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.

This podcast is intended for healthcare professionals only.

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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.

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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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The treatment of asymptomatic aortic stenosis, the move to composite endpoints in trials, IFR vs FFR and high-frequency low tidal volume ventilation for AF ablation are the topics John Mandrola, MD, discusses in today's podcast.

This podcast is intended for healthcare professionals only.

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I Aortic valve intervention for Asymptomatic AS

• Lindman editorial https://jamanetwork.com/journals/jamacardiology/fullarticle/2829881
• Trends https://pmc.ncbi.nlm.nih.gov/articles/PMC11308430/
• Podcast EARLY TAVR Nov 8, 2024 This Week in Cardiology Podcast https://www.medscape.com/viewarticle/1001865
• Faith Healing and Subtraction Anxiety https://www.ahajournals.org/doi/10.1161/circoutcomes.118.004665
• Early TAVR trial https://www.nejm.org/doi/10.1056/NEJMoa2405880
• EVOLVED https://jamanetwork.com/journals/jama/fullarticle/2825540
• AVATAR https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.121.057639

II Trial Endpoints

• Shepshelovich https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2830023
• Brown meta-analysis https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2785560

III IFR vs FFR—a debate b/w RCTs and observational data

• 5-year DEFINE https://jamanetwork.com/journals/jamacardiology/fullarticle/2824470
• 5-year SwedeHeart IFR https://doi.org/10.1016/j.jacc.2021.12.030
• Eftekhari meta-analysis https://doi.org/10.1093/eurheartj/ehad582
• Gotberg SWEDEHEART Registry https://doi.org/10.1016/j.jcin.2024.12.003
• Editorial of SWEDEHEART-Registry https://doi.org/10.1016/j.jcin.2024.12.014

IV High-frequency low-tidal-volume ventilation for AF ablation

• Osorio et al https://doi.org/10.1016/j.hrthm.2024.07.094

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Blanking period after AF ablation, periprocedural MI after PCI in non-STEMI, predicting AF after ischemic stroke, and the proper standards for mitral valve repair in primary mitral regurgitation are the topics John Mandrola, MD, discusses in today’s podcast.

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I AF blanking period

• CIRCA DOSE Research letter https://www.ahajournals.org/doi/10.1161/CIRCEP.124.013232
• Circa-Dose https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.119.042622
• COMPARE CRYO  https://doi.org/10.1016/j.jacep.2024.03.021
• Mohanty et al  10.1016/j.hrthm.2024.08.011
• Ruzieh, Foy, Mandrola Patients’ Lives Don’t Pause for Blanking Periods https://doi.org/10.1016/j.ahjo.2024.100497

II Periprocedural MI and Future events

• Circulation paper https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.124.070729

III AI to detect AF related stroke

• eClinical Medicine Paper  https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(25)00050-1/fulltext

IV Mitral Valve Repair

• JACC paper -- https://doi.org/10.1016/j.jacc.2024.10.108

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Silent cerebral embolism after LAAC, AI in ECG rhythm analysis, anti-thrombotic strategies in patients with AF and CAD, and subclinical AF are the topics John Mandrola, MD, covers in today’s podcast.

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I. Silent Cerebral Embolism after LAAC

• JAHA Case Series  https://www.ahajournals.org/doi/10.1161/JAHA.124.037968
• JACC  https://doi.org/10.1016/j.jacc.2018.12.039

II. AI Transforming Rhythm Monitor Reading

• Johnson and colleagues RCT https://www.nature.com/articles/s41591-025-03516-x

III. Anticoagulation Alone or OAC plus antiplatelets in patients with CAD and AF

• Rashedi and colleagues Meta-analysis https://doi.org/10.1016/j.jacc.2024.12.030
• AQUATIC https://clinicaltrials.gov/study/NCT04217447

IV. DOAC for Subclinical AF – A Subgroup Analysis of ARTESIA

Anticoagulation Uncertainty in Embolic Stroke of Undetermined Source https://www.medscape.com/viewarticle/anticoagulation-uncertainty-embolic-stroke-undetermined-2024a1000h5e

• Lancet Neurology Subgroup Analysis of ARTESIA 10.1016/S1474-4422(24)00475-7
• ARTESIA https://www.nejm.org/doi/full/10.1056/NEJMoa2310234
• NOAH https://www.nejm.org/doi/full/10.1056/NEJMoa2303062
• RE-SPECT ESUS https://www.nejm.org/doi/full/10.1056/NEJMoa1813959
• NAVIGATE ESUS https://www.nejm.org/doi/full/10.1056/NEJMoa1802686

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