and the association with the Digoxin serum concentration and heart failure status. They value this association in over 17,000 patients. At baseline 32% were receiving Digoxin. Baseline Digoxin use did not associate with risk of death, but even in these patients a serum concentration of greater than 1.2 nanograms per milliliter was associated with a 56% increase in mortality risk. For each .5 nanogram per milliliter increase in oxygen concentration the hazard ratio increased by 19% for overall mortality. This was irrespective of heart failure status. Furthermore, in patients who are newly started in Digoxin over the follow-up period, the risk and death and sudden death was higher. These data suggests a significant risk associated with Digoxin use for management of atrial fibrillation irrespective of heart failure status. Furthermore, serum valleys above 1.2 require close consideration of dose de-escalation. Whether there is any optimal dose, however, from the study is unclear. These data amongst a host of prior data strongly suggest again strategic use of Digoxin  principally for the management of atrial fibrillation.                                                 Moving on within the realm of atrial fibrillation, we review an article published in last month's issue of Circulation Research by Yan et al. entitled Stress Signaling JNK2 Crosstalk with CaMKII Underlies Enhanced Atrial Arrhythmogenesis. In this more acellular based study the mechanism underlying atrial arrhythmogenesis associated with aging was evaluated. Yan et al. sought to figure out whether the stress response JNK in calcium mediated arrhythmias might contribute to atrial arrhythmogenesis in aged transgenic mouse models. They demonstrated significant increased activity of JNK2 and aging atria, those furthermore associated with rhythmic remodeling. This association was mediated through CaMKII and ryanodine receptor channel function, with activation of the former leading to increased calcium leak mediated by the ladder. This in turn related to increase atrial fibrillation likelihood. Identifying novel targets for atrial fibrillation therapy is critical. Given atrial fibrillation is a complex disease process related to a multitude of risk factors it can be assumed that the contribution of any single factor may be mediated through distinct mechanisms.                                                 Aging in particular as well regarded, but considered to be non-modifiable risk factor for atrial fibrillation. Identifying genes or pathways, the immediate aging associated fibrillation, may take the risk of aging as no longer a non-modifiable thing. The finding of the significance of JNK2 and associate downstream effects with AF risks and aging hearts may hold potential in offering unique therapeutic targets.                                                 Finally, within the realm of atrial fibrillation, we're viewing article by Chen et al. in last month's issue of the Journal of the American Heart Association entitled Association of Atrial Fibrillation With Cognitive Decline and Dementia Over 20 Years: The ARIC-NCS Study. Multiple studies have suggested a significant association between atrial fibrillation risk of dementia. However, these studies have limited time follow-up and were often done and predominantly white patients. Thus, the authors sought to use the data from ARIC, the Atherosclerosis Risk in Communities Neurocognitive Study, to assess the risk of cognitive decline associated with atrial fibrillation. Amongst over 12,000 participants, a quarter of whom are black and half of whom are white, they noted 2100 patients developed atrial fibrillation and 1,150 develop dementia over a 20 year follow up period.                                                 There was a significantly greater risk of cognitive decline amongst those who developed atrial fibrillation. In turn incident atrial fibrillation for the follow-up period was associated with a higher risk of dementia even after adjusting for other clinical and cardiovascular risk factors such as incidents that ischemic stroke. These data further strengthened prior evidence of a direct link between atrial fibrillation and risk of cognitive decline and dementia. Understanding this long-term risk raises the need to additionally identify approaches to prevent this occurrence, which in turn is dependent on understanding the underlying mechanisms. The finding that the risk of cognitive decline dementias independent of ischemic stroke events raises concern that either subclinical micro-embolic events or other factors may be playing a role in this risk and in turn raises question as to how best to prevent them. Until better understood, however, the question of whether the association is causal remains to be seen.                                                 Changing gears yet again, we now delve into the realm of ICDs, pacemakers and CRT. Published in last month, issue of Heart Rhythm Tarakji et al. published a paper entitled 'Unrecognized venous injuries after cardiac implantable electronic device transvenous lead extraction.' Overall risk of transvenous lead extraction includes that of potentially fatal venous laceration. The authors sought to evaluate the incidence of venous injury that may be unrecognized based on microscopic study of extracted leads. Amongst 861 leads obtained from 461 patients they noted 80 leads or almost 9%. Amongst 15% of patients showed segments vein on the lead body, most of which were transmural including the tissue layer. However, in terms of clinical significance, only 1% had need for emergent surgical intervention for clinically significant venous laceration. Risk factors for having the entire vein on the lead included age of lead, ICD leads, and the use of the laser sheath.                                                 These findings suggest that there may be a high incidence of subclinical venous injury after lead extraction though rarely resulting clinically apparent sequelae. As would be expected, venous injury, including transmural removal of portions of the vein traversed by the lead, was more common amongst older leads, which generally more often require laser sheets and ICD leads. The question is however, whether this carries any direct clinical implications. One they may be considered is the potential additive risk of an advancing new lead through the same venous channel, particularly in the setting of potential transmural venous injury that already exists.                                                 Next in last month's issue of Heart Rhythm we review an article by Sharma at al. entitled 'Permanent His-bundle pacing as an alternative to biventricular pacing for cardiac resynchronization therapy: A multicenter experience.' The use of resynchronization therapy for treatment of patients with heart failure and wide QRS has been shown to offer morbidity and mortality benefits. However, many patients maybe non-responders, and recent studies on His bundle pacing of suggested potential clinical benefits. His bundle pacing essentially only requires one pacing catheter attached within the region of the His bundle Sharma et al. sought to evaluate the safety and success rates of His bundle pacing for patients who have either failed standard resynchronization therapy or in whom most tried as a primary intervention. They noted His bundle pacing was successful in 90% of patients with reasonable myocardial and His bundle capture thresholds. Patients in both groups exhibits significant narrowing of QRS morphology and improvement in left ventricular ejection fraction from a mean of 30 to 43%. However, a total of seven patients had lead related complications.                                                 These database on a retrospective analysis of two types of patients, those failing standard biventricular therapy, and those on whom his bundle pacing was attempted as a primary modality suggest overall safety and efficacy in a handful of experienced centers. The promise of His bundle pacing is that a may allow for more effective resynchronization than standard approaches. The high rate of success suggests that His bundle pacing maybe both safe and reasonable to pursue. However randomized trials across more centers are needed to fully prove its benefit, particularly as a primary modality of treatments.                                                 Next we review ICDs and chronic kidney disease. In last month's issue of JAMA cardiology by Bansal at al. entitled 'Long-term Outcomes Associated With Implantable Cardioverter Defibrillator in Adults With Chronic Kidney Disease.' While the benefit of ICDs in patients with low EF is widely recognized, modifying factors that may increase risk of death are not as well defined. These include things like advanced age and chronic kidney disease. Bansal et al. sought to evaluate long-term outcomes and ICD therapy in patients with chronic kidney disease. In retrospective study of almost 5,900 ambulatory patients amongst whom 1550 had an ICD, they found no difference in all cause mortality. However, ICD placement was associated with an increased risk of subsequent hospitalization due to heart failure or any cause hospitalization.                                                 In light of recent studies such as DANISH the robust sense of ICD benefit is being questioned. One of the thoughts for the absence of similar benefit to prior studies lies in the improving care of ambulatory heart failure patients. In patients with chronic kidney disease several questions rises to the risk with ICD, including infectious risk in dialysis patients and the concomitant mortality risk with renal dysfunction. The author suggested in retrospective study, no incremental benefit of ICDs in patients with chronic kidney disease and perhaps some element of added risk is related to hospitalization. However, this study has several limitations. It is retrospective and many patients received ICDs may have been perceived to be sicker in some way. Thus care must be taken in interpretation, but consideration of randomized studies to adjudicate benefit are likely necessary.                                                 Finally, within the realm of devices, we reviewed an article by Tayal et al. entitled "Cardiac Resynchronization Therapy in Patients With Heart Failure and Narrow QRS Complexes.' publishing the Journal of American College of Cardiology last month. Several parameters have been stressed to identify benefit of resynchronization therapy in patients with wide QRS include cross correlation analysis with tissue doppler imaging. However, many patients may have evidence in mechanical dyssynchrony even in the absence of an apparent wide QRS thus Tayal et al. sought to evaluate the benefit of resynchronization therapy amongst 807 patients with heart failure and a narrow QRS mean criteria in a randomized study. Of the 807 46% had delayed mechanical activation. Those without delay mechanical activation had underwent we standardization therapy and were associated with worse overall outcomes likely due to new delayed mechanical activation potentially related to CRT pacing. These data support the absence of a role for resynchronization therapy in patients with a narrow QRS. This is expected as resynchronization therapy likely offers the most benefit in patients with mechanical dyssynchrony that results from electrical dyssynchrony.                                                 Since by its very nature resynchronization therapy relies on non physiologic cardiac pacing thus compared to normal cardiac activation the nature of resynchronization pacing is desynchronization. These data support the absence of a role for resynchronization therapy in patients with heart failure and narrow QRS complexes.                                                 Moving on to cellular electrophysiology we review an article by Kozasa et al. published in last month's issue of Journal of Physiology entitled 'HCN4 pacemaker channels attenuate the parasympathetic response and stabilize the spontaneous firing of the sinoatrial node.' Heart rate is controlled by an interplay between sympathetic and parasympathetic components. In turn HCN4 abnormalities have been implicated in congenital sick sinus syndrome. The authors sought to clarify the contribution of HCN4 to sinus node autonomic regulation. They created a novel gain-of-function mouse where the HCN4 activity could be modulating from zero to three times normal. They then evaluated ambulatory heart-rate variability and responsive heart rate to vagus nerve stimulation. They found HCN4 over-expression did not increase heart rate, but attenuated heart-rate variability. It also attenuated bradycardic response to vagus nerve stimulation. Knockdown of HCN4 in turn lead to sinus arrhythmia and enhanced parasympathetic response. These data suggest HCN4 attenuates sinus node response to vagal stimuli thus stabilizing spontaneous firing of the node. The clinical application of this remain to be seen but are maybe important in that they highlight a mechanism for a heretofore poorly understood mechanism for how exactly HCN4 abnormalities may lead to sick sinus syndrome.                                                 Within the realm of ventricular arrhythmias we highlighted a number of articles published this past month. The first article we review was published in last month's issue of JACC clinical electrophysiology, entitled characterization of the electrode atomic substrate and cardiac sarcoidosis: correlation with imaging findings of scarring inflammation published by [inaudible 00:41:40] et al. In patients with cardiac sarcoidosis one of the questions is how to define the electronic atomic substrate, particularly before we entered the electrophysiology laboratory. Both active inflammation and replacement fibrosis maybe be seen in patients. The authors evaluated in 42 patients with cardiac sarcoidosis, the association between an abnormal electrograms and cardiac imaging findings including PET and Computed Tomography, as well as Cardiac MRI. They noted that amongst these 40 patients, a total of 21,000 electrograms were obtained, and a total of 19% of these were classified as abnormal. Most of the abnormalities occurred in the basal paravalvular segments and intraventricular septum. They further noted that many of these abnormalities in terms of electrograms were located outside the low voltage areas, particularly as it relates to fractionation. In about 90% of patients they notice late gadolinium enhancements and they noted abnormal FDG uptakes suggesting active inflammation in about 48%.                                                 However, it should be noted that only 29 of the 42 patients underwent cardiac imaging. Segments with abnormal electrograms tended to have more late gadolinium enhancement evidence scar transmurality, and also they noted that the association of abnormal PET scan did not necessarily occur with abnormal electrograms. Thus, they concluded that in patients with cardiac sarcoidosis and ventricular tachycardia pre-procedural imaging with cardiac MRI could be useful in detecting electroanatomic map abnormalities that may in turn be potential targets for substrate ablation. However, they were more likely associated with more scar transmurality and lower degrees of inflammation on PET scanning. These data are important in that they highlight potential non-invasive means by which to understand where substrate might occur in patients with the cardiac sarcoidosis. It is well recognized that cardiac sarcoidosis is associated with increased risk of ventricular arrhythmias. These risks have increased ventricular arrhythmias, might be targetable with ablation. Newer therapies might even offer non invasive means by which to perform ablation in patients best. Thus if we could identify non based on mechanisms of identifying the substrate, this will be even more critical.                                                 The critical findings of this particular paper lie in noting that most of the abnormalities still is in intra ventricular sePtum in basal segments, and also that it is MRI in late gadolinium enhancement and associates more with the abnormal electrograms. Interestingly, the absence of inflammation correlating with the presence of more abnormal electrograms suggests that it is not so much the act of inflammation as being reflected in the endocardial map, but the existence of scar.                                                 Next, again within JACC clinical electrophysiology we review an article by Porta-Sánchez et al. entitled 'Multicenter Study of Ischemic Ventricular Tachycardia Ablation With Decrement Evoked Potential Mapping With Extra Stimulus.' The authors sought to conduct a multicenter study of decrement evoked potential base functional tech ventricular tachycardia substrate modification to see if such mechanistic and physiologic strategies could result in reduction in VT burden. It is noted that really only a fraction of the myocardium in what we presume to be substrate based on the presence of low voltage areas are actually involved in the initiation and perpetuation of VT. Thus if we can identify the critical areas within the presumed substrate for ablation, this would be even a better way of potentially honing in on our targets. They included 20 consecutive patients with ischemic cardiomyopathy. During substrate mapping fractionated late potentials were targeted and an extra stimulus was provided to determine which display decrements. All patients underwent DEEP focus ablation with elimination being correlated with VT non-inducibility after radio-frequency ablation. Patients were predominantly male, and they noted that the specificity of these decrement evoked potentials to detect the cardiac isthmus for VT was better than that of using late potentials alone. They noted 15 of 20 patients were free of any VT after ablation of these targets over six months of follow-up, and there was a strong reduction in VT burden compared to six months pre ablation.                                                 They concluded that detriment evoked potential based strategies towards ablation for ventricular tachycardia might identify the functional substrate and those areas most critical to ablation. They in turn regarded that by its physiologic nature it offers greater access to folks to ablation therapies.                                                 This publication is important in that it highlights another means by which we can better hone in on the most critical regions for substrate evaluation in patients with ventricular tachycardia. The fact is more extensive ablation is not necessarily better and might result in increased risk of harm if we think about the potential effects of longer ablations or more ablation lesions. Thus if we could identify ways of only targeting those areas that are most critical to the VT circuits, we could perhaps short and ablation procedural time, allow for novel ways of approaching targeted ablation with limited amounts of ablation performed, or perhaps even improve overall VT outcomes by knowing the areas that are most critical to ensure adequate ablation therapy provided. However, we need to understand that this is still a limited number of patients evaluated in a non randomized manner. Thus whether or not more extensive ablation performed might have been better is as of yet unclear                                                 Staying within the realm of ventricular tachycardia we review an article published in last month's issue of Heart Rhythm by Winterfield et al. entitled the 'Impact of ventricular tachycardia ablation on healthcare utilization.' Catheter ablation of atrial tachycardia has been well accepted to reduce recurrent shocks in patients with ICDs. However, this is a potentially costly procedure, and thus effect on overall long-term health care utilization remains to be seen. The authors sought to evaluate in a large scale real world retrospective study the effect of VT ablation on overall medical expenditures in healthcare utilization. A total 523 patients met study inclusion criteria from the market scan database. After VT ablation median annual cardiac rhythm related medical expenditures actually decreased by over $5,000. Moreover the percentage of patients with at least one cardiac rhythm related hospitalization an ER visit decreased from 53 and 41% before ablation respectively, to 28 and 26% after ablation. Similar changes we're seeing in number of all cause hospitalizations and ER visits. During the year before VT ablation interestingly there was an increasing rate of healthcare resource utilization, but a drastic slowing after ablation.                                                 These data suggests that catheter ablation may lead to reduced hospitalization in overall healthcare utilization. The importance of these findings lies in understanding why we do the things we do. We can provide a number of therapies to patients, but we seek two different effects. One is the individual effect of improving their particular health. The second thing is trying to avoid increasing healthcare expenditures on a population level and making sure resources are utilized. If we can reduce recurrent hospitalizations and overall healthcare expenditure in patients by providing a therapy in addition to provide individual benefit, this is the optimal situation. These data suggests that VT ablation might provide such a benefits, that in fact it reduces overall healthcare utilization while improving overall outcomes.                                                 Next and finally within the realm of ventricular arrhythmias, we review more on the basic side the role of Titin cardiomyopathy leads to altered mitochondrial energetics, increased fibrosis and long-term life-threatening arrhythmias, published by Verdonschot et al. in last month's issue of European Heart Journal. It is known now that truncating Titin variants might be the most prevalent genetic cause of dilated cardiomyopathy. Thus, the authors sought to study clinical parameters and long term outcomes related to Titin abnormalities in dilated cardiomyopathy. They reviewed 303 consecutive and extensively phenotype dilated cardiomyopathy patients who underwent cardiac imaging, Holter monitoring, and endomyocardial biopsy and in turn also underwent DNA sequencing of 47 cardiomyopathy associated genes. 13% of these patients had Titin abnormalities. Over long-term followup they noted that these patients had increased ventricular arrhythmias compared to other types of dilated cardiomyopathy, but interestingly, they had similar survival rates. Arrhythmias in those Titin abnormal patients were most prominent in those who were subjected to an additional environmental trigger, including viral infection, cardiac inflammation, other systemic disease or toxic exposure. They also noted the cardiac mass was relatively reduced in titan admirable patients.                                                 They felt that all components of the mitochondrial electron transport chain we're simply up-regulated in Titin abnormal patients during RNA sequencing and interstitial fibrosis was also augmented. As a result, they concluded that Titin variant associated dilated cardiomyopathy was associated with an increased risk of ventricular arrhythmias, and also with more interstitial fibrosis. For a long time we have reviewed all non ischemic cardiomyopathy as essentially equal. However, more recent data has suggested that we can actually hone in on the cause. In turn, if we hone in on the cause, we might be able to understand the effects of specific therapies for ventricular arrhythmias based on that underlying cause. Patchy fibrosis might not be as amenable, for example, to ablation as discreet substrate that we might see in infarct related VT. Understanding the relative benefit in very specific types of myopathies might hold benefit in understanding how to, one, risk stratify these patients, and two, understand what type of therapy, whether pharmacologic or ablative, might result in greatest benefit to the patients.                                                 Changing gears entirely now to the role of genetics, we review multiple articles in various genetic syndromes published this past month. First, we reviewed an article by Providência et al. published in the last month's issue of heart entitled 'Impact of QTc formulae in the prevalence of short corrected QT interval and impact on probability and diagnosis of short QT syndrome.' The authors sought to assess the overall prevalence of short corrected QT intervals and the impact on diagnosis of short QT syndrome using different methods for correcting the QT interval. In this observational study they reviewed the sudden cardiac death screening of risk factors cohorts. They then applied multiple different correction formulae to the ECGs. They noted that the prevalence of individuals with the QTc less than 330 and 320 was extremely low, namely less than .07 and .02% respectively. They were also more frequently identified using the Framingham correction. The different QTc correction formulae could lead to a shift of anywhere from 5 to 10% of individuals in the cohort overall.                                                 They further noted, that based on consensus criteria, instead of 12 individuals diagnosed with short gut syndrome using the Bazett equation, a different number of individuals would have met diagnostic criteria with other formulae, 11 using Fridericia, 9 with Hodges, and 16 using the Framingham equation. Thus, they noted that overall the prevalence of short QT syndrome exceedingly low and an apparently healthy adult population. However, reclassification as meeting criteria might be heavily dependent on which QT correction formula is used. The importance of these findings is that not all QTs are created equal.                                                 Depending on how you compute the QT interval in which formula to use may affect how you actually risk characterize a patient. Unfortunately, these data do not necessarily tell us which is the right formula, but this highlights that it might be relevant to in the future evaluate the role of different formulae and identifying which is the most necessary to classify a patient.                                                 Moving on to an article published in last month's issue of the journal of clinical investigation by Chai et al. we review an article entitled 'Physiological genomics identifies genetic modifiers of Long QT Syndrome type 2 severity.' Congenital Long QT Syndrome is a very well recognized, inherited channelopathy associated life-threatening arrhythmias. LQTS type 2 is specifically caused by mutations in casein to encoding the potassium channel hERG. However, even with the mutation not all patients exhibit the same phenotype. Namely some patients are more at risk of life threatening arrhythmias in spite of having the same mutation as others who do not exhibit the same severity phenotype. The authors sought to evaluate whether specific modifiable factors within the remaining genetic code might be modifying the existing mutation. Thus, they sought to identify contributors to variable expressivity in an LQT 2 family by using induced pluripotent stem cell derived cardiomyocytes and whole exome sequencing in a synergistic manner.                                                 They found that patients with severely effected LQT 2 displayed prolonged action potentials compare to sales from mildly effected first-degree relatives. Furthermore, stem cells derived from patients were different in terms of how much L-type calcium current they exhibited. They noted that whole exome sequencing identified variants of KCNK17 and the GTP-binding protein REM2 in those patients with more severe phenotypes in whom greater L-type calcium current was seen. This suggests that abnormalities or even polymorphisms in other genes might be modifying the risk attributed to by mutations in the primary gene. This showcases the power of combining complimentary physiological and genomic analysis to identify genetic modifiers and potential therapeutic targets of a monogenic disorder. This is extraordinarily critical as we understand on one level that when we sequence a monogenic disorder that there might exist variants of uncertain significance, namely they have not been classified as disease causing, but could be. In turn, we also recognize that mutations in a family might effect different relatives differently. However, why this is has been relatively unclear.                                                 If we can understand and identify those patients who are most at risk of dangerous abnormal rhythms, this will be useful in how much to follow them, and what type of therapy to use in them. The fact that other genes might modify the risk even in the absence of specific mutations, suggests that novel approaches to characterizing the risk might help for the risk modified patients classification in general. Clinical use, however, remains to be seen.                                                 Moving on from long QT, we evaluate 'The Diagnostic Yield of Brugada Syndrome After Sudden Death With Normal Autopsy' noted in last month's issue of the Journal of American College of Cardiology and published by Papadakis et al. It is well known, the negative autopsies are not uncommon in patients, however, families might be wondering how at risk they are. Thus, the authors sought to assess the impact of systematic ajmaline provocation testing using high right precordial leads on the diagnostic yield Brugada syndrome in a large cohort of Sudden Arrhythmic Death syndrome families. Amongst 303 families affected by Sudden Arrhythmic Death Syndrome evaluation was done to determine whether or not there was a genetic inherited channelopathy cause. An inherited cardiac disease was diagnosed in 42% of the families and 22% of relatives Brugada syndrome was the most prevalent diagnosis overall amongst 28% of families. Ajmaline testing was required, however, to unmask the Brugada Syndrome in 97% of diagnosed individuals. Furthermore, they use of high right precordial leads showed a 16% incremental diagnostic yield of ajmaline testing for diagnosing Brugada syndrome.                                                 They further noted that a spontaneous type 1 regard or pattern or a clinically significant rhythmic event developed in 17% of these concealed regardless syndrome patients. The authors concluded the systematic use of ajmaline testing with high right precordial leads increases the yield of Brugada Syndrome testing in Sudden Arrhythmic Death Syndrome families. Furthermore, they noted that assessments should be performed in expert centers or patients could also be counseled appropriately. These findings are important and one of the big questions always becomes how aggressively to test family members of patients or of deceased individuals who experienced sudden arrhythmic death. Many of these patients have negative autopsies, and genetic autopsy might not be possible due to lack of tissue or blood products that can be adequately tested.                                                 The data here suggest that amongst a group of 303 sudden arrhythmic death, families that Brugada Syndrome is by far the most frequent diagnosis. If an inherited cardiac disease was identified. In turn, it is not ECG alone or echo alone that helps identify them, but requires drug provocation testing in addition to different electrode placements. Whether or not this will consistently offer benefit in patients in general or my result in overcalling remains to be seen next within the realm of genetic predisposition.                                                 We view an area where we don't know if there's a genetic predisposition in article published by Tester et al. entitled Cardiac Genetic Predisposition in Sudden Infant Death Syndrome in last month's issue of the journal of american college of cardiology. Sudden Infant Death Syndrome is the leading cause of post-neonatal mortality and genetic heart diseases might underlie some cases of SIDS. Thus the authors sought to determine the spectrum and prevalence of genetic heart disease associated mutations as a potential monogenic basis for Sudden Infant Death Syndrome. They study the largest cohort to date of unrelated SIDS cases, including a total of 419 individuals who underwent whole exome sequencing and targeted analysis for 90 genetic heart disease susceptibility genes. Overall, 12.6% of these cases had at least one potentially informative genetic heart disease associated variants. The yield was higher in those mixed European ancestry than those of European ancestry.                                                 Infants older than four months were more likely to host a potentially informative gene. Furthermore, they noted that only 18 of the 419 SIDS cases hold a [inaudible 01:01:26] or likely pathogenic variant. So in other words, only 4% of cases really had a variant that they could say was distinctly pathogenic or likely pathogenic. Thus, overall, the minority of SIDS cases have potentially informative variant in genetic heart disease susceptibility gene, and these individuals were mostly in the 4 to 12 month age group. Also, only 4% of cases had immediately clinically actionable variance, namely a variant, which is well recognized as pathogenic and where we could actually say that a specific therapy might have had some effect. These findings can have major implications for how best to investigate SIDS cases in families. It might suggest that SIDS cases where the individual was older, nearly 4 to 12 months of age might have a greater yield in terms of identifying variance.                                                 While this might not affect the deceased in fit, it might affect, families are planning on having another child in whom a variant can be identified.                                                 Finally, within the realm of genetics, we review an article published in last month's issue of Science Advances by Huang. et al. entitled 'Mechanisms of KCNQ1 Channel Dysfunction in Long QT Syndrome Involving Voltage Sensor Domain Mutations'. Mutations that induce loss of function of human KCNQ1 underlie the Long QT Syndrome type 1. While hundreds of mutations have been identified the molecular mechanism by which they result in impaired function are not as well understood. The authors sought to investigate impact of 51 specific variants located within the voltage sensor domain and emphasized effect on cell surface expression, protein folding, and structure. For each variant efficiency of trafficking of the plasma membrane, impact of proteasome inhibition, and protein stability were evaluated. They noted that more than half of the loss of function mutations were seen to destabilized structure of the voltage sensor domain, generally accompanied by mistrafficking and degradation by the proteasome.                                                 They also noted that five of the folding defective Long QT Syndrome mutant sites were located in the S0 helix, where they tend to interact with a number of other loss of function mutation sites in other segments of the voltage sensor domain. They suggested these observations reveal a critical role for the S0 helix as a central scaffold to help organize and stabilized KCNQ1 overall. They also note the importance of these findings is that mutation-induced destabilization of membrane proteins may be a more common cause of disease functioning in humans. The importance of these findings lies in better understanding why specific mutations lead to appa

Dr. Paul Wang:                  Welcome to the monthly podcast "On The Beat" for Circulation, Arrhythmia, and Electrophysiology. I'm Dr. Paul Wang, editor-in-chief, with some of the key highlights from this month's issue. We'll also hear from Dr. Suraj Kapa reporting on new research from the latest journal articles in the field.                                                 In our first manuscript this month, Cho and Associates investigate the need for readmission for Dofetilide reloading. The FDA labeling for Dofetilide loading states that Dofetilide must be initiated or reinitiated in hospital with continuous electrocardiographic monitoring.                                                 In this article, the authors retrospectively examine the hospital records for 138 patients admitted for Dofetilide reloading for atrial arrhythmias. Of these 138 patients, 102 were reloaded at a previously-tolerated dose, 30 with a dose higher than a previously tolerated dose, and 2 at a lower dose, with the prior dosage unknown in 4 patients.                                                 In 44 patients, or 31.9%, dose adjustment or discontinuation of Dofetilide was performed, although, torsades de pointes occurred in two patients admitted to increased Dofetilide dosage, no torsades de pointes was observed in patients loaded with the same dose of Dofetilide.                                                 This is 0 versus 6.7% or P = 0.05. In 30 out of 102 patients, 29.4% reloaded at a previously tolerated dose. Dofetilide dose adjustment was required. In 11 out of 30 patients or 36.7% admitted for an increase in dose, a dose adjustment or discontinuation was required.                                                 The authors therefore concluded that dosage adjustments or discontinuation were frequent, and that their observations support the need for hospitalization for Dofetilide reloading. In the next manuscript Tilman Maurer and Associates report a novel superolateral approach to creating a mitral isthmus ablation line.                                                 Because the creation of an endocardial mitral isthmus line with the end point of bidirectional block maybe challenging, the authors examine 114 patients with perimitral annular flutter without a prior mitral isthmus ablation line.                                                 The authors compared the initial group of 57 patients, group A, who underwent catheter ablation using a novel superolateral mitral isthmus ablation line connecting the left sided pulmonary veins with the mitral annulus along the base of the left atrial appendage visualized by selective angiography to another group of patients, 57 patients in groups B undergoing ablation using a conventional mitral isthmus ablation line connecting the left inferior pulmonary vein to the mitral annulus.                                                 The authors found that bidirectional block was achieved in 56 out 57 patients in group A, or 98.2%, and 50 patients in group B, or 87.7%, P=0.06. Ablation from within the coronary sinus was required significantly less for creation of a superolateral mitral isthmus ablation line compared to a conventional mitral isthmus ablation line, 7.0% versus 71.9%, P is less than 0.01.                                                 The need for epicardial ablation from within the coronary sinus in the total length of the mitral isthmus line, 29.3 versus 40.8 millimeters were predictors for unsuccessful bidirectional mitral isthmus blockade. Pericardial tamponade was observed in group A, but not in group B, 5.2% versus 0%, P=0.24.                                                 The authors, therefore, concluded that superolateral mitral isthmus ablation line has a higher acute success rate compared with conventional mitral isthmus ablation line with a low likelihood of needing ablation from within the coronary sinus.                                                 In our next paper, Cronin and Associates examine the relationship between right ventricular pacing frequency, and the incidence of ventricular arrhythmias leading to ICD shock.                                                 Using the altitude database, the authors examined 389 appropriate shocks, and 425,625 transmissions received from 8,435 patients over a mean follow-up of 15.0 months.                                                 Transmissions with 80 to 98% right ventricular pacing were associated with a hazard ratio of 1.56 for an appropriate shock in the subsequent week compared to less than 1% right ventricular pacing, P=0.04 using a time dependent Cox proportional hazard model, however, the authors found that greater than or equal to 98% right ventricular pacing trended towards a lower risk of appropriate shock. Hazard ratio 0.61.                                                 Lifetime cumulative percentage right ventricular pacing was similarly associated with an increased risk of appropriate shocks at 80 to 98% right ventricular pacing, but not greater than or equal to 98% right ventricular pacing.                                                 The authors, therefore, concluded that an increased frequency of right ventricular pacing is associated with an increased risk of appropriate ICD shocks until the right ventricular pacing is greater than or equal to 98%.                                                 In the next manuscript, Wesley O'Neal and Associates examined 12,241 patients from The Atherosclerosis Risk in Communities Study, ARIC study, the association of individual QT components, that is R-wave onset to R-wave peak, R-peak to R-wave end, ST-segment, T-wave onset to T-wave peak, and T-peak to T-wave end with the occurrence of sudden cardiac death.                                                 The authors identified a total of 346 cases of sudden cardiac death identified over a median followup of 23.6 years. The prolongation of the QT interval was associated with a 49% risk of sudden cardiac death. Of the components of the QT interval only the T-wave onset to T-peak component was associated with sudden cardiac death with each standard deviation increase, hazard ratio of 1.19.                                                 The authors found similar results when the QT interval components were included in the same model, thus the authors conclude that the risk of a sudden cardiac death is driven by prolongation of the T-wave onset to T-peak component.                                                 In the next article by Kalliopi Pilichou and Associates, the authors examined copy number variations or CNVs in arrhythmogenic cardiomyopathy patients. The author studied 160 arrhythmogenic cardiomyopathy proband genotype negative for 5 arrhythmogenic cardiomyopathy desmosome genes using conventional mutation screening.                                                 Using multiplex ligation dependent probe amplification, MLPA, 9 heterozygous copy number variations were identified in 11 or 6.9% of the 160 probands. Of these, the authors found that 5 had the least of the entire plakophilin-2 gene to a deletion of only the PRP2 [exon 00:08:45], 1 a deletion of the PRP2 exon 6211, and 1 a PRP2 duplication of the 5 UTR to exon 1. One the desmocollin 2 duplication of exon 7 to 9, and one large lesion of chromosome 18 comprising both DSC2 and desmoglein 2 genes.                                                 All probands were affected by moderate severe forms of disease and 10 or 32% of the 31 family members carrying one of these deletions met the diagnostic criteria for arrhythmogenic cardiomyopathy.                                                 The authors concluded that identifying the copy number variations may increase the yield of genetic testing. In family members carrying the copy number variations, but not displaying the phenotype other factors are likely involved.                                                 In the article by Rahul Samanta and Associates, the authors examined in 7 sheep a mean of 84 weeks post MI, the influence of intramyocardial adipose tissue on scar tissue identification during endocardial contact mapping, the authors found that endocardial electrogram amplitude correlated significantly with intramyocardial adipose tissue.                                                 Unipolar, Right = negative 0.48, bipolar R = negative 0.45, but not correlated with collagen. Unipolar, R = negative 0.36, bipolar, R = negative 0.43. Intramyocardial adipose tissue, dense regions of myocardium were reliably identified using endocardial mapping with thresholds of less than 3.7 millivolts and less than 0.6 millivolts respectively for unipolar, bipolar, and combined modalities.                                                 Unipolar mapping using optimal thresholding remained significantly reliable, an AUC of 0.76. During mapping of intramyocardial adipose tissue confined to punitive scar border zone regions. Bipolar amplitude range of 0.5 to 1.5 millivolts.                                                 The authors concluded that combined bipolar and unipolar voltage mapping with optimal thresholds may permit delineation of intramyocardial adipose dense regions of myocardium following infarction.                                                 In the next article by Kevin Leong and Associates, the authors examined the substraight in electrophysiologic mechanisms that contribute to the characteristic ECG of Brugada syndrome. The authors studied 11 patients with concealed type 1 Brugada syndrome and 2 healthy controls by performing noninvasive electrocardiographic imaging, or ECGI, and ECG recordings during an Ajmaline infusion.                                                 Following Ajmaline infusion the right ventricular outflow tract had the greatest increase in conduction delay and activation recovery interval prolongation compared to the right ventricle or the left ventricle. In controls there was minimal change in the JST point elevation, the conduction delay, or activation recovery intervals at all sites with Ajmaline.                                                 In Brugada syndrome patients, conduction delay in right ventricular outflow tract, but right ventricle or left ventricle correlated with a degree of JST point elevation. Pearson R 0.81.                                                 No correlation was found between the JST point elevation and activation recovery interval prolongation in the right ventricular outflow tract the right ventricle or the left ventricle.                                                  The authors, therefore, concluded that the degree of conduction delay in the right ventricular outflow tract and not prolongation or re-polarization time accounts for the ST or J-point elevation seen in type 1 Brugada syndrome pattern.                                                 In the next article by Jonas Diness and Associates, the authors investigate the role of inhibition with small conductance calcium activated potassium channels in atrial fibrillation termination.                                                 Since these channels are predominately expressed in the atria compared to ventricles, they are a particularly attractive drug target. With a total of 43 pigs atrial tachy pacing was performed until they developed sustained atrial fibrillation that could not be reverted by vernakalant administration.                                                 After the SK channel inhibitor AP14145 was administered, vernakalant resistant AF reverted to sinus rhythm and could not be re-induced by burst pacing. In open chest pigs both vernakalant and AP14145 significantly prolonged atrial refractory of this and reduced AF duration without affecting the ventricular refractory in this or blood pressure.                                                 The authors concluded that SK currents played a role in porcine atrial repolarization and their inhibition by AP14145 demonstrates an arrhythmic affects in a vernakalant resistant porcine model of atrial fibrillation.                                                 In our final article by Padmini Sirish and Associates, the authors examined the role of several ion transporters in action potential duration in cardiac function. The solute carrier SIC26A6, which is highly expressed in cardiomyocytes plays an important role in cardiac intracellular pH regulation.                                                 Using the SIC26A6 knockout mice, the authors found that ablation of SIC26A6 results in action potential shortening, reduced calcium transients, reduced sarcoplasmic reticulum calcium load, and decreased sarcomere shortening in the SIC26A6 knockout cardiomyocytes.                                                 Ablation of the SIC26A6 reduced fractual shortening and cardiac contractility in vivo. Intracelluar pH regulation is elevated in the SIC26A6 knockout cardiomyocytes consistent with the chloride bicarbonate exchange activities of SIC26A6.                                                 The SIC26A6 knockout mice exhibited bradycardia and fragmented QRS complexes supporting the role of SIC26A6 in the cardiac conduction system, therefore, the authors provided evidence that the role of SIC26A6 cardiac electrogenic chloride bicarbonate transporter in ventricular myocytes as well as intracellular pH regulation, excitability, and contractility.                                                 That's it for this month, but keep listening.  Suraj Kapa will be surveying all journals for the latest topics of interest in our field. Remember to download the podcast "On The Beat." Take it away Suraj. Suraj Kapa:                          Thank you very much Paul and welcome everybody back to "On The Beat," where we'll review hard hitting articles across the electrophysiologic literature. It is my pleasure to introduce you to 15 different articles published in the past month of September across all the journals in cardiovascular medicine.                                                 The first area that we will be focusing on is atrial fibrillation with a specific focus within the realm of anticoagulation, and we refer you to a paper published by [Kurshida Doll 00:16:55], entitled "Factors Associated With Anticoagulation Delay Following New-Onset Atrial Fibrillation," published in The American Journal Of Cardiology on October 15, 2017.                                                 In this publication Kurshida Doll, reviewed the frequency with which there is a delay in introduction of oral anticoagulation after a new diagnosis of atrial fibrillation, and the impact on overall outcomes. In a large electronic medical record they identify incident episodes of atrial fibrillation between 2006 and 2014.                                                 They used the CHADS2 score rather than the CHADS-VASc score to estimate overall risk, and then after this they reviewekud the outcomes of the patients. They found for those patients in whom oral anticoagulation would have been recommended, the median time to initiation was around five days, with an interquartile range of 1 to 43, with by far most patients receiving Warfarin with about 86%.                                                 Interestingly, about 98 strokes occurred between the time of new atrial fibrillation diagnosis, and the actual initiation of oral anticoagulation. Several factors led to this delay in oral anticoagulation including female gender, absence of hypertension, prior falls, and the presence of chronic kidney disease.                                                 However, ultimately, by 6 months over 90% of patients were on oral anticoagulants appropriately, though still a slightly higher proportion appropriately in men than woman.                                                 They noted that most patients with new diagnosis of atrial fibrillation and noted to have an elevated stroke risk started on oral anticoagulation within 1 week. Given these findings it is important to consider how we wait to introduce oral anticoagulation into patients after initial diagnosis given many initial diagnoses may be made by internists, or even in some cases by the patient themselves on a remote monitor or an ambulatory monitor it is important to consider how they are tied into the individual, who would feel most comfortable and who's most apt to prescribe oral anticoagulation.                                                 Changing gears within atrial fibrillation we next move on to cardiac mapping and ablation, and specifically focus on a paper published by Black-Maier et al, in the September edition of "Heart Rhythm" entitled "Risk Of Atrioesophageal Fistula Formation With Contact Force-Sensing Catheters."                                                 While atrioesophageal fistula formation is a relatively rare complication of atrial fibrillation ablation it can be life threatening, contact force catheters for ablation of atrial fibrillation have come into vogue as they are felt to improve procedural effectiveness and potentially reduce complications by improving individual understanding of contact with the myocardium and when contact is excessive.                                                 However, there's been little exploration of the actual risk of atrioesophageal fistula. An [inaudible 00:19:50] from the association they refused the mod database or the manufacturer and user facility device experience database for adverse event reports.                                                 Amongst almost 27,000 device reports they identified a total of 78 atrioesophageal fistula cases. About 1,200 of the reports were related to contact force-sensing catheters and about almost 1,500 were related to non contact force sensing catheters.                                                 Of the 78 atrioesophageal fistula cases reported the vast majority were the contact force-sensing catheters with a total number of 65, or about 5 times more than with non contact force-sensing catheters.                                                 Unfortunately, esophageal temperature increases were only mentioned in about 2.5% of cases in contact force and power settings were not consistently reported in order to come to any conclusions. They noted the overall mortality with atrioesophageal fistula in this population was around 56%, with really the vast majority surviving as a result of surgical repair as apposed to stenting or no intervention.                                                 While this data is somewhat skewed because it's based on self reported data by proceduralists, who are reporting back to the mod database, it is important to consider whether or not there is actually an increase complication rate associated with contact force-sensing catheters as these catheters do reflect a fundamentally different catheter than the non contact force-sensing catheters routinely used due to changes in the stiffness, and the mechanics of the catheter itself.                                                 It is important to consider when using any new catheter with any new options for monitoring, or that might alter the stiffness, or other mechanical properties of the catheter, whether or not application of similar power settings are relevant.                                                 While the data is potentially skewed in the status set it will be important to consider it going forward as to whether or not there are implications of some increased risk of complications, and how to mitigate these by altering our contact force and power setting decision making.                                                 Further study will be required in order to better understand these data and the implications. I would refer the readers also to an article published by [inaudible 00:22:02] in circulation where they reviewed the mechanism of atrioesophageal injury and also to another publication published in The Journal Of Cardiovascular Electrophysiology this past month by [inaudible 00:22:11], where they did a meta analysis of the overall benefit of contact force related catheters over non contact force related catheters.                                                 In that paper they demonstrated that based on this meta analysis there seems to be an overall benefit in terms of outcomes in contact force-sensing catheters without a difference in procedural complications. However, I would refer the reader to the fact that there are very limited randomized studies comparing contact force versus non contact force catheters.                                                 Next, also within the realm of cardiac mapping and ablation we reviewed a publication by Haldar, et al., entitled Resolving Bipolar Electrogram Voltages During Atrial Fibrillation Using Omnipolar Mapping, published in the last edition of Circulation Arrhythmia Electrophysiology. Also, reviewed by Dr. Wang in last months podcast.                                                 The importance of this article lays in an improved understanding of what we mean when we talk about voltage or substraight mapping. In his paper, Haldar, et al., tried to understand better what the bipolar electrogram might actually refer to when comparing traditional bipolar mapping versus omnipolar mapping.                                                 This becomes important as we consider a low voltage guided substraight modification for not just atrial fibrillation ablation, but also potentially for ventricular arrhythmia ablation. They sought to compare the use of peak-to-peak voltage for assessment of bipolar voltage with omnipolar peak-to-peak voltages in both sinus rhythm and atrial fibrillation.                                                 They demonstrated that in canines vertical orientation of a catheter relative to the underlying tissue consistently resulted in a higher bipolar voltage in both sinus rhythm and atrial fibrillation. Furthermore, they show that the max obtained ominipolar voltage were consistently larger than multi-horizontal and vertical voltages in both rhythms.                                                 Vector field analysis of these wave fronts during atrial fibrillation in particular, demonstrated the omnipolar electrograms can account for a collision in fractionation, and required an electrogram of voltages independent of these effects. Thus, they suggested that the omnipolar electrograms can use maximum voltages, and can separate the influence from directional factors, collision, or fractionation especially when compared with contemporary bipolar techniques.                                                 The implications of the study are several. First off, when performing substraight mapping we traditionally use what we can in terms of trying to get appropriate bipolar signal analysis. However, catheters have significantly evolved since the early studies of bipolar voltage mapping in terms of establishing voltage cutoffs.                                                 There are many different multipolar catheters with varying interelectrode spacing, but sometimes prefer parallel orientation to the underlying myocardium as opposed to vertical orientation. The fact that bipolar voltage can significantly vary based on both orientation of the catheter as well as the rhythm is important when considering whether a substraight actually exists in a specific location or not, and what "Normal voltage cutoffs," where specific patients should be."                                                 When we consider novel catheters with increasing complex design including introduction of mini electrodes as well as omnipolar electrodes, it is important to consider whether an assessment of "Normal voltage," should be the same. Further study will be required to better understand how to best analyze these results.                                                 Moving to a different form of management in atrial fibrillation we will next refer you to a paper by Borris [Madal 00:25:44] published in this last month's edition of Heart Rhythm, entitled Efficacy and safety of left atrial appendage closure with WATCHMAN in patients with or without contraindication to oral anticoagulation, 1-Year follow-up outcome data of the EWOLUTION  trial.                                                 The EWOLUTION trial was a prospective multi center registry looking at the outcomes of WATCHMAN patients, who had indication for closure based on European society of cardiology guidelines. They sought to evaluate a 1 year followup of these patients.                                                 The baseline CHADS-VASc score was on average about 4-1/2 with a mean age of over 73 years. Almost a third of the patients had prior transient ischemic attach or ischemic stroke. They noted that the vast majority of the patients had a successful WATCHMAN implantation with a 1,005 out of 1,025 patients having successful implantation, with only 3 of these 1,005 patients having any leak greater than 5 millimeters.                                                 The majority up to 87% had T-followup at least once after initial implantation. Interestingly, the vast majority only used antiplatelet therapy with only 8% having vitamin K antagonist used in the post WATCHMAN implantation period.                                                 There was a reasonably high mortality of 10% in the first year after implantation, though this was felt to typically reflect advanced age and other comorbidities. Also, interestingly almost 4% of patients had thrombus on their device, which was independent of the drug regimen used. In other words whether antiplatelet therapy or vitamin K antagonists.                                                 Overall, the ischemic stroke rate was relatively low at 1.1%, with a relative risk of 84% versus estimated historical data, and also with a relatively low major bleeding rate of only 2.6% and this predominately being non-procedure of device related.                                                 Thus, they concluded that LA closure with the WATCHMAN device had a high implant and sealing success, and it appeared to be safe and affective in reducing ischemic stroke risk given that the relative incidence was only 1.1%, despite the fact that the vast majority were not actually even using oral anticoagulation.                                                 There are trial ongoing in the United States to evaluate whether or not patients can be safely kept off of oral anticoagulation in the peri-implant period as in some countries standard of care is to place them on anticoagulants in the immediate post implantation period.                                                 However, two other things need to be noted in this real world analysis of outcomes with WATCHMAN. Almost 10% or 1 out of 10 patients died within 1 year of followup, thus whether or not better patient selection is required to understand those patients will receive maximal benefit from this invasive procedure might be considered.                                                 Further, more almost 4% had device related thrombus. What this means in terms of stroke risk especially over longterm followup needs to also be considered. I think overtime we'll get better understanding of what those risks might be for an endocardial system for a left atrial appendage occlusion.                                                 But, staying within the realm of stroke risk in atrial fibrillation, we next review the article by King, et al., published in The Journal Of American College Of Cardiology, in the September 2017 edition entitled, Left Atrial Fibrosis and Risk of Cerebrovascular and Cardiovascular Events in Patients With Atrial Fibrillation.                                                 Cardiac MRI to evaluate late gadolinium enhancements suggesting regional cardiac fibrosis and atrial fibrillation is slowly taking steam, but primarily as a method of assessing potential efficacy of atrial fibrillation ablation with greater amounts of delayed enhancement potentially suggesting an overall lower risk, or a lower likelihood of success of atrial fibrillation ablation.                                                 King, et al., sought to evaluate in a retrospective cohort study regarding the risk of cerebrovascular and cardiovascular major events associated with a degree of delayed enhancement in MRI. They reviewed 1,228 patients undergoing cardiac MRI to assess left atrial fibrosis between 2007 and 2015.                                                 They then staged these patients and stratified them according their [Utah 00:29:45] stage, which had been previously recorded for the degree of fibrosis seen. They demonstrated on followup that there was a significantly higher incidence of major cardiovascular and cerebrovascular events associated with higher degrees of late gadolinium enhancement with a relative risk ratio of about 1.67.                                                 However, the only individual component of these outcomes that remains significantly associated with advanced gadolinium enhancement was actually stroke or TIA, with a hazard ratio of 3.94, thus they concluded that severe LA late enhancement is associated with increased cerebrovascular events principally.                                                 This study is important in that it highlights another potential risk factor that may need to be considered when risk stratifying patients for their risk of stroke. We recognize that even some paroxysmal patients can have extensive left atrial fibrosis, and some persistent patients might not have a ton of atrial fibrosis.                                                 Whether this can further help risk stratified patients in terms of overall stroke risk, and might identify and help characterize low risk patients further needs to be considered.                                                 One of the key features of this evaluation needs to be also the mechanism. In theory patients with greater endocardial injury of the atrium might be more prone to clot formation, and thus it may seem reasonable to expect indeed when we have more left atrial fibrosis as suggested by delayed enhancement on MRI. There may in fact be a higher greater cerebrovascular event rate.                                                 Finally, changing gears a little bit within the realm of risk stratification and management for atrial fibrillation we focused on autonomics and specifically a publication by Stavrakis et al., in the last month edition of Jack Clinical Electrophysiology, entitled Low Level Vagus Nerve Stimulation Suppresses Postoperative Atrial fibrillation And Inflammation In A Randomized Study.                                                 The group, headed up by Sonny [Poe 00:31:42] have previously published on both tragus stimulation as well as low level of vagus nerve stimulation in patients undergoing atrial fibrillation ablation. In this particular study they sought to evaluate whether or not implantation of a low level of vagus nerve stimulator during cardiac surgery could reduce the risk of postoperative atrial fibrillation.                                                 They sutured a bipolar wire to the vagus nerve preganglionic fibers along the lateral aspect of the superior vena cava at the time of surgery. They then performed high frequency stimulation of 50% below the threshold for slowing the heart rate for 72 hours, and those randomized to the vagus nerve stimulation group.                                                 The secondary group was a sham cohort. They demonstrated amongst the 54 patients randomized to either group that the frequency of postoperative atrial fibrillation was almost a third in the low level of vagus stimulation group when compared with the control group.                                                 Interestingly, their frequency of atrial fibrillation was not only lower, but the level of inflammatory markers also decreased with both serum tumor necrose factor alpha and interleukin 6 levels being significantly lower in the low level vagus nerve stimulation cohorts.                                                 In line with prior data from atrial fibrillation ablation these data were suggesting that low level of vagus nerve stimulation can suppress postoperative atrial fibrillation and attenuate the inflammatory response.                                                 Also, in this past month there was a paper by [Yoo 00:33:09] et al., in The Journal Of The American Heart Association, specifically looking at the use of vagus nerve stimulation at the level of the tragus in patients with obstructive sleep apnea associated atrial fibrillation.                                                 Similar to prior work form the Oklahoma group, they demonstrated that in fact there is a beneficial effect on reduction of atrial fibrillation, and this is primarily mediated through attenuation of autonomic factors that mediate obstructive sleep apnea related atrial fibrillation.                                                 Moving away from atrial fibrillation, we next delve in cellular physiology first starting with an article published in Nature Scientific Report this past month, on very low density lipoprotein in metabolic syndrome, and how it modulates gap junctions and slows cardiac conduction.                                                 In the past year there have been multiple studies regarding specific cell types and how they might interplay with cardiac fibrosis, and risk of conduction slowing. In this publication we had all reviewed the effect of very low density lipoproteins, and their effect on cardiac conduction in, in vitro models.                                                 They demonstrated that primarily through down regulation of [conexion 00:34:21] 40 and conexion 43, very low density lipoproteins have significant impact on cardiac conduction with increased prolongation of the P-wave, PR-intervals, QR restoration, and QTC intervals.                                                 Thus, they concluded that very low density lipoproteins may contribute to the path of physiology of both atrial fibrillation and ventricular arrhythmias that can be seen in metabolic syndrome. This report is important because it highlights the fact that we can actually see other cell types including LDL causing a significant reduction in cardiac conduction and thus mediating arrhythmogenesis.                                                 In fact there was one other paper published just a couple weeks prior also in The Nature Of Scientific Reports by [Lee 00:35:04] et al., entitled Human Electronegative Low-Density Lipoprotein Modulates Cardiac Repolarization Via LOX-1-Mediated Alteration Of Sarcolemmal Ion Channels.                                                 They showed that LDL can actually result in QTC prolongation in patients with ischemic heart disease by specific mechanisms involving LOX-1. Recognition of the mechanisms behind which less traditional factors such as VLDL or LDL may mediate alterations in cardiac conduction are important when we consider our potential novel targets for treatment of arrhythmias in patients whether for prevention or for treatments.                                                 In light of this attempt to identify novel targets we next move on to another paper in the realm of cellular electrophysiology published by [Toib 00:35:52] et al., in The American Journal of Physiology, Heart and Circulatory Physiology, entitled Remodeling Of Repolarization And Arrhythmia Susceptibility In A Myosin-Binding Protein C Knockout Mouse Model.                                                 In hypertrophic cardiomyopathy there might be multiple mechanisms that might lead to increased risk of ventricular arrhythmias. These might be scar related due to the fact that patients can burn out from the hypertrophic cardiomyopathy overtime and get both endocardial, epicardial, and mid myocardial fibrosis, but what are the mechanisms that might mediate the development of ventricular arrhythmias and hypertrophic cardiomyopathy remain to be elucidated, and there's been very limited evaluation of the effect of repolarizing potassium currents on this risk.                                                 Thus, Toib, et al., studied myosin-binding protein C knockout mice to look at what happens with repolarizing potassium currents in his cohorts. They demonstrated that in these knockout mice there was a prolongation in the corrected QT interval when compared to the wild type mice with overt ventricular arrhythmias.                                                 They also demonstrated that there is action potential prolongation associated with a decrease for polarizing potassium currents, and a decreased MRNA levels of several key potassium channels subunits, thus, they concluded that in this specific subtype of hypertrophic cardiomyopathy needed by myocin combining protein C mutations that part of the ventricular arrhythmia risk might be due to a decrease in polarizing potassium currents in turn leading to increase in action potential and QT interval.                                                 The reason that this particular finding is important is in my highlight drug selection in specific types of hypertrophic cardiomyopathy. In my postulate for example the class 3 antiarrythmics drugs might actually increase risk in some subtypes of hypertrophic cardiomyopathy due to down regulation of potassium channel subunits.                                                 Consideration of this is critical when best evaluating how to mange and treat these patients. Changing gears to another method of channelopathy we focus within the realm of genetic channelopathies and specifically on Brugada syndrome.                                                 In this last month's edition of Heart Rhythm, Sierra, et al., published their series of longterm prognosis of drug induced Brugada syndrome. They reviewed a consecutive cord of 343 patients with drug induced Brugada syndrome, and compared their outcomes with 78 patients with a spontaneous type 1 pattern.                                                 The mean age of patients was around 41 years. Interestingly, about 4% of the patients had a clinical presentation of 7 cardiac deaths, and 25% had a clinical presentation of syncope. However, the majority of the patients were asymptomatic, around 71%.                                                 Most of the patients were female amongst the drug induced Brugada syndrome cohort. They demonstrated that there were less ventricular arrhythmias both induced string and electrophysiology study, and seen over followup of up to 62 months in the drug induced Brugada syndrome cohort as compared with the spontaneous type 1 cohort.                                                 Overall, the event rate in drug induced Brugada syndrome was 1.1% of [person year 00:38:54] versus 2.3% of person year in patients with spontaneous type 1 pattern.                                                 They suggested that presentation of sudden cardiac death or inducable ventricular arrhythmias at the time of VP study were independent risk factors associated with arrhythmic events in drug induced Brugada syndrome. However, if a patient was asymptomatic and had no inducible ventricular arrhythmias they had a significantly better prognosis with drug induced Brugada syndrome over a spontaneous type 1 pattern.                                                 Thus, they concluded that even in drug induced Brugada syndrome sudden cardiac death is possible. However, in asymptomatic patients without a prior clinical presentation of sudden cardiac death or inducible ventricular arrhythmias during electrophysiology study, they may be relatively safer than their spontaneous type 1 counterparts.                                                 This study highlights the importance of stratification of patients into the mechanism of how their genetic channelopathy presents whether as a spontaneous finding or as a finding in the setting of other events. Further prospective analysis, however, is needed to best guide how to manage these patients and in whom to put a defibrillator as I would note that almost 37% of these patients actually had an ICD placed with the vast majority without incident events.                                                 Speaking of implantable devices we next move to the realm of ICD pacemaker and CRT, and specifically we review the publication by Samar, et al., published in Jack Clinical Electrophysiology this past month on the diagnostic value of MRI in patients with implanted pacemakers and implanted cardiover defibrillators across the population.                                                 Does the benefit justify the risk of proof of concept study? Increasingly, MRIs are being done in patients with even Legacy defibrillators and permanent pacemakers. However, when assessing the benefit versus the risk it's important to understand did the MRI actually change outcomes, and this was a specific question that the authors tried to answer.                                                 They took patients with conventional or Legacy pacemakers or ICDs, and tried to evaluate what the actual benefit was on those patients in whom an MRI was done. They specifically asked four questions, one, did the primary diagnosis change, two, did the MRI provide additional information to the existing diagnosis, three, was the pre-MRI or tentative diagnosis confirmed, and four, did the patient management change?                                                 They noted there were no safety issues encountered in any of the 136 patients an MRI was performed. In 97% it was felt that MR added value to the patient diagnosis and managements, with 49% of investigators feeling that MR added additional valuable information to the primary diagnosis, and in nearly a third the MR actually changing the principle diagnosis and subsequent management of the patient.                                                 Increasing evidence suggesting that MRI can be safely performed even in Legacy pacemakers and ICDs, and the fact the MRI can wield important evidence related to diagnostics needs to be taken into consideration as investigators and other centers try to identify methodologies for safely performing MRIs in these patient cohorts.                                                 It seems thus far like MRI might justify risk of these procedures under controlled settings. Next, we move also within the realm of implantable cardioverted defibrillators, but to a different assessment published by Kawada et al., in this past months issue of Heart Rhythm where they sought to evaluate the comparison of longevity in clinical outcomes of implantable cardioverted defibrillator leads among manufacturers.                                                 They specifically sought to assess the longevity of [Lynox 00:42:35] SSD by [Atronic 00:42:36] leads compared with Sprint Fidelis by Matronic, Sprint Quattro by Matronic, and Endotac Reliance by Boston Scientific Leads. The reasoning for this was early failure of some of the biotronic Lynox leads has been reported. Thus, they retrospectively reviewed patients undergoing implantation with these different lead approaches between 2000 and 2013.                                                 They noted failure rates of the Lynox versus Spring Fidelis versus Endotac leads where 3.2% for a year, versus 3.4% for a year, versus 0.61% for a year respectively. No lead failure was notable with a followup [inaudible 00:43:13] in Sprint Quattro leads, thus, they felt that the survival probability of Lynox leads was comparable to Sprint Fidelis leads, and lower than that of Endotac or Sprint Quattro leads.                                                 They found that age was the primary predictor of Lynox lead failures with the patients less than 58 years old had significantly increased risk of lead failure compared with those greater than 58 years old, thus, they concluded that this was a first description of a lower survival rate for Lynox leads in an aging population.                                                 Early identification of leads that might be at risk of failure is critical in patient risk stratification. The finding that there might be other leads that might be at risk of failure highlights the importance of close monitoring of these leads in contribution to register data.                                                 I would note that within this study that it was primarily done at one center and the vast majority of patients actually received Lynox leads. Thus, further evidence was clinically required for more centers to understand what the mechanism of this risk is, and also whether the risk is born out consistently across multiple centers particularly because the vast minority got the one lead, but didn't have any lead failure encountered for.                                                 Further, speaking about defibrillators we focus on the different mechanism of failure, and specifically the publication by [Thogersen 00:44:38] et al., published in last months' edition of Circulation And Arrhythmia Electrophysiology entitled Failure To Treat Life Threatening Ventricular Tachy Arrhythmias In Temporary Implantable Cardioverted Defibrillators Implications For Strategic Programming.                                                 In this publication they did not so much focus on lead failure, but the failure the ICD due to potential strategic programming decision making on appropriately treating ventricular tachy arrhythmias. Their current consensus recommendations as far as using a generic rate threshold between 185 and 200 beats per minutes in primary prevention ICD patients, thus, they sought to determine in the case series what the relationship between program parameters and failure of modernizing ICDs to treat for VF actually worked.                                                 Between 2015 and 2017 at four institutions they reviewed cases where normally functioning ICDs failed to deliver timely therapy for VF. There were a small number of patients noted fitting this criteria with only 10 ambulatory patients. Five actually died from their untreated VF, whereas four had cardiac arrests through a witness requiring external shocks, and one was ultimately rescued by a delayed ICD shock.                                                 The main reason that they were not appropriately treated were that the ventricular fibrillation event did not satisfy the programmed detection criteria in nine out of ten patients. Seven of the patients had the slowest detection rates consistent with generic recommendations, but were never tested in the peer review trial for the manufacturers ICDs.                                                 Namely, the decision making on the appropriated generic rate threshold was tested on specific manufacturers ICDs, but didn't apply the decision making on programming on other manufactures ICDs. In some cases manufacturers specific factors were interacting with fast detection rates to withhold therapy such as enhancement in MIC wave oversensing.                                                 Thus, they demonstrated that in this population untreated VF despite recommendation programming, accounted overall for 56% of sudden deaths and 11% of all deaths in the overall cord of patients during the study period.                                                 Thus, over half of the cases where sudden death occurs in patients with ICDs appears to be due to untreated VF despite recommended programming. Thus, they concluded that these unanticipated interactions or complex decision making regrading generic program of parameters might in part lead to withholding of therapy inappropriately in ventricular fibrillation.                                                 This publication highlights the importance of thoughtful decision making when translating evidence based detection parameters both between manufacturers and applying them across individual patients.                                                 While the overall number of patients is quite low, mainly only ten patients who were affected by this event, the number of patients dying as a result of it is fairly high in terms of a percentage with 56% of sudden deaths occurring as a result of untreated VF from variation from recommended programming.                                                 Closer attention needs to be paid to understanding how to better assess which patients would benefit from the current generic rate thresholds as opposed to who will be harmed by it. It is possible that one size fits all approach will always result in some harm to some, while benefit to others as potentially cutting down the lower rate cutoff in some patients might lead to inappropriate therapies, which might be as life altering as untreated VF in many patients.                                                 Finally, keeping within the realm of defibrillation we review an article by [Layva 00:48:24] et al., published in last month's edition of The Journal of American College of Cardiology entitled Outcomes of Cardiac Resynchronization Therapy With or Without Defibrillation in Patients With Nonischemic Cardiomyopathy.                                                 There are several recent studies that have started to cast doubt on what the incremental benefit of defibrillation adage cardiac resynchronization therapy actually is in nonischemic cardiomyopathy.                                                 However, we also know that in patients with scar noted on MRI that there can be an increased risk of ICD therapy, thus, part of the difficulty that some individuals have is how we define the nonischemic cardiomyopathy cohorts. Namely, is all nonischemic cardiomyopathy crated equal and we can better risk stratify this population to subtypes some of whom might benefit from primary correction defibrillators and some of whom might not?                                                 Thus, in this study they aimed to determine whether CRTD is superior to CRTP in patients with nonischemic cardiomyopathy based on the presence or absence of left ventricular midwall fibrosis detected by cardiac magnetic resonance.                                                 There were a total of 68 patients who had midwall fibrosis, and 184 patients who had not, and all of them underwent the evaluation prior to CRT implantation. They noted that the presence of midwall fibrosis was an independent predictor of total mortality with a hazard ratio of 2.31 as well as total mortality or heart failure hospitalization.                                                 This sudden cardiac hazard ratio was about 3.75 with an increased risk attributable to the presence of midwall fibrosis. They also noted that total mortality or heart failure hospitalization, and total mortality or hospitalization for major adverse cardiac events was significantly lower in patients with CRT defibrillator than with CRT pacemaker in those with midwall fibrosis, but not in those without midwall fibrosis.                                                 These findings highlight that in some patients with nonischemic cardiomyopathy CRTD may be superior to CRTP, though these might be guided by the presence of abnormal substraights. The evaluation of what nonischemic cardiomyopathy means in an individual patient needs to be closely considered.                                                 Nonischemic cardiomyopathy is a blanket term for all those patients who do not have an ischemic cardiomyopathy and who may or may not have been fully evaluated for discrimination of another type of myopathy such as infiltrated myopathies for example sarcoidosis.                                                 The value of cardiac magnetic resonance imaging is being increasingly understood as it applies to both risk stratification, nonischemic cardiomyopathy, as well as the value in decision making as far as treatment of these patients. In a recent publication published this past month as well in Jack Electrophysiology, by [inaudible 00:51:13], et al., they reviewed the efficacy of implantable cardioverted defibrillator therapy in patients with nonischemic cardiomyopathy based on a meta analysis of existing trials.                                                 They demonstrated in a meta analysis of randomized controlled trials that compared to medical therapy ICD has significantly improved survival among patients with nonischemic cardiomyopathy with an injection fraction of less and equal to 35%. However, CRT defibrillator overall was not associated with statistically significant mortality death when compared to CRT pacemaker.                                                 These findings are actually complimentary to each other, but need to be considered in context. One of the indications for the recently published Danish study was the fact that not only is CRT being increasingly utilized appropriately in patients with nonischemic cardiomyopathies, but also guideline directed medical therapy has improved over the course of the last several years since the initial trials of defibrillator therapy as primary prevention.                                                 Furthermore, the trial was actually powered based on a 25% reduction in overall events. Thus, even if there's a smaller benefit it would not necessarily be powered to identify if this is statistically significant. One issue as stated is the fact that nonischemic cardiomyopathy might be a milieu of different causes in individual patients. Some of whom might be at high risk for sudden cardiac death and some of whom might not.                                                 The publication by Levya, et al., highlights that better attempts at risk stratification on the basis of either MRI or other modalities might be important in helping us further assess who actually benefits from ICD, however, when mixing in prior trials with more recent trials that existed at different areas of medical therapy, and different areas of appropriate use of devices such as CRT it is critical to consider whether or not the same cutoffs, the same power calculations still apply.                                                 It is doubtless that defibrillator therapy is needed in many patients with both ischemic and nonischemic cardiomyopathy even with improved therapies for these patients otherwise. However, this multitude of publications coming out to improve our assessment of the utility of ICDs should not necessarily call into question of whether or not ICDs are merited at all, but should call into question whether we understand and have come to the best form of risk stratification for those patients who would most benefit, and thus this is an opportunity for us to identify those patients better.                                                 Next, we will move to the realm of supraventricular tachycardia's and specifically an article published by [Yang 00:53:41], et al., in the last month's edition of Heart Rhythm, entitled Focal Atrial Tachycardia's From The Parahisian Region, Strategies From Mapping And Cather ablation.                                                 With focal atrial tachycardia's from the parahisian region can potentially be targeted from multiple different regions, the right atrial septum, the noncoronary cusp, and the right middle septum. However, the optical mapping and ablation strategy for these arrhythmias remains unclear, and thus they sought to investigate electrophysiology characteristics in optimal ablation sites for parahisian [inaudible 00:54:10] from these different areas.                                                 They reviewed 362 patients with atrial tachycardia's undergoing catheter ablation. They did DCG analysis and electrophysiology studies extensively on these patients. Overall, 91 patients had a parahistian origin. An ablation was successful in a majority of these up to 94.5%.                                                 The majority of these patients had their AT successfully eliminated from the noncoronary cusp with about 44 of the 91 having it targeted from this region, with the remaining 23 from the right atrial septum, and 19 from the right middle septum. They noted those who had an earliest potential at the distal HIS catheter tended to have their site of origin more successfully ablated from the noncoronary cusp.                                                 However, those with a greater [inaudible 00:54:55] in the proximal HIS catheter tended to more likely have successful ablation from the right atrial septum or right middle septum. The mean timing of the A potential in differentiating right and middle septum ATs from right atrial septum ATs, was that they attended to be later in right middle septum ATs, than right atrial septum ATs, or noncoronary cusp ATs.                                                 They noted that for atrial tachycardia's arising from the right atrial septum and right middle septum, an A to V ratio less than 1.22 predicted safe and successful ablation with a sensitivity of 88.4% and the specificity of 91.7%. Thus, they concluded that activation sequence and timing of the A and HIS catheter could provide clues for where the most likely successful site of ablation would occur for parahisian tachycardia's.                                       

In this episode of the Heart podcast, Associate Editor Dr. James Rudd is joined by Prof. James Moon. Prof. Moon is director of The Cardiovascular Magnetic Resonance Imaging Unit and The Centre for Rare Cardiovascular Diseases Unit, Barts Heart Centre, St Bartholomew's Hospital, London, UK. His group recently published a review article entitled "Cardiac MRI evaluation of myocardial disease". They discuss the growing impact of MRI for the diagnosis and non-invasive monitoring of many different heart diseases. Link to paper : http://heart.bmj.com/content/early/2016/06/27/heartjnl-2015-309077