Podcasts about American Heart Journal

Show Notes for Episode 42 of “The 2 View” – Pink cocaine, holiday heart syndrome, pertussis, research updates on Zepbound and Semaglutide, and much more. Segment 1 – Pink cocaine What is Pink Cocaine? Dea.gov. DEA: United States Drug Enforcement Administration. https://www.dea.gov/pink-cocaine What is Pink Cocaine? Poison.org. POISON CONTROL: National Capital Poison Center. https://www.poison.org/articles/pink-cocaine Segment 2 – Holiday heart syndrome Blackburn R, Ajetunmobi O, Mc Grath-Lone L, et al. Hospital admissions for stress-related presentations among school-aged adolescents during term time versus holidays in England: weekly time series and retrospective cross-sectional analysis. BJPsych Open. Cambridge University Press. Cambridge Core. Published November 19, 2021. https://www.cambridge.org/core/journals/bjpsych-open/article/hospital-admissions-for-stressrelated-presentations-among-schoolaged-adolescents-during-term-time-versus-holidays-in-england-weekly-time-series-and-retrospective-crosssectional-analysis/924EE2CD1A8CFAC30E7090674FCEAF72 Carey M, Al-Zaiti S, Kozik T, Pelter M. Holiday Heart Syndrome. ECG Puzzler. Researchgate.net. AJCC: American Journal of Critical Care. American Association of Critical-Care Nurses. https://www.researchgate.net/profile/Mary-Carey/publication/260446497HolidayHeart_Syndrome/links/573dda6308ae298602e6d0b1/Holiday-Heart-Syndrome.pdf Ettinger P, Wu C, De La Cruz Jr C, Weisse A, Ahmed S, Regan T. Arrhythmias and the “Holiday Heart”: Alcohol associated cardiac rhythm disorders. Sciencedirect.com. ScienceDirect. American Heart Journal. https://www.sciencedirect.com/science/article/abs/pii/000287037890296X Greenspon AJ, Schaal SF. The “holiday heart”: electrophysiologic studies of alcohol effects in alcoholics. Ann Intern Med. PubMed. NIH: National Library of Medicine: National Center for Biotechnology Information. Published February 1983. https://pubmed.ncbi.nlm.nih.gov/6824246/ Jain A, Yelamanchili V, Brown K, Goel A. Holiday Heart Syndrome. Nih.gov. NIH: National Library of Medicine: National Center for Biotechnology Information. Updated January 16. 2024. https://www.ncbi.nlm.nih.gov/sites/books/NBK537185/ Joglar JA, Chung MK, Armbruster AL, et al. 2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. AHA | ASA Journals. Published November 30, 2023. https://www.ahajournals.org/doi/10.1161/CIR.0000000000001193 Segment 3 – Pertussis CDC. About Whooping Cough. Whooping Cough (Pertussis). Updated April 2, 2024. https://www.cdc.gov/pertussis/about/index.html Center for Drug Evaluation, Research. FDA Drug Safety Communication: Death resulting from overdose after accidental ingestion of Tessalon (benzonatate) by children under 10 years of age. FDA: U.S. Food and Drug Administration. Published June 28, 2019. https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-death-resulting-overdose-after-accidental-ingestion-tessalon Pertussis. Who.int. World Health Organization. https://www.who.int/health-topics/pertussis Simma L, Gesch M. Eyelid Ecchymoses and Subconjunctival Hemorrhage in Pertussis. N Engl J Med. Published December 11, 2024. https://www.nejm.org/doi/full/10.1056/NEJMicm2409052 Something sweet – Research updates: Zepbound and Semaglutide Ernst D. Zepbound Approved for Obstructive Sleep Apnea in Patients With Obesity. Monthly Prescribing Reference. MPR: Medical Professionals Reference. Published December 20, 2024. https://www.empr.com/news/zepbound-approved-for-obstructive-sleep-apnea-in-patients-with-obesity/?utmsource=eloqua&utmmedium=email&utmcampaign=NWLTRMPRTOPTDrug-DatabaseSS-LAS-LI1-LI2-9654122924_AL&hmemail=1f%2FJfEV7hN5vJr6vg%2FQRqK0NA6IXtyO3&sha256email=092493d8223fdfa40d9e995176d13e5fc5b5211674db9deb440c025fd462c80c&hmsubid=&nid=1639413404&elqtrack=True Semaglutide shows promise as a potential alcohol use disorder medication. Research Update. Nih.gov. NIH: National Institute on Alcohol Abuse and Alcoholism. Published March 13, 2024. https://www.niaaa.nih.gov/news-events/research-update/semaglutide-shows-promise-potential-alcohol-use-disorder-medication Recurring Sources Center for Medical Education. Ccme.org. http://ccme.org The Proceduralist. Theproceduralist.org. http://www.theproceduralist.org The Procedural Pause. Emergency Medicine News. Lww.com. https://journals.lww.com/em-news/blog/theproceduralpause/pages/default.aspx Trivia Question: Send answers to 2viewcast@gmail.com Be sure to keep tuning in for more great prizes and fun trivia questions! Once you hear the question, please email us your guesses at 2viewcast@gmail.com and tell us who you want to give a shout-out to. Be sure to listen in and see what we have to share! Looking forward to another year together!

Recorded live at the Critical Care Canada Forum 2024, this episode is part of our special Cardiac ICU Series.Dr. Rebecca Mathew, cardiologist and critical care specialist at the University of Ottawa Heart Institute, joins us to discuss the latest refractory cardiac arrest practice updates, including antiarrhythmic drugs, defibrillation strategies, and the role of ECPR.Chapters: • Defining refractory cardiac arrest • Antiarrhythmic drugs: amiodarone vs. lidocaine • Defibrillation strategies: vector change and double sequential defibrillation • Emerging therapies: stellate ganglion blocks and electrical storm management • ECPR: who qualifies and what the trials say • Equity and feasibility challenges in cardiac arrest management • ICU recovery clinics and patient-centered outcomes • Clinical trials: barriers to enrollment and the need for changeReferences: 1. ROC ALPS Trial: 1. Kudenchuk PJ, Brown SP, Daya M, et al. Resuscitation Outcomes Consortium-Amiodarone, Lidocaine or Placebo Study (ROC-ALPS): Rationale and Methodology Behind an Out-of-Hospital Cardiac Arrest Antiarrhythmic Drug Trial. American Heart Journal. 2014;167(5):653-9.e4. doi:10.1016/j.ahj.2014.02.010. PMID: 24766974.[1] 2. DOSE VF: Cheskes S, Drennan IR, Turner L, Pandit SV, Dorian P. The Impact of Alternate Defibrillation Strategies on Shock-Refractory and Recurrent Ventricular Fibrillation: A Secondary Analysis of the DOSE VF Cluster Randomized Controlled Trial. Resuscitation. 2024;198:110186. doi:10.1016/j.resuscitation.2024.110186. PMID: 38522736 3. ARREST: Yannopoulos D, Bartos J, Raveendran G, et al. Advanced Reperfusion Strategies for Patients With Out-of-Hospital Cardiac Arrest and Refractory Ventricular Fibrillation (ARREST): A Phase 2, Single Centre, Open-Label, Randomised Controlled Trial. Lancet (London, England). 2020;396(10265):1807-1816. doi:10.1016/S0140-6736(20)32338-2. PMID: 33197396 4. INCEPTION: Ubben JFH, Suverein MM, Delnoij TSR, et al. Early Extracorporeal CPR for Refractory Out-of-Hospital Cardiac Arrest - A Pre-Planned Per-Protocol Analysis of the INCEPTION-trial. Resuscitation. 2024;194:110033. doi:10.1016/j.resuscitation.2023.110033. PMID: 37923112 Disclaimer:This episode is for educational purposes only and does not constitute medical advice. The views expressed are those of the hosts and guests and do not necessarily reflect their employers.

In today's episode, Dr. Rachael Forsythe (@ROForsythe), consultant vascular surgeon at NHS Lothian, leads a fictional case-based discussion with leaders in managing diabetic foot ulcers. Joining the conversation are Professor Andrew Boulton, Mr. Patrick Coughlin, Dr. David Armstrong, Dr. Dane Wukich, and Dr. Edgar Peters. Professor Boulton is a professor of medicine at Manchester University in England and is co-chair of the Malvern  Diabetic Foot Conference meeting. He served as president of numerous distinguished societies, including the International Diabetes Federation. Dr.  Coughlin (@Coughlin_pa) is a consultant vascular surgeon in Leeds, England. He is a very active member of the Vascular Society of Great Britain and Ireland Council and has a special academic and clinical interest in peripheral artery disease. Dr. Armstrong (@DGArmstrong) is a podiatric surgeon and professor of surgery at Keck School of Medicine of the University of California and director of the Southwestern Academic Limb Salvage Alliance. Dr. Armstrong is very well known for his work on amputation prevention, the diabetic foot and wound healing. Dr. Wukich (@DaneWukich) is a professor and chair of the Department of Orthopedics at the University of Texas, Southwestern and Medical Director of Orthopedic Surgery at UT Southwestern University Hospitals. Dr. Wich has an interest in foot and ankle surgery, including the management of diabetes-related complications. Dr. Edgar Peters is an associate professor of internal medicine, infectious diseases, and acute medicine at Amsterdam University Medical Centers, Dr. Peter's main interest is infection of the musculoskeletal system, particularly in patients with diabetes and is the Scientific Secretary of the International Symposium on the Diabetic Foot.    Malvern Diabetic Foot Conference info: https://www.facebook.com/MalvernDiabeticFootConference/ https://eu.eventscloud.com/website/8151/   If this episode was of interest to you, please take a listen to this Transatlantic Series episode where we speak with the authors of the SVS, ESVS, and IWGDFU joint guidelines on the management of peripheral arterial disease (PAD) in patients with diabetes.    Articles, resources, and societies referenced in the episode: DF Blog. “Oral Is the New IV. Challenging Decades of Blood and Bone Infection Dogma: A Systematic Review @bradspellberg @lacuscmedcenter @usc,” January 1, 2022. https://diabeticfootonline.com/2022/01/01/oral-is-the-new-iv-challenging-decades-of-blood-and-bone-infection-dogma-a-systematic-review-bradspellberg-lacuscmedcenter-usc/. Gariani, Karim, Truong-Thanh Pham, Benjamin Kressmann, François R Jornayvaz, Giacomo Gastaldi, Dimitrios Stafylakis, Jacques Philippe, Benjamin A Lipsky, and Lker Uçkay. “Three Weeks Versus Six Weeks of Antibiotic Therapy for Diabetic Foot Osteomyelitis: A Prospective, Randomized, Noninferiority Pilot Trial.” Clinical Infectious Diseases 73, no. 7 (October 5, 2021): e1539–45. https://doi.org/10.1093/cid/ciaa1758. Li, Ho-Kwong, Ines Rombach, Rhea Zambellas, A. Sarah Walker, Martin A. McNally, Bridget L. Atkins, Benjamin A. Lipsky, et al. “Oral versus Intravenous Antibiotics for Bone and Joint Infection.” New England Journal of Medicine 380, no. 5 (January 31, 2019): 425–36. https://doi.org/10.1056/NEJMoa1710926. Magliano, Dianna, and Edward J. Boyko. IDF Diabetes Atlas. 10th edition. Brussels: International Diabetes Federation, 2021. Østergaard, Lauge, Mia Marie Pries-Heje, Rasmus Bo Hasselbalch, Magnus Rasmussen, Per Åkesson, Robert Horvath, Jonas Povlsen, et al. “Accelerated Treatment of Endocarditis—The POET II Trial: Ration ale and Design of a Randomized Controlled Trial.” American Heart Journal 227 (September 2020): 40–46. https://doi.org/10.1016/j.ahj.2020.05.012. Price, Patricia. “The Diabetic Foot: Quality of Life.” Clinical Infectious Diseases 39 (2004): S129–31. Sharma, S., C. Kerry, H. Atkins, and G. Rayman. “The Ipswich Touch Test: A Simple and Novel Method to Screen Patients with Diabetes at Home for Increased Risk of Foot Ulceration.” Diabetic Medicine: A Journal of the British Diabetic Association 31, no. 9 (September 2014): 1100–1103. https://doi.org/10.1111/dme.12450. Shin, Laura, Frank L. Bowling, David G. Armstrong, and Andrew J.M. Boulton. “Saving the Diabetic Foot During the COVID-19 Pandemic: A Tale of Two Cities.” Diabetes Care 43, no. 8 (August 1, 2020): 1704–9. https://doi.org/10.2337/dc20-1176. Tone, Alina, Sophie Nguyen, Fabrice Devemy, Hélène Topolinski, Michel Valette, Marie Cazaubiel, Armelle Fayard, Éric Beltrand, Christine Lemaire, and Éric Senneville. “Six-Week Versus Twelve-Week Antibiotic Therapy for Nonsurgically Treated Diabetic Foot Osteomyelitis: A Multicenter Open-Label Controlled Randomized Study.” Diabetes Care 38, no. 2 (February 1, 2015): 302–7. https://doi.org/10.2337/dc14-1514. Wukich, Dane K., Katherine M. Raspovic, and Natalie C. Suder. “Patients With Diabetic Foot Disease Fear Major Lower-Extremity Amputation More Than Death.” Foot & Ankle Specialist 11, no. 1 (February 2018): 17–21. https://doi.org/10.1177/1938640017694722.

As many of you know, I have long argued (unsuccessfully until now) for a placebo-controlled trial of AF ablation. One group gets the ablation; the other gets a placebo or sham procedure. This way we can sort out the placebo-resistant effect of the ablation. Finally, here is the first report of one. Dr. Malcolm Finlay is an electrophysiologist at St Bartholomew hospital in London UK and primary investigator of the study. They recently published their feasibility study for AF ablation vs placebo. The American Heart Journal published the pilot study of 20 patients. Finlay and colleagues call it the ORBITA AF trial. But it's important to note that this was done separate from the ORBITA investigators at Imperial College. The larger study will have a different name. Here is a copy and paste:Twenty patients with PersAF (duration

Timestamps: 0:00 Intro To Podcast 1:26 Abstract 3:59 Research Introduction 27:58 Purpose Of Study and Hypothesis 31:28 Methods 38:04 Results 44:49 Discussion 48:52 Study Limitation 53:15 End of Paper & References Send me research here: https://dzuhxqwexxt.typeform.com/to/FQUNCT5G Find everything I do here: https://linktr.ee/nick.zei REFERENCES & NOTES 1. G.]. Washnis, & R. Z. Hricak, Discovery ofMagnetic Health (Nova Publishing Company, Rockville, MD, 1993). 2. ]. L. Oschman, Energy Medicine: The Scientific Basis (Churchill Livingston, New York, NY, 2000). 3. H. S. Burr, The Fields ofLife: Our Links with the Universe (Ballantine Books, New York, NY, ]972). 4. G. M. Baule & R. McFee, Detection of the Magnetic Field of the Heart, American Heart Journal 66 (1963), pp. 95-96. 5. R. Beck, Mood Modification with ELF Magnetic Fields: A Preliminary Exploration, Archaeus 4,48 (I 986). 6. J. L. Oschman, Biophysical Basis for Acupuncture, The Proceedings of the First Symposium ofthe Society for Acupuncture Research (Rockville, MD, January 23-24, 1993). 7. L. G. Russek & G. E. Schwartz, Energy Cardiology: A Dynamical Energy Systems Approach for Integrating Conventional and Alternative Medicine, Advances: The Journal ofMind-Body Health 12,4 1996), pp. 4-24. 8. D. Eisenberg, Encounters with Qi: Exploring Chinese Medicine (Norton & Company, New York, NY, 1995). 9. ]. M. Yang, Qigong for Health and Martial Arts: Exercises and Meditation (YMAA Publication Center, Boston, MA, 1998). 10. D. Gao, Chinese Medicine (Thunder's Mouth Press, New York, NY, 1997). 11. R. O. Becker, Evidence for a Primitive DC Electrical Analog System Controlling Brain Function, Subtle Energies 2,1 (1991), pp. 71-88. 12. ]. Thurnell-Read, Geopathic Stress: How Earth Energies Affict Our Lives (Element, Rockport, MA, 1995). 13. W. O. Schumann, On the Characteristic Oscillations of a Conducting Sphere which is Surrounded by an Air Layer and an Ionospheric Shell, Zeitschriji for Naturforschung 7a (1952), pp. 149-154 14. P. Andersen & S. A. Andersson, Physiological Basis ofthe Alpha Rhythm (Appleton­ Century Crofts, New York, NY, 1968). 15. G. A. Dillman & c. Thomas, Kyusho Jitsu: The Dillman Method ofPressure Point Fighting (GDKI, Reading, PA, 1992). 16. R. O. Becker & G. Seldon, The Body Electric: Electromagnetism and the Foundation of Life (William Morrow and Company, Inc., New York, NY, 1985). 17. R. O. Becker, Cross Currents: The Perils o f Electropollution, the Promise o f Electromedicine Qeremy P. Tarcher, Los Angeles, CA, 1990). 18. R. O. Becker, The Machine Brain and Properties of the Mind, Subtle Energies 1,2 (1990), pp. 79-97. 19. M. A. Morton & c. Dlouhy, Energy Fields in Medicine Qohn E. Fetzer Foundation, Kalamazoo, MI, 1989).

This week, please join author Judith Hochman, Editorialist Steven Bradley, and Guest Host Mercedes Carnethon as they discuss the article " Survival After Invasive or Conservative Management of Stable Coronary Disease" and editorial “If the Fates Allow: The Zero-Sum Game of ISCHEMIA-EXTEND.” Dr. Greg Hundley: Welcome everyone to our new year 2023, and we are here on this January 3rd edition of Circulation on the Run. I'm Dr. Greg Hundley, Associate Editor, Director of the Pauley Heart Center at VCU Health in Richmond, Virginia. Dr. Peder Myhre: I am Dr. Peder Myhre, Social Media Editor and doctor at the Akershus University Hospital and University of Oslo. Dr. Greg Hundley: Very nice. Well, welcome listeners and this week's feature, ah, very interesting. You know many times patients with stable coronary artery disease, we're seeing a lot in the literature about an invasive strategy versus a conservative strategy. But what happens long term for these patients? What's their prognosis? Well, more to come in the feature discussion. But first, how about we grab a cup of coffee and we discuss some of the other issues in this session. Peder, would you like to go first? Dr. Peder Myhre: Yes, Greg I would love to and the first paper today is very interesting and relates to one of the most important challenges globally, namely climate changes and extreme temperatures. And in this paper, which comes to us from corresponding author, Barrak Alahmad from Harvard Chan School of Public Health in the United States, together with a large international group of authors, investigated the associations between extreme temperatures and cardiovascular cause-specific mortality in 567 cities in 27 countries from 1979 to 2019. Dr. Greg Hundley: Wow Peder, that is a really large comprehensive study. So, how did they perform this analysis? What did they find? Dr. Peder Myhre: So Greg, the investigators collected city-specific daily ambient temperatures from weather stations and analyzed cause-specific cardiovascular mortality and excess deaths in association with extreme hot and extreme cold temperatures. And in total, the analysis included more than 32 million deaths from any cardiovascular cause, which were subdivided into deaths from ischemic heart disease, stroke, heart failure and arrhythmia and at extreme temperature percentiles. And that is defined as heat above the 99th percentile and as cold below the first percentile were associated with a high risk of dying from any cardiovascular cause, ischemic heart disease, stroke and heart failure as compared to the minimum mortality temperature, which is the temperature associated with least mortality. And Greg, across a range of extreme temperatures, hot days above the 97.5 percentile and cold days below the 2.5 percentile accounted for more than two and more than nine excess deaths for every thousand cardiovascular death respectively. And heart failure was associated with the highest excess death proportions from extreme hot and cold days. So Greg, it seems like extreme temperatures really impact the cardiovascular mortality across the globe. Dr. Greg Hundley: Yeah, beautiful description Peder. And I think what was really exciting about that particular article is you had results from 27 countries. Wow, so really quite a global study and very informative. Dr. Peder Myhre: Yes, indeed very impressive. Dr. Greg Hundley: Well, Peder my next study comes to us from the world of preclinical science. And Peder, these investigators led by Professor Jose Luis de la Pompa from CNIC, evaluated two structural cardiac diseases, left ventricular non-compaction and bicuspid aortic valve. And they wanted to determine if those two conditions were caused by a set of inherited heterozygous gene mutations affecting the notch ligand regulator, Mind bomb-1 and co-segregating genes. Dr. Peder Myhre: Okay Greg, so we are looking at mechanisms for non-compaction and bicuspid aortic valve. What did they find? Dr. Greg Hundley: Right Peder, so whole exome sequencing of the left ventricular non-compaction families identified heterozygous missense mutations in five genes co-segregating with E3 ubiquitin protein ligase-1 Mib-1 as well as left ventricular non-compaction. And corresponding mouse models showed that left ventricular non-compaction or bicuspid aortic valve in a notch-sensitized genetic background. Now, also gene profiling showed that increased cardiomyocyte proliferation and defective morphological and metabolic maturation in mouse hearts and human pluripotent stem cell cardiomyopathy. Biochemistry suggested a direct interaction between notch and some of the identified gene products. And so, these data Peder support a shared genetic basis for left ventricular non-compaction and bicuspid aortic valve with Mib-1 notch playing a crucial role. And thus, identification of heterozygous mutations leading to left ventricular non-compaction or bicuspid aortic valve may allow us to expand the genetic testing panel repertoire for better diagnosis and or risk stratification of both of these conditions, left ventricular non-compaction and bicuspid aortic valve. Dr. Peder Myhre: All right, that is really great and novel linking left ventricular non-compaction to bicuspid aortic valve, really great. And now Greg, we're going to go back to clinical science and we're going to talk about lipoprotein(a) or Lp(a). And as you know, elevated Lp(a) is a common risk factor for cardiovascular disease outcomes with unknown mechanisms. And the authors of this next paper coming to us from corresponding author Olli Raitakari from University of Turku in Finland, examined Lp(a)'s potential role in identifying youths who are at increased risk of developing adult atherosclerotic cardiovascular disease, ASCVD. And they did this by measuring Lp(a) in youths nine to 24 years old and linking that to a diagnosis of ASCVD as adults and also linking it to carotid intermediate thickness in the Young Finns Study. And in addition, these results were validated in the Bogalusa Heart Study. Dr. Greg Hundley: Oh, very nice Peder. So, what did they find? Dr. Peder Myhre: So Greg, those who have been exposed to high Lp(a) levels in youth and that was defined as greater than or equal to 30 milligrams per deciliter, had about two times greater risk of developing adult ASCVD compared to non-exposed individuals. In fact, all the following youth risk factors were independently associated with a higher risk. Lp(a), LD, cholesterol, body mass index and smoking all independently associated with ASCVD. And similar findings were made in the validation cohort who were participants with a high Lp(a) had 2.5 times greater risk of developing adult ASCVD compared to non-exposed individuals. And this also persisted in adjusted models. Now, what about the carotid intermediate thickness? In that analysis, there were no associations detected to youth Lp(a) levels in either of the cohorts. Dr. Greg Hundley: Very nice, Peder. So, great description of the utility of lipoprotein(a) measurements in the youth and for predicting future major cardiovascular events. Well, the next paper goes back to the world of preclinical science. And Peder, cardiac hypertrophy increases demands on protein folding, which causes an accumulation of misfolded proteins in the endoplasmic reticulum. Now, these misfolded proteins can be removed via the adaptive retro-translocation, poly-ubiquitylation and a proteasome mediated degradation process. The endoplasmic reticulum-associated degradation, ERAD, which altogether as a biological process and rate has not been studied in vivo. So, these investigators led by Dr. Christopher Glembotski from University of Arizona College of Medicine, investigated the role of ERAD in a pathophysiological model and they examined the function of the functional initiator of ERAD, VCP-interacting membrane protein and positing that the VCP-interacting membrane protein would be adaptive in pathological cardiac hypertrophy in mice. Dr. Peder Myhre: Thanks Greg. So, we're talking about degradation of the endoplasmatic reticulum and the association to hypertrophy. So, what did these investigators find, Greg? Dr. Greg Hundley: Right, Peder. So, this was really the first study to demonstrate that endoplasmic reticulum-associated protein degradation or ERAD is responsible for degrading and thus, regulating the levels of a cytosolic non-endoplasmic reticular protein. The results reported here describe a new mechanism mediating the pathological growth of the heart, such that in the healthy heart SGK-1 levels are low due to ERAD-mediated degradation. While in the setting of pathology, ERAD-mediated degradation of SGK-1 is disrupted, allowing the pro-growth kinase to accumulate and contribute to pathological cardiac hypertrophy. And so Peder, the clinical relevance of these findings is that the investigators found that a variety of proteins that constitute the ERAD machinery were decreased in both mouse and human heart failure samples while SGK-1 was increased, supporting the possibility that SGK-1 is a contributor to the disease phenotype. And this is notable and that these studies could lead to the development of new therapeutic approaches for managing pathological cardiac hypertrophy and heart failure that target the ERAD to restore efficient SGK-1 degradation. Dr. Peder Myhre: That was an excellent explanation of a very difficult topic. Thank you, Greg. Dr. Greg Hundley: Well, Peder how about we take a look and see what else is in the issue? And now I'll go first. Well, first there's an In Depth by Professor Ntsekhe entitled, "Cardiovascular Disease Among Persons Living with HIV: New Insights into Pathogenesis and Clinical Manifestations within the Global Context." And then, there's a Research Letter by Professor Verma entitled, "Empagliflozin in Black Patients Versus White Patients With Heart Failure: Analysis of EMPEROR results-Pooled." Dr. Peder Myhre: Great Greg and there is an On My Mind by Gabriel Steg entitled, "Do We Need Ischemia Testing to Monitor Asymptomatic Patients With Chronic Coronary Syndromes?" Very timely and interesting. And finally, there is an AHA Update from Michelle Albert, the President of the AHA entitled, "Tackling Adversity and Cardiovascular Health: It is About Time." Dr. Greg Hundley: All right. Well Peder, how about we get onto that feature discussion looking at survival after invasive or conservative management in stable coronary heart disease? Dr. Mercedes Carnethon: Thank you so much for joining us for this episode of Circulation on the Run. I'm Mercedes Carnethon, Professor and Vice Chair of Preventive Medicine at the Northwestern University, Feinberg School of Medicine. And I'm very excited today to have as a guest, Dr. Judith Hochman, who is going to be discussing the long-awaited findings from the ISCHEMIA-EXTEND trial that are looking at survival after invasive or conservative management of stable coronary disease. Really pleased to have you with us today, Judy to hear about these findings. Dr. Judith Hochman: It's a pleasure to be here. Dr. Mercedes Carnethon: Thank you. So, just to start off, can you tell us about this study? What motivated this long-term follow-up of this particular trial? Dr. Judith Hochman: Yeah, so as I think the viewers or the listeners will recall, we built on a wealth of data from COURAGE and BARI 2D, some of the landmark trials that looked at revascularization versus optimal medical therapy or guideline-directed medical therapy alone. We tested an invasive strategy versus a conservative strategy dating back already to 2012 is when we started. And we had a five component primary outcome, which included cardiovascular death, myocardial infarction or hospitalization for unstable angina, heart failure or resuscitated cardiac arrest. And at the end of 3.2 median years of follow-up, we saw no difference in the primary outcome in that the curves crossed with some excess risk upfront due to periprocedural MI and decreased risk of spontaneous MI long-term. But the net overall timeframe spent free of event was similar between the groups. So, we did observe improved quality of life for the invasive strategy, but in terms of clinical outcomes there was no difference. So, cardiovascular death at the end of that time period was no different between the groups, all-cause mortality was no different, non-cardiovascular death, there was actually an increase in the invasive group, which was somewhat of a mystery. We can get into that a little bit later because I think that becomes important. But 3.2 years meeting and follow-up is relatively short. So, everyone was very interested in what would the long-term outcomes be. So, we had another grant from the National Heart, Lung and Blood Institute to follow these patients long-term. And this is an interim report with seven years of follow-up, a median of 5.7 years. And the bottom line is that all-cause mortality was the same at seven years but for the first time, an invasive strategy resulted in lower cardiovascular mortality, which was very interesting and very exciting except that it was offset, exactly offset by the continued excess that we had previously observed in non-cardiovascular mortality. And that's basically the upshot of what we just reported and why we continue to follow patients and why we're going to continue to follow patients and have a final report in 2026. Dr. Mercedes Carnethon: This is really fantastic work. As you point out, the initial follow-up was fairly short and the findings were so critically important demonstrating that there were subtle differences between the two approaches but that overall, things appeared relatively similar. Did it surprise you? Oh, please correct me. Dr. Judith Hochman: I should point out that because there were less spontaneous MIs during follow-up and spontaneous MIs are associated with a heightened risk of subsequent death more so than the periprocedural MIs, we did hypothesize and we're very interested in longer term cardiovascular and all-cause mortality thinking that those reduced spontaneous MIs in the invasive group would be associated with reduced cardiovascular death and perhaps reduced mortality. As I did indicate, cardiovascular death mortality was reduced but all-cause mortality was the same with a hazard ratio of 1.0. Dr. Mercedes Carnethon: Well, nothing seems more clear than a hazard ratio of 1.0 with those very tight confidence limits so thank you so much. I'm really pleased that our editorialist, Dr. Steve Bradley was also able to join us today because to hear his thoughts about where this fits in the context of what we know can be really insightful. So, I'd really love to turn to you, Dr. Bradley. In your opinion, why was this study question so important and tell us a little bit about how you think the clinical field should use these findings. Dr. Steven Bradley: Absolutely and thanks for having me. I think there were some indication that perhaps the farther we follow the patients out from the original ISCHEMIA trial that we might start to see some evidence of benefit for revascularization. I think Dr. Hochman spoke about the evidence of more of these spontaneous myocardial infarctions that were happening in the non-revascularization arm of the study and an association with worse cardiovascular outcomes in patients that experience spontaneous events. And so, the thoughts might be that over time we would see the benefit of that. And certainly if you parse out cardiovascular versus non- cardiovascular outcomes, we do, we see lower rates of cardiovascular death in the patients who undergo revascularization but it's balanced out by non-cardiovascular death. And so, it becomes a zero sum game for a patient. They want to be alive, it doesn't matter by what mechanism. So, if we have a therapy that doesn't actually prolong their life but it leads to different mechanisms by which they have an outcome, that's important for us to understand. This adds to an already robust evidence-based that ISCHEMIA really did inform and it gives us that long-term trajectory to help us understand for patients what the implications are. I will note that and we've commented in the editorial and this is something that was shown in the original ISCHEMIA trial, that it's not just about mortality for patients, it's important that we help them live better as well. And certainly we know that revascularization is associated with quality of life improvement so that's an important part of the conversation with patients. But again, continuing to refine our understanding of what the implications of revascularization are for mortality is where this study leads us now. Dr. Mercedes Carnethon: Thank you so much. One of the things that I find so impressive about clinical trials of this scale are that you incorporate such a broad audience. I note that 36 countries contributed data to this particular trial. I wonder whether, did you have an opportunity to investigate whether these findings were similar in low and middle income countries as compared with higher income countries? And how would you expect clinicians in low and middle income countries to use this information? Dr. Judith Hochman: That's a great question and yes, the treatment effect was similar across regions, didn't really have any very low income regions but we did have India was in the study and a number of South American countries. And I think it's incredibly important for those countries where there are very limited resources to reassure them, the practitioners and their patients that just because they can't afford an expensive invasive procedure, stenting or bypass, does not mean it's going to cut their life shorter, it's not going to make them survive for a shorter amount of time. Therefore, they can limit the use of scarce resources to the most severely impaired in terms of quality of life, the patients with the most frequent angina. It also became extremely relevant during COVID. Dr. Mercedes Carnethon: Tell me more. Dr. Judith Hochman: Well, elective procedures were shut down during COVID and more publications that cited the ISCHEMIA trial to say that they felt comfortable not being able to do elective stenting in patients with stable ischemic heart disease that would've met the ISCHEMIA trial criteria, which by the way we should add was preserved ejection fraction, we excluded ejection fraction less than 35, patients had to be stable. They could not have had two coronary syndrome within the last few months. They could not have had angina refractory to medical therapy and they could not have had left main disease. So, those are key. There are other exclusion criteria but those are the key exclusion criteria. Dr. Mercedes Carnethon: Thank you for that. And I can really see a corollary and I appreciate the messaging around similar outcomes and preserving resources. And I think certainly even within our own country where we see vast differences in access to intensive medical therapies or tertiary care medical centers who do these procedures on a higher volume, at least we can feel reassured that outcomes may be quite similar as far as mortality. What do you- Dr. Judith Hochman: If they take their guideline-directed medical therapy. Dr. Mercedes Carnethon: Thank you for pointing that out. Dr. Judith Hochman: It's incredibly important. John Curtis' group looked at adherent patients by the modified Morisky score versus non-adherent patients. Non-adherent patients don't have as good a health status as adherent patients. So, just that also adds to a wealth of literature that you have much better outcomes if you actually take your medications. Dr. Mercedes Carnethon: No, I think that's a very good point. What are your thoughts, Steve on what the next steps might be? Dr. Steven Bradley: Well, I know that as was pointed out earlier, there's going to be the opportunity to see additional longer term follow-up beyond this interim analysis. So, it'll be interesting to see what that continues to show us in terms of understanding applications on mortality. I'll pose a question that we posed within our editorial around trying to identify non-fatal outcomes to see if there are any opportunity to capture those non-fatal outcomes to give us an understanding of potential mechanisms for why there is this cardiovascular versus non- cardiovascular mortality difference by treatment arm? Certainly, that may be helpful. Dr. Judith Hochman: Sorry. We're very, very interested in the excess in non-cardiovascular death. So, we are as a result of this interim analysis, revising our case report form, which was very lean, pragmatic because the funding is relatively limited to include especially collection of data around malignancy. Because as we reported before, the non-cardiovascular deaths were largely malignancy and to some extent infection. And what was driving the difference, the excess in non-cardiovascular death as we published in American Heart Journal in the invasive group was excess malignancy. Dr. Mercedes Carnethon: That's really interesting. Dr. Judith Hochman: To our deep surprise and shock, it appeared that the only variable associated with that excess risk was the number of tests or procedures you had that involve radiation. And of course, we're talking about medical doses of radiation. And this short timeframe, three and a half to seven years, which is when the curve started to diverge to three and a half, we filed to seven years is not thought to ... it's thought to be too short a timeframe for exposure to radiation to lead to excess malignancy. So, we have partnered with some radiation experts, we are adding much more details to our case report form, not only in terms of death from malignancy but just the occurrence of malignancy. Did you get malignancy during the course of follow-up? And that's really critically important. We are not adding information about additional myocardial infarctions. We think that the key, if we're going to focus on site burden and how much they can actually collect, is to look at the mechanisms of death and the occurrence of malignancy, whether that leads to death or not, those are our top priorities at this point. Dr. Mercedes Carnethon: I could go on and on, I'm learning so much speaking with the two of you. And again, that really is the primary goal of our podcast to really have an opportunity to extend beyond what's written in the paper and really hear directly from the authors who led the study to hear your thoughts as well as those of the editorialists on where this is going. I really want to thank you both for the time you've spent today to share with our audience of the Circulation on the Run podcast. Dr. Judith Hochman: You're very welcome. Dr. Steven Bradley: My pleasure. Dr. Mercedes Carnethon: I just want to thank all of our listeners for joining us on this really stimulating discussion today on this episode of Circulation on the Run. Please tune in next week where we will have more exciting discussions like this one. Thank you. Dr. Greg Hundley: This program is copyright of the American Heart Association 2023. 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.

Show Notes - All Things Afib - Episode 15: Dementia and Atrial Fibrillation with Dr. Jared Bunch As doctors, we often don't ask our patients (or their spouses) about “memory issues” or other signs of dementia, related to AFib. We usually ask about stroke, clots, and other heart functions but neglect to ask about the brain. My guest today is Dr. T. Jared Bunch, Head of Section for Heart Rythm Services at the University of Utah. Dr. Bunch specializes in the diagnosis and management of heart rhythm disorders. His current research involves defining mechanisms underlying the association between atrial fibrillation and dementia. He looks at therapeutic opportunities to lower the risk of cognitive decline, the integration of wearable and implantable devices to improve early diagnosis and treatment of arrhythmias, and improving mapping and catheter ablation of arrhythmias.Dr. Bunch is a section editor for Current Cardiology Risk Reports, Heart Rhythm Journal, and a guest editor for American Heart Journal. He is on the editorial boards of the Heart Rhythm Journal, Journal of Cardiovascular Electrophysiology, Heart, American Heart Journal, JACC electrophysiology, and the Journal of Innovations in Cardiac Rhythm Management. In addition, he is a Professor of Medicine at the University of Utah and Editor-in-chief of the Heart Rhythm Society.Join us for a discussion on the alarming connection between AFib and dementia, how to manage AFib and also assist in preventing brain decline, and the many exciting studies and trials, books and articles about the relationship between the two.All Things Afib is hosted by me, Dr. Armin Kiankhooy. As a board-certified cardiothoracic surgeon, my focus is on advanced treatments for heart and lung failure and minimally-invasive surgical treatments for atrial fibrillation such as the Hybrid Maze procedure. You can find me on staff at Adventist Health Heart and Vascular Institute in St. Helena California. Discussion points:Dr. T Jared Bunch intro and background What is dementia? Why should we care about its relation to AFib?An AFib/Dementia story– the salesman with AFib and “senior moments”Many times doctors neglect to ask patients about dementia and memory issues – only ask about stroke, clots, etc.Microbleeds, microclots, and hypoperfusionAssessing risk through blood panelsThe concussion/afib trialThe magnitude of risk for dementia is higher in younger patients – ages 60-70 vs. 70-90The impact of wearables and the Heartline TrialBenefits of anticoagulantsAppendage management, AFib, and dementiaCHADS VASC scores and AFib/dementiaWhat other tests/scores do you look at?The AFib Cure book and Dr. John DayClosing words: for anyone listening– Be your own advocate, ask questions, join the AFib online community, and find a doctor who will answer your questions/knows about AFib. There are treatments and ways to address Afib.Resources:Dr. T. Jared Bunch LinkedInDr. Bunch PublicationsJoin the Heartline Trial/Apple WatchThe Afib Cure BookStopAFib.orgDr. Kiankhooy LinkedInAll Things AFib WebsiteAll Things AFib TwitterAll Things AFib YouTube Channel

SUMMARY--What diuretic do you usually write for during CHF hospitalizations??   If you said furosemide you are not alone  One in a study in JACC 2013 looked at HF hospitalizations in 2009 and 2010 – In total 251,472 patients got a loop diuretic during their hospitalization and almost 87% got just furosemide, about 3% only got bumex, while only 0.4 received only torsemide.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4038646/#R11  What is the difference between bumetanide and furosemide? Nothing—or at least nothing we care about. No hard outcomes, no patient oriented outcomes.  Bumetanide is stronger—An article from 2015 in American Heart Journal states bumetanide is about 40 times stronger than furosemide- thus at times you might have your sphincter tighten when you go to write for 120-160mg of furosemide but feel comfortable writing for 3-4mg of bumex. They also discuss how bumetanide also appears to have a higher more consistent bioavailability at around 80-100% while furosemide seems to range from 10-100% depending on the study. Conclusion: the benefits for bumetanide are there in theory but no hard outcomes that I could find. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4346710/  What about torsemide??The bioavailability of torsemide is 76% to 96% and as I mentioned before furosemide hangs out around 10% to 100%. In addition, furosemide bioavailability can decrease by up to 30% with food while torsemide is not affected by food consumption.https://oce.ovid.com/article/00006562-199701000-00009https://pubmed.ncbi.nlm.nih.gov/3709617/  HOWEVER, no patient cares about bioavailability they want to know if they will live longer or live better (patient oriented outcomes)??  First paper- 2001 Nov;111(7):513-20.American Journal of Medicine we have a paper titled“Open-label randomized trial of torsemide compared with furosemide therapy for patients with heart failure” This was open-label trial of 234 patients who were randomized to torsemide or furosemide and followed for 1 yr. The outcome was heart failure readmissions and it occurred significantly less in the torsemide group, only 17% of the time compared to 32% in the furosemide group. https://pubmed.ncbi.nlm.nih.gov/11705426/ That is almost a 50% relative reduction for heart failure hospitalization at one year! This is an outcome both patients and hospitalist would love to see! Second paper-In 2002- a year later-European Journal of Heart Failure a paper titledTorasemide in chronic heart failure: results of the TORIC studyThis was the published results of the ‘TOrasemide In Congestive Heart Failure (TORIC)' study- It was an open-label, non-randomised, post-marketing surveillance trial. The individuals who were prescribed torsemide on top of their other CHF medications for 12 months had almost a 50% relative reduction in mortality!! That may not seem like a lot but remember this is only 12 months and the outcome was DEATH! In absolute terms roughly 2% of participants died in the torsemide group and 4% died in the furosemide/other diuretic group. PLUS, those in the torsemide group also had an improvement in their NYHA functional heart class.https://pubmed.ncbi.nlm.nih.gov/12167392/  Finally, there is a meta-analysis from 2019 in Journal of Cardiovascular Medicine titledTorsemide versus furosemide and intermediate-term outcomes in patients with heart failure: an updated meta-analysis  Which looked at a total of 14 randomized trials and just over 8000 pts and found torsemide to have both fewer heart failure hospitalizations and those individuals taking torsemide were more likely to have an improvement in their new york heart association class but they didnt find a difference in mortality.https://pubmed.ncbi.nlm.nih.gov/30950982/ Currently there is 6000 pt randomized trial that is underway and will be done in august 2023. https://clinicaltrials.gov/ct2/show/NCT03296813  That is it, that is all that I could find!!!! However, with the evidence clearly in favor of torsemide, why have I never even considered it before doing this lecture?? Likely 2 problems 1) It is what we have always done and it is hard to change practice! Furosemide was approved for medical use in 1964.Torsemide was approved in 1993. We as providers get into a rut, the next drug we prescribe is likely to be one of the most recent drugs we prescribed. If you show me the last 10 hypertension medications you prescribed then with almost 90-100% certainty I can guess the next one that you are going to prescribe.  2) There use to be a cost issue when furosemide was generic and torsemide was not. However, now these are both old drugs and per goodrx down here in Florida they only differ by about 1.50$ per month, but we are saving hospitalizations which cost 1000$.  A paper from 2000 in Pharmacoeconomics titled “Healthcare costs of patients with heart failure treated with torasemide or furosemide” found torsemide average hospitalization cost per patient each year was $1000 while those in the furosemide group had an average cost of $1500 dollars, and this was back when torsemide wasn't nearly as cheap as it is now.  I know I have given you a lot of numbers but a good take away is- Torsemide compared to furosemide has a NNT at 10.5 months to prevent a heart failure hospitalization around 6!!! https://pubmed.ncbi.nlm.nih.gov/10977385/ https://www.medscape.com/viewarticle/771976_8  Even if the number is off a little because of study design flaws like blinding and sample size the evidence does appear to continually point the direction of benefit towards torsemide. Even if you doubled it, a NNT of 12, it is still really good.

Welcome to Episode 8 of “The 2 View,” the podcast for EM and urgent care nurse practitioners and physician assistants! Show Notes for Episode 8 of “The 2 View” – A Pediatric Special Bronchiolitis Chapman S. Bronchiolitis: evidence for practice? Evidentlycochrane.net. Published February 15, 2018. Accessed August 6, 2021. https://www.evidentlycochrane.net/bronchiolitis-evidence-practice/ Kirolos, A, Manti, S, Blacow, R, et.al. A Systematic Review of Clinical Practice Guidelines for the Diagnosis and Management of Bronchiolitis. Oxford Academic: The Journal of Infectious Diseases. Published November 1, 2020. Accessed August 6, 2021. https://academic.oup.com/jid/article/222/Supplement_7/S672/5549996?login=true R. Abaya, MD; K. Crescenzo, RN; E. Delgado, MD; et.al. Emergency Department Clinical Pathway for Evaluation/Treatment of Children with Bronchiolitis. The Children's Hospital of Philadelphia. Bronchiolitis Clinical Pathway — Emergency Department. Chop.edu. Published September 2005. Accessed August 6, 2021. https://www.chop.edu/clinical-pathway/bronchiolitis-emergent-evaluation-clinical-pathway Image on Following Page --> https://bit.ly/2VSKInN Rose, E, MD. Pediatric Fever and Infections. EM:RAP CorePendium. Emrap.org. Published July 6, 2021. Accessed August 6, 2021. https://www.emrap.org/corependium/chapter/recWjNx3zLXggj7co/Pediatric-Fever-and-Infections Schroeder AR MD, Marlow JA MD, Bonafide CP MD, MSCE. Improving Value in Bronchiolitis Care. JAMA Network Open. Published 2021. Accessed August 6, 2021. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2776436 Kawasaki's Kubota M, Usami I, Yamakawa M, Tomita Y, Haruta T. Kawasaki Disease With Lymphadenopathy And Fever As Sole Initial Manifestations. EMA September 2008. Emrap.org. Published September 2008. Accessed August 6, 2021. https://www.emrap.org/episode/ema-2008-9/abstract26 Mizuta M, Shimizu M, Inoue N, et al. Serum ferritin levels as a useful diagnostic marker for the distinction of systemic juvenile idiopathic arthritis and Kawasaki disease. Mod Rheumatol. PubMed.gov. Published July 19, 2016. Accessed August 6, 2021. https://pubmed.ncbi.nlm.nih.gov/27433933/ Saguil A MD, MPH, Fargo MV MD, MPH, Grogan SP MD, MBA. Diagnosis and Management of Kawasaki Disease. Am Family Physician. Published March 15, 2015. Accessed August 6, 2021. https://www.aafp.org/afp/2015/0315/p365.html Son MBF, Newburger JW. Kawasaki Disease. Pediatrics in Review: An Official Journal of the American Academy of Pediatrics. Published February 2018. Accessed August 6, 2021. https://pedsinreview.aappublications.org/content/39/2/78 Whitney, D MD; Dorland, K BSN; Beus, J MD; et.al. Emergency Department and Inpatient Clinical Pathway for Evaluation/Treatment of Children with Kawasaki Disease or Incomplete Kawasaki Disease. The Children's Hospital of Philadelphia. Kawasaki Disease or Incomplete Kawasaki Disease clinical pathway — Emergency Department and Inpatient. Chop.edu. Published January 2018. Accessed August 6, 2021. https://www.chop.edu/clinical-pathway/kawasaki-disease-incomplete-kawasaki-disease-clinical-pathway *Image on Following Page* --> https://bit.ly/2VSKInN Pediatric Fever Kaufman J, Fitzpatrick P, Tosif S, et al. Faster clean catch urine collection (Quick-Wee method) from infants: randomised controlled trial. BMJ. Published 2017. Accessed August 6, 2021. https://www.bmj.com/content/357/bmj.j1341 Pantell RH, Roberts KB, Adams WG, et al. Evaluation and Management of Well-Appearing Febrile Infants 8 to 60 days old. Pediatrics: Official Journal of the American Academy of Pediatrics. Published August 2021. Accessed August 6, 2021. https://pediatrics.aappublications.org/content/148/2/e2021052228 Figure 1: https://bit.ly/2VSKInN Figure 2: https://bit.ly/2VSKInN Figure 3: https://bit.ly/2VSKInN Tran A, Fortier C, Giovannini-Chami L, et al. Evaluation of the Bladder Stimulation Technique to Collect Midstream Urine in Infants in a Pediatric Emergency Department. PLoS One. Published March 31, 2016. Accessed August 6, 2021. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0152598 COVID in Kids CDC. Information for Pediatric Healthcare Providers. Cdc.gov. Published July 14, 2021. Accessed August 6, 2021. https://www.cdc.gov/coronavirus/2019-ncov/hcp/pediatric-hcp.html Chiotos, K MD, Davis, D MD, Kerman, C MD, et.al. Clinical Pathway for Evaluation and Treatment of Patients with Active COVID-19 Infection. The Children's Hospital of Philadelphia. Acute COVID-19, clinical pathway — all settings. Chop.edu. Published June 2020. Accessed August 6, 2021. https://www.chop.edu/clinical-pathway/covid-disease-clinical-pathway Image on Following Page --> https://bit.ly/2VSKInN Coronavirus outbreak and kids. Harvard.edu. Published August 2, 2021. Accessed August 6, 2021. https://www.health.harvard.edu/diseases-and-conditions/coronavirus-outbreak-and-kids Dong Y, Mo X, Hu Y, et al. Epidemiology of COVID-19 Among Children in China. Pediatrics: Official Journal of the American Academy of Pediatrics. Published June 2020. Accessed August 6, 2021. https://pediatrics.aappublications.org/content/145/6/e20200702 Ives-Tallman, C MD, Guest, B DO. Novel Coronavirus 2019 (COVID-19). EM:RAP CorePendium. Emrap.org. Published July 30, 2021. Accessed August 6, 2021. https://www.emrap.org/corependium/chapter/rec906m1mD6SRH9np/Novel-Coronavirus-2019-COVID-19 Ouldali N MD, Pouletty M MD, Mariani P MD, et al. Emergence of Kawasaki disease related to SARS-CoV-2 infection in an epicentre of the French COVID-19 epidemic: a time-series analysis. Lancet Child & Adolescent Health. Published July 2, 2020. Accessed August 6, 2021. https://www.thelancet.com/journals/lanchi/article/PIIS2352-4642(20)30175-9/fulltext Parcha V, Booker KS, Kalra R, et al. A retrospective cohort study of 12,306 pediatric COVID-19 patients in the United States. Sci Rep. PubMed.gov. Published May 13, 2021. Accessed August 6, 2021. https://pubmed.ncbi.nlm.nih.gov/33986390/ Mike & Martha's Something Sweet Abbasi B, Kimiagar M, Sadeghniiat K, et.al. The effect of magnesium supplementation on primary insomnia in elderly: A double-blind placebo-controlled clinical trial. J Res Med Sci. PubMed.gov. Published December 2012. Accessed August 6, 2021. https://pubmed.ncbi.nlm.nih.gov/23853635/ Gottlieb, M MD, Riddell, J MD, Cooney, R MD, et.al. Maximizing the Morning Commute: A Randomized Trial Assessing the Effect of Driving on Podcast Knowledge Acquisition and Retention. Annals of Emergency Medicine: An International Journal. Annemergmed.com. Published April 28, 2021. Accessed August 6, 2021. https://www.annemergmed.com/article/S0196-0644(21)00162-1/fulltext Guerrera MP MD, Volpe SL PhD, Mao JJ MD. Therapeutic Uses of Magnesium. American Family Physician. Published July 15, 2009. Accessed August 6, 2021. https://www.aafp.org/afp/2009/0715/p157.html Recurring Sources Center for Medical Education. Ccme.org. http://ccme.org The Proceduralist. Theproceduralist.org. http://www.theproceduralist.org The Procedural Pause. Emergency Medicine News. Lww.com. https://journals.lww.com/em-news/blog/theproceduralpause/pages/default.aspx The Skeptics Guide to Emergency Medicine. Thesgem.com. http://www.thesgem.com Trivia Question: Send answers to 2viewcast@gmail.com Last month we asked you a trivia question regarding Wellens syndrome. It was a 2-part question and we asked: Who is Wellens syndrome named after and in what year did he co-author the paper that describes what we now know as Wellens syndrome? The answer was: Cardiologist Dr. Henrich Wellens described, with his co-authors, what we now know as Wellens syndrome in 1982 in the American Heart Journal. The winner this month is Mike Sprosty, PA. Mike actually came to our live Original Emergency Medicine Boot Camp in July! It was great to meet him. Maybe he'll use the prize to check out another one of Center for Medical Education courses, or he'll give it to a friend. Be sure to keep tuning in for more great prizes and fun trivia questions! Once you hear the question, please email us your guesses at 2viewcast@gmail.com and tell us who you want to give a shout-out to.

James de Lemos MD is a Professor of Medicine and holds the Sweetheart Ball-Kern Wildenthal, MD, Ph.D. Distinguished Chair in Cardiology at UT Southwestern Medical Center. Dr. de Lemos completed his Medical school at Harvard and Internal Medicine Residency at UT Southwestern, where he also served as Chief Medical Resident.  He completed a fellowship in Cardiovascular Medicine and served on the faculty at the Brigham and Women's Hospital before returning to UT Southwestern in 2000. He is an invited member of the Association of University Cardiologists, the American Society of Clinical Investigation, and the Association of American Physicians. He has mentored >30 post-doctoral research trainees and authored over 300 manuscripts. He is the Executive Editor for Circulation and previously served on the editorial board of the Journal of the American College of Cardiology, the American Journal of Cardiology, and the American Heart Journal. He has won several teaching and mentorship awards including 2015 Women in Cardiology Mentoring Award by the American Heart Association and the 2020 Distinguished Mentor Award from the American College of Cardiology. As a medical student, Dr. James de Lemos was often hesitant to reach out to mentors because he didn't want to impose on their time. Today, he considers mentorship one of his great joys, one he finds immensely rewarding. Today. Dr. de Lemos shares his philosophy around mentorship thru various perspectives: as a mentee and as a mentor; for research, career, and life. He sheds light on the importance of finding the right mentors earlier in life and the joys of being a part of a mentees' early accomplishments. It's clear that mentorship is the favorite part of Dr. de Lemos' job. Pearls of Wisdom: 1. Mentors are looking for mentees that do what they say they're going to do when they say they're going to do them. 2. The right mentor is oftentimes more important than the right project. Find out about the mentor before signing up: how successful have they been working with other mentees at your level? Will they work in your best interest? Is it fun to work with them? 3. Don't look only for career mentors. Look for life mentors. Oftentimes, these are the people who remind you that the journey is more important than the destination. 4. What muscles should medical students work to build? First, challenge yourself to pass it forward through teaching. Then, in clinics,  practice deliberate decision-making and empathy with humor. Finally, train yourself to be efficient.

Learn about whether it’s better to be a big fish in a small pond or a small fish in a big pond, a mysterious, ancient city called Cahokia that’s, weirdly, just outside St. Louis, and how AI might be able to catch heart disease with a selfie. Curiosity Daily is a finalist in the 2020 Discover Pods Awards, and we need your vote to win! Please vote for Curiosity Daily for Best Technology & Science Podcast via the link below. It's free and only takes a minute. Thanks so much! https://awards.discoverpods.com/vote/ Is It Better to Be a Big Fish in a Small Pond or a Small Fish in a Big Pond? By Kelsey Donk Even When You’re A Member Of An Elite Group, It Can Be Demoralising To Rank Lower Than Your Peers. (2020, September 24). Research Digest; Research Digest. https://digest.bps.org.uk/2020/09/24/even-when-youre-a-member-of-an-elite-group-it-can-be-demoralising-to-rank-lower-than-your-peers/#more-40380  Zell, E., & Lesick, T. L. (2020). Taking Social Comparison to the Extremes: The Huge-Fish-Tiny-Pond Effect in Self-Evaluations. Social Psychological and Personality Science, 194855062095653. https://doi.org/10.1177/1948550620956535  Cahokia Was the Mysterious, Massive Ancient City in ... St. Louis? By Reuben Westmaas Newitz, A. (2016, December 13). Finding North America’s lost medieval city. Ars Technica; Ars Technica. https://arstechnica.com/science/2016/12/theres-a-1000-year-old-lost-city-beneath-the-st-louis-suburbs/  Mound 38 – Monks Mound – Cahokia Mounds. (2015, October 23). Cahokiamounds.Org. https://cahokiamounds.org/mound/mound-38-monks-mound/  Woodhenge - Cahokia Mounds, Illinois. (2020). Scienceviews.Com. https://scienceviews.com/indian/woodhenge.html  AI Might Be Able to Catch Heart Disease with a Selfie by Kelsey Donk “Selfies” could be used to detect heart disease. (2020). EurekAlert! https://www.eurekalert.org/pub_releases/2020-08/esoc-cb082120.php  Christoffersen, M., Frikke-Schmidt, R., Schnohr, P., Jensen, G. B., Nordestgaard, B. G., & Tybjærg-Hansen, A. (2014). Visible Age-Related Signs and Risk of Ischemic Heart Disease in the General Population. Circulation, 129(9), 990–998. https://doi.org/10.1161/circulationaha.113.001696  Lin, S., Li, Z., Fu, B., Chen, S., Li, X., Wang, Y., Wang, X., Lv, B., Xu, B., Song, X., Zhang, Y.-J., Cheng, X., Huang, W., Pu, J., Zhang, Q., Xia, Y., Du, B., Ji, X., & Zheng, Z. (2020). Feasibility of using deep learning to detect coronary artery disease based on facial photo. European Heart Journal. https://doi.org/10.1093/eurheartj/ehaa640  Schnohr, P., Lange, P., Nyboe, J., Appleyard, M., & Jensen, G. (1995). Gray hair, baldness, and wrinkles in relation to myocardial infarction: The Copenhagen City Heart Study. American Heart Journal, 130(5), 1003–1010. https://doi.org/10.1016/0002-8703(95)90201-5  Subscribe to Curiosity Daily to learn something new every day with Ashley Hamer and Natalia Reagan (filling in for Cody Gough). You can also listen to our podcast as part of your Alexa Flash Briefing; Amazon smart speakers users, click/tap “enable” here: https://www.amazon.com/Curiosity-com-Curiosity-Daily-from/dp/B07CP17DJY See omnystudio.com/listener for privacy information.

Are you trying to keep up with the latest medical literature but now you can go out for dinner, go to pubs, and send your kids to school...oh wait no...they're still stuck at home...nevermind...your ears are still in the right place!In this months episode:...Lung ultrasound scans for heart failure follow up... (06:30)D. Araiza-Garaygordobil, R. Gopar-Nieto, P. Martinez- Amezcua, et al., A randomized controlled trial of lung ultrasound guided therapy in heart failure (CLUSTER-HF study), American Heart Journal (2020), https://doi.org/10.1016/ j.ahj.2020.06.003 ...Depression and the risk of cardiovascular disease... (09:40)Rajan, Selina et al. “Association of Symptoms of Depression With Cardiovascular Disease and Mortality in Low-, Middle-, and High-Income Countries.” JAMA psychiatry, e201351. 10 Jun. 2020, doi:10.1001/jamapsychiatry.2020.1351...The link between mental health and the immune system... (14:45)Shields, Grant S et al. “Psychosocial Interventions and Immune System Function: A Systematic Review and Meta-analysis of Randomized Clinical Trials.” JAMA psychiatry, e200431. 3 Jun. 2020, doi:10.1001/jamapsychiatry.2020.0431...When to look for primary hyperaldosteronism?... (18:00)Brown, Jenifer M et al. “The Unrecognized Prevalence of Primary Aldosteronism: A Cross-sectional Study.” Annals of internal medicine vol. 173,1 (2020): 10-20. doi:10.7326/M20-0065...Migraines are not as benign as we might think... (22:56)Kurth, Tobias et al. “Association of Migraine With Aura and Other Risk Factors With Incident Cardiovascular Disease in Women.” JAMA vol. 323,22 (2020): 2281-2289. doi:10.1001/jama.2020.7172...Technology takeover of T1 Diabetes care... (31:22)Agarwal, Shivani, and Anne R Cappola. “Continuous Glucose Monitoring in Adolescent, Young Adult, and Older Patients With Type 1 Diabetes.” JAMA vol. 323,23 (2020): 2384-2385. doi:10.1001/jama.2020.7058...ICU outcomes in the elderly, not all bad news... (36:30)Haas, Lenneke E M et al. “Outcomes of Intensive Care Patients Older Than 90 Years: An 11-Year National Observational Study.” Journal of the American Geriatrics Society, 10.1111/jgs.16624. 27 Jun. 2020, doi:10.1111/jgs.16624JOURNALBITES (42:00)Ketamine for rapid tranquillisationDiscrimination and hypertensionDOACs in end-stage renal failureClarithromycin + DOACs= bleedingHaloperidol for headachesPutting Type 2 diabetes into remission: DIRECT style....Hookworm & Multiple Sclerosis...Tanasescu, Radu et al. “Hookworm Treatment for Relapsing Multiple Sclerosis: A Randomized Double-Blinded Placebo-Controlled Trial.” JAMA neurology, e201118. 15 Jun. 2020, doi:10.1001/jamaneurol.2020.1118Check out the awesome infographics on Twitter @JournalSpotting or our website

Duke cardiology fellow, Rahul Loungani, interviews Dr. Jonathan Piccini, director of the Electrophysiology Clinical Trials Program and Arrhythmia Core Laboratory at Duke University, about atrial fibrillation management in patients with heart failure. They discuss rate vs rhythm control and strategies for both, new onset AF in the context of critical illness, wearable devices in AF, escalation of therapy in AF, ideal patient for catheter ablation, and AF patients with cardiac resynchronization therapy. On the CardioNerds Heart Failure topic page you’ll podcast episodes, references, guest experts and contributors, and so much more. Take me to the Heart Failure Topic Page Take me to episode topics page Acute Decompensated Heart Failure Primer – Youtube Jonathan P. Piccini, MD, MHS is a clinical cardiac electrophysiologist and Associate Professor of Medicine at Duke University Medical Center and the Duke Clinical Research Institute. His research interests include the conduct of clinical trials and the assessment of cardiovascular therapeutics for the care of patients with heart rhythm disorders. At present, he is the Director of the EP Clinical Trials Program and Arrhythmia Core Laboratory at Duke University. He also serves on the Clinical Working Group of the American Heart Association’s Get With The Guidelines – Atrial fibrillation (GWTG-Afib) registry program. He is an associate editor for the American Heart Journal and serves on the editorial board of Heart Rhythm, the European Heart Journal, and the Journal of Cardiac Electrophysiology. He is the Principal Investigator of the data and coordinating center for ORBIT AF, a 25,000 patient registry focused on quality of care and improving outcomes in patients with atrial fibrillation. He is also the PI of the GENETIC AF clinical trial, the first clinical trial to study genotype-directed rhythm control therapy for atrial fibrillation. He also serves on the steering committees of multiple international randomized trials focused on the treatment of atrial fibrillation.  Dr. Piccini has more than 175 publications in the field of heart rhythm medicine. Clinically, his focus is on the care of patients with atrial fibrillation and complex arrhythmias, with particular emphasis on catheter ablation and lead extraction. Dr. Rahul Loungani completed medical school at the medical university of SC and then traveled to Baltimore for internal medicine training in the Osler Residency Program at the Johns Hopkins Hospital.  Here he fell in love with the management and hemodynamics of critically ill patients. He is currently a third-year cardiology fellow at Duke University Medical Center where he will also be pursuing fellowship in advanced heart failure and transplant cardiology next year. His current interests are in Cardiac amyloid, In particular its arrhythmic manifestations, early diagnosis, and novel therapeutics. He also loves teaching the housestaff and was awarded the Cassell-Saperstein award at Duke,  recognizing the fellow who most demonstrates a commitment to teaching and passion for clinical education. Outside of the hospital loves being a new dad to baby Arya

In 1495, a mysterious and deadly plague struck the city of Naples. Over the next 500 years, the medical attempts to understand and treat this new disease -- syphilis -- would mold and shape medicine in surprising ways. In this episode, Tony Breu and I will perform an historical and physiological biography of syphilis, covering the development of germ theory, epic poetry, mercury saunas, intentionally infecting patients with malaria, magic bullets, and lots and lots of experiments on poor rabbits. This presentation was performed live at the American College of Physicians’ national meeting in Philadelphia on April 11, 2019.   Sources (WARNING -- LONG LIST):   Swain, K. ‘Extraordinarily arduous and fraught with danger’: syphilis, Salvarsan, and general paresis of the insane. Lancet Psychiatry 5, (2018).   Kępa, M. et al. Analysis of mercury levels in historical bone material from syphilitic subjects – pilot studies (short report). Kępa Małgorzata 69, 367-377(11) (2012).   Forrai, J. Syphilis - Recognition, Description and Diagnosis. (2011). doi:10.5772/24205   Parascandola, J. From mercury to miracle drugs: syphilis therapy over the centuries. Pharm Hist 51, 14–23 (2009).   Eisler, C. Who Is Dürer’s ‘Syphilitic Man’? Perspect Biol Med 52, 48–60 (2009).   Rothschild, B. M. History of Syphilis. Clin Infect Dis 40, 1454–1463 (2005).   Schwartz, R. S. Paul Ehrlich’s Magic Bullets. New Engl J Medicine 350, 1079–1080 (2004).   Fee, E. The wages of sin. Lancet 354, SIV61 (1999).   O’Shea, J. ‘Two Minutes with Venus, Two Years with Mercury’-Mercury as an Antisyphilitic Chemotherapeutic Agent. J Roy Soc Med 83, 392–395 (1989).   Mahoney, J., Arnold, R., Sterner, B. L., Harris, A. & Zwally, M. Penicillin Treatment of Early Syphilis: II. Jama 251, 2005–2010 (1984).   Waugh, M. Role played by Italy in the history of syphilis. Sex Transm Infect 58, 92–95 (1982).   Thorburn, A. Fritz Richard Schaudinn, 1871-1906: protozoologist of syphilis. Sex Transm Infect 47, 459–461 (1971).   CROSBY, A. W. The Early History of Syphilis: A Reappraisal. Am Anthropol 71, 218–227 (1969).   Clark, E. G. & Danbolt, N. The Oslo study of the natural history of untreated syphilis An epidemiologic investigation based on a restudy of the Boeck-Bruusgaard material a review and appraisal. J Chron Dis 2, 311–344 (1955).   MUNGER, R. S. Guaiacum, the Holy Wood from the New World. J Hist Med All Sci IV, 196–229 (1949).   Thomas, E. & r, W. Rapid Treatment of Early Syphilis with Multiple Injections of Mapharsen. J Nerv Ment Dis 99, 88 (1944).   WIEDER, L., FOERSTER, O. & FOERSTER, H. MAPHARSEN IN THE TREATMENT OF SYPHILIS: FURTHER EXPERIENCES. Arch Dermatol Syph 35, 402–413 (1937).   THON, L. SHOULD THE INTERNIST KNOW SYPHILIS? J Amer Med Assoc 97, 994–996 (1931).   Sarton, G. The Earliest Printed Literature on Syphilis, being Ten Tractates from the Years 1495-1498. Karl Sudhoff , Charles Singer , Henry E. Sigerist. Isis 8, 351–354 (1926).   COLE, H., GERICKE, A. & SOLLMANN, T. THE TREATMENT OF SYPHILIS BY MERCURY INHALATIONS: HISTORY, METHOD AND RESULTS. Arch Dermatol Syph 5, 18–33 (1922).   Mason, U. Observation: Use and Abuse of Salvarsan. J Natl Med Assoc 3, 340–3 (1911).   Fleming, A. & Colebrook, L. ON THE USE OF SALVARSAN IN THE TREATMENT OF SYPHILIS. Lancet 177, 1631–1634 (1911).   Evans, A. The Treatment of Syphilis by Salvarsan (Dioxy-diamido-arseno-benzol). Brit Med J 1, 617 (1911).   Boeck, W. History, Theory and Practice of Syphilisation. New Engl J Medicine 73, 20–25 (1865).   Veale, H. Remarks on Syphilis and Its Treatment. Edinb Medical J 10, 10–26 (1864).   LaFond RE and Lukehart SA, Biological Basis for Syphilis. Clinical Microbiology Reviews 2006.   Secher L et al, Treponema pallidum in peripheral nerve tissue of syphilitic chancres. Acta dermato-venereologica 1982.  Hollander DH, Turner TB, The role of temperature in experimental treponemal infection. American journal of syphilis, gonorrhea, and venereal diseases, 1954   Eagle H, et al. The effect of hyperpyrexia on the therapeutic efficacy of penicillin in experimental syphilis. American journal of syphilis, gonorrhea, and venereal diseases, 1947.   Kampmeier RH, Syphilis therapy: an historical perspective. Journal of the American Venereal Disease Association 1976.   Pachner AR, Spirochetal Diseases of the CNS. Neurologic clinics, 1986.   Sell S et al, Experimental syphilitic orchitis in rabbits: ultrastructural appearance of Treponema pallidum during phagocytosis and dissolution by macrophages in vivo. Laboratory investigation; a journal of technical methods and pathology, 1982.   Taylor SH, Diuretics in cardiovascular therapy. Perusing the past, practising in the present, preparing for the future. Zeitschrift für Kardiologie, 1985.   Ovchinnikov NM, [Treponema pallidum in peripheral nerves of rabbit syphiloma]. Vestnik dermatologii i venerologii, 1975.   Cheek DB, Wu F, The Effect of Calomel on Plasma Epinephrine in the Rat and the Relationship to Mechanisms in Pink Disease, Archives of Disease in Childhood, 1959   Vogl A, The discovery of the organic mercurial diuretics, American Heart Journal, 1950   Schwemlein GX et al, Penicillin and fever therapy in early syphilis, Journal of the American Medical Association, 1948.   Stringham JS, On the Diuretic Effects of Mercury in a Case of Syphilis. The Medical and physical journal, 1807   Evanson RL et al, Effect of mercurial diuretics on tubular sodium and potassium transport in the dog. The American journal of physiology, 1972   Sell S and Salman J, Demonstration of Treponema pallidum in Axons of Cutaneous Nerves in Experimental Chancres of Rabbits, Sexually Transmitted Diseases, 1992   Penn CW, Avoidance of Host Defences by Treponema pallidum in Situ and on Extraction from Infected Rabbit Testes, Microbiology 1981.   Beutler B and Munford RS, Tumor Necrosis Factor and the Jarisch–Herxheimer Reaction, The New England Journal of Medicine 1996.   Radolf JD et al, Treponema pallidum: doing a remarkable job with what it's got. Trends in Microbiology, 1999   Tight RR, Perkins RL, Treponema pallidum infection in subcutaneous polyethylene chambers in rabbits. Infection and immunity, 1976   Salazar JC et al, Treponema pallidum Elicits Innate and Adaptive Cellular Immune Responses in Skin and Blood during Secondary Syphilis: A Flow-Cytometric Analysis. The Journal of Infectious Diseases, 2007   Azevedo BF et al, Toxic Effects of Mercury on the Cardiovascular and Central Nervous Systems. Journal of Biomedicine and Biotechnology 2012,   Clarkson TW and Magos L, The Toxicology of Mercury and Its Chemical Compounds, Critical Reviews in Toxicology 2008.   Fitzgerald TJ, The Th1/Th2-like switch in syphilitic infection: is it detrimental? Infection and immunity, 1992   Batterman RC et al, THE SUBCUTANEOUS ADMINISTRATION OF MERCAPTOMERIN (THIOMERIN®): Effective Mercurial Diuretic for the Treatment of Congestive Heart Failure. Journal of the American Medical Association, 1949   Batterman RC, The status of mercurial diuretics for the treatment of congestive heart failure. American Heart Journal, 1951   Bleich HL et al, The Role of Regional Body Temperature in the Pathogenesis of Disease, The New England Journal of Medicine, 1981   Vander Veer JB et al, The Prolonged Use of an Oral Mercurial Diuretic in Ambulatory Patients with Congestive Heart Failure. Circulation 1950   Cox DL et al, The outer membrane, not a coat of host proteins, limits antigenicity of virulent Treponema pallidum. Infection and immunity, 1992.   Fildes P, The Mechanism of the Anti-bacterial Action of Mercury. Br J Exp Pathol, 1940   Clarkson TW, THE MECHANISM OF ACTION OF MERCURIAL DIURETICS IN RATS; THE METABOLISM OF 203Hg‐LABELLED CHLORMERODRIN. British Journal of Pharmacology and Chemotherapy, 1965   Engelkens HJ et al, The localisation of treponemes and characterisation of the inflammatory infiltrate in skin biopsies from patients with primary or secondary syphilis, or early infectious yaws. Genitourinary Medicine, 1993   Belum GR et al, The Jarisch–Herxheimer reaction: Revisited. Travel Medicine and Infectious Disease, 2013   Arando M et al, The Jarisch–Herxheimer reaction in syphilis: could molecular typing help to understand it better? Journal of the European Academy of Dermatology and Venereology, 2018.   Butler T, The Jarisch–Herxheimer Reaction After Antibiotic Treatment of Spirochetal Infections: A Review of Recent Cases and Our Understanding of Pathogenesis. The American Journal of Tropical Medicine and Hygiene, 2016   Carlson JA et al, The Immunopathobiology of Syphilis: The Manifestations and Course of Syphilis Are Determined by the Level of Delayed-Type Hypersensitivity. The American Journal of Dermatopathology 2011.   Aronson IK and Soltani K, The enigma of the pathogenesis of the Jarisch-Herxheimer reaction. The British Journal of Venereal Diseases, 1976   Sellato TJ et al, The Cutaneous Response in Humans to Treponema pallidum Lipoprotein Analogues Involves Cellular Elements of Both Innate and Adaptive Immunity, The Journal of Immunology 2001   Spiller HA, Rethinking mercury: the role of selenium in the pathophysiology of mercury toxicity. Clinical Toxicology 2017   Sell S et al, Reinfection of chancre-immune rabbits with Treponema pallidum. I. Light and immunofluorescence studies. The American journal of pathology 1985.    Grant SS and Hung DT, Persistent bacterial infections, antibiotic tolerance, and the oxidative stress response, Virulence 2013   Lant AF, Modern diuretics and the kidney. Journal of Clinical Pathology, 1981   Kamath SU et al, Mercury-based traditional herbo-metallic preparations: a toxicological perspective, Archives of Toxicology 2012.   Yeter et al, Mercury Promotes Catecholamines Which Potentiate Mercurial Autoimmunity and Vasodilation: Implications for Inositol 1,4,5-Triphosphate 3-Kinase C Susceptibility in Kawasaki Syndrome. Korean Circulation Journal 2013   Wöβmann W et al, Mercury intoxication presenting with hypertension and tachycardia. Archives of Disease in Childhood, 1999   Giacani L et al, Identification of the Treponema pallidum subsp. pallidum TP0092 (RpoE) Regulon and Its Implications for Pathogen Persistence in the Host and Syphilis Pathogenesis. Journal of Bacteriology 2013.   Edwards AM, From tooth to hoof: treponemes in tissue‐destructive diseases. Journal of Applied Microbiology, 2003   Wolgemuth CW, Flagellar motility of the pathogenic spirochetes. Seminars in Cell & Developmental Biology 2015.   Solomon HC and Kopp I, Fever Therapy. The New England Journal of Medicine 1937.   Rice KM et al, Environmental Mercury and Its Toxic Effects. Journal of Preventive Medicine and Public Health 2014.   Drusin LM, Electron microscopy of Treponema pallidum occurring in a human primary lesion. Journal of bacteriology 1969.   McNeely MC et al, Cutaneous secondary syphilis: Preliminary immunohistopathologic support for a role for immune complexes in lesion pathogenesis. Journal of the American Academy of Dermatology 1986.   Borenstein LA et al, Contribution of rabbit leukocyte defensins to the host response in experimental syphilis. Infection and immunity 1991.   Cabot RC et al, Case 51-1976 — Bicentennial CPC — Syphilis, Diarrhea and Death in the 1820's. The New England Journal of Medicine 1976.   Hobman JL and Crossman LC, Bacterial antimicrobial metal ion resistance. Journal of Medical Microbiology 2015   Gelpi A and Tucker JD, After Venus, mercury: syphilis treatment in the UK before Salvarsan. Sexually Transmitted Infections 2015.   MacHaffie et al, A study of the effectiveness of mercurial diuretics in treatment of cardiac decompensation. The American Journal of Cardiology 1958   Aberer W et al, Ammoniated mercury ointment: outdated but still in use. Contact Dermatitis 1990   Farhi D, Dupin N, Origins of syphilis and management in the immunocompetent patient: Facts and controversies. 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Dr Wong:             Welcome to the monthly podcast, "On The Beat, for Circulation: Arrhythmia, and Electrophysiology." I'm doctor Paul Wong, editor in chief, with some of the key highlights from this month's issue. We'll also here from Dr. Suraj Kapa reporting on new research from the latest journal articles in the field.                                 In our first article, Mathew Daly and associates examine whether a high-resolution, 9 French, infrared thermography catheter can continuously image esophageal temperatures during atrial fibrillation catheter ablation. The infrared temperature catheter was inserted nasally or orally into the esophagus, adjacent to the left atrium. Endoscopy was performed within 24 hours to document esophageal injury. Thermal imaging showed that 10 out of 16 patients experienced one or more events where the peak esophageal temperature was greater than 40 degrees centigrade. Three patients experienced temperatures greater than 50 degrees centigrade and one experienced greater than 60 degrees centigrade. Analysis of temperature data from each subject's maximal thermal event revealed high radius, 2.3 degrees centigrade per millimeter and rates of change 1.5 degrees centigrade per second, with an average length of esophageal involvement of 11.0 millimeters.                                 Endoscopy identified three distinct thermal lesions, all in patients with temperatures greater than 50 degrees centigrade, all resolving within two weeks. The authors concluded that infrared thermography, high-resolution mapping of esophageal temperatures during catheter ablation may be performed. Esophageal thermal injury occurs with temperatures greater than 50 degrees centigrade, and was associated with large spacial-temporal gradients.                                 In our next article, Nitesh Sood and associates reported on the real-world incidence and predictors of perioperative complications in transvenous lead extractions involving ICD leads in the NCDR ICD registry. Lead extraction was defined as removal of leads implanted for greater than one year. Predictors of major perioperative complication for all extraction procedures, 11,304, and for high voltage leads, 8,362, or 74% across 762 centers were analyzed, using univariate and multivariate logistic regression. Major complications occurred in 258, or 2.3% of the extraction procedures. Of these, 258 procedures with a complication, 41 or 16% required urgent cardiac surgery. Of these, 14 or 34% died during surgery. Among the total 98, or 0.9% deaths reported, 18 or 0.16% of the total occurred during extraction.                                 In multivariate, logistic regression analysis of all extractions, female sex, admission other than electively for the procedure, three or more leads extracted, longer implant duration, dislodgement of other leads, patients' clinical status, requiring lead extraction, such as infection or perforation, were associated with increased risk of complications. For high voltage leads, smaller lead diameter, a flat versus round coil shape, in greater proximal surface coil area, were multivariate predictors of major perioperative complications.                                 The rate of major complications and mortality with transvenous lead extraction is similar in the real world compared to single center studies from high volume centers. There remains a significant risk of urgent cardiac surgery with a very high mortality, and planning for appropriate cardiothoracic surgical backup is imperative.                                 In our next paper, Bence Hegyi and associates, have reported on the repolarization reserve in failing rabbit ventricular myocytes, and the role of calcium and beta-adrenergic effects on delayed and inward rectifier potassium currents. The authors measured the major potassium currents, IKr, IKs, IK1, and their calcium and beta-adrenergic dependence in rabbit ventricular myocytes, in chronic pressure, in volume overload, induced heart failure, and compared them to age-matched controls.                                 The authors made a number of observations. One, action potential duration was significantly prolonged only at lower pacing rates, 0.2 to 1 Hertz, in heart failure under physiological ionic conditions and temperature. Two, beat to beat variability of action potential duration was also significantly increased in heart failure. Three, both IKr and IKs were significantly regulated in heart failure under action potential clamp but only when cytosolic calcium was not buffered. Four, CaMKII inhibition abolished IKs upregulation in heart failure, but did not affect IKr. Five, IKs response to beta-adrenergic stimulation was also significantly diminished in heart failure, and, six, IK1 was also decreased in heart failure regardless of calcium buffering, CaMKII inhibition or beta-adrenergic stimulation.                                 These observations changed when cytosolic calcium was buffered. The action potential prolongation in heart failure was also significant in higher pacing rates. The authors concluded that in heart failure, calcium dependent up regulation of IKr and IKs counter-balances the reduced IK1, maintaining the repolarization reserve, especially at higher heart rates. In physiologic conditions, unlike conditions of strong cytosolic calcium buffering. Under beta-adrenergic stimulation, reduced IKs responsiveness, severely limits the integrated repolarizing potassium current in repolarization reserve in heart failure, increasing the arrhythmia propensity.                                 In the next paper, Christopher Piorkowski and associates report on the feasibility of a combined endo-epicardial catheter approach for mapping the ablation of atrial fibrillation. The authors studied 59 patients with permanents pulmonary veins isolation and had further symptomatic recurrences of paroxysmal atrial fibrillation, persistent atrial fibrillation, or atrial tachycardia. These patients underwent repeat ablation using bi-atrial endo- and epicardial mapping and ablation. Identification of arrhythmia substrates and selection of ablation strategy were based on sinus rhythm voltage mapping. In all patients, endo-epicardial mapping ablation were feasible using standard technologies of catheter access, three dimensional mapping, and radiofrequency ablation.                                 Epicardial mapping and ablation did not add procedural risk. Exclusively, epicardial low voltage substrate were found in 14% of patients. For the first time, novel epicardial conduction abnormalities located in the epicardial fiber network were described in human patients, 19% of the cohort. Epicardial ablation was needed in 80% of the patients. Over 23 months of follow up, freedom from arrhythmia recurrence was 73%. The authors used continuous monitoring and three months blanking period. Freedom from ATR of greater than two minutes was defined as the primary end-point.                                 The authors concluded that endo-epicardial mapping ablation was feasible and safe. Epicardial ablation increases transient mortality of ablation lesions. Further studies will be needed to demonstrate reproducibility and long-term outcomes, and how the technique compares to other methods.                                 In the next article, Michael Wolf and associates examined the long-term results of substrate modification for ablation of ventricular tachycardia using substrate elimination, targeting local, abnormal ventricular activities, or LAVA, post-myocardial infarction. They reported on 159 consecutive patients undergoing first ablation, age 65, 92% with ICDs, 54% with storms, and 73% with appropriate shocks. LAVA were identified in 92% and VT was inducible in 73%. Complete LAVA elimination after ablation was achieved in 64% and non-inducibility was achieved in 85%. During a median follow-up of 47 months, single procedure, ventricular free survival was 55%, 10% storms, and 19% shocks. The ventricular arrhythmia free survival was 73% after one year and 49% after five years.                                 Complete LAVA elimination was associated with improved outcomes, ventricular arrhythmia free survival of 82% at one year and 61% at five years. The subgroup treated with multi-electrode mapping and real-time image integration had improved ventricular arrhythmia free survival, 86% at one year and 65% at four years. Repeat procedures were also performed in 18% of patients. The outcomes improved, 69% ventricular arrhythmia free survival during a median follow-up of 46 months.                                 In a single center study, substrate modification, targeting LAVA for post myocardial infarction ventricular tachycardia resulted in a substantial reduction in ventricular tachycardia storm and ICDs shocks with up to 49% of patients free of arrhythmias at five years after a single procedure. Complete LAVA elimination, multi-electrode mapping, and real-time integration were associated with improved ventricular arrhythmia free survival.                                 In the next paper, Jean-Baptiste Gourraud and associates examined the safety and feasibility of transvenous lead extraction in adults with congenital heart disease over a 20 year period at a single center. The authors reported on 71 transvenous lead extraction procedures in 49 patients with adult congenital heart disease, mean age 38 years in which a total of 121 leads were extracted. The primary indication for extraction were infection in 48%, lead failure in 31%. A laser sheath was required in 46% and a femoral approach in 8%. Complete transvenous lead extraction was achieved in 92% of the leads. 49% of the patients had transposition of the great arteries. In multivariate analysis, lead duration was predictive of transvenous lead extraction failure. No perioperative death or pericardial effusion was observed. Subpulmonary, atrioventricular valve regurgitation increased in eight patients, five of whom had TGA and were independently associated with ICD leak or valvular vegetation.                                 After a median of 54 months of follow up after the first lead extraction, three deaths occurred independently from lead management. The authors concluded that despite complex anatomical issues, transvenous lead extraction can be achieved successfully in most adult congenital heart disease patients using advanced extraction techniques. Subpulmonary AV valve regurgitation is a prevalent complication, particularly in patients with transposition of the great arteries.                                 In the next paper, Gabriela Orgeron and associates examined the incidence of ventricular arrhythmias and follow-up in ARVC patients grouped by the level of indication for ICD placement, based on the 2015 International Task Force Consensus Statement Risk Stratification Algorithms for ICD Placement in arrhythmogenic right ventricular dysplasia/cardiomyopathy. In 365 of arrhythmogenic right ventricular dysplasia/cardiomyopathy patients, the authors found that the algorithm accurately differentiates survival from any sustained VT/VF among the four risk groups, p < 0.001. Patients with a Class I indication had significantly worst survival from VT/VF than patients with a Class IIa indication or a Class IIb. However, the algorithm did not differentiate survival free from VF or V flutter between patients with Class I and Class II indications. Adding Colter results, less than 100 PVCs per 24 hours to the classification, helps differentiate the risk.                                 Patients with a high PVCs burden, greater than 1000 PCVs per 24 hours had a poor survival from both VT/VF and VF and V flutter.                                 In the next paper, Takeshi Kitamura and associates studied eight patients that had bi-atrial tachycardia, a rare form of atrial macroreentrant tachycardia, in which both atria form a critical part of the circuit and were mapped using an automatic, high resolution, mapping system. 708 patients had a history of persistent atrial fibrillation, including septal or anterior left atrial ablation before developing bi-atrial tachycardia. One of the patients had a history of atrial septal path closure with a massively enlarged right atrium. The authors found that 9 atrial tachycardias, with a median cycle length of 334 milliseconds had three different types. Three were peri-mitral and peri-tricuspid reentrant circuit, three utilized the right atrial septum in a peri-mitral circuit, and three utilized only the left atrium and the left right atrial septum.                                 Catheter ablation successfully terminated eight of the nine bi-atrial tachycardias. The authors found that all patients who developed bi-atrial tachycardia had an electrical obstacle on the intraseptal left atrium, primarily from prior ablation lesions.                                 In our next paper, Kwang-No Lee and associates randomized 500 patients with paroxysmal atrial fibrillation to one of two strategies after pulmonary vein isolation. One, elimination of non-PV triggers in 250 patients, group A, or, two, step-wise substrate modification using complex fractionated atrial electrogram or linear ablation until non-inducibility of atrial tachyarrhythmias was achieved, 250 patients in group B. Recurrence of atrial tachyarrhythmias was higher in group B compared to group A. 32% of patients in group A experienced at least one episode of recurrent atrial tachyarrhythmia after the single procedure, compared to 43.8% in group B. P-value of 0.012 after a median follow-up of 26 months. Competing risk analysis showed that the cumulative incidence of atrial tachycardia was significantly higher in group B compared to group A (p= 0.007).                                 The authors concluded that elimination triggers as the end-point of ablation in paroxysmal atrial fibrillation patients decreased long-term recurrence of atrial tachyarrhythmias compare to non-inducibility approach achieved by additional empiric ablation.                                 In our final paper of the month, Roland Tilz and associates reported on 10 year outcome after circumferential pulmonary vein isolation using a double lasso and three dimensional electro anatomic mapping technique. From 2003 to 2004, 161 patients with symptomatic drug refractory paroxysmal atrial fibrillation underwent electro-anatomical mapping guided circumferential pulmonary vein isolation. The procedure end-point was absence of pulmonary vein spikes thirty minutes after isolation, after a single procedure and a median follow up of 129 months, stable sinus rhythm was present in 32.9% of patients based on Holter-ECGs and telephonic interviews. After multiple procedures, mean 1.73 and median follow up of 123.4 months, stable sinus rhythm was seen in 62.7% of patients. Progression towards persistent atrial fibrillation was observed in 6.2%.                                 The authors concluded that although the 10-year single procedure outcome in patients with paroxysmal atrial fibrillation was low, 32.9%, it increased to 62.7% after multiple procedures and the progression rate to persistent atrial fibrillation was remarkably low.                                 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. Dr Kapa:               Thank you Paul, and welcome back everybody to Circulation’s “On the Beat”, where we'll be discussing hard hitting articles across the electrophysiology literature.                                 Today, we'll be reviewing 22 separate articles of particular interest, published in January 2018. The new year saw plenty of articles that are of particular interest either for the future of our field of for present management of our patients. First, within the realm of atrial fibrillation, we'll review several articles within the realm of anticoagulation and left atrial appendage occlusion.                                 The first article we'll review is by Yong et al in the American Heart Journal, volume 195, entitled "Association of insurance type with receipt of oral anticoagulation in insured patients with atrial fibrillation: A report from the American College of Cardiology NCDR PINNACLE registry." In this publication, the author sought to evaluate the effect of insurance type on the appropriate receipt of anticoagulant therapy, specifically looking at warfarin versus NOACs. They reviewed retrospectively over 360,000 patients and found significant differences in appropriate prescription of anticoagulants, irrespective of which anticoagulant was considered. Medicaid patients received less appropriate anticoagulant prescription than those who were privately insured on Medicare or military insured. Furthermore, those on military or private insurances had a higher rate of NOAC prescription than those with Medicare.                                 Furthermore, there was an even wider disparity in NOAC use than warfarin use amongst differently insured patients. These data are important in that they highlight potential variability in appropriate management of patients based on insurance type. Of course, there are many issues that might impact this, such as health care access or available pharmacy coverage of specific medications. Furthermore, the authors do not dive into the impact on outcomes based on the therapy availability.                                 The next article we'll review is by Jazayeri et al, entitled "Safety profiles of percutaneous left atrial appendage closure and lysis: An analysis of the Food and Drug Administration Manufacturer and User Facility Device Experience (MAUDE) database from 2009 to 2016" published in the Journal of Cardiovascular Electrophysiology in volume 29 issue 1. Here, the authors sought to evaluate the overall safety profiles of procedures performed with different percutaneous left atrial appendage occlusion devices, including LARIAT and WATCHMAN. They review 356 unique reports and compared outcomes pre- and post- approval of the WATCHMAN device. The look at the specific composite outcome of stroke, TIA, pericardiocentesis, cardiac surgery, and death. They noted that this composite outcome occurred more frequently with WATCHMAN than with LARIATs, and this is irrespective of pre- or post- approval status.                                 These findings highlight the importance of postoperative monitoring in evaluation of overall outcomes. The reason by which there was more frequent negative outcomes in the WATCHMAN than LARIATs need to be considered. Obviously there's several limitations in the MAUDE database, similar with all large databases. However, it does highlight the importance of considering the mechanisms or sure decision making necessary, not just amongst patients and their providers but amongst operators of the staff or amongst physicians and industry executives. To determine how to optimize devices going forward.                                 Speak of left atrial appendage occlusion devices and the potential future of these, we next review an article by Robinson et al, entitled "Patient-specific design of a soft occluder for the left atrial appendage" published in nature biomedical engineering, in volume two in the year 2018. Robinson et al used 3D printing to create a soft, immunocompatible, biocompatible, endocardial implant to occlude the left atrial appendage. They use the individual CT of an in vivo pig to three D print using a specialized material, a left atrial appendage occlusion device, and demonstrated feasibility of achieving adequate occlusion. This paper is important and is one of the initial [inaudible 00:22:03] to how three D printing may be used to optimize patient care. In fact, three D printing has the potential to overturn medical manufacturing and device development.                                 Anatomy tends to be more often patient-specific than not. That's one size fits all implant designs may not be optimal, and resulting exclusion or inadequate occlusion amongst many patients. Decide of three D printable patient specific rapidly prototype soft devices that are biocompatible and hemocompatible, holds the potential to revolutionize the occlusion.                                 Staying in the field of left atrial appendage occlusion, we next review an article by Lakkireddy et al entitled "left atrial appendage closure and systemic homeostasis: The LAA homeostasis study" published in JACC. The authors sought to evaluate the effect of epicardial-versus endocardial left atrial appendage occlusion on systemic homeostasis, including effects on neuro-hormonal profiles of patients. They performed a prospective, single center, observational study, including 77 patients, about half of whom received endocardial versus epicardial device. Interestingly, they noted that the epicardial left atrial appendage occlusion cohort exhibited significant decrease in blood adrenaline, noradrenaline and aldosterone levels. Those are not seen with endocardial devices. Internal epicardial devices are associated with increases in adiponectin and insulin levels as well as a decrease in free fatty acids and consistently lower systemic blood pressure.                                 These data suggest a significant difference in the effect of epicardial versus endocardial closure left atrial appendage on neurohormonal profile. The authors propose several mechanisms for these findings but not the exact mechanisms as yet unclear. Several factors potentially could lead to these findings. One is that epicardial ligation may result in more total ischemia of the left atrial appendage than endocardial closure. Another potential mechanism maybe that the presence for material in the pericardial space versus in the bloodstream may have different effects on neuro-hormonal profile. However, these significant differences in outcomes highlight the importance of considering whether all approaches of left atrial appendage occlusion are considered equal. Many flaws of this study is that it's observational and not randomized. Does it possible those receiving epicardial closure may have been perceived to be lower risk for epicardial puncture, in this, as result, had better long-term outcomes.                                 Changing gears now but staying within the realm of atrial fibrillation, we next review elements for cardiac mapping and ablation. The first article we review is one that has received significant press, published by Marrouche et al entitled "Catheter ablation for atrial fibrillation with heart failure" in the New England Journal of Medicine, volume 378. It is well recognized that morbidity and mortality are higher in heart failure patients who also have atrial fibrillation. Marrouche et al published the results of the CASTLE-AF trial, which attempted to determine if catheter ablation [inaudible 00:24:46] better outcomes among patients with heart failure and atrial fibrillation. They randomized 179 patients to ablation and 184 to medical therapy, which consisted of either rate or rhythm control. Inclusion criteria were those with NYHA class II to IV heart failure, LVEF of 35% or less, and an ICD.                                 The primary endpoint was a composite where the death from many causes or hospitalizations for worsening heart failure. They noted over a median of three as a follow up, the end-point was reached in 28.5% of the ablation group and 44.6% of the medical therapy group, accounting for a significant hazard ratio of 0.62. Furthermore, fewer patients that in the ablation group died from any cause, were hospitalized for worsening heart failure, or died from cardiac causes. These data made a big splash because they're highly supportive of the premise that catheter ablation may be beneficial in some patients with atrial fibrillation and heart failure, often beyond that of medical therapy alone.                                 One major strength of this paper is that the actual AF burden was tracked by the ICD, so we know for sure whether or not the procedure was successful and how controlled the atrial fibrillation was. One thing to note however, is that subgroup analysis suggest that those with more symptomatic heart failure, namely NYHA class III to IV, not benefit as much from ablation. Furthermore, it's also important to note that the five years expected mortality in patients was higher than predicted in the CASTLE-AF trial, however overall these trials highly suggest that the potential benefit that ablation may hold over conventional medical therapy. Extrapolation to comparison with the utility of interventions such as biventricular pace with AV node ablation, however, remains to be considered.                                 Next, we review an article by Chugh et al entitled "Spectrum of atrial arrhythmias using ligament of Marshall in patients with atrial fibrillation" published in Heart Rhythm volume 15, issue 1. They reviewed the spectrum of presentations associated with arrhythmogenesis attributed to the ligament of Marshall, amongst patients with atrial fibrillation. They demonstrate that nearly a third of those patients, ligament of Marshall associated arrhythmias had a pulmonary vein ligament connection, that variously required ablation, the left lateral ridge, the mitral annulus, or alcohol ablation. In addition, they noted about a quarter of patients had atrial tachycardia attributable to the ligament, and the remaining had periatrial reentry requiring either ablation or alcohol injection of the ligament to attain a conduction block.                                 The relevance of this publication, albeit it is of a small number of patients and a small center, lies in highlighting on the right mechanisms by which the ligament of Marshall may contribute to arrhythmogenesis. Namely, can include direct venous connections, inhibition to inaudibility to attain mitral block, and directly attributed atrial arrhythmias. Recognition of the various ways and situations under which the ligament of Marshall may play a role in arrhythmogenesis in atrial fibrillation patients, may optimize physician decisions to look for identify and target the ligaments. What is not as well understood however is the frequency with which ligament of Marshall plays a significant role in arrhythmogenesis in atrial fibrillation.                                 Moving gears, we next review an article by Pathik et al entitled "Transient rotor activity during prolonged three-dimensional phase mapping in human persistent atrial fibrillation" published in a special issue of JACC Clinical Electrophysiology, that focus on atrial fibrillation specifically, in volume 4 issue 1. Pathik et al sought to validate three-dimensional phase mapping system for persistent atrial fibrillation. Commercially available rotor mapping systems project the heart into two dimensions based on a three-dimensional catheter. Instead, Pathik et al used a combination of basket catheters along with the non-left atrial surface geometry to construct three D representations of phase progression. Amongst 9 out of 14 patients, they identified 34 rotors, with all these rotors being transients. Of particular interest, the rotors were only seen in areas of high electric density, where internal electric distances were shorter. They also noted the single wave front is also the most common propagation pattern. The importance of this publication lies in considering two things. First is the three dimensional representation of rotor position and the feasibility of this, and the second is really the high electro-density necessary to observe for others.                                 This has been one of the main problems in rotor analysis, namely what the spacial and temporal density is, that is required to identify rotors, especially given how transient they often are. The presence of rotors does not necessarily mean they're ablation targets in all patients. However, the question still remains regarding the optimal approach to mapping rotors, it needs to be remembered that rotors actually are meant to represent three dimensional scrollway phenomena, that cannot necessarily always be reflected in traditional two D mapping schema. Furthermore, to be remembered that when we claim three-dimensional mapping, this just reflects a two-dimensional surface being wrapped in three dimensions to reflect overall internal surface geometry but it does not take into account transmural activation.                                 Thus, taking into account all these elements it should be remembered as sometimes, it is possible that a rotor might exist but it's just not evident based on the two-dimensional representation or a two-dimensional representation that looks like a rotor may in fact not be a rotor when you consider it in a three-dimensional media.                                 Our last article within the realm of cardiac mapping and ablation we will consider is by Zghaib et al, entitled "Multimodal examination of atrial fibrillation substrate: Correlation of left atrial bipolar voltage using multielectrode fast automated mapping, point by point mapping, and magnetic resonance imaging intensity ratio", published in JACC Clinical Electrophysiology, in the same volume as the previous article. The authors sought to compare fast automated mapping with multiple electrodes versus point by point mapping and correlate with weighed gadolinium enhancement as seen by MRI, termed the image intensity ratio.                                 We all recognize that bipolar voltage is critical to recognizing and evaluating substrate. It's traditionally used in decay regions of substrate in both the atrium and ventricles. However, whether a newer automated approach used to characterize substrate perform equally well in comparison with traditional point to point mapping is still unknown. Thus, the authors in 26 patients perform cardiac MRI and mapping endocardial using both voltage mapping techniques. They noted that for each unit increase in image intensity ratio on MRI, in other words, increasing late enhancement, there was 57% reduction of bipolar voltage. They also noted that the bipolar voltage using other fast elevating mapping or point by point was significantly related with actual differences in calculated voltage, becoming more dissimilar in the extreme of high and low voltage areas.                                 The relevance of this publication is highlight in the potential utility of fast automated mapping in creating accurate voltage maps. The correlation of voltage values with image-intensity ratios suggest the utility of either approach. In turn, correlation with MRI suggest a pathologic correlate for all of these findings. However, whether substrate characterization guide ablation carries incremental benefit remains to be seen.                                 Changing gears but staying in the realm of atrial fibrillation, we next review elements of risk stratification and management. The first article we review is by Friedman et al, entitled "Association of left atrial appendage occlusion and readmission for thromboembolism amongst patients with atrial fibrillation undergoing concomitant cardiac surgery", published in JAMA, volume 319, issue four. Friedman et al sought to evaluate whether surgical left atrial appendage occlusion let to a reduction in long-term thromboembolic risk in a large database of Medicare recipients. They included the primary outcome as readmission for thromboembolism, including stroke, TIA, or systemic embolism, in up to three years of follow-up. With secondary end-points including hemorrhagic stroke, all-cause mortality, and a composite end-point of all outcomes.                                 Amongst more than 10,000 patients, there were almost 4,000 patients receiving surgical occlusion of left atrial appendage. Surgical occlusion was associated with a reduction in thromboembolic risk, OR of 6%, all cause mortality, 17 versus 24%, and the composite end-point, 21 versus 29%. However, interestingly, surgical occlusion was only associated with reduction in thromboembolic risk compared with no occlusion amongst those discharged without anticoagulation and those discharge with it. Namely, the thromboembolic risk reduction was primarily seen in those where the surgical occlusion, those who were sent home without any sort of anticoagulation. These data suggest that surgical occlusion leads to reduction of thromboembolic risk overall. As any large database based study, there are massive flaws in the database itself. Namely, we're relying on the coding of hospitals and operators. To know exactly what was done and what happens latter.                                 However, these data are hypothesis generating. One key element is the fact that surgical left atrial appendage occlusion was only superior in reducing thromboembolic risk amongst those discharged without anticoagulation. This raises the question as why. Was left atrial appendage completely closed in these patients? In which case, they may be at further increased risk or that the operators felt that there is a high risk for other reasons that cannot be cleaned from an administrative datasets? While the data support consideration of the benefit of left atrial appendage occlusion in a surgical manner, a kin to what has been seen in papers on WATCHMEN and other approaches, and how is the critical nature of randomized trials in this regard.                                 We next review an article published in JAMA Cardiology, volume three issue one by Inohara et al, entitled "Association of atrial fibrillation clinical phenotypes with treatment patterns and outcomes: A multicenter registry study." Traditionally classification of AF has depended largely on factors such as the nature of AF, paroxysmal versus persistent, LA size, and other factors such as extend of the late enhancement. Inohara et al sought to evaluate whether cluster analysis could better define heterogeneity of AF in the population. They included an observational cohort of almost 10,000 patients admitted to 124 sites in the United States in the ORBIT-AF registry.                                 Outcome was a composite major address cardiovascular and neurological events or major bleeding. Amongst these patients, they identified four clusters, including one those with lower rates of risk factors and comorbidities than other clusters, two, those with AF at younger ages and with comorbid behavior disorders. Three, those with AF with tachycardia-bradycardia type syndromes and had devices for sinus node dysfunction, and four, those with AF with other risk factors such as a coronary disease. Those in the first cluster had significantly lower risks of major events. All clusters were noted to have symptom dissociation to specific clinical outcomes.                                 These data are interesting and highlight the highly heterogeneous nature of classifying risk attributable to atrial fibrillation. When broad datasets associated atrial fibrillation with specific outcomes. Maybe suggest an attribution to all patients with atrial fibrillation. However, this single relationship was specific to the outcomes suggest the limitation of applying outcome as approach to understand atrial fibrillation impacts and outcomes, namely depending on clusters that may take into account patient age or comorbidities, it may be irrelevant in discriminating patient outcomes than the traditional paradigm in the same paroxysmal versus persistent or depending on the left atrial size.                                 These data also highlight the importance of considering the inclusion criteria in randomized trials of atrial fibrillation before stripling real world outcomes to patients who don't fit within that trial.                                 Next, we will be reviewing an article by Chou et al entitled "Relationship of aging and incident comorbidities to stroke risk in patients with atrial fibrillation," published in JACC, volume 71 issue two. Chou et al sought to evaluate the effect of aging and evolving instant comorbidities to stroke risk in patients with atrial fibrillation. Many large database studies or trials where added baseline CHADSVASC score and the then ensuing follow up period to define risk over time of ischemic stroke.                                 The authors hypothesized that as patients age, develop new comorbidities that would change the score, may be more predictable of long-term outcomes than the score itself. They included over 31,000 patients who do not have comorbidities to CHADSVASC aside from age and sex but had atrial fibrillation. They didn't calculate a delta score defined as the difference between the baseline and follow up scores. The mean baseline score was 1.29 with an increase in 2.3 during follow up, with an average delta of one. The score may not change over follow up in 41% of patients. Interestingly, significantly more patients had a delta CHADSVASC of one or more and develop ischemic stroke than non-ischemic stroke. The delta CHADSVASC was shown to better predictor of ischemic stroke than either baseline or follow up CHADSVASC score. This data suggest that additive shifts in the CHADSVASC score over time may be more predictive of stroke risk than the actual score itself.                                 These findings are thoughtful and logical. They indicate the potential impact of continued aging or acquisition identification of new comorbidities. In some patients, potential discovery or new comorbidities or follow-up; for example, hypertension and coronary artery disease may lead to reclassification of stroke risk. That is important to maintain close follow up of atrial fibrillation patients, and not to show a continued need or lack of need of anticoagulation on the basis of a baseline evaluation. This also holds relevance single center long-term outcomes in patients specific scores. Whether is acquisition of new comorbidities or presence of baseline comorbidities or predict a long-term score, should we consider when assessing the need for anticoagulation, particularly in perceived initially low risk cohorts who go on to develop ischemic stroke.                                 Lastly, within the realm of atrial fibrillation, we review an article by Hussain et al, entitled "Impact of cardiorespiratory fitness on frequency of atrial fibrillation, stroke, and all-cause mortality" published in the American Journal of Cardiology, volume 121 issue one. Hussain et al review the effect of cardiorespiratory fitness on overall outcomes and incidence of atrial fibrillation and outcomes amongst patients with atrial fibrillation. Amongst over 12,000 individuals prospectively followed up after treadmill exercise test, they noted 1,222 had a incidence of AF, 1,128 developed stroke, and 1,580 died. For every 10% increase in functional layover capacity, there was a 7% decrease in risk of incident AF, stroke, or death.                                 Similarly, in those who developed AF, stroke was lower in those with higher functional aerobic capacity. These findings support the notion known to other areas of cardiovascular disease that better cardiorespiratory fitness is associated with better outcomes, in this case to stroke, incident AF, or mortality. Furthermore, even on the presence of AF, those with better functional capacity had a lower risk of stroke. These data highlight the continued importance of counseling patients on the benefits of physical fitness even in the setting of already present AF.                                 Moving on to a different area of electrophysiology, we review the realm of ICD pacemakers and the CRT.                                 The first article review is by Sze et al entitled "Impaired recovery of left ventricular function in patients with cardiomyopathy and left bundle branch block" published in JACC volume 71 issue 3. Patients with left bundle branch block and cardiomyopathy are known to respond to CRT therapy. Thus the investigators sought to evaluate whether guideline medical therapy in patients with reduced LVEF and left bundle branch block, afford a beneficial first line approach therapy. The reason for this currently guidelines suggest waiting at least three months before consideration of CRT has had as some patients may recover on guideline directed medical therapy without the need for device implantation.                                 They review patients with a LVEF of less or equal than 35% and baseline ECG showing left bundle branch block. In evaluating left ventricular ejection fraction at follow up of three to six months. They excluded patients with severe valvular disease, and already present cardiac device, an LVAD, or heart transplant. Among 659 patients meeting criteria, they notice 74% had a narrow QRS duration of less than 120 whereas 17% had QRS duration greater than 120, and the remainder had a QRS duration greater 120 but was not left bundle branch block. The mean increase in the left ventricular ejection fraction on guideline directed medical therapy was in those with a narrow QRS duration and least in those with left bundle branch block, 8.2%.                                 Furthermore, when comparing mean LVEF improvement, those with on versus non-on guideline directed medical therapy, there was virtually no difference in rates of recovery. Furthermore, composite end-point of heart failure hospitalization mortality was highest in those with left bundle branch block. These data suggest that those with bundle branch block and cardiomyopathy received less overall benefit from guideline directed medical therapy over the three to six months follow up period. Whether this is due to already more severe myopathic process to start with or due to the CRT is unclear. However, it may suggest that in some patients, left bundle branch block may benefit from inclusion of CRT early in their disease course as known the significant number of patients up to three to six months guideline directed medical therapy with insufficient DF recovery may then benefit from CRT. As well as intervening earlier may result in better outcomes, especially knowing the high and term raise mortality in heart failure hospitalization remains to be seen.                                 A trial studying early implantation of CRT on these patients may be relevant.                                 The next article review is by Gierula et al entitle "Rate-response programming tailored to the force-frequency relationship improves exercise tolerance in chronic heart failure" published in JACC Heart Failure, in volume six, issue two. The authors sought to evaluate whether tailored rate-response programming improved exercise tolerance in chronic heart failure. The double blinded, randomized, control, crossover study, they compared the effects of tailored programming on the basis of calculated force-frequency relationship, defined as including critical heart rate, peak contractility, and the slope, multidimensional programming and exercise time and maximal oxygen consumption. They demonstrate amongst 98 enrolled patients that rate-response settings limiting heart rate raise to below the critical heart rate led to create exercise timing and higher peak oxygen consumption.                                 These data suggest that personalizing rate-response therapies may improve exercise time and oxygen consumption values in patients with heart failure and pacing devices. The main limitation of the study is that the number of patients was small, 90, and then the number of patients crossing over was even smaller, 52. However, highlights the potential of working closely between device programmers and consideration of individual's characteristics and their exercise needs in determining optimal programming strategy.                                 Finally, within the realm of devices, we review an article by Hawkins et al, entitled "Long-term complications, reoperations, and survival following cardioverter defibrillator implant" published in Heart, volume 104 issue three. Hawkins et al sought to evaluate the long-term complications and risk of reoperation associated with defibrillator implantations in a large [inaudible 00:41:56] population of 300,410 patients, they noted over a 30-month follow up period there was a 12% reoperation rate within the year of implant. This is most prominent for CRT devices, with a risk of 18% in one year post-implant. Furthermore, CRT had the highest rate of early complications, with device complexity, age, or the presence of atrial fibrillation being significantly associated with complication risk.                                 Mortality also increased over time from 5% within the first year to nearly a third after five years. However, younger patients exhibited five years survival similar to the general population with a progressive decline of this as older patients were considered. These findings highlight several critical issues. First, they report a high one year reoperation rate for a variety of reasons. This finding highlights the importance of considering protocols to minimize the need for reoperation. Furthermore, they note the higher rate amongst CRT patients, with seems logical given the likely longer associated procedural risk and need for more leads. Finally, the impact of age on expectant survival are to be taken into consideration with the device and the life-saving potential of the defibrillator.                                 Moving on to cellular electrophysiology, review one article by Zhang et al, entitled "Reduced N-type calcium channels in atrioventricular ganglion neuron are involved in ventricular arrhythmogenesis" published at the journal of the American Heart Association, in volume seven issue two. Zhang et al reported a rat model of ventricular arrhythmogenesis and characterized the role of atrioventricular ganglion neurons in risk of arrhythmogenesis as well as the mechanism for this risk this model relates in humans to the attenuated cardiac vagal activity in heart failure patients, which is known to relate to their arrhythmic risk. The demonstrated reduced N-type calcium channel in these AV ganglion neurons, which project innervating systems to the myocardium, resulting in increased risk of PVCs, and increased susceptibility to induction of ventricular arrhythmias with programmed stimulation.                                 The relevance of the intrinsic cardiac nervous system arrhythmogenesis has become increasingly prominent as methods to study it have improved. Understanding the direct and most relevant inputs may facilitate better understanding of risk of arrhythmias in patients. In the case of this study by Zhang et al, the critical finding is that disorder of the atrioventricular ganglion neurons may lead to increased susceptibility for ventricular arrhythmogenesis. Clinical relevance includes consideration of effects on this specific ganglion when performing ablation on for other conditions, and potential long-term effect on arrhythmogenic risk, as well as potentially relevant functional explanations for arrhythmogenesis.                                 Moving on to the genetic channelop, these are considered two separate articles. The first one by Bilmayer et al, entitled "ExomeChip-Wide analysis of 95,626 individuals identified ten novel loci associated QT and JT intervals" published in Circulation: Genomic and Precision Medicine, in volume 11 issue 1. This whole exome study reviewed several novel loci that modified the QT and JT intervals. They include over 100,000 individuals and identified ten novel loci not previously reported in the literature. This increases the number of known loci that impact from ventricular portal adjacent by nearly one third. These loci appear to be responsible for myocyte and channel structure and interconnections that internally impact the ventricular repolarization.                                 While long QT syndrome be characterized amongst the known genes in 75% of affected individuals, that also means one fourth long QT syndrome cannot be characterized based on known genes impacting ventricular repolarization. The identification of novel loci or novel that may be affect repolarization kinetics to unique means are critical to define novel therapies as well as in genetic counseling the patients in potential effects on family members when screening them for potential disease risk. These findings should assess an opportunity for further studying the mechanisms by which these loci modulate QT and JT intervals and the potential contribution to phenotypic risk.                                 The second paper within this realm we review is by Zumhagen et al, entitled "Impact of presynaptic sympathetic imbalance on long QT syndrome by positron emission tomography" published in Heart, volume 104. The authors sought to evaluate by a PET scan the impact of sympathetic heterogeneity on long-QT syndrome risk. Amongst 25 patients with long-QT syndrome, including long-QT type I and II, and 20 ostensibly healthy controls, they noted that regional retention in disease were similar between affected patients and controls. However, regional washout rates were higher in the lateral left ventricles in patients with long-QT syndrome. Internal global washout rates were associated with greater frequency of clinical symptoms. That's there seem to be some relationship between regional and global sympathetic heterogeneity, particularly during washout, with overall risk in long-QT syndrome patients.                                 These findings report the notion for sympathetic imbalance, partly mediating the risk attributable to long-QT syndrome. The findings on PET suggest regional imbalance of presynaptic cathecholamine and reuptake and release, being one mechanisms. This was most prominent in long-QT I patients who also often drive most benefit from left sided sympathectomy. The novelty of these findings is in the potential role of imaging to determine basic contributors to congenital long-QT syndrome in given patients. The larger prospect of size would really need to be evaluated this further.                                 Moving on to the realm of ventricular arrhythmias, we review three different articles. The first one, by Hamon et al, entitled "Circadian variability patterns predict and guide premature ventricular contraction ablation, procedural disability, and outcomes" published in Heart Rhythm, volume 15 issue one. Hamon et al sought to evaluate whether circadian variability of PVC frequency can predict optimal drug response intraprocedurally during PVC ablation. One of the main problems of PVC ablation is when PVC are infrequent and tend to disappear during the procedure, achieving procedural success or attaining sufficient frequencies of PVCs to map becomes very difficult. Next, they use Holter monitoring in the ambulatory stripe to define three groups. Those of higher PVC burden during faster heart rates, those with higher PVC burden during slower heart rates, and those with no correlation between their PVCs burden and their heart rate.                                 More than half the one hundred and one patients included a high burden of PVCs at fast rate while 40% had no correlation between the two and 10% had higher burden in slower heart rates. Almost one third of patients taken for ablation have infrequent PVCs during a procedure, while the best predictor of this being a low ambulatory PVC burden of less than 120 per hour. Isoproterenol infusion was only useful in lessening PVCs in those with PVCs associated with fast heart rates. The isoproterenol washout or phenylephrine where used with those associated with slower heart rates.                                 Interestingly, not a single drug was effective in inducing PVCs in those with infrequent PVCs that have not heart rate correlation in the ambulatory stages. They noted that outcomes ablates were similar amongst those with higher heart rate associated PVCs and non-heart rate correlated PVCs previously responded to a drug. But, [inaudible 00:48:08] noted only a 15% success rate from ablation in infrequent PVCs in patients who lacked correlation between PVC burden and heart rate and who were unresponsive to drug previously. These data are important highlighting the potential for further defining idiopathic PVC ablation needs and likelihood of success based on ambulatory data, by correlating PVC burden with heart rate and their circadian variability, it's possible to predict likelihood specific intraoperative drugs working when dealing with infrequent intraprocedural PVCs.                                 Furthermore, the finding of lack of correlation with slower or fast heart rate in terms of PVC burden is associated with the poor success rate unless those PVCs are drug responsive. Highlights the potential benefit of performing preoperative antiarrhythmic drug testing to get likelihood of ablation success in this patients.                                 The next article we review is by Lee et al, entitled "Incidence and significance of the lesions encountered during epicardial mapping and ablation of ventricular tachycardia in patients with no history of prior cardiac surgery or pericarditis" published in Heart Rhythm, volume 15 issue one. Lee et al sought to determine the frequency of pericardial lesions, impeding mapping in patients without prior surgery, operative procedure, or pericarditis, in other words virgin hearts. Amongst 155 first time attempts of access, 8% had pericardial lesions. The only clinical predictor was the presence of severe renal impairment.                                 In addition, no patients with supposedly normal hearts had a lesions. Notably, those with a lesion had more frequent impairment in mapping and lower overall success rates; there were similar complication rates as those without the lesions. These data are relevant in highlighting the ease of mapping of pericardial access may not always be present, even when dealing with inversion of pericardial space. A lesion may be present in patients, particularly with severe renal disease. Advising patients of this possibility prior to the procedure and considering that epicardial access may be impaired in a fair number of patients, even the absence of prior history of surgery, epicardial access or pericarditis isn't important.                                 The final article we'll review within the realm of ventricular arrhythmias is by Kumar et al, published in Journal of Cardiovascular Electrophysiology, volume 29 issue one, entitled "Right ventricular scar-related ventricular tachycardia in nonischemic cardiomyopathy: Electrophysiological characteristics, mapping, and ablation underlying heart disease." Kumar et al sought to evaluate the substrate and outcomes associated with right ventricle scar related ventricular tachycardia ablation in nonischemic patients at large, but particularly in those with neither stroke or coronary artery disease as potential explanations for this scar. They reviewed 100 patients consecutively over half of whom had ARVC and the remainder was sarcoid or RV scar of unclear origin. Those with RV scar of unknown origin tend to be older compared to the ARVC patients, and had more severe LV dysfunction compared with saroid patients.                                 However, the scar distribution extend was similar within all these groups. Furthermore VT/VF survival was higher in those with RV scar of unknown origin. The velocity of survival free or death or cardiac transplant and VT/VF survival seen in sarcoid patients. These data suggest that close to one third of patients, RV scar related VT may have VT of unknown cause. Total outcome was superior overall to those with defined myopathic processes. What's most interesting is, over follow up, none of those with RV scar of unknown origin develop any further findings to reclassify them as sarcoid or ARVC. It is possible this group reflects some mild form of either disease however. Again, the exact pathophysiologic process remains unclear. These findings may help in counseling patients who are in long-term expected outcomes from ablation intervention.                                 The final article we'll review this month is within the realm of other EP concepts that may be broadly applicable, published by van Es et al, entitled "Novel methods for electrotissue contact measurement with multielectrode catheters", published in Europace, volume 20 issue one. In this publication, the authors sought to evaluate the potential utility of a novel measure on evaluating electro tissue contact. With multielectrode catheters it is known that one of the problems with assessing contact is a contact force that cannot be used. Electro with coupling index is often used but even this has fragile problems, especially when you get into high impedance areas, that can be affected by surrounding ion impedance structures. Due to the fact that measuring contacts forces challenging in such multielectrode catheters, the authors measure electric interface resistance by applying a low level electrical field, pushing neighboring electrodes. They compared the effectiveness of assessing contact by this approach without using contact force in a poor side model.                                 They know that this measure was directly correlated with contact force in measuring tissue contacts. These findings support a role for aversion of an active electrode location and determining tissue proximity and contact-based on the coupling between the electrodes on multipolar catheters in the tissue. These findings may be highly useful when there is a variety of catheters where contact force cannot be implemented. Further studies on the methods and cutoff to establish tissue proximity on the end of contact will be also needed.                                 To summarize, however, as a term was brilliant here that was not well explained, active electrical location is actually a phenomenon that occurs in nature. This is seen in deep sea fish, which actually have multiple electrodes oriented around its body. They emit a small electrical field that results in a general impedance field surrounding the fish. This essentially is the way of visualizing the world around them. Perturbations based on proximity to different structures, whether they are live or death, and based on whether they are live or death, results in changes in the perturbations of this resistive fields, resulting in proximity determination by the fish. Several individuals are looking into potential applications of this to understanding tissue proximity when using catheters in the body. This consideration of impedance is fundamentally different than the traditional measure impedance were used by traditional generator.                                 I appreciate everyone's attention to this key and hardening articles that we've just focus on or this past month of cardiac electrophysiology across literature. Thanks for listening. Now back to Paul. Dr Wong:             Thanks Suraj, you did a terrific job surveying all journals for the latest articles on topics of interesting in our field. There's not an easier way of staying in touch with the latest advances. These summaries and the list of all major articles in our field for month can be downloaded from the Circulation: Arrhythmia and Electrophysiology website. We hope that you find the journal to be the go to place for everyone interested in the field.                                 See you next month.  

Episode 117: Tom Bouthillet is the EMS Battalion Chief of Hilton Head Island Fire Rescue and Program Director of the South Carolina Resuscitation Academy. He is Editor-in-Chief of several websites devoted to Emergency Cardiovascular Care, an EMS 10 Award recipient, and has taught nationally in the Critical Care Transport (CCEMT-P) program out of UMBC. His writings have been referenced in the American Heart Journal, the Journal of the American College of Cardiology: Cardiovascular Interventions and the EP Lab Digest. We talk about EMS life on Hilton Head, his new promotion, Tom's early interest in cardiovascular care, the Academy and leadership.

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.                                            This month's issue of Circulation: Arrhythmia, and Electrophysiology has a number of groundbreaking and fascinating articles. Let's start with the first article by Christopher Andrews and Associates on the novel use of noninvasive electrocardiographic imaging in patients with arrhythmogenic right ventricular cardiomyopathy.                                            The authors compared 20 genotyped arrhythmogenic right ventricular cardiomyopathy patients to 20 control patients using electrocardiographic imaging, ECGI, a method for noninvasive cardiac electrophysiology mapping. They found that ARVC patients had a longer ventricular activation duration, with a mean of 52 milliseconds versus 42 milliseconds with a p-value of 0.007, as well as a prolonged mean epicardial activation recovery interval, a surrogate for local action potential duration with a median of 275 milliseconds versus 240 milliseconds with a p-value of 0.014.                                            In addition, the authors observed abnormal epicardial activation breakthrough locations with regions of nonuniform conduction and fractionated electrograms. These abnormal activation patterns correlated with late gadolinium enhancement using cardiac magnetic resonance scar imaging. This study suggests that electrocardiographic imaging may be a promising tool for the diagnosis and follow-up of patients with ARVC.                                            In the next article, Thomas Fink and Associates report the results of the prospective randomized Alster-Lost AF trial, comparing ablation strategies in patients with symptomatic persistent or long-standing persistent atrial fibrillation. The study compared standalone pulmonary vein isolation, the PVI-only approach, with a stepwise approach of PVI followed by complex fractionated atrial CFAE ablation and linear ablation, the substrate modification approach. Patients were randomized one-to-one to each study group. The primary study endpoint was freedom from recurrence of any atrial tachyarrhythmia at 12 months after a 90-day blanking period. 118 of 124 enrolled patients were analyzed. 61 in the p-value only group and 57 in the substrate modification group. The pulmonary vein isolation only group had a one-year freedom from arrhythmia recurrence of 54%, which was similar to the 57% recurrence rate in the substrate modification group, p = 0.86. Thus, this study confirms in a population of persistent and long-standing persistent atrial fibrillation that there is no significant benefit to the addition of CFAE ablation to pulmonary vein isolation only.                                            In the next paper, John Papagiannis and associates studied AV nodal reentrant tachycardia in patients with congenital heart disease. In this multi-centered, retrospective study, the authors compared catheter ablation of AV nodal reentrant tachycardia in 51 patients with complex congenital heart disease, with 58 patients with simple congenital heart disease.                                            There was no significant difference between the groups in terms of growth parameters, the use of 3D imaging, or type of ablation, radio frequency versus cryoablation. The procedure times, fluoroscopy times were longer in the complex group compared to the simple group. There were also significant differences between the groups in terms of acute success of ablation, 82% versus 97%; the risk of AV block, 14% versus 0%; and the need for chronic pacing, all significant in favor of the simple congenital heart disease group. There were no permanent AV block observed in patients who underwent cryoablation.                                            After a mean, 3.2 years of follow up, the long-term success was 86% in the complex group, and 100% in the simple group, p = 0.004. Thus, the authors concluded that the complexity of congenital heart disease affects the outcome of AV nodal reentrant tachycardia catheter ablation.                                            In the next paper, Moloy Das and associates studied whether the presence of abnormal intra-QRS peaks would indicate altered activation and might predict ventricular arrhythmias in cardiomyopathy patients. The authors examined the 99 patients with ischemic or nonischemic cardiomyopathy undergoing primary prevention ICD implantation, with a mean left ventricular ejection fraction of 27%. After a median follow up of 24 months, 20% of patients had arrhythmic events. Using a multivariate, Cox regression model that included age, left ventricular ejection fraction, QRS duration, and QRS peaks, only QRS peaks was an independent predictor of arrhythmic events with a hazard ration of 2.1. ROC analysis revealed that a QRS peak value of greater than or equal to 2.25 identified arrhythmic events with a greater sensitivity than QRS duration, 100% versus 70%, with p < 0.05, and a negative predictive value of 100%, compared to 89% for QRS duration, p < 0.05. Thus, the authors concluded that this novel QRS morphology index may be a promising additional tool in sudden death risk stratification.                                            In our next paper, Yoshiyasu Aizawa and associates studied J wave changes during atrial pacing in patients with and without idiopathic ventricular fibrillation. In eight patients with idiopathic ventricular fibrillation, and 17 patients without idiopathic ventricular fibrillation, having J waves, the J wave amplitude was measured before, during and after atrial pacing. All of the patients with ventricular fibrillation did not have any structural heart disease. The idiopathic ventricular fibrillation patients were younger than the non-idiopathic ventricular fibrillation patients, and had larger J waves with more extensive distribution. The J wave amplitude decreased from 0.35 millivolts to 0.22 millivolts when the R-R intervals shortened, a decrease of greater than, equal to 0.005 millivolts in the J wave amplitude was observed in six of eight idiopathic ventricular fibrillation patients while the J wave amplitudes were augmented in nine out of 17 non-idiopathic ventricular fibrillation subjects. The authors therefore concluded that the different response patterns of J waves to rapid pacing suggested different mechanisms that is early repolarization in idiopathic ventricular fibrillation patients, and conduction delay in non-idiopathic ventricular fibrillation patients.                                            Our final paper of the month was written by Jim T. Vehmeijer and colleagues, who examined the utility of recent guidelines and consensus documents for ICD implantation for sudden death protection in adults with congenital heart disease. The authors examined an international, multi-center registry, having 25,790 adult congenital heart disease patients, and identified all sudden cardiac death cases, which were then matched to living controls by age, gender, congenital defect and surgical repair. They used conditional logistic regression models to calculate odds ratios, and receiver operating characteristic curves. In their first analysis, they identified 124 cases and 230 controls. In total, 41% of sudden cardiac death cases, and 17% of controls had an ICD recommendation based on the 2014 consensus statement on arrhythmias in adult congenital heart disease, with an odds ratio of 5.9. A similar analysis of the 2015 European Society of Cardiology guidelines showed that 35% of cases and 14% of controls had an ICD recommendation, respectively with an odds ratio of 4.8. The authors concluded that a minority of sudden cardiac death cases had an ICD recommendation according to these guidelines, while the majority of sudden cardiac death victims remained under-recognized, emphasizing the need for continued critical, clinical reasoning when deciding on ICD implantation in adult congenital heart disease patients.                                            And now, here with the review of the highlights from the articles from journals throughout the world, in the past month is Dr. Suraj Kapa. Dr. Suraj Kapa:                 Thank you, Paul. Today we'll be discussing hard-hitting articles that have been published within the last month across the electrophysiologic literature. First, we'll be focusing on the topical area of atrial fibrillation, with an initial foray into the realm of anticoagulation. The first article we will be focusing on was published by Yao, et al., in the Journal of the American College of Cardiology in volume 69, entitled Non-Vitamin K Antagonist Oral Anticoagulant Dosing in Patients with Atrial Fibrillation and Renal Dysfunction. In the study, Yao, et al, demonstrated that the dosing of direct oral anticoagulants in a real world patient sample, with preexisting renal dysfunction was inappropriately dosed in as many as 43% of patients. Specifically, in these patients, there was overdosing of the direct oral anticoagulants. Moreover, as many as 13% of patients were underdosed.                                            The overdosing of these patients led to increased bleeding risks, without an incremental stroke benefit compared with cohorts that were appropriately dosed. In turn, underdosing led to increased stroke risk without an incremental reduction in bleeding risk. These results are provocative in that they indicate, in a real life sample of patients, frequent inappropriate dosing of direct oral anticoagulants. This identifies the need for better guidelines, or better adherence to guidelines, in management of these patients to improve clinical outcomes.                                            In another article with the realm of anticoagulation management of atrial fibrillation patients, was published by Labovitz, et al. in Stroke, in volume 48, entitled Using Artificial Intelligence to Reduce the Risk of Nonadherence in Patients on Anticoagulation Therapy. They demonstrated in a small randomized study that a smart phone based artificial intelligence program could be used to monitor anticoagulation adherence, and in fact, improve it. The program utilized features available on all smart phones to identify the patient, the medication, and active ingestion of the medication by the patient in real time.                                            With this approach, they noted the plasma drug concentration levels indicated 100% adherence in the intervention group, namely those using the artificial intelligence program, while in the control group, only 50% of patients had adherence to the medications. Overall, there was an absolute improvement in adherence amongst patients on direct oral anticoagulants by as many as 67%. These findings are provocative given data suggestive of the lack of appropriate adherence to anticoagulant therapy amongst patients.                                            Changing paths from anticoagulation management, the next article we choose to focus on was published within the realm of cardiac mapping in ablation for atrial fibrillation. It was published by Das, et al. in JACC: Clinical Electrophysiology in volume three, entitled Pulmonary Vein Re-Isolation as a Routine Strategy Regardless of Symptoms, The PRESSURE Randomized Controlled Trial. In this randomized trial, Das, et al, demonstrated that aggressive reevaluation of patients undergoing pulmonary vein isolation after index ablation for pulmonary vein reconnection, with the intent to re-ablate, significantly reduced arrhythmia recurrence. In addition, there was a commented improvement in quality of life. It has been well-recognized that even in the absence of clinical recurrence, a large number of patients, after index pulmonary vein isolation, may have pulmonary vein reconnection. However, it has always been unclear whether aggressive reevaluation and re-isolation of reconnected veins holds value, has been unclear. Further study is needed to evaluate the cost effectiveness and the risk-benefit ratio of such an invasive approach to reevaluate pulmonary vein isolation, irrespective of the evidence of clinical atrial fibrillation recurrence, however.                                            Changing gears, with the realm of atrial fibrillation, we will now focus on risk stratification and management. Pathik, et al, in JACC: Clinical Electrophysiology, published in volume three, have progressed to complement their work on the role of risk stratification, and risk factor management in patients with atrial fibrillation, to evaluate the cost-effectiveness and clinical effectiveness of such risk factor management clinics in atrial fibrillation, that they termed the SENSE Study. They demonstrated that there was significant cost and clinical benefits to aggressive risk factor targeting clinics for patients with atrial fibrillation, specifically, utilizing supervised approaches to weight-loss, improvements in fitness and reduction in other clinical risk factors such as diabetes, hypertension, or other risks. The patients had a significantly decreased risk of arrhythmia occurrence. In addition to this, there was an actual incremental cost benefit of $62,000 for quality adjusted life year saved. These findings suggest that such an aggressive risk factor mediated approach to management of patients with atrial fibrillation holds significant promise, not just in the reduction of arrhythmia occurrence, but also in potential healthcare cost savings.                                            Our next article within the realm of risk stratification and management relates to identification of patients with atrial fibrillation, in otherwise normal population-wide cohorts. Krivoshei, et al, in Europace volume 19, studied algorithms applied to information gathered on pulse-wave signals via smartphone-based LED light/camera lens. They demonstrated that using such a tool on patients, atrial fibrillation can be discriminated from sinus rhythm with sensitivity specificity of above 95%. We recognize the critical importance of early detection of atrial fibrillation, particularly in high-risk cohorts for stroke. Early identification of patients may identify those patients for initiation of anticoagulation, even if asymptomatic or minimally symptomatic. Our so-termed subclinical atrial fibrillation patients, which we identify by prior clinical trials, have an increased risk of stroke. However, the main hurdle to implementation of such technology has been the high cost, applied to traditional medical interventions. However, use of ever-advancing ambulatory technologies, such as smartphones or in the future, smart watches, may held the promise to identify atrial fibrillation via cheaper mechanisms.                                            The last article within the realm of atrial fibrillation risk stratification and management that we'll choose to focus on is that by Gaeta, et al, published in Europace in volume 19. They performed a systematic review and meta-analysis of existing trials, regarding whether epicardial fat depot was associated with atrial fibrillation. They demonstrated via their meta-analysis that there is, in fact, a significant association between epicardial fat and atrial fibrillation risk, with more epicardial fat being associated with more persistent, rather than paroxysmal forms of atrial fibrillation, as well as any atrial fibrillation versus none. However, the role of epicardial fat in arrhythmogenesis remains unclear. While many studies suggest an association, causation remains to be proven. A recent review, however, published by Antonopoulos, et al, in the Journal of Physiology in June 2017, has multiple suggestive pathways by which paracrine effects of epicardial fat on the heart and vice versa, may lead to alterations in normal cardiac function. Thus, while this remains an association, there are evolving principles that might further support causation.                                            Changing topics, we'll next focus on four major articles within the realm of ICDs, pacemakers, and CRT managements. Lyons, et al, in JACC: Heart Failure, volume five, studied the impact of current versus previous cardiac resynchronization therapy guidelines on the proportion of patients with heart failure eligible for therapy. They evaluated the effect of changing guidelines based on increased bodies of evidence, related to indications for resynchronization therapy on real world patient samples. They demonstrated that these further refined guidelines would decrease by as many as 15% those patients eligible for cardiac resynchronization therapy. However, while their study demonstrates that fewer patients may qualify, as far as receiving benefit from resynchronization therapy, at least two studies published in the same month have demonstrated that even amongst patients who meet guidelines, there is severe under-utilization/under-referral for such devices. These studies by Marzec, et al, in JAMA Cardiology, as well as by Randolph, et al, in American Heart Journal, demonstrated that there's frequent under-utilization and under-referral of patients meetings indications for resynchronization therapy.                                            Keeping on the same topic in resynchronization therapy, Barra, et al, in Heart, volume 103, looked at sex-specific outcomes with addition of defibrillation to resynchronization therapy in patients with heart failure. They demonstrated in a multi-central observational cohort study that the addition of defibrillator resynchronization therapy in patients meeting primary prevention indications for device implant, primarily conferred benefit in men, rather than women. In the same month, Randolph, et al, in the American Heart Journal, demonstrated that resynchronization therapy offered potential greater benefits in women over men. Interestingly, this study by Barra, et al, conversely demonstrates that the concomitant addition of defibrillator therapy does not necessarily further improve outcomes on women, with the primary benefit being conferred to men. Whether this differential is effected by relative rates of arrhythmogenic myopathy is in men versus women remains unclear. However, the findings are provocative.                                            Keeping within the realm of appropriateness of defibrillator therapies, Luni, et al, performed a meta-analysis of randomized controlled trials published in the Journal of Cardiovascular Physiology, in volume 28, on the mortality effect of ICDs in primary prevention in nonischemic cardiomyopathies, including six studies that met criteria. They found that while there was an overall significant survival benefit in patients receiving ICDs in the setting of nonischemic cardiomyopathy. Once accounting for those on adequate beta-blockade, and ACE or ARP 00:22:56 therapy, there was no statistical difference conferred by primary prevention ICD use.                                            This complements an article published by Al-Khatib, et al, in JAMA Cardiology, in the same month, which also suggested that the overall mortality benefit was present in nonischemic patients, though in their case, they did not evaluate the granularity of appropriateness based on current management at the time of ICD implant. These findings further previous findings from a Danish study that the survival benefit of primary prevention ICD in nonischemic cardiomyopathy might not be anywhere near the same as those conferred with ischemic cardiomyopathy. However, the perceived lower relative mortality benefit, compared to earlier clinical trials, namely partly due to improvements in the clinical and pharmacologic management of such patients.                                            The final paper we'll choose to focus on within the realm of device therapies was published by Doppalapudi, in the Journal of Cardiovascular Electrophysiology, in volume 28. They looked at the significant discrepancy between estimated and actual longevity in St. Jude Medical implantable cardioverter defibrillators. While amongst a small number of patients of only 40, they demonstrated that up to 74% of these patients had a significant discrepancy between actual and estimated battery life, specifically amongst current or promotes defibrillator devices. This discrepancy was most significant in the 18 months prior to reaching electrical replacement medication. These findings suggest the need for more frequent monitoring of such devices to look for rapid battery depletion.                                            Switching topics away from device therapies, we next focus on the realm of sudden death in cardiac arrest. The first paper we'll focus on was published in Circulation, in volume 135, by Halliday, et al, and focused on the association between mid-wall late gadolinium enhancements, and sudden cardiac death in patients with dilated cardiomyopathy in mild and moderate left ventricular systolic dysfunction. In his publication, Halliday demonstrated that the presence of mid-wall late gadolinium enhancements on MRI identified patients at risk of sudden cardiac death, with a hazard ratio up to 35.9 for border sudden cardiac death, amongst dilated cardiomyopathy patients with such mid-wall dilated enhancements. The incremental value of MRI is evolving in the risk stratification of patients, though it has not quite met inclusion in guidelines for decision making regarding those who most benefit from ICDs. However, studies like this are provocative in the sense of identifying those patients most at risk.                                            Within the realm of cardiac arrest, we next focus on the role of out-of-hospital cardiac arrest, and how to improve management of these patients. Boutilier, et al, published in Circulation, in volume 135, optimization of drone networks to deliver automated external defibrillators. They demonstrated via simulation model that using a drone network system to deliver AEDs to patients suffering sudden cardiac arrest could decrease the time to response by as much as six minutes and 43 seconds compared to traditional approaches, such as 911 in urban areas, or as much as 10 minutes and 34 seconds in rural areas. These findings are highly provocative. However, they need to be applied to clinical real world situations. The first attempt at such was actually published this month as well, by Claesson, et al, in the Journal of the American Medical Association, and demonstrated the feasibility of implementing a drone network within real world case example, and the efficacy of the same. These disruptive technologies have the potential to improve emergency care, and out of hospital cardiac arrest survival.                                            Next, we move on to studies in electrophysiology. The first article we will focus on is by De Jesus, et al, published in Heart Rhythm, volume 14, on antiarrhythmic effects of interleukin 1 inhibition after myocardial infarction. De Jesus, et al, in this study, demonstrated that the use of anakinra and interleukin 1 beta antagonist would improve conduction velocity, calcium handling, spontaneous and inducible ventricular arrhythmias, and action potential duration dispersion, in canine models. These findings of potential antiarrhythmic effects were due to increased expression of connexin 43, and sarcoplasmic reticulum calcium ATPase. While in isolation, this might seem a general article, it complements multiple recent studies that suggest a significant role for targeting inflammatory pathways, not just in infarct pathogenesis, but in arrhythmogenesis.                                            Lazzerini, et al, this month as well, demonstrated in the European Heart Journal, the link between systemic inflammation and arrhythmic risk based on a review of the existing literature. In addition, Yucel, et al, demonstrated in Nature Scientific Reports the relationship between lipopolysaccharides and electrophysiology dysfunction in stem cell direct cardiomyocytes, which they felt partly may be mediated through interleukin pathways. Finally, though as of yet unpublished, a clinically available interleukin 1 beta inhibitor, canakinumab, has been shown in preliminary data to reduce major cardiovascular events in a randomized, double-blind, placebo-controlled trial, when combined with optimal medical therapy in patients with post myocardial infarction. These potential clinical benefits complement translational benefits seen to date. However, whether these are conferred by primary inflammatory pathways, arrhythmogenic pathways, or interactions between both remains to be seen.                                            The next article we will focus on is by Chauveau, et al, published in Circulation: Arrhythmia Electrophysiology, volume 10. They looked at induced pluripotent stem cells derived cardiomyocytes in producing in vivo biological pacemaker function. They demonstrated that in canines with atrioventricular block, injection of such derived cardiomyocytes into the epicardial surface of the heart, demonstrated inherent pacemaker activity with global cardiac activation. In fact, this activation in pacemaker activity increased over time, up to four weeks of maturation, and also demonstrated responsiveness to epinephrine and alterations with day and night variation. However, the intrinsic rates tend to be quite low, in the 50 to 60 beat per minute range. The potential to restore pacemaker activity in patients with severe conduction disease, holds the potential to dynamically progress options in care for patients with electrophysiologic disease. However, even though these findings are promising, significant remaining questions include ensuring the robustness of the heart rate conferred by these biologic pacemakers, the durability of pacemaker activity, and the arrhythmogenic potential of such interventions.                                            Within the realm of cellular electrophysiology, the final article we will choose to focus on was published by Barbic, et al, in American Journal of Physiology, heart and Circulatory Physiology, in volume 312, entitled Detachable Glass Microelectrodes for Recording Action Potentials in Active Moving Organs. They demonstrated that a new glass microelectrode could allow for determinational cellular actional potential duration in actively moving organs. This is a profound potential advance in the physiologic evaluation of both in vitro and in vivo translational cellular models of cardiac activation. Traditional patch clamping action potential studies required immobilization of cells being studied, whether by mechanical or pharmacologic means. However, directed efforts to immobilize cells can alter electrophysiologic parameters. The ability to record cellular action potentials in actively moving cells, for example the beating heart, may offer studies of cellular electrophysiology, that more closely approximate real world physiology.                                            Our next area of focus will be on genetic channelopathies, including long QT syndrome, Brugada, catecholaminergic polymorphic ventricular tachycardia and others. The article we choose to focus on this month, within this realm, was published by Pappone, et al, in Circulation: Arrhythmia and Electrophysiology, volume 10. They focus on electrical substrate elimination in 135 consecutive patients with Brugada syndrome. They demonstrated in this large cohort of patients that the arrhythmogenic electrical substrate associated with the Brugada syndrome primarily localized to the right ventricular epicardium, and an ablation of such region led to normalization of electrocardiogram and non-inducibility ventricular arrhythmias acutely in all patients, and over a long term in all but two patients.                                            These findings complement prior work by Nademanee and others that support a role for targeting substrate in the region of the right ventricular epicardium, in preventing recurrent ventricular arrhythmias in patients with Brugada syndrome, and in normalizing the electrocardiographic Brugada pattern. At the translational level, prior work has demonstrated that the same SCN mutations associated with Brugada syndrome confer accentuated transmittal gradients within the realm of the right ventricle, along with preferential prolongations of action potentials in the right ventricular epicardial myocytes. However, it remains to be seen whether the specific genetic cause of individual patient's Brugada pattern or Brugada syndrome is associated with discreet pathologic and inter-ablation findings and success rates.                                            Next, moving on to the realm of ventricular arrhythmias, we focus on three major articles published in the past month. The first article is published by Vaseghi, et al, in the Journal of the American College of Cardiology, volume 69, entitled Cardiac Sympathetic Denervation for Refractory Ventricular Arrhythmias. They demonstrated that cardiac sympathetic denervation may be an effective therapy in many patients with intractable ventricular arrhythmias, with a greater than 50% reduction in sustained VT, ICD shock, transplant or death over one year follow-up. Not only this but nearly one third of patients no longer required antiarrhythmics. However, bilateral sympathectomy is far superior over left sided only sympathectomy. Furthermore, advanced heart failure and VT cycle length were associated with poor outcomes. These findings suggest a role for bilateral sympathectomy in management of patients presenting with intractable ventricular arrhythmias. However, patient identification and selection in terms of the ideal cohorts for such therapy, and how to identify such cohorts remains to be seen.                                            Our next article regards advances in attaining epicardial access. Di Biase, et al, published in Heart Rhythm, volume 14, the initial international multi-centered human experience with the novel epicardial access needle embedded with a real time pressure frequency monitor to facilitate epicardial access. They looked specifically at feasibility and safety of this novel approach. While in only 25 patients, they did demonstrate that epicardial access can be successfully obtained with only one complication of a delayed pericardial effusion. With evolving indications for epicardial access, including for left atrial appendage occlusion, epicardial ganglia modulation, and ventricular arrhythmia mapping and ablation, development of novel tools to minimize the risks associated with epicardial ablation, particularly in individuals who do not perform it routinely, is critical. However, whether these variable approaches hold significant advances in randomized trials, beyond traditional approaches, remains to be seen.                                            Within the realm of ventricular arrhythmias, the last article we will choose to focus on was published by Acosta, et al, in Europace, volume 19. They looked at the long-term benefit of first line peri-implantable cardioverter-defibrillator implant ventricular tachycardia substrate ablation in secondary prevention patients. This study complemented prior data from SMASH-VT supporting a role for early ablation to reduce future arrhythmia events in patients receiving defibrillators. In their study, they demonstrated that early ablation was associated with a decreased recurrence of ventricular arrhythmias and defibrillary shocks over an average of almost four years. However, it addressed patients with lower ejection fractions, namely less than 35%, received less benefit. Though this was mostly conferred by while having similar frequency of VT recurrence, having an overall lower burden compared to those who did not have ablation. Practice patterns continue to vary in the decision making with regards to performing early ablation in such patients. Furthermore, whether or not a mortality benefit exists with early ablation remains relatively unclear and unproven. However, there's an evolving body of evidence to support the notion that aggressive, early intervention with invasive procedures in patients receiving ICDs, and at high risk for ventricular arrhythmias, may make sense.                                            The final article we will focus on that has been published in the past month, is published by Turagam, et al, in the International Journal of Cardiology, volume 236, entitled Practice Variation in the Re-initiation of Dofetilide: an Observational Study. Turagam, et al, surveyed 347 providers in the U.S. and worldwide, and demonstrate significant practice variability when re-initiating dofetilide. They know that up to 21% of providers always admit patients to the hospital for dofetilide re-initiation, while 37% of physician admit patients less than 10% of the time. Interestingly, the duration off of dofetilide ranging anywhere from three days to more than a year, did not necessarily significantly affect the rate of decision to re-initiate dofetilide, after prior cessation. One key finding of this was the 4% of physicians reporting major adverse events with drug re-initiation in patients. This was despite the vast majority of these patients tolerating de novo initiation. Given the prolific effects of antiarrhythmetic drugs, strategies to reduce those potential risks are critical. In fact, multiple groups such as the Cardiac Safety Research Consortium, within the same month, had sought to publish recommendations for long-term electrocardiographic monitoring, in drug developments. It must be realized the consideration of the impact of antiarhythmetic drug managements may not always be well outlined by existing protocols. And thus, further study is likely required to inform current clinical practice.                                            It was my pleasure to introduce to you some of the major heart hitting articles published in the part month across the electrophysiologic literature. While none of this is really touching on every single major advance, we hope to identify those that hold potential, measure immediate clinical potential, or those that hold potential for future advancements within our field. Thank you. Dr. Paul Wang:                I hope you enjoyed this month's podcast On the Beat, Circulation: Arrhythmia and Electrophysiology. We've had a number of groundbreaking and fascinating studies. See you next month.

According to the American Heart Association obesity is the number one reason that greatly enhances mortality and morbidity among adolescence.  The prevalence of obesity places children and adolescents at risk for many diseases and conditions.  What is the common thread of obesity found in children and adolescence?  Children that are susceptible to type II diabetes may have a genetic predisposition.  However, the largest single contributor to the condition are unhealthy diets; followed by sedentary lifestyles (i.e., television viewing and computer use).  For itself, sedentary lifestyles contribute to an already increasing and alarming rate of cardiovascular disease. ReferencesAmerican Heart Association. (n.d.). Cardiovascular conditions of childhood. Retrieved from http://www.heart.org/HEARTORG/Conditions/More/CardiovascularConditionsofChildhood/Cardiovascular-Conditions-of-Childhood_UCM_314135_SubHomePage.jsp#Downey, M. (2001). Obesity as a disease entity . American Heart Journal, 142(6), 1091-1094. doe: 10.1067/mhj.2001.119421.Jelalian, E., & Hart, C. N. (2009). Pediatric obesity. In M. Roberts, & R. Steele, Handbook of pediatric psychology, (4th ed) (pp. 446–463). New York, New York: Guilford.Pulgarón, E. R. (2013). Childhood obesity: A review of increased risk for physical and psychological co-morbidities. Clinical Therapeutics, 35(1), A18–A32. doi: 10.1016/j.clinthera.2012.12.014.Raj, M., & Kumar, R. K. (2010). Obesity in children & adolescents. Indian Journal of Medical Research, 132(5), 598-607. PMID:21150012.

According to the American Heart Association obesity is the number one reason that greatly enhances mortality and morbidity among adolescence.  The prevalence of obesity places children and adolescents at risk for many diseases and conditions.  What is the common thread of obesity found in children and adolescence?  Children that are susceptible to type II diabetes may have a genetic predisposition.  However, the largest single contributor to the condition are unhealthy diets; followed by sedentary lifestyles (i.e., television viewing and computer use).  For itself, sedentary lifestyles contribute to an already increasing and alarming rate of cardiovascular disease. ReferencesAmerican Heart Association. (n.d.). Cardiovascular conditions of childhood. Retrieved from http://www.heart.org/HEARTORG/Conditions/More/CardiovascularConditionsofChildhood/Cardiovascular-Conditions-of-Childhood_UCM_314135_SubHomePage.jsp#Downey, M. (2001). Obesity as a disease entity . American Heart Journal, 142(6), 1091-1094. doe: 10.1067/mhj.2001.119421.Jelalian, E., & Hart, C. N. (2009). Pediatric obesity. In M. Roberts, & R. Steele, Handbook of pediatric psychology, (4th ed) (pp. 446–463). New York, New York: Guilford.Pulgarón, E. R. (2013). Childhood obesity: A review of increased risk for physical and psychological co-morbidities. Clinical Therapeutics, 35(1), A18–A32. doi: 10.1016/j.clinthera.2012.12.014.Raj, M., & Kumar, R. K. (2010). Obesity in children & adolescents. Indian Journal of Medical Research, 132(5), 598-607. PMID:21150012.

Barbara Riegel, DNSc, RN, FAAN, FAHA, has been selected as the 10th recipient of the Claire M. Fagin Distinguished Researcher Award at the University of Pennsylvania School of Nursing. Dr. Riegel will present the Fagin Lecture about her research journey on April 5, 2012, at Penn Nursing. Dr. Riegel, the Edith Clemmer Steinbright Chair of Gerontology and director of the Center for Biobehavioral Research at Penn Nursing, is internationally recognized for her research in heart failure. Through her interdisciplinary research, Dr. Riegel has advanced knowledge about the management of patients with heart failure and has contributed to guidelines that have changed the care provided to those with acute myocardial infarction. Her articles have been published in Heart & Lung, the American Heart Journal, the Journal of Cardiovascular Nursing, and the European Journal of Cardiovascular Nursing. Dr. Riegel is editor of The Journal of Cardiovascular Nursing and a fellow in both the American Academy of Nursing and the American Heart Association.

Barbara Riegel, DNSc, RN, FAAN, FAHA, has been selected as the 10th recipient of the Claire M. Fagin Distinguished Researcher Award at the University of Pennsylvania School of Nursing. Dr. Riegel will present the Fagin Lecture about her research journey on April 5, 2012, at Penn Nursing. Dr. Riegel, the Edith Clemmer Steinbright Chair of Gerontology and director of the Center for Biobehavioral Research at Penn Nursing, is internationally recognized for her research in heart failure. Through her interdisciplinary research, Dr. Riegel has advanced knowledge about the management of patients with heart failure and has contributed to guidelines that have changed the care provided to those with acute myocardial infarction. Her articles have been published in Heart & Lung, the American Heart Journal, the Journal of Cardiovascular Nursing, and the European Journal of Cardiovascular Nursing. Dr. Riegel is editor of The Journal of Cardiovascular Nursing and a fellow in both the American Academy of Nursing and the American Heart Association.

AIR DATE: February 16, 2012 at 7PM ETFEATURED EXPERT: FEATURED TOPIC: “All Things Lipids (Cholesterol 101)” Episode 6 of “Ask The Low-Carb Experts” features the topic “All Things Lipids (Cholesterol 101)” with blogger and doctoral candidate in Nutritional Sciences at the University of Connecticut  where he will be graduating this Spring. He is the creator and maintainer of Cholesterol-and-Health.Com and is the author of two blogs, The Daily Lipid at Cholesterol-and-Health.Com and Mother Nature Obeyed at WestonAPrice.org. He is also a frequent contributor to Wise Traditions, the quarterly journal of the Weston A. Price Foundation. Chris is the author of five publications in peer-reviewed journals, including a letter to the editor of the Journal of the American College of Cardiology criticizing the conclusions of a widely publicized study about the effect of saturated fat on blood vessel function, and letter to the editor of the American Heart Journal arguing that the effect of cholesterol ester transfer protein inhibitors on vitamin E metabolism should be studied before these drugs are deemed safe for preventing heart disease, a hypothesis published in Medical Hypotheses about the molecular mechanism of vitamin D toxicity and the involvement of vitamins A and K in this mechanism, a pilot study in humans suggesting that vitamin E protects against some of the negative effects of sugar consumption published in the Journal of Nutritional Biochemistry, and a review published in Nutrition Reviews about the potential for green tea to prevent or treat nonalcoholic fatty liver diseases. Chris Masterjohn has thoroughly studied the impact of cholesterol on your health and the answers he has discovered might just surprise you. If you have questions about cholesterol, HDL, LDL, triglycerides and more then this is the podcast for you. Here are some of the questions Chris addressed in this podcast: DARREL ASKS:My cholesterol has been high for quite a while. I was previously on Lipitor which made me feel pretty bad (old and feeble even though I’m neither) so I quit. This week my doctor got back my blood work and noticed my number was high (295) and insisted I go back on Lipitor. He said I was a ‘heart attack brewing’. I don’t want to and need some ammunition. Point me in the right direction. MARK ASKS:I have a senior lady that her doctor has recommended her to take statins for a while. She doesn’t want to go on them, and her doctor just ran an Lp(a) test and hers was at 80. I seem to recall that statins don’t really affect Lp(a) and it’s mostly genetic. I’m not sure of her triglyceride/HDL ratio at this time, but should she be worried? Seems that Lp(a) is only an issue if you have heart disease or a lot of inflammation. JOHN ASKS: http://diabetes.diabetesjournals.org/content/early/2011/05/18/db11-0085 Question: Is MGmin LDL the silver bullet of atherosclerosis? I’ve read suggestions that small, dense LDL is the killer, but I see studies suggesting that large, fluffy LDL can also be atherogenic. JAMIE ASKS:In some countries (like Australia) you cannot get your cholesterol measured down to “small dense” and “large fluffy”. They only measure the basics, Triglycerides, HDL, LDL and Total cholesterol. From these numbers, is there a good ratio to indicate good health versus poor health? SHARON ASKS:My husband has high cholesterol which is made worse by another necessary medication he takes. Triglycerides were over 700; he is taking very high doses of statins, bring it to 600; We started Paleo (no sugars; no grains; full-fat dairy and meats) and blood results after two weeks showed them at 199. Is this possible to have such a dramatic change so quickly from this diet? If followup blood work shows continued improvement, what is the number that would get his doctor to take him off of the statins? SAM ASKS:I’m a 42-year-old male with little to no family history of heart disease. My latest VAP results include: Tot LDL-Chol Direct 167 H mg/dLTot. HDL-Cholesterol Dir. 52 mg/dLTot. VLDL-Cholesterol Dir. 23 mg/dLSum Total Cholesterol 241 H mg/dLTriglycerides-Direct 75 mg/dLTot. NonHDL Chol(LDL+VLDL) 189 H mg/dLTotal apoB100 – calc. 118 H mg/dLLP(a) Cholesterol 4.0 mg/dLIDL Cholesterol 23 H mg/dLReal LDL-Cholesterol 140 H mg/dLSum Total LDL-C 167 H mg/dLREAL-LDL Size Pattern A ARemnant Lipoprot(IDL+VLDL3) 37 H mg/dL My doctor insists I take a statin such as Lipitor. I say I may not need it. Which one of us is right? Also, is it possible that statins inhibit the formation of arterial plaque over time? PAUL ASKS:What are your thoughts on all the alarmism surrounding glycation and fructation? KAREN ASKS:I’m about to have blood work done to be underwritten for term life insurance. I’m concerned that my cholesterol levels may have elevated because I’ve only been LC’ing for about 9 months. If it comes back bad, do you have any advice for how to explain what’s going on to help mitigate the consequences? LEO ASKS:It’s been almost 2 years since going low carb. Before that time I was taking fenofibrate for almost 8 years because of very high trig (700 -380) and low HDL (37) because of eating SAD. Now my trig is 100 – 75, HDL is 57 and still improving without taking meds. I read that eating saturated fat and red wine will help increase HDL. At my last doctor visit he suggested in begin statins because my total cholesterol was 250 and my LDL was 148 and to see a cardiologist. I asked that he do the test for determining large and small LDL particles to which he replayed he was not qualified to request that test! I also mentioned to him that the LDL level is really a fictitious number gathered by the Friedewald equation. Would you suggest I see a cardiologist and check further? Would it be a good idea to request a CAC score, Lp(a) and test for density particles of LDL? WILLY ASKS:How are you? My question is what is Lp(a)’s role in heart disease and should we really even track it. As I recall Dr. Kurt Harris from the panu blog has what is considered a high level yet has a very low calcium score. While some on Dr. Davis heart scan blog have levels lower than his and suffer from high calcium scores or other cardiovascular issues. If we should be concerned with this lipid what is the best way to lower it? Niacin? Saturated Fats? Low Carb? I wonder if Lp(a) is just the new kid on the block for Big Pharma trying to keep the lipid hypothesis alive. VALERIE ASKS:Chris, In your most recent interview with Chris Kresser you indicate that a TC:HDL ratio of 4 might be cause for concern and should be evaluated. My husband and I just got our results back, our ratios are 4.3 and 4.6. We can rule out recovering from obesity and fatty liver disease. What do you advise we do if anything? Get retested to establish our averages? Without going into too much detail, we have been following a WAPF/Paleo diet for 4 years, we are healthy and fit, I am 47, my husband is 40. Next, I have in my notes a TC range of 180-250 as found in traditional cultures. Can you also provide a range for HDL and LDL? And last, what foods, herbs, supplements, and food preparation techniques would you advise to support a healthy LDL receptor uptake process? KYLE ASKS:There seems to be a growing interest in the blogosphere with the work of Dr. Ray Peat. A major tenet of Peat’s philosophy revolves around the toxicity of virtually any dose of polyunsaturated fats (PUFA)–both n3 and n6. Given your past work on EFAs and PUFAs in general, I’d love to hear your thoughts on Dr. Peat’s stance. LUKE ASKS:What is the relation of lipid volume in the blood and speed of blood flow in the arteries and the body in general? (e.g, the documentary “Supersize Me” made a big deal about animal fat causing slower measured blood flow) ELLEN ASKS:I believe higher cholesterol levels are healthier and protective against many illnesses. If my normal total cholesterol is around 205, and I make a diet change that has the effect of dropping my total cholesterol to 165, am I compromising the protective aspect of cholesterol? LDL is also lower at 92 and HDL has stayed about the same (55). Trigs are at 92. CRP is .75 and HbA1c is 5.5. MACKAY ASKS:Patient just came back with very high cholesterol, but sub markers were phenomenal. HDL 99Triglycerides 66HSCRP .4 Positive for celiac, although eats very little wheat. Total cholesterol 450. What could cause this? EDWARD ASKS:Regarding lab measurements…lipid panels: Cholesterol measurement – what is actually being measured in standard lipid profiles, and what is being estimated? Is LDL calculated based on your TG measurement? DEANNA ASKS:My stepdad has high cholesterol (mostly high Triglycerides) and has for many years—I have attached his lab report from last May—his numbers were better. Total cholesterol 252Triglycerides 534HDL 33Testosterone 235Free testosterone 8.9 He takes: 160mg Fenofibrate, Benicar, Lovaza, DHEA, Niacin, and just started taking Red Yeast Rice. My mother thought he was on a statin—but Fenofibrate and Lovaza aren’t statins are they? Are they just as bad? Haven’t heard much discussion on these meds. Filed Under: , ,