The controversial KETO-CTA study, tough decisions in subclinical AF, and another potentially huge benefit for GLP-1 agonist drugs are discussed by John Mandrola, MD, in this week's podcast.

This podcast is intended for healthcare professionals only.

To read a partial transcript or to comment, visit:

https://www.medscape.com/twic

I The KETO-CTA Study

• JACC Advances Paper: https://www.jacc.org/doi/10.1016/j.jacadv.2025.101686
• Meta-analysis https://doi.org/10.1016/j.ajcnut.2024.01.009

II Subclinical AF – Anticoagulate or Not?

Anticoagulation in Subclinical AF May Offer Little Benefit

https://www.medscape.com/viewarticle/anticoagulation-subclinical-af-may-offer-little-benefit-2025a1000b31

Treat AFib ‘Diagnosed’ by Smartwatch

https://www.medscape.com/viewarticle/treat-afib-diagnosed-smartwatch-2025a1000avp

• JAMA NO paper https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2833437
• NOAH https://www.nejm.org/doi/full/10.1056/NEJMoa2303062
• ARTESIA https://www.nejm.org/doi/full/10.1056/NEJMoa2310234
• McIntyre meta-analysis https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.123.067512
• Singer et al https://pmc.ncbi.nlm.nih.gov/articles/PMC2777526/
• Stroke paper https://www.ahajournals.org/doi/full/10.1161/STROKEAHA.123.045843
• American Journal of Medicine paper https://pubmed.ncbi.nlm.nih.gov/38331136/

III GLP1a for Treatment of Fatty Liver Disease

• ESSENCE trial https://www.nejm.org/doi/10.1056/NEJMoa2413258

Features

• CABG Still Superior to Stents Despite FAME 3 Endpoint Swap

https://www.medscape.com/viewarticle/cabg-still-superior-stents-despite-fame-3-endpoint-swap-2025a1000ao5

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The FDA approval of TAVR for asymptomatic AS, digital health, subcutaneous vs transvenous ICD, and cryptogenic stroke in young adults are discussed by John Mandrola, MD.

This podcast is intended for healthcare professionals only.

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I  FDA announces approval for TAVR in pts with asymptomatic AS

• Edwards Press Release https://www.edwards.com/newsroom/news/2025-05-01-edwards-tavr-receives-fda-approval-for-patients-with-asymptomatic-severe-aortic-stenosis
• Transcatheter Aortic-Valve Replacement for Asymptomatic Severe Aortic Stenosis (EARLY TAVR) https://www.nejm.org/doi/full/10.1056/NEJMoa2405880
• EARLY TAVR: A Positive Trial That Fails to Inform Clinical Decisions https://www.medscape.com/viewarticle/early-tavr-positive-trial-fails-inform-clinical-decisions-2024a1000kec
• Asymptomatic Aortic Stenosis: 'Time to Act' or Not So Fast? https://www.medscape.com/viewarticle/asymptomatic-aortic-stenosis-time-act-or-not-so-fast-2025a10005o9

II PPG that Can Distinguish source of Tachycardia

• Machine-learning guided differentiation between photoplethysmography waveforms of supraventricular and ventricular origin https://doi.org/10.1016/j.cmpb.2025.108798

III PRAETORIAN -XL trial

• Device-related Complications in Transvenous Versus Subcutaneous Defibrillator Therapy During Long-term Follow-up: the PRAETORIAN-XL Trial https://www.ahajournals.org/doi/abs/10.1161/CIRCULATIONAHA.125.074576
• Subcutaneous or Transvenous Defibrillator Therapy (PRAETORIAN trial) https://www.nejm.org/doi/full/10.1056/NEJMoa1915932
• Subcutaneous or Transvenous Defibrillator Therapy Letter to Editor https://www.nejm.org/doi/full/10.1056/NEJMc2034917
• The PRAETORIAN Trial: Guarded Approach to Subcutaneous ICD Best https://www.medscape.com/viewarticle/937156

IV Stroke in Young People

• Burden of Modifiable Risk Factors in Young-Onset Cryptogenic Ischemic Stroke by High-Risk Patent Foramen Ovale https://www.ahajournals.org/doi/10.1161/STROKEAHA.124.049855
• Migraine: A Key Factor in Young Adults With Unexplained Stroke https://www.medscape.com/viewarticle/migraine-key-factor-young-adults-unexplained-stroke-2025a10009jj
• U.S. stroke rate declining in adults 75 and older, yet rising in adults 49 and younger ASA statement https://newsroom.heart.org/news/u-s-stroke-rate-declining-in-adults-75-and-older-yet-rising-in-adults-49-and-younger
• Increasing stroke in the young https://doi.org/10.1016/j.ajpc.2020.100085

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AI and ECGs, novel ways to treat hypertension, combined lipid-lowering therapy after myocardial infarction, PFA and silent stroke, a move toward accountability in AF ablation, and pacing issues in TTVR are the topics John Mandrola, MD, discusses in this week's podcast.

This podcast is intended for healthcare professionals only.

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I Help with ECGs in the ED

AI Shows Promise for Rapid NSTEMI Diagnosis

https://www.medscape.com/viewarticle/ai-shows-promise-rapid-nstemi-diagnosis-2025a10009pw

• Buscher et al https://doi.org/10.1093/eurheartj/ehaf254

II A Novel way to Treat HTN

A Pacemaker to Control BP Gets FDA Breakthrough Designation

https://www.medscape.com/viewarticle/pacemaker-control-bp-gets-fda-breakthrough-designation-2025a10009t3

• JAHA paper https://www.ahajournals.org/doi/10.1161/JAHA.120.020492
• Backbeat https://clinicaltrials.gov/study/NCT06059638

III Type of PFA may matter for Silent Cerebral Lesions

• Paper https://www.ahajournals.org/doi/10.1161/CIRCEP.125.013719

IV Accountability coming to US AF ablation

• Heart Rhythm Society Releases a Document on Establishing Centers of Excellence for AF ablation -- Press Release https://www.hrsonline.org/news/new-white-paper-on-atrial-fibrillation-centers-of-excellence/

V Pacing in Patients with Undergoing Transcatheter Tricuspid Valve Replacement

• Paper https://doi.org/10.1016/j.hrthm.2025.02.004

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The FAME 3 trial 5-year results, TAVR at 5 years, pacers after TAVR, and mavacamten not a wonder drug are the topics John Mandrola, MD, discusses in this week’s podcast.

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I FAME 3 at Five Years

Stents as Good as Surgery for Triple-Vessel Disease https://www.medscape.com/viewarticle/noninvasive-stents-good-surgery-triple-vessel-disease-2025a10007l4

• Main trial NEJM https://www.nejm.org/doi/full/10.1056/NEJMoa2112299
• Circulation 3-years https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.123.065770
• 5-year results Lancet 10.1016/S0140-6736(25)00505-7 https://linkinghub.elsevier.com/retrieve/pii/S0140673625005057

II TAVR in Low-Risk Patients at 5 years

5-Year TAVR, Surgery Outcomes Similar in Low-Risk Patients

https://www.medscape.com/viewarticle/5-year-tavr-surgery-outcomes-similar-low-risk-patients-2025a10007zl

• EVOLUT Low-Risk 5 years https://www.jacc.org/doi/10.1016/j.jacc.2025.03.004
• EVOLUT Editorial – We're Halfway There https://www.jacc.org/doi/10.1016/j.jacc.2025.03.428
• PARTNER 3 Low-Risk https://www.nejm.org/doi/full/10.1056/NEJMoa2307447
• NOTION at 5 years https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.118.036606

III The Matter of Pacemakers After TAVI

• JACC IV Study Badertscher https://www.jacc.org/doi/10.1016/j.jcin.2025.03.028
• Assessing the quality of reporting of harms in randomized controlled trials published in high impact cardiovascular journals
•  

IV Mavacamten Looks to Have Specific Indications

• EXPLORER HCM 10.1016/S0140-6736(20)31792-X External Link
• VALOR HCM https://jamanetwork.com/journals/jamacardiology/fullarticle/2809050
• BMS Press Release https://news.bms.com/news/details/2025/Bristol-Myers-Squibb-Provides-Update-on-Phase-3-ODYSSEY-HCM-Trial/

FINAL THOUGHTS

• PRAGUE 25 https://bmjopen.bmj.com/content/12/6/e056522

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The TAP-IT, STRIDE, FreshUP, and SINGLE SHOT CHAMPION trials are discussed by John Mandrola, MD, in this week's podcast.

This podcast is intended for healthcare professionals only. To read a partial transcript or to comment, visit: https://www.medscape.com/twic

I TAP IT 

TAP IT trial https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.124.073521

II STRIDE

LANCET Ref 10.1016/S0140-6736(25)00509-4

SUMMIT HF https://www.nejm.org/doi/full/10.1056/NEJMoa2410027

III FRESH UP

No Need to Restrict Fluids in Stable Heart Failure

https://www.medscape.com/viewarticle/no-need-restrict-fluids-stable-heart-failure-2025a10008bu

Nature (Trial) https://www.nature.com/articles/s41591-025-03628-4

SODIUM HF https://pubmed.ncbi.nlm.nih.gov/35381194/

IV PFA for AF ablation

SINGLE SHOT CHAMPION https://www.nejm.org/doi/full/10.1056/NEJMoa2502280

ADVENT https://www.nejm.org/doi/full/10.1056/NEJMoa2307291

Foy et al https://pmc.ncbi.nlm.nih.gov/articles/PMC11852674/

MANIFEST REDO Study https://doi.org/10.1093/europace/euaf012

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Trials from the 2025 American College of Cardiology scientific sessions, including the WARRIOR, PROTECT TAVI, DAPATAVI, and SOUL are reviewed by John Mandrola, MD

This podcast is intended for healthcare professionals only.

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I Thank you Comments

II WARRIOR Women’s IschemiA TRial to Reduce Events In Non-ObstRuctive CAD

• Keep Fighting INOCA After Neutral WARRIOR Trial https://www.medscape.com/viewarticle/keep-fighting-inoca-after-neutral-warrior-trial-2025a10007uf

III Cerebral Embolic Protection in TAVI

• PROTECT TAVI https://www.nejm.org/doi/full/10.1056/NEJMoa2415120
• PROTECTED TAVR https://www.nejm.org/doi/full/10.1056/NEJMoa2204961
• Instrumental Variables in Randomized Trials https://evidence.nejm.org/doi/10.1056/EVIDctw2400204

IV  DAPATAVI

• SGLT2 Inhibitors Progressing to New Standard After TAVI https://www.medscape.com/viewarticle/sglt2-inhibitors-progressing-new-standard-after-tavi-2025a100081y

• Dapagliflozin in Patients Undergoing Transcatheter Aortic-Valve Implantation https://www.nejm.org/doi/full/10.1056/NEJMoa2500366

V SOUL Study of Oral Semaglutide and CV outcomes in Diabetes

• Oral GLP-1 Receptor Agonist Reduces CV Risk https://www.medscape.com/viewarticle/oral-glp-1-receptor-antagonist-reduces-cv-risk-2025a10007kr

• Oral Semaglutide and Cardiovascular Outcomes in High-Risk Type 2 Diabetes https://www.nejm.org/doi/full/10.1056/NEJMoa2501006

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Stopping oral anticoagulation after AF ablation, the core problem with paradoxes like the smoker’s paradox, chronic total occlusion PCI, and an ACC/EHRA preview are discussed by John Mandrola, MD, in this week's podcast.

This podcast is intended for healthcare professionals only.

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I Oral Anticoagulation after Successful AF Ablation

• Iwawakie et al https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2831851
• OCEAN protocol paper https://doi.org/10.1016/j.ahj.2017.12.007

II Smoker’s Paradox

• Presch et al https://www.jacc.org/doi/10.1016/j.jcin.2024.12.028
• Gupta et al https://doi.org/10.1161/JAHA.116.003370

III CTO PCI

• Main sub-analysis paper Bangalore et al https://doi.org/10.1016/j.jacc.2025.01.029
• DECISION CTO https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.118.031313
• Main EURO CTO trial https://doi.org/10.1093/eurheartj/ehy220
• 3-year MACE of EURO CTO https://eurointervention.pcronline.com/article/three-year-outcomes-of-eurocto-a-randomized-multicentre-trial-comparing-revascularization-and-optimal-medical-therapy-for-chronic-total-coronary-occlusions
• EXPLORE https://www.jacc.org/doi/abs/10.1016/j.jacc.2016.07.744
• ISCHEMIA CTO https://www.clinicaltrials.gov/study/NCT03563417
•  

IV ACC and EHRA Preview

Mandrola’s 5 Trials to Look for at the 2025 American College of Cardiology Scientific Sessions https://www.medscape.com/viewarticle/mandrolas-5-trials-look-2025-american-college-cardiology-2025a10006zu

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A large trial in cardiac pacing finally published, PVCs and cardiomyopathy, cannabis, CV risk and the danger of observational studies, and the tale of two disparate statin trials are the topics John Mandrola, MD, discusses in this week’s podcast.

This podcast is intended for healthcare professionals only.

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I BioPace Trial

• Trial manuscript https://doi.org/10.1093/europace/euaf029

II Another Belief Challenged in EP this week—PVCs and CM ‘

• UC Paper https://doi.org/10.1016/j.jacep.2025.01.004
• JACC Review https://doi.org/10.1016/j.jacc.2024.03.416
• Lee et al https://heart.bmj.com/content/105/18/1408

III Cannabis and CV Risk

• Cannabis and MACE in JACC Advances: https://www.jacc.org/doi/10.1016/j.jacadv.2025.101698
• Zeraatkar –Grilling the data https://doi.org/10.1016/j.jclinepi.2024.111278
• PLOS-1 10.1371/journal.pone.0199705

IV Cardio-oncology

• Jacc Onc Substdy https://www.jacc.org/doi/10.1016/j.jaccao.2024.11.008
• Editorial https://www.jacc.org/doi/10.1016/j.jaccao.2025.01.006
• STOP CA JAMA 2023 https://jamanetwork.com/journals/jama/fullarticle/2807988
• PREVENT https://evidence.nejm.org/doi/10.1056/EVIDoa2200097

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Listener feedback, resistant hypertension, K-binders for MRA use in heart failure, nutritional epidemiology, and a positive study for vitamin D are the topics John Mandrola, MD, discusses in this week's podcast.

This podcast is intended for healthcare professionals only.

To read a partial transcript or to comment, visit:

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I Listener Feedback

• Califf editorial https://www.jacc.org/doi/10.1016/j.jaccas.2020.01.003

II Resistant HTN

• Positive Topline Results for Lorundrostat in Hypertension

https://www.medscape.com/viewarticle/positive-topline-results-lorundrostat-hypertension-2025a100062e

III K-Binding

• REALIZE K Trial https://doi.org/10.1016/j.jacc.2024.11.014
• Packer Editorial https://doi.org/10.1016/j.jacc.2025.01.011
• Diamond Trial EHJ https://doi.org/10.1093/eurheartj/ehac401
• REALIZE K Commentary https://www.medscape.com/viewarticle/realize-k-new-potassium-binder-help-keep-spiro-board-2024a1000m2c

IV Butter vs Plant-based Oils and Mortality

• JAMA-IM Study https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2831265
• Is Red Meat Healthy? Multiverse Analysis Has Lessons Beyond Meat https://www.medscape.com/viewarticle/red-meat-healthy-multiverse-analysis-has-lessons-beyond-meat-2024a10008qv
• Cookbook Review https://doi.org/10.3945/ajcn.112.047142

V Vitamin D

• Impact Factor https://www.medscape.com/viewarticle/rare-win-vitamin-d-this-time-ms-2025a10005ul
• D-Lay trial https://jamanetwork.com/journals/jama/fullarticle/2831270

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Listener feedback on asymptomatic aortic stenosis (AS), transcatheter aortic valve replacement (TAVR) vs surgical aortic valve replacement (SAVR), coronary artery calcium (CAC), and revascularization for patients with ischemic LV dysfunction are discussed by John Mandrola, MD, in today's podcast.

This podcast is intended for healthcare professionals only.

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I Aortic Valve Intervention for Asymptomatic AS

Asymptomatic Aortic Stenosis: “Time to Act” or Not So Fast?

https://www.medscape.com/viewarticle/asymptomatic-aortic-stenosis-time-act-or-not-so-fast-2025a10005o9

EARLY TAVR: A Positive Trial That Fails to Inform Clinical Decisions

https://www.medscape.com/viewarticle/early-tavr-positive-trial-fails-inform-clinical-decisions-2024a1000kec

• Reddy et al: https://doi.org/10.1016/j.jacc.2024.12.031
• Wallach editorial https://doi.org/10.1016/j.jacc.2025.01.020
• Guerrero https://www.tctmd.com/slide/tavr-young-patients-current-treatment-patterns-us

II CAC - Coronary Artery Calcium

• Coronary Artery Calcium Testing—Too Early, Too Late, Too Often https://jamanetwork.com/journals/jamacardiology/fullarticle/2830950

• CAUGHT-CAD https://jamanetwork.com/journals/jama/fullarticle/2831115

III CABG, PCI or Meds for Ischemic LV Dysfunction

• STICH https://www.nejm.org/doi/full/10.1056/NEJMoa1100356
• STICHES https://www.nejm.org/doi/full/10.1056/NEJMoa1602001
• REVIVED BCIS https://www.nejm.org/doi/full/10.1056/NEJMoa2206606
• EHJ paper https://doi.org/10.1093/eurheartj/ehaf080

IV Preview

• https://www.medscape.com/viewarticle/shed-lead-and-injuries-should-cath-labs-go-lead-free-2024a1000hnb

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