Podcasts about coapt

Send us a textThe prosthetics and orthotics industry is witnessing significant consolidation and technological advancement, with Hanger's recent acquisition of Coapt being a prime example of this evolution.• Coapt's pattern recognition technology transforms how upper extremity amputees control prosthetic devices• Traditional myoelectric systems use only two sensors while Coapt's system employs an array of 18 sensors• Machine learning algorithms decode neurological intent, making prosthetic control more intuitive• Upper extremity amputations represent only about 20% of all amputations, creating a niche market• Blair Lock, Coapt's CEO, built the company over 13 years without outside investment• The "slow burn" approach to business growth can be necessary and beneficial in specialized medical technology• Additive manufacturing plays multiple roles in prosthetics: from prototyping to clinical fabrication• Regulatory requirements significantly impact the economics of prosthetic technology• Myoelectric technology has potential applications beyond prosthetics: exoskeletons, industrial robotics, and other human-machine interfacesSubscribe to the Prosthetics and Orthotics Podcast for more insights into the technological advancements shaping patient care.Support the show

In this episode, Dr. Valentin Fuster delves into the latest research surrounding the use of the mitral clip for patients with severe functional mitral regurgitation, comparing the results of three major trials: the French MITRA-FR trial, the American COAPT trial, and the Reshape HF 2 trial. While the COAPT and Reshape HF 2 trials show positive outcomes, especially in reducing hospitalizations and improving heart failure symptoms, the French trial saw no benefit, prompting debate over the influence of left ventricular volume and disease severity on treatment success, with expert opinions calling for further studies and individualized meta-analyses.

In this episode, Dr. Valentin Fuster delves into the latest research surrounding the use of the mitral clip for patients with severe functional mitral regurgitation, comparing the results of three major trials: the French MITRA-FR trial, the American COAPT trial, and the Reshape HF 2 trial. While the COAPT and Reshape HF 2 trials show positive outcomes, especially in reducing hospitalizations and improving heart failure symptoms, the French trial saw no benefit, prompting debate over the influence of left ventricular volume and disease severity on treatment success, with expert opinions calling for further studies and individualized meta-analyses.

Venous closure devices, GLP1-s linked to blindness and cancer, resisting the urge to do an ECG, and transcatheter edge-to-edge repair (TEER) for secondary mitral regurgitation are the topics discussed this week. This podcast is intended for healthcare professionals only. To read a partial transcript or to comment, visit: https://www.medscape.com/twic I Listener Feedback Venous vascular closure system vs. figure-of-eight suture following atrial fibrillation ablation: the STYLE-AF Study https://doi.org/10.1093/europace/euae105 II GLP1-s and Blindness Risk of Nonarteritic Anterior Ischemic Optic Neuropathy in Patients Prescribed Semaglutide https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2820255 Locke Twitter  https://x.com/doc_BLocke/status/1808972226655629610 When to Start a Statin Is a Preference-Sensitive Decision https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.117.029808 III GLP1-s and Cancer Glucagon-Like Peptide 1 Receptor Agonists and 13 Obesity-Associated Cancers in Patients With Type 2 Diabetes https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2820833 IV Screening ECG Routine Electrocardiogram Screening and Cardiovascular Disease Events in Adultshttps://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2820721 Clinical outcomes in systematic screening for atrial fibrillation (STROKESTOP)  https://doi.org/10.1016/S0140-6736(21)01637-8 Implantable loop recorder detection of atrial fibrillation to prevent stroke (The LOOP Study) https://doi.org/10.1016/S0140-6736(21)01698-6 IV TEER for Secondary Mitral Regurgitation Randomized investigation of the MitraClip device in heart failure: Design and rationale of the RESHAPE-HF2 trial design https://doi.org/10.1002/ejhf.3247 Percutaneous repair of moderate-to-severe or severe functional mitral regurgitation in patients with symptomatic heart failure: Baseline characteristics of patients in the RESHAPE-HF2 trial and comparison to COAPT and MITRA-FR trials https://onlinelibrary.wiley.com/doi/full/10.1002/ejhf.3286 Jun 21, 2024 This Week in Cardiology Podcast https://www.medscape.com/viewarticle/1001237 Stats Blog https://www.r-bloggers.com/2023/07/the-benjamini-hochberg-procedure-fdr-and-p-value-adjusted-explained/ You may also like: The Bob Harrington Show with the Stephen and Suzanne Weiss Dean of Weill Cornell Medicine, Robert A. Harrington, MD. https://www.medscape.com/author/bob-harrington Questions or feedback, please contact news@medscape.net

In this enlightening episode of "Conversations with Rich Bennett," sponsored by Eco-Cool HVAC, host Rich Bennett engages with three remarkable individuals in the field of prosthetic technology. Tom Zdon shares his empowering story of adopting an advanced prosthetic arm after a life-altering accident, highlighting the enhanced functionality provided by COAPT's control systems that interpret neural signals. Jonas Seeberg, owner of Real Life Prosthetics, discusses the customization and personalization of prosthetics that cater to individual needs, enhancing users' quality of life. Michelle Gent-Jamin, from Align Rehabilitation, adds depth to the conversation by explaining the rehabilitation process and the critical role of tailored therapy in integrating prosthetics into daily life. This episode sheds light on the technological advancements, personal triumphs, and collaborative efforts shaping the future of prosthetic technology. Here are links for you to bookmark, save, follow, memorize, write down, and share with others:Real Life Prosthetics™ | Restoring Real Life Ability Since 2001Align Rehabilitation | Amputee Physical Therapy Specialists | MD & DE (alignrehab-pt.com)This episode is sponsored by Eco-Cool HVACAlign Rehabilitation's grand opening is Friday, May 3 from 11-2. Explore our brand new amputee rehabilitation facility, equipped with the SoloStep overhead track system, and meet President, Michelle Jamin, amputee physical therapy specialist. Heavy hors d'oeuvres and refreshments will be provided! While you're here, stop by our neighbors at Real Life Prosthetics (STE D) and tour the expansion of their lab. You will get to Eco-Cool HVACYOUR FRIEND IN THE SUMMERS & WINTERS! Heating & Air Conditioning Service and Repair, Furnace & BoilDisclaimer: This post contains affiliate links. If you make a purchase, I may receive a commission at no extra cost to you.Support the Show.Follow the Conversations with Rich Bennett podcast on Social Media:Facebook – Conversations with Rich Bennett & Harford County LivingFacebook Group (Join the conversation) – Conversations with Rich Bennett podcast group | FacebookTwitter – Conversations with Rich Bennett & Harford County LivingInstagram – Harford County LivingTikTok – CWRB (@conversationsrichbennett) | TikTok Sponsors, Affiliates, and ways we pay the bills:Recorded at the Freedom Federal Credit Union StudiosHosted on BuzzsproutRocketbookSquadCast Contests & Giveaways Subscribe by Email ...

Commentary by Dr. Valentin Fuster

In this special episode of AbbottTalks, recorded live from DeviceTalks West in October 2023, we celebrate a pivotal moment in medical innovation: the 20th anniversary of Abbott's MitraClip™, a revolutionary device introduced in 2003. In the episode, the inventor of the MitraClip, Frederick St. Goar, MD, Interventional Cardiologist, El Camino Health, and Abbott's Santosh Prabhu, PhD, Divisional VP, Global Product Development, discuss the journey of the MitraClip, reflecting on its inception, evolution, and lasting impact on cardiac care over the past two decades. Dr. Goar provides insights into the early challenges and motivations behind inventing the MitraClip, emphasizing its role in transforming minimally invasive cardiac procedures. He reflects on the initial concept, design iterations, and clinical experiences with the device. Dr. Prabhu discusses the continuous enhancements made to the MitraClip since its inception, focusing on improved safety, efficacy, and usability. He highlights the MitraClip's role in reducing hospitalizations and improving patient outcomes, as evidenced by the five-year results from the landmark COAPT™ trial. The episode pays tribute to the legacy of the MitraClip, acknowledging its significant contribution to medical technology and patient care and emphasizing the importance of interdisciplinary collaboration and patient-centric approaches in medical innovation. Thank you to Zeus for sponsoring this episode of AbbottTalks. For more information about Zeus go to www.ZeusInc.com. Thanks for listening to this episode of the AbbottTalks podcast. Please subscribe to the DeviceTalks Podcast Network. COAPT Trial Release -https://abbott.mediaroom.com/2023-03-05-Late-Breaking-Data-from-Landmark-COAPT-TM-Trial-Show-Long-Term-Benefits-of-Abbotts-MitraClip-TM-Device MitraClip History - https://www.abbott.com/corpnewsroom/products-and-innovation/the-mitraclip-story.html#:~:text=MitraClip's%20story%20starts%20in%20California,The%20idea%20was%20unheard%20of.

Commentary by Dr. Valentin Fuster

Commentary by Dr. Valentin Fuster

Pattern recognition harnesses residual muscle signals to help individuals control their upper limb prosthetic device intuitively. In this episode, Sam and Brendan explore this fascinating technology with Blair Lock, CEO and Co-founder of Coapt, and Shawn Robinson, Regional East Coast Manager at Coapt.Visit coaptengineering.com to discover more and explore the Coapt compatibility tool. Connect with Blair Lock and Shawn Robinson on LinkedIn.  Mentioned in the episode: Limb Loss and Preservation Registry Osseointegration AMI ProcedureRPNI Surgery  Many thanks to our sponsor, Knit-Rite! Explore Knit-Rite's Lightweight Torso-Interface.  Watch the latest SPS Unpacked to discover WillowWood's META Core foot. Visit spsco.com  Also, email us!   The O&P Check-in is a bi-monthly podcast featuring the latest orthotics and prosthetics news, trends, best practices, regulations and policies. Designed for O&P professionals, join Brendan Erickson and Jacki Green as they interview guests and share the latest advancements in the industry. 

O emisiune cu scurte povestiri dramatizate, biblice sau misionare, produse de colegii şi colaboratorii noştri din Iaşi, pentru ascultătorii Radio Vestea Bună!

Witam Państwa, nazywam się Jarosław Drożdż, pracuję w Centralnym Szpitalu Klinicznym Uniwersytetu Medycznego w Łodzi, skąd nagrywam podcast Kardio Know-How. W tym odcinku kontynuuję omawianie badań kongresu ACC.Szczegółowy TRANSKRYPT do odcinka.Podcast jest przeznaczony wyłącznie dla osób z profesjonalnym wykształceniem medycznym.

No Click Valvar de hoje temos grandes insights sobre os 5 anos do COAPT.

Transcatheter Edge-to-edge Repair Of Functional Mitral Regurgitation In Heart Failure: Final Five-year Results From The COAPT Trial

Keto-Like Diet, Bempedoic Acid (CLEAR Outcomes), BIOVASC, COAPT

Mitraclip: 5 anos do COAPT by Cardiopapers

Cardiovascular professionals are coming together for ACC.23 in New Orleans, March 4-6, to learn the latest practice-changing breakthrough research and trials results from around the world. In this View episode, guest host Deepak Bhatt MD, MPH, FACC, offers a preview of some of the hottest trials at ACC.23.   Kicking us off on Day 1, Saturday, March 4, we will hear the positive outcomes from the CLEAR OUTCOMES trial and the favorable data for structural heart disease coming out of the TRILUMINATE trial.  Day 2, Sunday, March 5, can't be missed! Among the many presentations: UK MINI MITRAL weighs the minimally invasive approach versus conventional sternotomy for mitral valve repair surgery and the RENOVATE COMPLEX PCI trial that examines intravascular imaging-guided versus angiography-guided procedural optimization in complex percutaneous coronary intervention – a subject of particular interest to interventionalists. And that's just the beginning: the 5-year final results from the COAPT trial are in; the 3-year outcomes from the EVOLUT low risk trial sound positive and continue to be in favor of TAVR; the BIOVASC trial data will be released, and it's likely the findings will continue to be in favor of complete revascularization strategies in patients presenting with acute coronary syndromes and multivessel coronary disease.  On Monday, the last day of the conference, Dr. Valentin Fuster will present the FREEDOM COVID ANTICOAG trial, discussing anticoagulation strategies in non-critically ill hospitalized COVID patients. Next up, the STELLAR trial, a study of sotatercept in combination with background therapy for the treatment of pulmonary arterial hypertension, will be presented. And finally, the findings of the collaborative analysis of participants in the three major trials are also scheduled: the PROMINENT, REDUCE-IT, STRENGTH trials.  Be sure to check back on Eagle's Eye View throughout the meeting for further updates.  Subscribe to Eagle's Eye View

Commentary by Dr. Valentin Fuster

It's another session of CardioNerds Rounds! In these rounds, Dr. Natalie Stokes (Formerly FIT at University of Pittsburgh and now General Cardiology Faculty at University of Pittsburgh) and Dr. Karan Desai (formerly FIT at University of Maryland and now General Cardiology faculty at Johns Hopkins) join Dr. Rick Nishimura (Professor of Medicine at Mayo Clinic) to discuss the nuances of managing mitral regurgitation through real cases. Dr. Nishimura has been an author or Chair of the ACC/AHA valve guidelines going back 20 years and has been recognized internationally as one of the world's best educators, so you don't want to miss the #NishFactor on these #CardsRounds! Audio editing by CardioNerds academy intern, Pace Wetstein. This episode is supported with unrestricted funding from Zoll LifeVest. A special thank you to Mitzy Applegate and Ivan Chevere for their production skills that help make CardioNerds Rounds such an amazing success. All CardioNerds content is planned, produced, and reviewed solely by CardioNerds. Case details are altered to protect patient health information. CardioNerds Rounds is co-chaired by Dr. Karan Desai and Dr. Natalie Stokes.  Speaker disclosures: None Challenging Cases - Atrial Fibrillation with Dr. Hugh Calkins CardioNerds Rounds PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Show notes - Mitral Regurgitation with Dr. Rick Nishimura Case #1 Synopsis: A man in his 70s with a history of non-ischemic cardiomyopathy (last known LVEF 15-20%) and atrial fibrillation, presented with decompensated heart failure in the setting of moderate to severe mitral regurgitation. He was diuresed, transitioned to GDMT, and referred to cardiac rehabilitation. Over the next 6 months, he continued to have debilitating dyspnea (NHYA Class IIIa) and his outpatient physicians were limited on titrating GDMT further due to hypotension. A TEE was done which demonstrated EF 15%, severe MR by color and quantitation (EROA of 0.5 cm2; Regurgitant Volume of 65 mL), systolic flow reversal in the pulmonary vein and severe tricuspid regurgitation. We were asked how we would approach this case Case #1Takeaways In attempting to keep the evaluation of chronic mitral regurgitation relatively simple, we should ask ourselves three primary questions: (1) What is causing the MR; (2) How much MR is there; and (3) What is the hemodynamic consequence of the MR.To the first question of what is the etiology of the MR – a simple framework is to think of the etiology as an issue of the valve (primary) or an issue of the ventricle/atria (secondary). There is further classification that can be made based on the Carpentier Classification which speaks to the valve leaflet movement and position (normal leaflet motion, excessive leaflet motion [e.g., prolapse], or restricted in systole and/or diastole [e.g., rheumatic heart disease]).During rounds, Dr. Nishimura provided some historical context in that the original valve guidelines had recommendations for intervention on primary mitral regurgitation and not secondary – given that it is considered a disease of the ventricle. Trials like the COAPT trial have greatly shifted our practice in treating secondary mitral regurgitation. Though, we have to be familiar with which patients with secondary MR would truly derive benefit from mitral valve interventionIn regards to the COAPT trial, patients with moderate to severe (3+) or severe (4+) mitral regurgitation who remained symptomatic despite maximally tolerated guideline-directed medical therapy (GDMT) were included. Dr. Nishimura makes the point that about one-third of patients intended to be enrolled in the trial were not included because they improved so much on GDMT. And thus, when evaluating patients for consideration of mitral valve intervention in secondary MR – a...

No Click Valvar de hoje, temos insights sobre um aspecto interessante, os aspectos clínicos relevantes sobre os critérios de inclusão dos famosos Trials COAPT e Mitra-FR na prática diária!

Novo episódio da nova temporada do ValveCast!.O melhor Podcast sobre Valvopatias do Brasil!.Hoje, Tiago Bignoto fala de todos os detalhes de uma publicação fantástica! COAPT Trial, o uso de MitraClip na Insuficiência Mitral Funcional..Está imperdível!

Hoje é dia de estreia da nova temporada do ValveCast!.O melhor Podcast sobre Valvopatias do Brasil!.Hoje, Tiago Bignoto fala de todos os detalhes da publicação dos 3 anos de acompanhamento dos pacientes do COAPT Trial.

I read from coagulum to coapt.   That "bison" phrase in the fun holiday list was obviously a reference to "bicentennial" but in the moment I couldn't hear that because my eyes took over my brain.  It was so obvious!      The word of the episode is "coalesce".     Featured in a Top 10 Dictionary Podcasts list! https://blog.feedspot.com/dictionary_podcasts/     Backwards Talking on YouTube: https://www.youtube.com/playlist?list=PLmIujMwEDbgZUexyR90jaTEEVmAYcCzuq     dictionarypod@gmail.com https://www.facebook.com/thedictionarypod/ https://twitter.com/dictionarypod https://www.instagram.com/dictionarypod/ https://www.patreon.com/spejampar 917-727-5757

This week's episode features a panel discussion in regard to Covid-19. Please join authors Kathryn Larson, Christopher deFilippi, James de Lemos, and Biykem Bozkurt as they discuss their articles regarding temporary myocarditis and Covid-19 vaccination. Dr. Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and its editors. We're your co-hosts, I'm Dr. Carolyn Lam, associate editor from the National Heart Center and Duke National University of Singapore. Dr. Greg Hundley: And I'm Dr. Greg Hundley, associate editor, director of the Pauley Heart Center at VCU Health in Richmond, Virginia. Dr. Greg Hundley: Carolyn, this week, oh my goodness. It's a forum, almost a triple or quadruple feature, and you know what we're going to be discussing? COVID-19 vaccinations and their relationship potentially to myocarditis. We're going to have our associate editors and our deputy editor involved, be really interesting. But before we get to that, how about we start in with the papers in the issue. Would you like to go first? Dr. Carolyn Lam: Absolutely. And my first paper is so interesting. It identified a novel underlying mechanism of graft arteriopathy, or otherwise known as coronary allograft vasculopathy, a devastating development of heart transplant in which arterial intimal thickening limits coronary blood flow and could lead to transplant failure. Dr. Greg Hundley: Oh wow, Carolyn. So, what did they find? Dr. Carolyn Lam: Well, this was Dr. Martin from Yale Cardiovascular Research Center and colleagues. What they did is they used both human coronary allograft vasculopathy and renal transplant samples as well as murine models, basically, and found that TET methylcytosine dioxygenase 2, or TET2, is a critical negative regulator of vascular smooth muscle cell apoptosis in graft arteriopathy and vascular injury. Enhancing smooth muscle TET2 activity with a high dose of ascorbic acid rescued donor vascular smooth muscle cells apoptosis and intimal thickening in murine transplant vasculopathy. Furthermore, TET2 expression and activity were repressed in arterial vascular smooth muscle cells in human and mouse graft arteriopathy compared to controls. Dr. Carolyn Lam: Interferon gamma signaling in vascular smooth muscle cells resulted in TET2 repression. Preventing donor vascular smooth muscle cell apoptosis with high dose ascorbic acid may therefore represent a safe and cost-effective therapeutic strategy for limiting graft arteriopathy in patients undergoing solid organ transplant. Neat, huh? Dr. Greg Hundley: You bet, Carolyn. Really an interesting article on limiting graft arteriopathy. Dr. Greg Hundley: Well, Carolyn, my next paper comes to us from Dr. Greg Stone and colleagues at the Cardiovascular Research Foundation. It involves the randomized COAPT trial. Remember that in the COAPT trial, there were 614 heart failure patients with 3+ or 4+ secondary mitral regurgitation and had trans-catheter mitral valve repair with the MitraClip, reduced mitral regurgitation, heart failure hospitalizations and mortality as well as improving quality of life compared with guideline directed medical therapy alone. So the authors here, Carolyn, sought to examine the prognostic relationship between mitral regurgitation reduction and outcomes in trans-catheter mitral valve repair versus guideline directed medical therapy alone. Dr. Carolyn Lam: Wow, okay. So, what did they find, Greg? Dr. Greg Hundley: Right, Carolyn. So, among patients with heart failure and severe, grade 3+ or 4+ secondary mitral regurgitation randomized to trans-catheter mitral valve repair with the MitraClip versus guideline directed medical therapy, the reduction of MR to 2+ was strongly associated with subsequent two year freedom from death and heart failure hospitalization and improved quality of life regardless of whether this reduction to 2+ MR was achieved by trans-catheter clip or guideline directed medical therapy alone. And the improvement in long term prognosis was similar after this mitral regurgitation reduction to grade 2+ compared with grade 0 or 1+ in both arms, although the mitral regurgitation reduction was a little more durable over time after the trans-catheter mitral clip. Dr. Greg Hundley: So Carolyn, the take-home message is that substantial benefits are realized even if mitral regurgitation is reduced to only 2+. Dr. Carolyn Lam: Nice, Greg. Thanks. Dr. Carolyn Lam: Now, this next paper, oh, close to my heart. We know that individuals of South Asian ancestry actually represent 23% of the global population, corresponding to 1.8 billion people, and that they have a substantially higher risk of atherosclerotic cardiovascular disease compared with most other ethnicities. However, what is the magnitude of that enhanced risk, the extent to which it is captured by existing risk estimators, and what are its potential mechanisms? Dr. Carolyn Lam: This was studied in this beautiful paper. Dr. Khera from Massachusetts General Hospital and colleagues used data from the large UK Biobank prospective cohort study to investigate the relationship between South Asian ancestry and incident atherosclerotic cardiovascular disease within the context of contemporary medical care. Their findings confirmed an approximate doubling of atherosclerotic cardiovascular disease risk among South Asian compared with European individuals that was not captured by the pooled cohort equations. The higher risk of atherosclerotic cardiovascular disease persisted despite adjustment for a broad range of potential clinical, anthropometric, and lifestyle mediators. Hypertension, diabetes, and central adiposity explain a greater proportion of risk of atherosclerotic cardiovascular disease in South Asian compared with European individuals. Dr. Greg Hundley: Wow, Carolyn. So, a lot of data here. How do we take all this and put it together clinically? Dr. Carolyn Lam: Well, the results confirm and extend the current guidelines that consider South Asian ancestry a risk-enhancing factor in assessing future risk for atherosclerotic cardiovascular disease. Residual risks that persisted after accounting for a range of potential mediators may relate to differences in social determinants of health, unmeasured risk factors and genetics and so on, that this warrants further investigation. Whether a targeted intervention can attenuate the outsized impact of diabetes or central adiposity among South Asian individuals also warrants further attention. Dr. Carolyn Lam: This is accompanied by a beautiful editorial entitled The South Asian Enigma: Solving a Puzzle of Global Importance, love that, from Drs. Kandula from Northwestern University Medical Center and Kanaya from University of California San Francisco. Dr. Greg Hundley: Very nice, Carolyn. I just want you to know, after being quizzed last week on phospholamban, I went and did a little bit of studying, okay? So I get to bring to you, Carolyn, this week, a paper on phospholamban. But I'm going to spare you from the quiz. Dr. Greg Hundley: All right. Dr. Carolyn Lam: Yay! Dr. Greg Hundley: This comes to us from Professor Fadi Akar from Yale University. Carolyn, arginine 14 deletion is the calcium regulatory protein phospholamban, so hPLN R14 deletion. It has been identified as a disease-causing mutation in patients with an inherited cardiomyopathy, and mechanisms underlying the early arrhythmogenic phenotype that predisposes carriers of this mutation to sudden death with no apparent structural remodeling really remain unclear. Dr. Carolyn Lam: Interesting, Greg. So, what did they find? Dr. Greg Hundley: Right, Carolyn. Adverse electrophysiological remodeling was evident in the absence of significant structural hemodynamic changes, and the R14 deletion hearts exhibited increased arrhythmia susceptibility compared to their wild-type counterparts. Underlying this susceptibility was preferential right ventricular action potential prolongation that was unresponsive to beta-adrenergic stimulation. A steep repolarization gradient at the LV/RV interface provided the substrate for inter-ventricular activation delays and ultimately local conduction block during rapid pacing. This was followed by the initiation of macroreentrant circuits supporting the onset of ventricular tachycardia. And then once sustained, these circuits evolved into high frequency rotors, which in their majority were pinned to the right ventricle. Importantly, these rotors exhibited unique spatio-temporal dynamics that promoted their increased stability in the R14 deletion compared to the wild-type hearts. Dr. Greg Hundley: So Carolyn, in summary, this research found the crucial role of primary electrical remodeling caused by the hPLN R14 deletion mutation. These inherently arrhythmogenic features form the substrate for adrenergic-mediated VT at early stages of the PLN R14 deletion induced a cardiomyopathy. Dr. Carolyn Lam: Oh, and ties up very nicely about how we mentioned that this dilated cardiomyopathy is associated with lots of ventricular arrhythmias that we discussed last week. Really cool. Dr. Carolyn Lam: Well, let's do a little tour around what else there is in today's issue. Tracy Hampton presents from the literature discussing how excessive exercise may damage mitochondria and impair glucose control in a publication from Cell Metabolism. Data on an oral antisense oligonucleotide for PCSK9 inhibition was published in Science Translational Medicine. Dr. Carolyn Lam: And there's a paper on structuring clinical text with AI. How very interesting, published in Patterns. There's an On My Mind paper by Dr. Berger on summoning strength to question the placebo in reducing. Dr. Greg Hundley: Right, Carolyn. Also in the mail bag, there is a reply to the Quintao and Cazita from Professor Brunham entitled High-Density Lipoprotein Cholesteryl Ester Transfer Protein and Sepsis. And then finally, from Dr. Goldstein, an ECG challenge. Does this ischemia pattern look right? Dr. Greg Hundley: Well, Carolyn, this is going to be a really interesting feature forum discussion today on COVID-19 vaccinations and myocarditis. How about we get on to that discussion? Dr. Carolyn Lam: Yep. A really important issue now. Yup, let's go. Dr. Greg Hundley: Welcome, listeners. We have a very exciting, really series, of feature discussions. We're going to call it a forum, and focusing on COVID-19 vaccine associated myocarditis. We really have four manuscripts to discuss today. We have Dr. Kathryn Larson from the Mayo Clinic in Rochester. We have another author, Dr. Chris deFilippi from Inova Health, really in the Washington DC metro area. We have our executive editor, Dr. James deLemos from UT Southwestern in Dallas, Texas. And then also one of our senior associate editors, Dr. Biykem Bozkurt from Baylor College of Medicine in Houston, Texas. Welcome to everyone. Dr. Greg Hundley: Well, first, listeners, we're going to start with Dr. Larson. So, Kathryn, can you tell us a little bit about the background and the hypothesis that you were testing in your research project, and then a little bit about your study design and what were the results of your study? Dr. Kathryn Larson: Absolutely. Well, first off, thank you so much for having me, Greg. It's a pleasure to be here and in such good company. My study really grew out of a clinical interest in a number of patients that had presented to our institution and other institutions that we had been in discussion with of really young male patients with no significant past medical history who were coming in two to three days after receiving their COVID vaccines, most often the second dose, and presenting with laboratory and clinical findings consistent with myocarditis. I think in a lot of arteriosity and what the course of their illness may be and what the best course of treatment may be, that really drove our hypothesis to try and describe other cases that were coming up and that we had heard about from a lot of our colleagues around the country and around the world. Dr. Kathryn Larson: Our paper really grew out of a case series of eight patients, and they're from the United States and from Italy, and they're of eight patients who were diagnosed with laboratory and clinical and imaging findings consistent with myocarditis after receiving their COVID-19 vaccines. Our patients had received either the Pfizer BioNTech or the Moderna vaccines, the mRNA vaccines. Really, only two of our patients had previously been infected with COVID at all, and so most of these patients were coming in with really no relevant medical history. They were really young in age, between 21 and 56 years old, and basically all patients except for one developed their symptoms after receiving the second dose of the vaccine. Dr. Kathryn Larson: The timeline was generally about two to three days after that dose and was often accompanied by other symptoms which we have seen and heard about things like myalgias, subjective fevers, chills, and kind of a general malaise. They presented really with very typical features of myocarditis, chest pain, one of the patients had a more pleuritic type of chest pain, and had ECG changes, troponin elevations, elevated inflammatory markers, and most importantly cardiac MRI findings that were significant and really diagnostic of myocarditis. Dr. Kathryn Larson: There was a good amount of investigation into other potential causes and none other identified in any of those eight patients. All thankfully had a relatively unremarkable course clinically and all are currently doing very well. There was mild reductions in LV function, no clinically significant heart failure, and at last known contact, those patients really had recovery of LV function and are essentially back to baseline. Dr. Greg Hundley: Excellent. Well, listeners, we're going to move to another part of the country, and again, Dr. Chris deFilippi is in the Washington metro area. Chris, you also have a case series. Can you describe for us what you were looking at with your study, and then what were your study results? Dr. Chris deFilippi: Greg, first, thank you for having me here today. As a regular listener to Circulation on the Run, it's really a privilege to actually be able to participate and contribute to it. First, I would have to say was a little bit of serendipity. We recognized one case out of the ordinary with respect to suspected myocarditis in early March, and given our location around Washington DC, some of our faculty were former active military and serve in the reserves and one returned and said, "The military is beginning to find a small series of cases." Dr. Chris deFilippi: We've worked hard within our academically oriented independent health system to develop a research clinical trials network, and we called upon our cardiologists and cases started coming forward actually fairly rapidly, drawing upon five hospitals in our network. Combining our efforts with UT Southwestern, we identified seven individuals. They were all men or young adults in their 20s and 30s. Six out of seven had received the mRNA vaccines. Most of them had developed symptoms between three to seven days after their second vaccination. Dr. Chris deFilippi: Very similar to Kathryn's presentation, we did an extensive evaluation, of course including advanced imaging with MRI using the Lake Louise criteria, but also did a lot of serologic measurements. I think it was remarkable that troponin values using still a conventional assay ranged from mild elevations, 0.34 to as high as 44 milligrams per milliliter. Dr. Chris deFilippi: All patients fortunately had resolution of symptoms within several days and returned back to normal life and then all return follow-ups seemed to remain symptom-free. Again, we looked for multiple other etiologies including autoimmune disease, other respiratory infections, and these were all effectively negative. Dr. Greg Hundley: Very nice. Well now, listeners, we're going to head south, down to Dallas, Texas and bring in Dr. James deLemos. James, you also have a case report and did some extensive study, I believe, in your patient in terms of investigating perhaps mechanisms. Could you share with us your study and some of your findings? Dr. James deLemos: Yeah. Thanks, Greg. Ours was like Kathryn and Chris's experience, purely serendipitous. I was on service in late January at our university hospital and we had a case that came in three days after receiving the Moderna vaccine with what appeared to be clearly myocarditis in temporal association with the vaccine. At that time, we reported it to the CDC, but there was really not much, if anything, and so what we decided to do was pull together a translational team. We brought together clinical pathologists, immunologists, infectious disease experts, and a panel of folks to think about how we might get at a potential mechanism, obviously in a highly exploratory fashion because this was one case and at this point we really didn't know whether this was a true causal association or just circumstance. Dr. James deLemos: What we did was really a broad exploratory analysis, comparing our index case with a number of vaccinated controls, COVID infected controls, and normal controls. We did autoantibody panels, cytokine panels. We looked at flow cytometry for cell fractions, and really tried to see if there was a signature for our case that distinguished it from these other control groups. Dr. James deLemos: I think one important thing we didn't see was an exuberant or over exuberant response in terms of the spike antibody. That was also not seen in several other cases from Chris and Kathryn. The antibody response seemed to be in the normal range of what would be expected after the vaccine. We also didn't see broad spread inflammation in our case compared to controls. There were several cytokines that were upregulated, some of which have been reported in myocarditis, and there were some natural killer cell subsets that would seem to be upregulated, and then several autoantibodies as well that have been reported in myocarditis. But interestingly, none of the poor prognosis autoantibodies that had been reported, which may in part, we think, explain why these cases seem to be doing quite well. Dr. James deLemos: I'd emphasize it's one case, so we recognize this is purely exploratory and hopefully will set the stage for other people as they try to investigate this in more depth. Dr. Greg Hundley: Thank you, James. Well, Biykem, you've been spending a large segment of time, the last year, really year and a half, trying to put together for us at the American Heart Association what may be operative in these patients receiving these vaccines, and also really studying COVID-19. It sounds like what we're hearing amongst all three of these, young men, really a myocarditis that develops after the second vaccine. We have typically elevated troponins, there's MRI findings. You've put together a review. Maybe you could start to share with us what have you learned over this past year and a half? Dr. Biykem Bozkurt: Thank you, Greg. As my colleagues have alluded to, the characterization of the presentation is pretty concordant. What I did in the review was to review all the case reports and case series published to date, which summed up to 61 cases. Additionally, I looked at what has been reported by the Vaccine Adverse Event Reporting System by the CDC and their internal analyses, and also looked at the reports that came from Israel as well as the US military, which is a large cohort and population base reporting. Dr. Biykem Bozkurt: The messages for the clinicians, number one, the presentation in most of these reports have been pretty unified in the sense that most patients presented day two or day three after the second dose of mRNA vaccination. Secondly, most if not all had cardiac troponin elevation along with chest pain on presentation. The majority of the patients, more than 90, 95 in the case series, had EKG abnormality, usually with ST elevation. When we're to examine the echo findings, about two thirds or sometimes in the case series about 40% of abnormalities and only a small percentage had LV systolic dysfunction with EF less than 50. Dr. Biykem Bozkurt: When done as was the case in all the case series and case reports, cardiac MRI was always abnormal. They were very self-limited. Important concepts are, these were very self-limited cases. All of them recovered and were discharged and had resolution of their symptoms, biomarker findings as well as imaging findings. Dr. Biykem Bozkurt: Now, let's look at the benefits versus risk concept that was examined at the CDC level. The current reporting in the VAERS system, the Vaccine Adverse Event Reporting System, is about 12.6 cases per million doses of vaccination. This is after 300 million doses being given in the US and about 170 million individuals being vaccinated in the US. Of those, when compared to what we have been expecting in the population, there appears to be a temporal association that the CDC has confirmed. If we were to look at the risk versus benefits ratios, it's very clear that COVID-19 is a deadly disease. It results in mortality even amongst the younger population, somewhere at the order of 0.1 to 1% per 100,000 people being infected. So for 12 to 39 years old, where the myocarditis risk is felt to be higher, still we need to keep in mind, that risk is very low. 12 per million doses, compared to about 0.1 to 1 death for about 100,000 infections. Dr. Biykem Bozkurt: And of course, if we were to add the number of hospitalizations, ICU stays, cardiac involvement, which we know is seen in about 12 to 20% of hospitalized patients by cardiac troponin elevation, as well as multisystem inflammatory syndrome that is seen in young populations, the benefits significantly outweigh the risks. In terms of mechanisms which James has alluded to, the things that are coming as potential signals or hypothesized mechanisms include the following. There could be molecular mimicry between the spike protein and the self-antigens. Currently, that experimental data, antibodies against spike protein have been reported to cross react with human proteins including alpha myogen. Other mechanisms could be vaccine and it making a response triggering a pre-existing dysregulated immunopathological pathway in predisposed patients. But mind you, we don't right now have a pattern of who's predisposed to myocarditis. It doesn't look like comorbidities as we have seen with COVID-19 infection. Dr. Biykem Bozkurt: And in James' case, there was no predisposition to cardiomyopathy identified by a gene variant that are known to be associated, so those were negative in the case reports that James had mentioned. There was increased frequency of autoantibodies in that case report that James had published. Again, this may be in reaction to the inflammation or injury rather than being the cause. It may be the outcome, but still it raises a concern whether autoantibody formation is one of the mechanisms. Dr. Biykem Bozkurt: Male predisposition is a known risk for myocarditis. We've known this even before the vaccine related myocarditis cases. In the experimental as well as population based studies in the past, young males have a higher predisposition than females or older age, and it's thought to be due to the differences related to sex hormones, especially testosterone, being pro-inflammatory. But of course, in the passive vaccine adverse event reporting, we also do know that the chest pain presentation did not appear to be as different among males compared to females and the imaging and studies were done in less frequency in females, so there may be also a bias toward work-up in females which needs to be further examined. Dr. Biykem Bozkurt: The most important message we'd like to put out there is the benefits highly outweigh the risks, but there needs to be recognition that there is such a risk for clinicians, and definitely do an appropriate work-up for patients presenting with chest pain to the emergency room or to the clinical setting for an appropriate work-up to be carried out including EKG, cardiac troponin in all patients, followed by imaging, such as cardiac MRI and/or other imaging as necessary depending on the symptomatology, the age, as well as the findings on the troponin and EKG. And cardiology moment is essential for those ones who are diagnosed with myocarditis. The treatment strategies in the case reports range all the way from non-steroidal colchicine to IV steroids to intravenous immunoglobulin. Probably the way to approach these cases is if it's very self-limited with resolution of symptoms and biomarkers within two or three days, they may not need to resort to very intensive therapy, but if the case is with unrelenting symptoms, persistent biomarker abnormality, an imaging finding higher level of intense geo-treatment with intravenous steroids or IV immunoglobulin may be considered. Dr. Biykem Bozkurt: So far in the published reports, there have not been any bad outcomes such as death and/or requirement for mechanical circulatory support, but again, further research is needed. Dr. Greg Hundley: Very nice, Biykem. Well, listeners, we're going to go back through our authors and just really quickly, Kathryn, Chris, James, Biykem, what study, maybe in 15 seconds, do you think might need to be performed next in this sphere of research? And then second, what's the one point that you think we ought to emphasize as we close out going forward? So, both questions for each author. Kathryn, we'll start with you. Dr. Kathryn Larson: Okay, cool. I think I'll bring a little bit of an imaging bias as that's my personal interest. I'd really like to see a lot of the data that's already out there from these patients both at their baseline studies, and I'd really like to see their follow-up studies in terms of what happens to things like LV function and in terms of their MRI findings. I think that could be really helpful given the amount of weight that imaging has in the diagnosis of these patients. Dr. Kathryn Larson: I think the biggest take-away for me in a lot of these discussions that we were having is, these are very rare issues and incidents when patients are presenting with these, and I think the vast majority of the information we have at hand is that these are self limited, there's good recovery of any decline in LV function, and that I think overall the clinical course is favorable. Dr. Greg Hundley: Very nice. Chris? Dr. Chris deFilippi: First, I shouldn't be promoting my colleague's work, but I've got to say that Biykem's review was terrific. I know I did a lot of background reading in this case presentation. I've gone through that review a couple times and it's clearly, I think, helped my thinking on this topic. As Biykem mentions in that review, the recording of myocarditis can have a number of biases either under or over reporting, basically what's available in the public and what sort of people are thinking about. I think looking at it from a population health standpoint, the risk benefits are so favorable for the benefits of vaccination. We knew that even a month ago, we know that even more today. But I think it would be great to get an understanding, recognizing that there may be cases of unrecognized myocarditis, myocardial fibrosis, at a population level in what we would assume would generally be very healthy, young adult males, do we see more cardiac related hospitalizations over time? Do we see more sudden death? I think we should just affirm that, hopefully we can affirm that isn't the case and keep moving forward. Dr. Chris deFilippi: That being said, I'm still really a big advocate for vaccination and the benefits of vaccination combined with these very small risks. Dr. Greg Hundley: Very nice. James? Dr. James deLemos: I'd say really two avenues for research. I'd echo Kathryn's point that we need longer term follow-up data for patients that have this syndrome. To do that we're going to have to collaborate, because each of us individually see very few cases, because fortunately this is rare, and we're going to need registries that look at longer term follow-up of patients with vaccine associated myocarditis. And then really getting to Chris' point on the front end, I think that's what's needed are prospective studies measuring high sensitivity troponin and cardiac MRI in younger individuals who get vaccinated, so we study them not once they get the disease, but trying to determine whether there might be even less severe versions of myocardial injury that are occurring after the vaccine and try to understand why that's the case, because mRNA vaccines are here to stay. They're remarkable advances. And let's understand what this apparently self limited myocarditis is all about. Dr. James deLemos: The take-home message I'd echo is that this is important and all of us even had angst about recording and talking about this, because we don't want this ever to be misconstrued to suggest that these vaccines, which are absolutely remarkable, don't have a favorable risk benefit, even for our cardiac patients. These data in no way affect the safety and efficacy of the vaccine, even in people with underlying cardiac disease, who are some of the ones that have the greatest priority to get vaccinated. Dr. Greg Hundley: And finally, Biykem. Dr. Biykem Bozkurt: I think I echo all my colleagues' sentiments in the necessity for prospective and imaging and biomarker. The way to do that, as James alluded to, is we should right now develop a consortium for a registry, and we should have a bioregistry. I would urge us to not solely consider it for vaccine related entity, but also COVID-19. So I think we need to straddle the whole concept of COVID-19 itself, the infection plus the vaccinated individuals and follow them in a prospective manner with the known biomarkers, the cardiac biomarkers as well as imaging, but also the thing that is lacking right now is to characterize them with a specific immune cell populations as to what is rising, what kind of response we've seen, with the changes that we're seeing in males and others, and capture further mechanistics, perhaps signaling. Quite a few of this phenotyping is needed in these individuals as well as perhaps a genotyping characterization and maybe a tissue characterization. Dr. Biykem Bozkurt: I think the consortium will need to entail pathologies as well as immunopathology along with biomarkers and imaging. And of course, prospectively following these individuals. As was done in certain other vaccines in the past may give us a totally different signal and prevalence. Dr. Biykem Bozkurt: Take-home message, I fully agree. Being able to get a message of the risk is low compared to benefit. While we're calling for, the necessity for further research is a delicate balance of what the scientists have to straddle. Yes, the vaccine is very safe. It's been shown in numerous, several randomized clinical trials. Current data actually validates that because it's a few cases in millions of doses of the safest vaccine. But for those very few cases, for those very few cases we need to be on the alert and treat them appropriately and not miss those diagnoses. Dr. Biykem Bozkurt: One other message I'm going to share is the rapidly evolving conceptualization of myocarditis. The lymphocytic myocarditis concept that historically was the gold standard characterization of myocarditis with other viruses is, I think, rapidly changing now with the recognition of what we saw with COVID-19 itself, as well as now with the vaccine. It does not seem to be the classical characterization of myocarditis, so again, understanding of myocardial injury, cardiomyocyte injury is now a continuum beyond what we used to call the path to MI and injury, now straddling all the way to a concept of injury that is much different than the lymphocytic myocarditis we've seen with other viruses, which we need to embrace. Dr. Greg Hundley: Very nice. Well, listeners, we want to thank Dr. Kathryn Lawson, Dr. Chris deFilippi, Dr. James deLemos, Dr. Biykem Bozkurt, for this wonderful forum discussion on COVID-19 vaccine associated myocarditis. Dr. Greg Hundley: Well, thank you so much and on behalf of Carolyn and myself, we want to wish you a great week and we will catch you next week On the Run. Dr. Greg Hundley: This program is copyright of the American Heart Association 2021. Dr. Greg Hundley: 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, visit AHAJournals.org.  

FDA 批准MitraClip治疗心力衰竭继发的二尖瓣返流 NEJM 达格列净在射血分数下降的心功能不全的患者中的作用Circulation 恩格列净治疗心力衰竭过程中心脏和肾脏的获益Lancet 支持联合使用ARNI、β受体阻滞剂、盐皮质激素拮抗剂和SGLT2抑制剂作为心衰的新标准治疗Nature PCSK9抑制剂可增强肿瘤的免疫治疗的疗效MitraClip 2019年3月，FDA为MitraClip经导管二尖瓣修复装置增加了新的适应症，用于治疗症状性心力衰竭症状合并继发性或功能性二尖瓣返流（SMR或FMR）。《COAPT研究：经导管二尖瓣修复术治疗心力衰竭患者》New England Journal of Medicine，2018年12月 (1) 左心室功能不全伴有二尖瓣返流的心力衰竭患者预后较差。研究的目的是评价经导管二尖瓣修复术是否能改善预后。研究纳入了心衰、合并中重度二尖瓣返流患者614人，这些患者在使用指南指导下的、最大剂量药物治疗后仍有症状，随机分为经导管二尖瓣修复术加药物治疗（器械组）和单纯药物治疗组（对照组）。器械组24个月内因心力衰竭住院的比例为35.8/100人年，对照组为67.9/100人年（风险比 0.53，P < 0.001）；器械组24个月全因死亡率为29.1%，对照组为46.1%（风险比 0.62，P10mm2或返流量>30ml）的患者，EF介于15%-40%，随机分入器械组（经皮二尖瓣修复加药物治疗）和对照组（单纯药物治疗）。这篇文章汇报了24个月的随访结果24个月时，器械组全因死亡和心衰住院的患者占63.8%，对照组为67.1%（风险比 1.01，无统计学意义）。器械组的全因死亡率为34.9%，对照组为34.2%（风险比 1.02，无统计学意义）。器械组心衰住院比例为55.9%，对照组61.8%（风险比 0.97，无统计学意义）。结论：在心力衰竭合并严重二尖瓣返流的患者中，经皮二尖瓣修复加药物治疗与单纯药物治疗相比，在2年内心衰死亡或住院的风险没有显著降低。小羽点评：MitraClip治疗心力衰竭合并继发性或功能性二尖瓣返流患者的两项大型临床研究COAPT研究和MITRA-Fr研究的结果并不一致，但是FDA根据COAPT研究的结果还是批准了MitraClip治疗心衰的适应症。现在也有文献讨论这种治疗心衰策略的机制，但似乎仍不足以解释我心中的疑惑——这种治疗策略究竟有没有大规模推广的理论基础和确凿的证据。慢性心功能不全治疗 —— SGLT2抑制剂钠-葡萄糖协同转运蛋白2（SGLT2）表达于肾近端小管，介导约90%的滤过葡萄糖的重吸收。SGLT2抑制剂促进肾脏对葡萄糖的排泄，因此可降低血糖、降低血压和体重，通常不会导致低血糖。2020年5月，FDA批准达格列净用于治疗射血分数降低的心衰患者，用以降低心血管死亡和因心力衰竭再住院的风险。这是SGLT2抑制剂中首个获批，用于治疗射血分数降低、纽约心功能分级II-IV级的患者。《DAPA-HF研究：达格列净在射血分数下降的心功能不全的患者中的作用》New England Journal of Medicine，2019年11月 (3)在这个III期、安慰剂对照研究中，纳入了选取了4744名患者纽约心功能分级II-IV级的、射血分数低于40%的患者接受达格列净10mg qd或安慰剂治疗。随访18.2个月，达格列净治疗组主要心血管事件的风险比0.74；心衰恶化的风险比为0.70；心血管死亡风险比0.82；全因死亡危险比为0.83。糖尿病与非糖尿病患者相似；与容量不足、肾功能不全和低血糖相关的不良事件发生频率在治疗组之间没有差异。结论：达格列净可减少心衰恶化或心血管死亡的风险。《DAPA-HF研究亚组分析：达格列净对有或没有糖尿病的射血分数下降的心功能不全的患者的治疗作用》JAMA，2020年3月 (4)DAPA-HF研究中有54%的参与者并未患糖尿病。其中糖尿病患病情况分三种：（1）患糖尿病（有糖尿病史或糖化血红蛋白≥6.5%，n=2,139），（2）前驱糖尿病（糖化血红蛋白5.7%～6.5%；n=1,748），（3）没有糖尿病（糖化血红蛋白＜5.7%；n=839）。患糖尿病的参与者中有更多黑人，心功能更差，更可能有缺血性改变。试验结束时（中位随访时间为，16.6～18.0个月），糖尿病、前驱糖尿病和无糖尿病亚组的风险均出现了相似且与达格列净相关的显著降低（风险比分别为0.75、0.74和0.67；无交互作用）。最常见的不良反应是容量不足和肾损伤，其发生率与治疗或糖尿病状况不相关。结论：射血分数降低的心衰患者中，即使没有糖尿病，使用达格列净仍可以显著降低了心衰恶化或心血管死亡的风险。《DAPA-HF研究亚组分析：达格列净和利尿剂联用治疗射血分数下降的心功能不全的研究》Circulation，2020年7月 (5)DAPA-HF研究中，根据患者是否在服用利尿剂，将患者分为无利尿剂组、利尿剂40mg/d组。这四组患者中，达格列净降低了这些亚组的主要终点时间的风险，风险比分别为0.57、0.83、0.77和0.78。达格列净疗效和治疗的耐受性在各个亚组是一致的。在随访期间，大多数患者的利尿剂剂量没有变化。结论：达格列净在各个利尿剂亚组中的安全性和有效性是一致的。《DAPA-HF研究亚组分析：达格列净和沙库巴曲缬沙坦联用治疗射血分数下降的心功能不全的研究》JACC Heart Failure，2020年7月 (6)DAPA-HF研究中，根据患者是否在随机服用沙库巴曲缬沙坦进行分析。其中10.7%的参与者在基线时接受了沙库巴曲缬沙坦治疗， 这些患者通常来自北美和欧洲，心功能通常更差、血压更低。心血管死亡或心衰恶化的风险比，在服用沙库巴曲缬沙坦人群中为0.75；在未服用沙库巴曲缬沙坦人群中为0.74。次要终点和安全终点，包括与低血容量有关的事件，两组都是相似的。结论：两种药物联合使用可进一步降低射血分数下降的心功能不全患者的发病率和死亡率。《DAPA-HF研究亚组分析：达格列净对门诊射血分数降低心衰的恶化的影响》Circulation，2020年10月 (7)DAPA-HF研究中，根据心衰住院、心衰恶化或心血管死亡为终点事件进行亚组分析，达格列净组22.2%的患者出现终点事件、安慰剂组为28.8%，风险比0.73，P

This week's episode features author Peter Schwartz and Associate Editor Sami Viskin as they discuss the article "Exercise Training-Induced Repolarization Abnormalities Masquerading as Congenital Long QT Syndrome." TRANSCRIPT BELOW: Dr. Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and it's editors. We're your co-hosts, I'm Dr Carolyn Lam, associate editor from the National Heart Center and Duke National University of Singapore. Dr. Greg Hundley: And I'm Dr. Greg Hundley, associate editor, director of the Pauley Heart Center at VCU Health in Richmond, Virginia. Well, Carolyn, this week's feature, we're going to learn a little bit more about long QT syndrome and whether or not those that are athletes should continue exercise training. Maybe some can and before, we thought that they couldn't. But before we get to that, how about we take a look at some of the other papers in this issue. Dr. Carolyn Lam: Wow, that was a good hook, Greg. But yes, I want to tell you about this first paper, which is all about weight loss and changes in body composition. So, we know that intentional weight loss is associated with a lower risk of heart failure and atherosclerotic cardiovascular disease, especially among patients with type 2 diabetes. However, what is the contribution of baseline measures and longitudinal changes in fat mass versus lean mass and waist circumference to that risk of heart failure and myocardial infarction in patients with diabetes? Dr. Carolyn Lam: Well, investigators led by Dr. Pandey from UT Southwestern and colleagues evaluated more than 5,000 adults from the Look AHEAD Trial without prevalent heart failure. Fat mass and lean mass were predicted using validated equations and compared with DEXA measurements in a subgroup. Adjusted Cox models were then used to evaluate associations of baseline and longitudinal changes in fat mass, lean mass, and waist conference over one and four years follow up with the risk of overall heart failure, HFpEF, and HFrEF and myocardial infarction. Dr. Greg Hundley: Interesting, Carolyn. So, what did they find? Dr. Carolyn Lam: So, among patients with type 2 diabetes and who were overweight or obese, fat mass and lean mass could be estimated using anthropometric equations with good overall agreement compared with DEXA, so that's the first finding. Next, a decline in fat mass and waist conference, but not lean mass, were each significantly associated with a lower risk of heart failure, but not myocardial infarction. Dr. Carolyn Lam: Furthermore, a decline in waist circumference was significantly associated with a lower risk of HFpEF, but not HFrEF. Fatness and waist circumference may represent key modifiable targets for lifestyle interventions to reduce the risk of heart failure with preserved ejection fraction in type 2 diabetes. Cool, huh? Dr. Greg Hundley: Yeah. Very nice, Carolyn. Well, my first paper comes from Professor Davide Capodanno, and it's examining self-expanding bioprostheses for TAVR. So, Carolyn, there are few randomized trials comparing these bioprostheses for transcatheter aortic valve replacement or TAVR, and no trials have compared TAVR bioprostheses with the supra-annular design. So, this SCOPE 2 trial was designed to compare the clinical outcomes of the ACCURATE neo and the CoreValve Evolut valves. Dr. Greg Hundley: Now, it's a randomized trial performed at 23 centers in six countries between April 2017 and April 2019. And patients greater than 75 years with an indication for transfemoral TAVR as agreed by the heart team were randomly assigned to receive treatment with either the ACCURATE neo, so there are 398 of those patients, or the CoreValve Evolut bioprostheses, also 398 patients. The primary endpoint powered for non-inferiority of the ACCURATE neo valve was all-cause death or stroke at one year. The key secondary endpoint powered for superiority of the ACCURATE neo valve was new permanent pacemaker implantation at 30 days. Dr. Carolyn Lam: Okay. So, what were their results? Dr. Greg Hundley: Well, Carolyn, the transfemoral TAVR with the self-expanding ACCURATE neo did not meet non-inferiority compared to the self-expanding CoreValve Evolut in terms of all-cause death or stroke at one year. And was associated with a lower incidence of new permanent pacemaker implantation. In secondary analyses, the ACCURATE neo was associated with more moderate or severe aortic regurgitation at 30 days and cardiac death at 30 days and one year. Cardiac death at 30 days was 2.8% versus only 0.8% with the CoreValve Evolut. And moderate or severe aortic regurgitation at 30 days was 10% versus only 3% and they were significantly increased again in that ACCURATE neo group. Dr. Carolyn Lam: Wow. Okay. Thanks for that, Greg. Well, my next paper is from the basic science world. Dr. Colucci from Boston University Medical Center and colleagues tested the hypothesis that sarco/endoplasmic reticulum, calcium ATPase or SERCA, which is a major regulator of calcium homeostasis in the heart, whether or not it plays a critical role in mediating mitochondrial calcium and mitochondria-dependent apoptosis in response to reactive oxygen species. Dr. Carolyn Lam: So, in adult rat ventricular myocytes expressing an oxidation-resistant mutant of SERCA in which the cysteine-674 was replaced by serine. Mitochondrial calcium and the rise in mitochondrial calcium to exposure to an oxidant were decreased as was apoptotic myocyte death by mitochondrial pathways. Mice with the same SERCA mutation were protected from adverse cardiac remodeling, apoptosis, and progression to heart failure following chronic aortic constriction. Dr. Greg Hundley: Mm-hmm (affirmative) Carolyn, so this is another one where I get to ask you, what were the take home messages and what were the clinical implications? Dr. Carolyn Lam: I thought you'd ask that, Greg. So, these findings indicate that by contributing to sarcoplasmic reticulum calcium load, the chronic oxidative activation of SERCA may play a critical role in promoting the adverse effects of hemodynamic overload leading to pathologic remodeling. These findings illustrate the importance of post-translational modifications of SERCA and raise the possibility that the expression of a redox-insensitive form of SERCA may be of value in the treatment of heart failure. Dr. Greg Hundley: Very nice, Carolyn. Well, my next paper also comes from the world of basic science and looks into the mediators of atrial fibrillation. So, as some background, Carolyn, ibrutinib is a Bruton's tyrosine kinase inhibitor with remarkable efficacy against B-cell cancers. But it also increases the risk of atrial fibrillation, which remains poorly understood. Dr. Greg Hundley: So, the investigators performed electrophysiologic studies on mice treated with ibrutinib to assess the inducibility of atrial fibrillation. In human subjects, again, one of the strengths of some of these basic science papers in Circulation, the pharmacovigilance database or VigiBase, was queried to determine whether drug inhibition of an identified candidate kinase was associated with increased reporting of atrial fibrillation. Dr. Carolyn Lam: Oh, that's really interesting, Greg. So, it seems like these authors were working toward understanding the mechanism of atrial fibrillation in those receiving ibrutinib. So, what did they find? Dr. Greg Hundley: Right, Carolyn. So, the authors found that using chemoproteomic profiling they were able to identify a short list of candidate kinases that was narrowed by additional experimentation, leaving C-terminal Src kinase or CSK, as the strongest candidate for ibrutinib-induced atrial fibrillation. Cardiac-specific CSK knockouts in mice led to increased AFib, left atrial enlargement, fibrosis, and inflammation, phenocopying ibrutinib treatment. Disproportionality analyses in VigiBase confirmed increased reporting of AFib associated with kinase inhibitors blocking CSK versus non-CSK inhibitors with reporting odds ratio of eight. So, Carolyn, perhaps CSK inhibition is the mechanism by which ibrutinib leads to atrial fibrillation. Dr. Carolyn Lam: Wow. That is convincing. Well, there are other really nice papers in today's issue. First, there's a research letter by Dr. Iglesias on the effects of fentanyl versus morphine on ticagrelor-induced platelet inhibition in patients with STEMI, the PERSEUS randomized trial. There's also a research letter by Dr. Young entitled the characteristics and outcome of COAPT eligible patients in the MITRA-FR trial. Another research letter by Dr. Zhang on specific modified mRNA translation system. Dr. Greg Hundley: Very nice, Carolyn. Well, I've got an exchange of letters by Dr. Spal, Whitlock, and Kebabs regarding the article, Impact of Left Atrial Appendage Exclusion on Short-Term Outcomes in Isolated Coronary Artery Bypass Graft Surgery. And then our own Mark Link discusses changes for practicing physicians regarding the new AFib guidelines. Dr. Greg Hundley: And finally, Dr. Vera Bittner has a perspective piece on the new 2019 ACC/AHA Guidelines on the primary prevention of cardiovascular disease. So, this new primary prevention guideline two fills a critical gap by pulling together and updating, as appropriate, guidance on nine topic areas of risk assessment, diet, exercise and physical activity, obesity, type 2 diabetes mellitus, blood cholesterol, hypertension, smoking cessation, and aspirin use. Dr. Carolyn Lam: Nice. Well, Greg, guess what? That brings us to the last issue in 2020. Can you believe it, Greg? It's been just so great working with you. It's been such a privilege working with Circulation. And, drum roll, new for 2021, Circulation on the Run is returning with a new format. Watch out for it. Let me give you a hint, it's going to come with a double feature per issue. Isn't that great, Greg? Dr. Greg Hundley: Absolutely. Some of the things that you hear folks really enjoy those opportunities we have with authors to review their papers. Well now, with many of the issues next year, we'll have two feature discussions. Dr. Carolyn Lam: Exactly. So, you've been listening to Circulation on the Run, but we've been listening to you, too. So, join us again in 2021 for our new features and new format. Thanks. Dr. Greg Hundley: And yes, Carolyn, but first, we've got to go and listen to this issue's feature discussion and talk about that long QT syndrome, exercise training-induced repolarization abnormalities. They can masquerade, perhaps, as long QT syndrome. Dr. Carolyn Lam: Cool. Dr. Greg Hundley: Welcome, listeners, to our feature discussion today. And we're very fortunate, we have Prof. Peter Schwartz from Istituto Auxologico Italiano in Milan and our own associate editor, Dr. Sami Viskin from Tel Aviv Medical Center. And we're going to be reviewing exercise training induced repolarization abnormalities, masquerading as congenital long QT syndrome. Well, first Peter, we'd like to start with you. And could you tell us, or provide us with some of the background information of why you wanted to perform this study and what hypothesis did you want to address? Prof. Peter Schwartz: The background is a very simple and I've been involved in the long QT syndrome since exactly 50 years. And as a partial result of that, I developed the idea that usually I... despite my making many errors in many areas, usually I don't miss the diagnosis of long QT syndrome. As a matter of fact, the study that you're publishing now is the result of a complete serendipity. It was not planned. We had to no hypothesis. It simply started because at one point I entered the impression that we might've made a diagnostic error and this bothered me very much. Prof. Peter Schwartz: It all started about eight, 10 years ago. When in some cases of our patients in whom we had made a clear diagnosis of long QT syndrome. At their yearly controls, we found that the LQT had been completely normalized. So I was pretty upset about it because I couldn't understand it. And my first reaction a natural reaction was to blame my associates, "We have made a mistake. You've did an error. There was an error in measurement." But as a matter of fact, there were no errors. Prof. Peter Schwartz: So I start thinking, "What the hell is going on here?" Now we are in a fortunate position because due to my long standing activity in the long QT syndrome, we are a referral center for all cases or most cases in Italy where people are suspected have the long QT syndrome. In Italy by law, anyone who wants to practice any type of sport at an amateur level or pro-competitive level, needs to have an eligibility certificate. So they have to go to sport doctors and it eases when the problems arise because not infrequently these doctors with somewhat limited experience in diagnosing prolongation and abnormalities in the QT intervals, are worried to make a mistake because a mistake can be a fatal one if the subject allow them to practice pause or die suddenly on to field. So they tend to refer them to us. Prof. Peter Schwartz: And so the advantage in my position was that we had a large number of these kids or young people coming to us. When I started to realize that it was not one accident, but another accident, another situation where these young people who clearly had to stop training in an intensive way, because they will no longer allowed by the sport doctors to practice sport. And the normalization of the T-wave abnormalities of the QT interval. I said, "Well, I mean, there must be something here." Prof. Peter Schwartz: So we start collecting the data, increasing the numbers, and I think it should be evident there was no design. I mean, it was a clinical observation that was evolving with time, but with adequate numbers. And then of course at one point we start following it more carefully, everything. And these led to the actual numbers that, in my opinion, were sufficiently strong to junior agents in need to publish it and to give a message because essentially this situation in one in which is very possible that even good and experienced doctors make a mistake. And the mistake could be a very bad thing, because if you miss the long QT syndrome and there is, of course, the patient is at risk of dying. But if you leave it, someone is affected and he is not affected, you are affecting his or her quality of life because they cannot practice sport, you generate anxiety. So a proper diagnosis is important. This was the basis of our study. Dr. Greg Hundley: Very good. So, it sounds like you're going to be performing a cohort study. Can you describe for us a little more specifically, how many subjects did you include? And who did you include in this cohort? And what measurements did you address? Prof. Peter Schwartz: So essentially we looked at the consecutive cases, sent to us by sport doctors with a suspicion of long QT syndrome. They were, if I remember, correctly 310 such individuals about 100 were found not to have the long QT syndrome. And these doctors were concerned they made the wrong measurement and measurement error. All the things that happened that are very well-known. About the remaining 200 in, I think about 120, we had a genetic confirmation of the long QT syndrome. We found disease causing mutation. So, that was pretty clear. Prof. Peter Schwartz: Then we had a group of individuals who are genotype-negative. We know very well. I mean, I proposed this thing in 1979, 1980, confirmed it in 1999, that there are some individuals affected by the long QT syndrome. But whoever I did a normal QT interval and that's a possibility, who are genotype-negative. Prof. Peter Schwartz: So, it's not surprising that in some cases we have genotype-negative individuals, but with a pattern so clear in terms of long QT syndrome that will make it to diagnosis. Within this group of genotype negative, there was another, let's call it a subgroup. I think it was about 15, 18% of the entire group who were genotype-negative, no family, sorry, neither had an event, a typical, absolutely typical electrocardiographic pattern with a fairly long QT interval QTc in the range of 490. So clearly prolonged significant repolarization abnormalities. Prof. Peter Schwartz: But when they were stopped in terms of exercise within three, four or five months, their pattern normalized completely, the QTc went back to normal, repolarization abnormalities disappeared. So this is the group on which we did focus and focusing for the next studies. And in some of them, when we told them, "You don't have the long QT syndrome, is a reaction that we interpret is due to the mechanical stretch of your heart because of very intense exercise training." Prof. Peter Schwartz: Some of them did return to practice sport in a very intensive way and all these patterns reappeared again, proving, I think this was the most important point. I mean, shows that you can go back and forth if you stretch the heart in this way, the abnormalities reappear. Prof. Peter Schwartz: So this is the essence of the study that carries in my opinion, a number of practical implications, because I think that now, when we are dealing with these youngsters, where we would be making a complete diagnosis. In some cases, I actually started even beta blockers, which is... I mean, afterwards it turns out to be an error and it bothers me, because I don't like to make an error with these patients. But they were so clear. I mean, I could have bet anything that they are affected by the long QT syndrome. But within four or five, six months, they were completely back to normal. Prof. Peter Schwartz: So the essence of the studies that we think the youngsters who practice intensely sport, some of them react to these physiological similar situation in an abnormal way. In analogies like with the food allergy. I mean, if you take something that bothers you and the point is, then you just avoid it. With exercise, of course is more difficult for other reasons, but probably it's the quantity of exercise. Prof. Peter Schwartz: Now, one change I've observed in recent years is that for youngsters practicing sports, a lot of things have changed. I've done a lot in sports myself soccer, tennis before moving toward golf. But in our days we were just playing, yes, we were playing a lot. But what has changed now is that all these kids have a trainer. They are sent for regular exercise two hours a day, five days a week. And that is probably too much for some of them. Prof. Peter Schwartz: So we need to recognize that there are certain individuals who, for whatever reason, I suppose that there is a genetic predisposition tend to react to these excessive amount of exercise training with abnormalities in their electrocardiogram. And for them, probably the logical thing is to reduce the amount of exercise. I would not stop it completely, they should reduce the dose and then have probably a normal life. Prof. Peter Schwartz: This is also raises the analogy with drug-induced long QT syndrome. When you have a parent in normal individuals who take any drug that contains an IKr blocker and they could develop to a certain point and the long QT syndrome. Now the situation with exercise is probably not so severe. I don't think the risk is so high, but clearly it is people have a tendency to react to  possibly a variety of stimuli with QT prolongation. so they should be more careful about it. Dr. Greg Hundley: You know, I'll tell you, I think the world thanks you for your just observational skills and working through that whole situation that you observed in a very precise, organized fashion to bring us this interesting result. Well, Sami, can you help... Obviously this caught your eye as an associate editor at Circulation. What else attracted you to this study? And how would you like to comment on what Dr. Schwartz has just provided to us? Dr. Sami Viskin: Well, in Circulation, we were immediately attracted to this study, especially coming from Peter. Peter has been a pioneer in the entire area for long QT for many, many years. We call him Mr. QT because of his contributions to the field. So we're immediately interested in the paper, which is fascinating. It came a few months after we had reviewed a different paper that deals with patients who have the positive-phenotype, for long QT syndrome and have negative-genotype. Dr. Sami Viskin: That was a paper published in the July issue of Circulation with senior author Connie Bezzina. They performed a genome-wide association study to 1,800 patients with long QT, and they compared them with 10,000 healthy individuals. And what they found in these patients who represented 11% of the entire long QT syndrome population was that even though they do not have mutations, they tend to have several genetic variance together. None of them is severe enough to cause the disease but present by itself when they were in their group together in a single individual, then they create the phenotype of long QT syndrome, which is as severe as the phenotype of those who have bona fide mutations.   Dr. Sami Viskin: So, that article was like the background for this one. And in fact, one of the arguments one could do is that the athlete's described by Peter could just have phenotype-positive, genotype-negative long QT, but what Peter would make sure to stress is that they do have electrocardiogram, but not only they do not have symptoms, they have a low pre-test probability of having the disease because they were discovered by screening and also they have a negative family history. So it's a different group of individuals what Peter is describing here. And time will tell. I mean, I'm sure we will be seeing more publications on this, and I will tell you, it's probably that we just looking at a new form of acquired long QT syndrome. Time will tell. Dr. Greg Hundley: Very nice. Just briefly, both gentlemen, maybe in 20 seconds or so, what do you think is the next study that needs to be performed in this new group that's been discovered? Prof. Peter Schwartz: Greg, we have already started the next study. We are going to compare 700 relatively younger athletes who have intensive exercise and who have a completely normal QTc and completely normal T wave to all our subjects that have defined these phases in our study that performing a similar level of exercise show these changes. And then we are collecting their DNA, and we're going to have an whole exome study for the possibility of identifying some genetic markets that might predispose to something like this. Prof. Peter Schwartz: One possibility that I'm interested in is the possibility that the underlying mechanism, maybe something related to the so-called sex activated trainers, which might lead to an increase in intracellular calcium and produces alterations. There are other possibilities, but this is one. And in doing this study, we are also going to begin to look at echocardiography and imaging to see if there are different patterns in terms of mechanics that might contribute to explain. Prof. Peter Schwartz: So the point is that on the one hand we wanted and we did confirm the clinical data. So, we know that we are dealing with a factor and we think that's a fact as practical implications for management. Now, the next questions, which I wish to attack as well is why is it, what is the underlying mechanisms? Dr. Greg Hundley: Very good, Sami. Dr. Sami Viskin: That exactly the direction we were expecting to see if they have a similar polygenic risk score factor as in the study by Bezzina. Dr. Greg Hundley: Very nice, well listeners, this has been a wonderful discussion. And we also want to thank Dr. Peter Schwartz for all of his efforts for many years in this area of long QT syndrome and bringing this new finding to light that there is now an observation that not necessarily are all long QTs. Number one of the 300 subjects, 100 actually didn't have it. And then there are some that are phenotype-positive, but not genotype-positive. And we have more to learn about the variance that swings with the presence of the long QT after strenuous exercise. Well, on behalf of Carolyn and myself, we want to thank Peter, thank Sami Viskin and wish all of you a great week. And we will catch you next week on the Run.   This program is copyright the American Heart Association, 2020.  

Commentary by Dr. Valentin Fuster

Tessa Lau, founder and CEO of Dusty Robotics, updates us on the FieldPrinter building layout robot. She discusses how the company pivoted away from its initial product idea, its custom localization, mapping and navigation technology, building relationships with builders, and scaling its field operations team. We also discuss the expansion of Waymo's driverless robotaxi program around Phoenix. Where will the service head to next and when? We discuss. Bert Swift and Blair Locke, CEO & Co-founder of Coapt, join us to discuss the state of robotic prosthetics. Bert, who lost an arm to childhood cancer, shares his story and how a robotic prosthetic has changed his life.

In this week’s episode Ankur Kalra asks Dr Suzanne J Baron, Director of Interventional Cardiovascular Research at Lahey Hospital & Medical Center: How do we measure the value of a novel technology? During her interventional cardiology fellowship, Dr Baron became fascinated by the implementation of novel technologies. She earned her degree in Clinical Epidemiology and spent a year working at the FDA’s Device Evaluation unit. In 2019 Dr Baron presented the results of her late-breaking trial, COAPT. Ankur invites Suzanne to discuss the economic analysis of the study and to give a short introduction to cost-effectiveness analysis. Suzanne provides an overview of the trial and they talk about the importance of understanding the value and benefits of new devices from both the patient and the health-economic point of viewpoint. What convinced Dr Baron to become an interventional cardiologist? How does Dr Baron interpret the results of the COAPT trial in light of MITRA FR? What is good value from a health-economic perspective? Tune in to listen to this week’s episode of Parallax. Hosted by @AnkurKalraMD. Produced by @RadcliffeCARDIO. Submit your questions to Ankur via: podcast@radcliffe-group.com.

Commentary by Dr. Valentin Fuster

Commentary by Dr. Valentin Fuster

Researchers examine whether Transcatheter Mitral Valve Clip can improve clinical outcomes in patients with severe functional mitral valve regurgitation.

Suzanne Baron and C. Michael Gibson discuss important new details from these two structural heart disease trials.

Cardiovascular experts, Drs. JoAnn Lindenfeld, Javid Moslehi and Richa Gupta from Vanderbilt University Medical Center and Dr. Enrico Ammirati from Milan, Italy join Amit and Dan for a two part discussion about all things to consider for myocarditis in general (part 1) and COVID-19 myocarditis and heart transplantation in the COVID-19 era (part 2). Flutter Moment by Barrie Stanton (RN). On the CardioNerds Myocarditis page you will find podcast episodes, infographic, youtube videos, references, tweetorials and guest experts & contributors, flutter stars and so much more. Take me to the Myocarditis Series Page  Take me to the COVID-19 Series Page Take me to the Episode Topics Page Dr. JoAnn Lindenfeld, is a Professor of Medicine and the Director of Heart Failure and Heart Transplantation Section at Vanderbilt Heart and Vascular Institute.  She is the past president of the Heart Failure Society of America and serves on editorial boards of numerous journals including JACC, JACC Heart Failure and JHLT.  She is also a member of the AHA/ACC/HFSA heart failure guideline writing committee and was previously chair of the HFSA practice guidelines for the 2006 and 2010 guidelines. In addition to this she’s been an investigator in multiple large-scale clinical trials including the COAPT trial and has served on numerous steering committees, end point committees and data and safety monitoring committees. She is the author of a more than 300 original papers, reviews, and book chapters in the field of heart failure and heart transplantation. Dr. Javid Moslehi is an associate professor of medicine at Vanderbilt University Medical Center where he is the director of the cardio-oncology program.  He is a clinical cardiologist and basic/translational biologist interested in cardiovascular complications associated with novel molecular targeted cancer therapies and the implications of these on our knowledge of basic cardiovascular biology. At Vanderbilt he runs an independent basic and translational research laboratory and program with a focus on signal transduction in the myocardium and vasculature as well as establishing pre-clinical models of cardiotoxicity involving novel targeted oncologic therapies. Dr. Enrico Ammirati is an assistant professor of cardiology and advanced heart failure and transplant cardiologist in Milan, Italy at the Niguarda Hospital with a special research interest and expertise in acute myocarditis and acute heart failure.  He is a fellow of the European Society of Cardiology and has won numerous awards, he has also published incredibly important work on the distinction between fulminant and nonfulminant myocarditis and the prognostic implication of histologic subtypes.  His research interests also include the role of adaptive immunity in heart transplantation and atherosclerosis and he is the author of well over 100+ peer reviewed publications.

Commentary by Dr. Valentin Fuster

CEO and co-founder of Coapt, Blair Lock, discusses the focus of his work in the field of prosthetic control. Tune in to learn the following: How the Coapt control system is different than and superior to traditional systems of prosthetic control Why it's so important for functionality to train the system to recognize when the user is not performing a prescribed motion How the future development of subcutaneous sensors could significantly improve the muscle signals detected and decoded by the Coapt control system Coapt is focused on the control of upper limb powered prosthetic devices. This means that they don't make anything that you necessarily see; they make the control system that operates behind the scenes. The system is a finely-tuned neurological decoder that takes signals from the human body and converts them to control commands in real time for robotic hands, wrists, and elbows. Lock explains the physiology of muscle contraction and movement, describing processes that emit a “concert of noise and information” at a low electrical level that is detected by the Coapt system and then used to teach algorithms to learn the personalized “music” of each wearer. In fact, it is the user that teaches the device what is intuitive to them, making the prosthesis even more functional and tuned to the individual. Interested in learning more? Press play and check out https://www.coaptengineering.com/announcement.html.

Vanderbilt fellows, Richa Gupta and Jessica Huston, interview past HFSA president Dr. JoAnn Lindenfeld, Director of Heart Failure and Heart Transplantation Section at Vanderbilt Heart and Vascular Institute about the nuts and bolts of cardiac transplantation. Topics discussed include organ allocation, recipient selection, high risk donors, short and long term complications, and what non-transplant physicians should know about immunosuppressive medications. 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 Dr. JoAnn Lindenfeld, is a Professor of Medicine and the Director of Heart Failure and Heart Transplantation Section at Vanderbilt Heart and Vascular Institute.  She is the past president of the Heart Failure Society of America and serves on editorial boards of numerous journals including JACC, JACC Heart Failure and JHLT.  She is also a member of the AHA/ACC/HFSA heart failure guideline writing committee and was previously chair of the HFSA practice guidelines for the 2006 and 2010 guidelines. In addition to this she’s been an investigator in multiple large-scale clinical trials including the COAPT trial and has served on numerous steering committees, end point committees and data and safety monitoring committees. She is the author of a more than 300 original papers, reviews, and book chapters in the field of heart failure and heart transplantation. Dr. Richa Gupta completed medical school at the Johns Hopkins School of Medicine and stayed on for internal medicine training in the Osler Residency Program at the Johns Hopkins Hospital.  She is currently a third-year cardiology fellow at Vanderbilt University Medical Center where she will also be pursuing fellowship in advanced heart failure and transplant cardiology next year.  Her current interests include post-transplant outcomes, the genetics of tachycardia-induced cardiomyopathy, the sequelae of mechanical circulatory support and applications of cardiac MRI. She also loves teaching the housestaff and medical students and getting them excited about all things heart failure.  Outside of the hospital she loves horror movies, food, travel and good exercise. Dr. Jessica Huston is an Advanced Heart Failure and Cardiac Transplant fellow at Vanderbilt University Medical Center where she also completed her Cardiovascular Medicine fellowship and served as chief fellow. Prior to her time at Vanderbilt she completed residency at the University of Utah. Her clinical and research interests include pulmonary vascular remodeling in heart failure, pulmonary hypertension and right ventricular failure. Outside the hospital she enjoys exploring the outdoors with her son.

In our final episode of the year, Ankur has an long conversation with Sukh Nijjer from Imperial College London about the most impactful, exciting and controversial clinical trials of 2019. Sukh and Ankur also discuss how these trials might change practice in the future, and how practice patterns and decisions differ between the US and the UK. In light of an emerging trend of shared decision making between physicians of different specialities and patients with a vast amount of information at their fingertips, Sukh and Ankur examine what tools they use to reconcile the growing data from clinical trials. Trials discussed in detail include those presented at the ACC in New Orleans: PARTNER 3 & Evolut Low Risk on TAVR/TAVI, and SAFARI & COAPT on radial vs femoral access; presented at the ESC in Paris: THEMIS and ISAR-REACT 5 on DAPT post-PCI, DAPA-HF on SGLT2i’s for heart failure, and COMPLETE on PCI of non-culprit lesions in STEMI; presented at TCT in San Francisco: TWILIGHT on DAPT post-PCI, and EXCEL at 5 years on PCI vs CABG in left main CAD; and finally, presented at AHA in Philadelphia: ISCHEMIA on medical vs invasive approaches in ischemic events. Submit your question to Ankur via: podcast@radciffe-group.com. Hosted by @AnkurKalraMD. Produced by @RadcliffeCARDIO.

Commentary by Dr. Valentin Fuster

Dr Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and its editors. I'm Dr Carolyn Lam, associate editor from the National Heart Center and Duke National University of Singapore. Dr Greg Hundley: And I'm Dr Greg Hundley, associate editor from the Pauley Heart Center in Richmond, Virginia, from VCU Health. Dr Carolyn Lam: You know what, Greg, I may have a hoarse voice today and I'm a little bit scratchy, but my goodness, I couldn't be more excited about this issue. It's the TCT issue. Dr Greg Hundley: Well Carolyn, I cannot wait to discuss with our listeners the feature article that compares Apixaban and a P2Y12 inhibitor without Aspirin, versus regimens with Aspirin in patients with AFib who have ACS, whether managed medically or with PCI, or also those undergoing elective PCI that experience regimens that include vitamin K antagonists, aspirin, or both, but more to come later. Carolyn, should I start with my first discussion article and we grab a cup of coffee? Dr Carolyn Lam: You bet, Greg. Dr Greg Hundley: So my first article is from Seung-Jung Park from the Asan Medical Center at the University of Ulsan College of Medicine. So Carolyn, here's our first quiz question. In terms of Ticagrelor, have studies been performed in those from Asia evaluating bleeding risk? Dr Carolyn Lam: You know, I have to admit, Greg, I'm not totally familiar with the literature, but I do know that it's a very important question for us practicing in Asia. We have a perception that the bleeding risk, especially intracranial bleeding, may be higher in Asians. Dr Greg Hundley: Absolutely. Well, in this multicenter trial, 800 Korean patients hospitalized for acute coronary syndromes with or without ST elevation, and intended for invasive management, were randomly assigned to receive in a one to one ratio, Ticagrelor with a 180 milligram loading dose, and then 90 milligrams twice daily, or Clopidogrel with a 600 milligram loading dose and 75 milligrams daily thereafter, and the primary safety outcome was clinically significant bleeding, which was a composite of major bleeding or minor bleeding according to the PLATO outcomes criteria at 12 months. Dr Carolyn Lam: Oh, so what did they find? Dr Greg Hundley: Well Carolyn, at 12 months, the incidence of clinically significant bleeding was higher in the Ticagrelor group than in the Clopidogrel group. So it was 11.7% versus 5.3, and that included major bleeding and fatal bleeding. They were also higher in the Ticagrelor group. The incidents of death from cardiovascular causes, myocardial infarction or stroke, was not significantly different between the Ticagrelor group and the Clopidogrel group, although there was a strong trend toward a higher incidence in the Ticagrelor group with a P value of 0.07. So consequently, Carolyn, these results identified safety concerns regarding bleeding complications of standard dose Ticagrelor in East Asian, Korean patients with acute coronary syndromes, and therefore large adequately powered randomized trials are needed to determine the optimal antithrombotic regimen in this patient population. Dr Carolyn Lam: Very important data for our patients, as is this next paper, which really examines the cost effectiveness of transcatheter mitral valve repair versus medical therapy in patients with heart failure and secondary mitral regurgitation. Now, these are results from the COAPT trial. As a reminder, the COAPT trial demonstrated that edge-to-edge transcatheter mitral valve repair using the MitraClip resulted in reduced mortality and heart failure hospitalizations and improved quality of life when compared with maximally tolerated guideline directed medical therapy in patients with heart failure and three to four plus secondary mitral regurgitation. In the current paper, first author Dr Baron from Lahey Hospital and Medical Center in Burlington, Massachusetts and St. Luke’s Mid America Heart Institute in Kansas City, as well as corresponding author Dr Cohen from University of Missouri, Kansas City, and their colleagues used data from the COAPT trial to perform a formal patient level economic analysis of the COAPT from the perspective of the US healthcare system, and they found that although the follow up costs were lower with the MitraClip compared with guideline directed medical therapy, and lower by more than $11,000 per patient. However, the cumulative two year costs remain higher by about $35,000 per patient with the transcatheter mitral valve repair, and this is all due to the upfront costs of the index procedure. Now when in trial survival, health, utilities, and costs were modeled over a lifetime horizon, transcatheter mitral valve repair was projected to increase life expectancy by 1.13 years, and quality adjusted life years, or QALYs, by 0.82 years at a cost of $45,648, yielding a lifetime incremental cost effectiveness ratio, or ICER, of $40,361 per life year gained, and $55,600 per QALY gained. Dr Greg Hundley: Very interesting. So how do we interpret these results for clinical practice? Dr Carolyn Lam: Ah, good question. So in order to place this in context, perhaps the most comparable case is the use of transcatheter aortic valve replacement, or TAVR. So based on the partner 1B trial, the ICER for TAVR, compared to medical therapy, was $61,889 per QALY gains. So this is very similar to what you just heard as the ICER for the transcatheter mitral valve repair. The cost effectiveness is also comparable for other commonly used treatments such as the implantable cardiac defibrillators for biventricular pacing, and was interestingly substantially more than the cost effectiveness of continuous flow LVADs, for example, and this is really discussed in a beautiful editorial by Dr Bonow, Mark, and O'Gara, and in this editorial, I think it's really important that they say the cost effectiveness projections really need to be placed in the context of continuing uncertainties regarding the interpretation of COAPT compared to that of the MITRA-FR trial, which reported no benefit of transcatheter mitral valve replacement compared to medical therapy, and so they warn that the current cost effectiveness analysis is not a carte blanche for interventional cardiologists to dramatically escalate their use of MitraClip procedure, and the data do support the thoughtful and deliberate use of this potentially life lengthening procedure in carefully selected patients and under very careful circumstances. You've got to read their editorial. Dr Greg Hundley: That sounds excellent, Carolyn. I really like that, putting that editorial that puts that data in perspective. Well, my next study really emanates from the ABSORB III trial, and it's from Dr Dean Kereiakes at the Christ Hospital Heart and Vascular Center. The manuscript addresses the long-term cardiovascular event rates among bioresorbable vascular scaffolds and drug eluting metallic stents. Dr Carolyn Lam: Greg, remind me, what were the results of the original ABSORB trial? Dr Greg Hundley: Right, Carolyn. So the ABSORB III trial demonstrated non-inferior rates of target lesion failure, cardiac death, target vessel myocardial infarction, or ischemia driven target lesion revascularization at one year with the bioresorbable vascular scaffolds compared with cobalt chromium everolimus-eluting stents, but between one year and three years, and therefore the cumulative to 3 year time point, the adverse event rates, particularly for target vessel myocardial infarction and scaffold thrombosis, were increased with this bioresorbable vascular scaffold. Dr Carolyn Lam: Ah, I see. Okay, so this current study evaluated the outcomes from three to five years beyond the implantation? Dr Greg Hundley: Exactly. So what this study did is they looked at an interval of time between three and five years out, and they found reductions in the relative hazards for the bioresorbable vascular scaffolds compared to the common coated stents, and that particularly occurred for target lesion failure, either cardiac death or target vessel MI or ischemia driven target revascularization when compared to the earlier zero to three year time period. So therefore Carolyn, the authors conclude that improved scaffold design and development techniques to mitigate that zero to three year bio resorbable vascular scaffold risk may enhance the late benefits that one sees in this three to five year time point, because of the complete bioresorption. Dr Carolyn Lam: So that's interesting Greg. Well, my next paper is kind of related. It is the first report of a randomized comparison between magnesium based bioresorbable scaffold and sirolimus-eluting stent in this clinical setting of STEMI with one year clinical and angiographic follow-up. So this study is from the Spanish group, Dr Sabaté and colleagues from the Interventional Cardiology Department and Cardiovascular Institute in Barcelona in Spain, and they found that at one year when compared to the sirolimus-eluting stent, the magnesium based bioresorbable scaffold demonstrated a higher capacity of vasal motor response to pharmacological agents, either endothelium, independent or dependent, at one year. However, the magnesium based bioresorbable scaffolds were also associated with a lower angiographic efficacy, a higher rate of target lesion revascularization, but without thrombotic safety concerns. Dr Greg Hundley: Wow, Carolyn, very interesting, and Dr Lorenz Räber and Yasushi Ueki wrote a very nice editorial on this whole topic of bioresorbable scaffolds, and they wonder about some of the unfulfilled prophecies. Great for our readers to put these two articles together. Now, how about in that mailbox, Carolyn? What have you got in there? Dr Carolyn Lam: First there's a research letter by Dr Kimura entitled Very Short Dual Antiplatelet Therapy After Drug-eluting Stent Implantation in Patients with High Bleeding Risk, and that's insights from the STOPDAPT-2 trial. There's another research letter by Dr Lopes entitled The Hospitalization Among Patients with Atrial Fibrillation and a Recent Acute Coronary Syndrome, or PCI, Treated with Apixaban or Aspirin, and that's insights from the AUGUSTUS trial. A very interesting perspective piece by Dr Rob Califf entitled The Balanced Dysfunction in the Health Care Ecosystem Harms Patients, a really, really interesting read, especially those working in the U.S. healthcare system. An ECG challenge deals with fast and slow, long and shorter. I would love to give you a clue to what it is. It's got to do with the atrial ventricular nodes, but I'll let you take a look and test yourself. There’re highlights from the TCT by Drs Giustino, Leon, and Greg Stone, and finally there's Highlights from the Circulation Family of Journals by Sara O'Brien. Dr Greg Hundley: Very nice, Carolyn. Well, I've got just a couple reviews. Richard Whitlock in a primer provides a nice historical review of anticoagulation for mechanical valves. How do we get here in anticoagulating this particular patient population? Next, Dr Mark Brzezinski from Brigham Women's Hospital in the Harvard Medical School in an on my mind piece provides very elegant figures, beautiful figures, demonstrating inadequate angiogenesis within the fibrous cap of atherosclerotic plaques, and indicates this could be a source or thought of as a contributing factor toward plaque rupture. What an issue, and I can't wait to get onto that featured discussion. Dr Carolyn Lam: For our featured discussion today, it is a super-hot topic, and a question that comes up again and again in clinical practice. What is the right antithrombotic therapy in patients with atrial fibrillation and acute coronary syndrome, not just those treated with PCI, but also in those treated medically? Well guess what? We're going to have answers right here. I'm so pleased to have with us Dr Renato Lopes, who's a corresponding author from Duke Clinical Research Institute and our associate editor, Dr Stefan James from Uppsala University in Sweden. Wow. Very, very important question here. Renato, could you just start by outlining what is the AUGUSTUS trial? Dr Renato Lopes: The AUGUSTUS trial was basically one of the four trials trying to give an answer, or help answering about the antithrombotic therapy in patients with anti fibrillation and/or NACS and/or PCI. So in other words, this combination of patients undergoing PCI who require antiplatelet therapy and also patients with AFib who requires anticoagulation therapy, and in summary, what the AUGUSTUS trial did was randomize patients to Apixaban versus VKA, or aspirin placebo in a double blind fashion, and this was a two by two factorial design. So these were basically the two questions that we wanted to answer. Is Apixaban better than VKA, and is it safe to drop aspirin from this treatment strategy? Remembering that everybody received a P2Y12 inhibitor for at least eight months. So this was basically the design of the AUGUSTUS trial, trying to answer two questions in the same study, a two by two factorial design. Dr Greg Hundley: Very, very nice. And Renato, if I could, I mean I said it in the intro, but may I make sure I got it right. This is the only trial in the field that included patients with ACS that was managed medically. So that's a very important group of patients that we still don't know what the best regimen is, is that right? Dr Renato Lopes: That is correct. The other trials, the PIONEER, the RE-DUAL PCI and the VPCI, they only included patients undergoing PCI, and when we designed the trial, we thought that it would be important to also include the whole spectrum of ACS, including not only the PCI treated patients, but also the medically managed patients. Dr Greg Hundley: Well, super. So could you tell us now what were the results? Dr Renato Lopes: So first, in terms of the breakdown, we found that the breakdown of the PCI, ACS versus elective PCI, was really nice. We had about 60% of the trial being ACS patients, and about 39%-40% elective PCI, and then within the PCI, I think that our results pretty much reflect practice in a lot of parts of the world, which was about 39% medically managed and about 61% PCI treated patients. So to begin with, I think a very nice breakdown that gives us power to look at these three separate groups: ACS medically managed, ACS PCI treated, and also elective PCI, which allows us to understand the whole spectrum of coronary disease in patients also with AFib, and in summary, what we showed for the primary endpoint, which was clinical major or relevant non-major bleeding. Let's start with the Apixaban versus VKA comparison, and we show that Apixaban was safer than VKA in all three groups, in the ACS medically managed, in the PCI treated patients, and also in the elective PCI patients. There was no significant direction for those three subgroups, although it was borderline 0.052, just showing maybe a little bit less pronounced results in the elective PCI group, but nonetheless, I would say that in general, very consistent, and in terms of Aspirin for the primary endpoint, also no difference, no interaction among those three groups. In other words, as we increase substantially the risk of bleeding about two folds in all the three groups, ACS medically managed, PCI treated patients, and elective PCI patients, with about again, two fold increase in bleeding compared to placebo. If we go to ischemic events, again, that's our hospitalization and other that are ischemic events. In terms of Apixaban versus VKA, the results were very consistent with the overall trial among these three groups, and in terms of as ACS versus placebo, the results also for the ischemic events were also similar among the three groups. So again, reassuring that the main results of the trial were very consistent, regardless how patients were managed in terms of the ACS, medically or through PCI, and also included in the elect PCI group. Dr Carolyn Lam: Thank you for explaining that so well. Stephan, I would love for you to take us under the hood. What were the editors thinking when we saw this paper, why we're highlighting it now, and what do you think are the implications? Dr Stefan James: The AUGUSTUS trial was unique in many aspects. I think Renato highlighted a few of them. As he told, there have been several similar trials without the other DOAX, factor 10A inhibitors and the dabigatran, but the AUGUSTUS trial was larger. It includes, as you mentioned previously, patients with ACS and medical management, and it also was designed as a two by two factorial design. So it actually asks two different questions and made two different randomizations, both anticoagulation with the two different agents, Warfarin versus Apixaban, but also Aspirin versus placebo, and so it's possible from this trial to understand more of the different aspects of treating patients, these complex patients with atrial fibrillation, NACS or PCI, and gave the study group and us an opportunity to better understand all these complexities. So with that, I'd like to turn to Renato and try to, with that background that I just outlaid, and you just try to make us understand what are the clinical implications of these aspects of the trial and the treatment of Apixaban and Aspirin in these patients? Dr Renato Lopes: I think we were in the area that we desperately needed randomized data, because basically until five years ago, the standard of care of treating these patients was the classic triple therapy with Aspirin, Clopidogrel, and Warfarin, and this was based on no randomized trials and all observational data, and we know how problematic this is, and this field has evolved tremendously almost year after year since the PIONEER trial, since the RE-DUAL trial, and this year, we had AUGUSTUS and ENTRUST and I think now, as Mike Gibson used to say, that we have about 2.8 million different combination of antithrombotic strategies to treat these patients because we have different anticoagulants, different anti-platelets, different doses, different durations, different types of stents, which makes it really impossible for physicians or for any guidelines to contemplate all these options. So we really needed a few trials to at least try to give a few options that are evidence based and not just based on low quality of data, and I think now, if you look at the Augustus results, and the totality of the data from all these trials, which now is about almost 11,000 patients all together, actually almost 12,000 patients all together. I think that what we know today is that yes, the initial period in hospital for some time it's important to use Aspirin. I think this is an important point to highlight, Stephan, that Aspirin still needs to be used for the acute treatment, and I would say at least for the first few initial days while patients are still in the hospital, but then by the time of discharge, which sometimes might be five days, six days, seven days, I think that now the totality of data show that it's reasonable to drop Aspirin for most patients. So based on the AUGUSTUS results, what we show is that if you're going to use anticoagulation as Apixaban at the dose that is approved for stroke preventions in atrial fibrillation, combined with a P2Y12 inhibitor without Aspirin after the initial period, you have the best outcomes in terms of lower rates of bleeding, lower rates of hospitalizations, and we don't have to pay a cost in terms of ischemic events when we actually drop Aspirin and keep only the NOAC, in this case was Apixaban, plus a P2Y12 inhibitor, which most of the time was Clopidogrel, and here with AUGUSTUS, we basically show that this is true for patients with AFib and ACS, irrespective of the management with medical managing, with medical therapy, or with PCI. So I think that's an additional piece that that is true irrespective of how we're going to treat your ACS patient, or if the patient basically underwent elective PCI, and I think we learned today that the classic treatment therapy of VKA plus Aspirin plus P2Y12 inhibitor, so in other words, the triple classic triple therapy should generally be avoided. Dr Stefan James: Thank you Renato. I think that that was a very complete answer in this complex arena. I'd like just to mention that of course the AUGUSTUS, as well as the other trials, have their limitations, as all trials. Although it was large, it was powered for safety, for bleeding events, and it was not powered for ischemic events. Having said that, we still want to look at ischemic events and clinical outcomes, and to what degree do you think we can do that? What conclusions can we draw from an ischemic point of view because of the fact that the trial was underpowered for that interpretation? Dr Renato Lopes: That is a great question, Stephan, and in fact, if we look at events like stent thrombosis, they are very rare, and if you really want to attack a significant difference between Aspirin versus placebo in patients having stent thrombosis, we're really going to need a trial with about 30-40,000 people, which would be not feasible and not doable. So we need to be cautious when we analyze those events in the power trial for ischemic events. Nonetheless, there was a signal, if you look at all trials, and even in the meta-analysis that we published recently, that dropping Aspirin probably increased the risk of ischemic events, not in a statistically significant fashion, but nonetheless, this trend exists. The signal exists. So probably keeping Aspirin, add some protection for ischemic events, primarily stent thrombosis and myocardial infarction. The problem is a tradeoff. The problem is that the cost of adding aspirin is too high. So now the question to us, Stephan, is to look further into our data and in the combined data sets that we're trying to work with the other authors and try to identify, okay, Aspirin really increased the risk of bleeding, but is there a group of patients who might benefit from a little bit longer Aspirin? So that's the first question. Who are those patients? May be complex PCI, maybe bifurcation lesions, maybe multiple lesions, multiple stents, and second, if we decide to give Aspirin longer, how much longer should we give? Because again, the cost is very high in terms of bad bleeds. So we are trying now to identify what is the trade off, and who most benefit from keeping Aspirin longer, and for how long in a way the cost might be worth it to pay in exchange of potentially save some ischemic events? And with that, we can further refine the treatment that I think I highlighted before. For most patients, I think what I said before is probably reasonable. We can drop Aspirin by the time of discharge after a few days, but for a few patients, for some patients, it might be wise to keep Aspirin a little bit longer, and we are trying now to identify first, who those patients are and second, form how much longer should we keep Aspirin, since the 40,000 patient trial is very unlikely to happen. Dr Stefan James: I like his interpretation, Renato, although I wanted to highlight that there are limitations, I think this trial is extremely informant for clinicians. We learned a lot how to treat these very complex patients with complex treatments. Dr Carolyn Lam: No, I couldn't have agreed more. I mean quoting Mike Gibson, 2.8 million combinations. Well, at least we've talked about some of them here and had a very clear take home message, although with the caveats that we were discussing. Thank you so much, Stefan and Renato. This was really a great discussion, and thank you audience for joining us today. You've been listening to Circulation on the Run. Don't forget to tune in again next week. This program is copyright American Heart Association 2019.  

C. Michael Gibson speaks with Michael Mack about the COAPT Trial 3-year outcomes and results.

Recorded on site at TCT, COAPT investigator Dr Neal S Kleiman and Ankur discuss the realities of establishing an academic career as an interventional cardiologist. Neal explains why it is important to wear multiple hats and balance academia with a clinical presence. Digging more into the practicalities of everyday work-life, Neal reflects on the challenges of reporting to multiple bosses who have different goals, and how geography enabled him to move between cathlab and academia. Neal also shares what he looks for in early career academic cardiologists. Submit your question to Ankur via: podcast@radciffe-group.com. Hosted by @AnkurKalraMD. Produced by @RadcliffeCARDIO.

In this Live Friday CME recap podcast, Dr. Santiago Garcia, a cardiologist with Minneapolis Heart Institute, provides an overview of percutaneous mitral valve repair; specifically the MitraClip. Objectives:    Upon completion of this podcast, participants should be able to: Recognize that mitral valve regurgitation is highly prevalent and detrimental to the quality of life and survival. Select the differences between functional and degenerative mitral regurgitation. Describe the mechanism of action of percutaneous repair and clinical data to support its clinical use. Identify indications for the determination of surgical mitral valve repair and replacement. CME credit is only offered to Ridgeview Providers for this podcast activity. Complete and submit the online evaluation form, after viewing the activity.  Upon successful completion of the evaluation, you will be e-mailed a certificate of completion honoring you 1 CME/CEU credit in approximately 2 weeks.  You may contact the accredited provider with questions regarding this program at  rmccredentialing@ridgeviewmedical.org. Click on the following link for your CME credit: CME Evaluation: "Percutaneous Mitral Valve Repair" - CME Internet Enduring Activity (**If you are listening to the podcasts through iTunes on your laptop or desktop, it is not possible to link directly with the CME Evaluation for unclear reasons. We are trying to remedy this. You can, however, link to the survey through the Podcasts app on your Apple and other smart devices, as well as through Spotify, Stitcher and other podcast directory apps and on your computer browser at these websites. We apologize for the inconvenience.)  The information provided through this and all Ridgeview podcasts as well as any and all accompanying files, images, videos and documents is/are for CME/CE and other institutional learning and communication purposes only and is/are not meant to substitute for the independent medical judgment of a physician, healthcare provider or other healthcare personnel relative to diagnostic and treatment options of a specific patient's medical condition.” -----  FACULTY DISCLOSURE ANNOUNCEMENT  It is our intent that any potential conflict should be identified openly so that the listeners may form their own judgments about the presentation with the full disclosure of the facts. It is not assumed any potential conflicts will have an adverse impact on these presentations. It remains for the audience to determine whether the speaker’s outside interest may reflect a possible bias, either the exposition or the conclusions presented. Santiago Garcia, MD has received honoraria from Abbott Vascular. An independent review of his presentation confirms he is following EBM guidelines, as MitraClip is the only trans-catheter mitral valve repair (TMVr) therapy that delivers a treatment option for patients with significant symptomatic mitral regurgitation. Santiago Garcia, MD works with Abbott Vascular engineers and provides feedback on new MitraClip designs, and does not endorse Abbott Vascular. There is NO commercial tie to Abbott Vascular products, and NO impact on this specific Ridgeview CME presentation/podcast. Santiago Garcia, MD has received honoraria from Medtronic. An independent review of his presentation confirms he is following EBM guidelines. Santiago Garcia, MD provides training and consultation for chronic total occlusion devices (stents). He does NOT endorse Medtronic products and NO commercial tie to Medtronic products, therefore has NO impact on his Ridgeview Medical Center CME presentation. Santiago Garcia, MD has received honoraria from Edwards Lifesciences. An independent review of his presentation confirms he is following EBM guidelines. Santiago Garcia, MD is a speaker and proctor for Edwards Lifesciences. He does NOT endorse Edwards Lifesciences products. There is NO commercial tie to Edwards Lifesciences products, therefore there is NO impact on this CME presentation. All other planning committee members and presenters have disclosed they have no significant financial relationship with any cardiovascular device companies that have been disclosed and the NO conflict of interest exists with Santiago Garcia, MD’s presentation/educational event. ----- SHOW NOTES: Welcome back everyone to Ridgeview Podcast: CME Series! It's Live Friday CME recaps. Jason Hicks here, and it's my pleasure to host this episode. Thanks for joining us on this lovely fall day. In this episode, we are joined by Dr. Santiago Garcia, staff interventional cardiologist with Minneapolis Heart Institute. He is going to enlighten us on some of the particulars of percutaneous mitral valve repair. Most specifically, the Mitraclip, which is effectively the mitral clip procedure for the indication of mitral regurgitation. So pour a cup of coffee, and chill out on the porch; and get ready to take in some cutting edge cardiology here on Ridgeview Podcast CME Series with Dr. Santiago Garcia. CHAPTER 1: Alright all you stellar continuing educationalists. Yep, that's a real word. It's time to digest some of this excellent info. According to the study out of Mayo Clinic that Dr. Garcia discusses, the prevalence of mitral valve disease (MVD) is actually higher than aortic valve disease (AVD). Both increase with age. But by the age of 75, 1 in 10 will have MVD, and it is higher than AVD. About 4 million in the U.S. have mitral regurgitation (MR), and about half are eligible for therapy. However, there are a relatively small number that actually go on to get mitral valve surgical therapy, due to the fact that the guidelines are fairly stringent for this. Asymptomatic, severe mitral regurgitation, as well as patients with symptoms can benefit greatly by surgical therapy. Some definitions and quick discussion though, regarding mitral regurgitation. What is it? Mitral regurgitation is just that. Regurgitation through the mitral valve into the left atrium during systole. It results in a systolic murmur. Standard diagnosis is made by echocardiogram, usually transthoracic echo (TTE). This will tell us about the severity of the MR. Also, remember that many people are asymptomatic with this, even in the setting sometimes of severe MR. The guidelines for mitral valve open surgery are sort of complicated, but Dr. Garcia summarizes as follows: Primary, also known as degenerative mitral regurgitation (DMR) and secondary MR. Primary (or DMR) deals with pathology of the leaflets. Leaflets are attached to the muscle of the heart. These patients in general have more tissue than what they actually need. Secondary MR is, most commonly, due to previous MI. The scar on the wall of the heart pulls on the valve and the leaflet are therefore pulled down. Functional MR is also a form of secondary MR and has to do with LV dysfunction and no actual valve structure abnormality. There tends to be a different treatment algorithm for each type of MR.  There is no class, one indication for surgery for secondary MR. A large randomized trial concluded there was no benefit in surgery in patients also undergoing CABG. With primary MR, surgery has a class 1 indication, as long as there are symptoms and a EF of at least 30%. In asymptomatic patients, repair is recommended if A-fib is present, pulmonary hypertension, and a very experienced surgeon. There are only a few such surgeons in the country. The likelihood of surgical success must be >95% in order to proceed with surgical correction. Mitral valve (MV) surgical repair is the overall standard of care. The most pathology site is the P2 scallops, with excessive tissue and a flail posterior leaflet, as mentioned by Dr. Garcia. A resection and then reapproximation of this tissue is performed. A valve ring is often placed as well. About 50% of patients who may qualify for percutaneous therapy. Coming up next, Dr. Garcia will go into the background and some of the intricacies of the MitraClip procedure. CHAPTER 2: The MitraClip device is the only commercial available device in the United States for primary or degenerative MR.  The guidelines give percutaneous therapy a class 2B indication. These are high risk patients, who typically have had previous sternotomy or are older than 80. FMR (functional mitral regurgitation), which is discussed and defined in Cardiology Review, 2010, by Schmitto et.al, "as a systolic retrograde flow from the left ventricle into the left atrium due to reduction and/or elimination of the normal systolic coaptation of the mitral valve leaflets." The valve structure is essentially normal, but the function of the valves during systole is not, and therefore results in regurgitation. FMR did not previously have an indication for surgery until the COAPT, which was recently published in the New England Journal of Medicine, resulted in FDA approval. This trial took over a decade to perform, and the results were impressive, but another trial would be needed to have a class 1 indication. EVEREST 2 was another trial that helped lead to approval of the device. So, how are mitral regurgitation patients approached in general? A TEE (transesophageal echocardiogram) is performed. There are separate criteria for FMR and DMR. These criteria were used in the clinical trial mentioned. However, some of these criteria are now obsolete, given there are other devices, for instance the XTr, that can now be used, and more of these patients could now potentially be treated with percutaneous therapy. In addition, if the mitral valve area is small, this therapy can lead to iatrogenic mitral valve stenosis. Is this useful for CHF patients? Well, in the COAPT and EVEREST 2 trials, patients needed to be on optimal medical therapy. If patients' MR improved significantly with medical therapy alone, then they would not be procedural candidates. If their MR was no better in the setting of optimal medical therapy, then they would be candidates for the procedure. How is this procedure done? First, venous access is obtained; then the left atrium is accessed from the right atrium. The left atrium in navigated. With the clip opened, the catheter/device enters the left ventricle, then grabs valve tissue. The clip is closed and then the device is deployed. Basically, the device truly clips together the leaflets of the mitral valve in order to close the gap that results in severe regurgitation. This is obviously very visual, so please check out the presentation slides to Dr. Garcia's presentation. The posterior, superior quadrant of the atrial septum is where the puncture will take place. This allows for maneuverability down toward the ventricle. This is all done under TEE guidance. Therefore it is done under general anesthesia. The clip is best situated in A2 P2 (the anterior and posterior 2nd scallops of the valve). There are long and short clip arm device options, and the size of the leaflets and their degree of retraction will dictate which device is used. The leaflets are basically clipped together, creating two orifices from the original one. A +2 mitral regurg indicates good success post-procedure. And the goal is also not to cause mitral stenosis. Left atrial pressure reduction is also a goal here; such as a reduction of 10mmHg, as mentioned by Dr. Garcia. Stay tuned for the next segment where Dr. Garcia discusses the COAPT trial, and some of the other studies that led to approval of this innovative procedure. CHAPTER 3: COAPT was the pivotal trial for patients with FMR for a mitral clip device. Again, this is a class 2B indication for the procedure. It was hypothesized that by impacting mitral regurgitation, we could decrease preload and CHF readmissions. It (COAPT) compared to 300 pts in each study are, one with medical therapy and one with medical therapy and the clip. There was almost a 50% reduction in admissions. The NNT (number needed to treat) to prevent one hospital admission was 3. In addition, a mortality reduction of 40% was seen, with an NNT of 6. Overall, to prevent 1 event, either heart failure admission or death, the NNT is 4. This is unprecedented in terms of a device trial. The COAPT showed a complication rate of

In this week's View, guest host Dr. Deepak Bhatt offers a preview of some of the hottest trials at TCT 2019, taking place September 25-29 in San Francisco, CA, including TWILIGHT, AUGUSTUS ACS, PORTICO, PARTNER 3 Low-Risk Computed Tomography Substudy, Three-Year Outcomes from COAPT, Five-Year Outcomes from PARTNER 2A, Five-Year Outcomes from EXCEL, COMPLETE Timing Substudy, Cost-Effectiveness Analysis from COAPT, Health Status Outcomes from PARTNER 3, and Five-Year Outcomes from IVUS-XPL.

C. Michael Gibson and David Cohen discuss adding years to life and adding life to years with the MitraClip.

Commentary by Dr. Valentin Fuster

In this week's View, guest host Dr. Deepak Bhatt offers a preview of some of the hottest trials at ACC.19, taking place March 16-18 in New Orleans, including the Apple Heart study, results of the open-label extension of the PIONEER-HF trial, the HoT-PE study, results of the PARTNER 3 trial, Self-Expanding TAVR or SAVR in Patients at Low Risk of Surgical Mortality, echocardiographic outcomes from the COAPT trial, primary results of the AUGUSTUS trial, MOMENTUM 3, 1-year outcomes from the CardioMEMS post-approval study, the First Randomized Human Experience with a Ticagrelor Reversal Agent, the DEFINE PCI trial, MRUSMI, primary results of the GLOBAL LEADERS adjudication sub-study, the CLEAR Wisdom Trial, the CREOLE Study, DECLARE, REDUCE-IT, the STOPDAPT-2 trial, SMART-CHOICE, ODYSSEY OUTCOMES, and IRAD.

Roxana Mehran talks TMVR after COAPT and MITRA-FR and what this means for patients with Michael Reardon and Ted Feldman.

After the results of the COAPT trial were released, Dr. Kapadia, joined a panel of experts in imaging Dr. Griffin, heart failure Dr. Starling, heart surgery Dr. Mick, and structural intervention Dr. Krishnaswamy to discuss best practices in the treatment of functional mitral regurgitation in heart failure patients. Read more about key findings of the COAPT trial.

https://accadandkoka.com/wp-content/uploads/2018/10/ajkirtane-e1539632763902.jpg ()Ajay Kirtane, MD The life of a clinical trialist involves juggling multiple demands.  Beyond the purely scientific questions are the clinical interests of the patient and the personal demands on the physician. Our guest on this episode is Ajay Kirtane, MD, Associate Professor of Medicine at Columbia University Medical Center in New York.  In this conversation with Anish Koka, Dr. Kirtane shares his professional journey and his perspective on one of the most surprising and hopeful clinical trials in recent times, the COAPT trial of mitral valve repair in patients with congestive heart failure. GUEST: Ajay Kirtane, MD.  https://www.columbiadoctors.org/ajay-j-kirtane-md (Website) and https://twitter.com/ajaykirtane?lang=en (Twitter) LINKS: Stone G, et al.  https://www.nejm.org/doi/full/10.1056/NEJMoa1806640 (Transcatheter mitral valve repair in patients with heart failure). (in New England Journal of Medicine, 2018) WATCH ON YOUTUBE: https://youtu.be/Fpp2QZ6k7Gc (Watch the episode) on our YouTube channel. Support this podcast

Coapt Complete Control is a pattern recognition technology that gives upper limb prosthesis users more control through myoelectric signals than previously possible. Listen to Blair Lock, MScE, P.Eng, and CEO of Coapt talk about founding the company and the great technology they provide.  To Learn more about Coapt: https://www.coaptengineering.com/

Nicole Kelly debuts her first edition of Loud and Proud on Public House Media by welcoming the owner of CoApt Complete Control Blair Lock. Nicole dives into the journey of how she was able to obtain such a revolutionary piece of equipment that has not changed her world.

Nicole Kelly debuts her first edition of Loud and Proud on Public House Media by welcoming the owner of CoApt Complete Control Blair Lock. Nicole dives into the journey of how she was able to obtain such a revolutionary piece of equipment that has not changed her world.