The moderate aortic stenosis TAVR trial, blinded withdrawal in the DECISION digoxin trial, CTO-PCI vs no CTO-PCI 10-year results, and the P4 trial 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: 

https://www.medscape.com/twic

I PROGRESS Trial 

PROGRESS Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2607326PROGRESS Trial Editorial https://www.nejm.org/doi/full/10.1056/NEJMe2613400Genereux Classification https://academic.oup.com/eurheartj/article/38/45/3351/4002776

II Withdrawing Digoxin in the DECISION trial 

DECISION Trial Substudy https://academic.oup.com/eurheartj/article/47/38/5545/8674856DECISION Trial - Main Trial https://www.nature.com/articles/s41591-026-04406-6Efficacy and Safety of Digitalis Glycosides in HF: Meta-analysis https://jamanetwork.com/journals/jama/fullarticle/2848972RADIANCE trial https://www.nejm.org/doi/full/10.1056/NEJM199307013290101PROVED trial https://www.jacc.org/doi/10.1016/0735-1097(93)90403-N

III DECISION CTO Trial at 10 Years 

DECISION-CTO Trial 10-Year Outcomes 10.1016/j.jacc.2026.10.068DECISION-CTO Main paper https://doi.org/10.1161/CIRCULATIONAHA.118.031313EURO-CTO trial https://eurointervention.pcronline.com/article/three-year-outcomes-of-eurocto-a-randomized-multicentre-trial-comparing-revascularization-and-optimal-medical-therapy-for-chronic-total-coronary-occlusionsCOMET-CTO trial https://pmc.ncbi.nlm.nih.gov/articles/PMC9868942/EXPLORE Trial https://www.ahajournals.org/doi/10.1161/JAHA.123.033556ORBITA-CTO trial https://www.jacc.org/doi/10.1016/j.jacc.2026.03.027

IV The P4 Trial 

Coronary CT Angiography Cuts Procedural Time Relative to IVUS-Guided PCI https://www.medscape.com/viewarticle/coronary-ct-angiography-cuts-procedural-time-relative-ivus-2026a1001684

P4 Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2610771

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 

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The ASPIRED syncope RCT, two studies in coronary artery calcium scoring, and the LEAP-Block trial of CSP vs RV pacing 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 Syncope 

ASPIRED Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2605812REMOSYNCED Trial https://clinicaltrials.gov/study/NCT05066347

II TWO CAC Studies 

Atherosclerosis in Young Adults and Risk of Mortality Over 30 Years https://jamanetwork.com/journals/jamacardiology/fullarticle/2855732Predictive Utility of CAC Score Added to PREVENT Score https://jamanetwork.com/journals/jama/fullarticle/2853347

III Conduction System Pacing vs Standard RV Pacing for AV block 

LEAP-Block Trial https://jamanetwork.com/journals/jama/fullarticle/2855975Meta-analysis: CSP vs RV Pacing in Preserved or Mildly Reduced EF https://doi.org/10.1016/j.cjca.2026.04.009

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Listener feedback on the nonobstructive HCM trials, AI-enhanced visits, timing of non-culprit PCI in STEMI, new tricuspid valve intervention, and EP at a crossroads 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 Listener Feedback

  Koelemen meta-analysis https://www.medrxiv.org/content/10.64898/2026.09.08.26362195v1.full.pdf

  Improving SCD Risk Stratification in HCM https://pmc.ncbi.nlm.nih.gov/articles/PMC11026183/

II More on Nonobstructive HCM

  Communication on Post-Hoc Analysis of ODYSSEY (mavacamten)

  Mavacamten in Nonobstructive HCM 10.1016/j.jacc.2025.12.092

III Complete vs Staged PCI in STEMI With Multivessel Disease 

  Immediate vs Staged CR in Multivessel Disease and STEMI: Meta-Analysis https://doi.org/10.1016/j.jcin.2026.07.033

  Timing of Nonculprit PCI for STEMI and Multivessel Disease: Editorial https://doi.org/10.1016/j.jcin.2026.08.009

  COMPLETE Trial https://www.nejm.org/doi/full/10.1056/NEJMoa1907775

  FLOWER MI Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2104650

  FRAME AMI Trial https://doi.org/10.1093/eurheartj/ehac763

  iMODERN Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2512918

  COCUA Trial https://doi.org/10.1016/j.ahj.2023.01.020

  MULTISTARS Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2307823

  OPTION STEMI Trial 10.1016/S0140-6736(25)01529-6 External Link

  CULPRIT SHOCK Trial https://www.nejm.org/doi/full/10.1056/NEJMoa1710261

  BioVasc Trial Substudy https://eurointervention.pcronline.com/article/immediate-versus-staged-complete-revascularisation-in-patients-presenting-with-stemi-and-multivessel-disease

  Main BioVasc Trial 10.1016/S0140-6736(23)00351-3 External Link

  FULL REVASC Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2314149

IV A Call to Action for Electrophysiologists 

  Twenty Years at the Crossroads 10.1016/j.jacep.2026.09.023

  EP at a Crossroads - Josephson 2007 https://doi.org/10.1016/j.hrthm.2006.12.045

  EP at a Crossroads: A Revisit - Josephson 2016 https://doi.org/10.1016/j.hrthm.2016.07.024

V FDA Approves Another Tricuspid Valve Repair System

  Press release https://www.edwards.com/newsroom/news/2026-10-21-fda-approval-of-edwards-lifesciences--pascal-preci

  TRIC I HF Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2606934

  CLASP II TR Trial https://pubmed.ncbi.nlm.nih.gov/42855029/

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 

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Some promising studies in amyloidosis, aficamten in nonobstructive HCM, costs of the microaxial flow pump in cardiogenic shock, and more on the VESALIUS trial of evolocumab 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 Light Chain Amyloidosis – A Potentially Helpful Drug

Anselamimab Does Not Reduce Light-Chain Amyloidosis Deaths

https://www.medscape.com/viewarticle/anselamimab-does-not-reduce-light-chain-amyloidosis-deaths-2026a1000z79

II Aficamten in Nonobstructive HCM: The ACACIA trial

III Microaxial Flow Pump Cost Analysis of Danger Shock

IV More on Evolocumab at ESC: Vesalius Trial Substudies

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

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Listener feedback on POET II, sham control trials in atrial fibrillation, ICDs in HCM, and agenda laundering 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 Listener Feedback

POET II Response-Tailored or Standard-Duration ABX for Infectious Endocarditis

POET I Trial https://www.nejm.org/doi/10.1056/NEJMoa1808312POET II Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2607887

II PVI-SHAM-AF trial Back in the News

GAP-AF Trial https://www.ahajournals.org/doi/10.1161/circep.115.003337PVI-SHAM-AF Trial 10.1016/S0140-6736(26)01558-8 External LinkWhy Sham Studies Are a Sham in 2026 10.1016/j.hrthm.2026.09.056 External LinkThe Indispensable Role of Sham Controls in Evaluating Interventional Therapies 10.1016/j.hrthm.2026.10.001 External Link

III ICDs in HCM

I CDs for the Prevention of SCD in High-Risk Patients with HCM https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.125.078597ICDs in HCM: Editorial https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.126.079687

IV Agenda Laundering

How Commercial “Agenda Laundering” Shapes Critical Care https://www.bmj.com/content/395/bmj-2026-100963

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

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Listener feedback on DANISH-CRT, the POET II trial, a mechanistic study in obesity and AF, the DANCODE trial of slowing CAC progression, and more on GLP-1 drugs are the topics John Mandrola, MD, discusses in this week's podcast.

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I Listener Feedback

DANISH-CRT Trial 10.1016/S0140-6736(26)01597-7 Identifying LV Posterior Wall Delay in RBBB Using Lead V8 https://doi.org/10.1016/j.jacep.2026.03.009 Using Lead V8 as a Tool to Improve Patient Selection in CRT https://doi.org/10.1093/europace/euaf194

II POET II Response-Tailored or Standard-Duration Antibiotics for Endocarditis

POET I https://www.nejm.org/doi/10.1056/NEJMoa1808312 POET II https://www.nejm.org/doi/full/10.1056/NEJMoa2607887

III Obesity and AF – A Neat Study from the Team in Prague

LA Remodeling and Functional Maladaptations in Obesity https://www.ahajournals.org/doi/10.1161/CIRCHEARTFAILURE.126.014509

IV Reducing CAC: The DANCODE Trial

DANCODE Trial https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.126.082363

V Two Big RCTs of New GLP-1 Drugs

TRIUMPH-1 Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2604169 SYNCHRONIZE-2 Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2607219

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

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Listener feedback, pulmonary embolism intervention, simple vs complex in BiV pacing, exercise in AF, and TAVR for paradoxical low-flow, low-gradient aortic stenosis 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 Listener Feedback LBBP ICD Lead

LEADR LBBAP Trial https://pubmed.ncbi.nlm.nih.gov/41110529/

TRIC-I-HF trial

TRIC-I-HF Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2606934 Growth of Tricuspid Interventions in Germany https://www.jacc.org/doi/10.1016/j.jcin.2025.05.030

II Treatment of Acute Intermediate-High Risk PE – the PRAGUE-26 Trial

PRAGUE-26 Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2608012

III Targeting CS leads in CRT devices – DANISH-CRT Trial

DANISH-CRT Trial 10.1016/S0140-6736(26)01597-7

IV Exercise for AF, Especially When There Is LA Disease

Physical Activity and Risk of Incident AF in Atrial Cardiomyopathy https://www.jacc.org/doi/10.1016/j.jacadv.2026.102999

V Paradoxical Low-Flow, Low-Gradient AS – REBOOT-PARADOX

REBOOT-PARADOX trial 10.1016/j.jacc.2026.08.017 ROTAS Trial https://heart.bmj.com/content/110/20/1223

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

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Another ESC recap, listener feedback on two trials, and a paper on GLP-1 effects on inflammation from the SELECT trial 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 Correction on PROFID Trial

II Listener Feedback

III Fifth Universal Definition of MI

Fifth Universal Definition of MI https://doi.org/10.1093/eurheartj/ehag101 Foy/Mandrola Editorial on Troponin Use and Interpretation https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2777967

IV New ESC HF Guidelines

ESC Guidelines for Management of HF https://doi.org/10.1093/eurheartj/ehag100 Sanjay Kaul on X https://x.com/kaulcsmc/status/2094959683215958158?s=20 Geographic Disparities in TOPCAT https://pmc.ncbi.nlm.nih.gov/articles/PMC5065247/

V AIR STEMI Trial

AIR-STEMI Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2605373 CR Strategies After MI https://www.jacc.org/doi/10.1016/j.jacc.2024.04.051 PRAMI Trial https://www.nejm.org/doi/full/10.1056/NEJMoa1305520 COMPLETE Trial https://www.nejm.org/doi/full/10.1056/NEJMoa1907775 FULL REVASC Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2314149

VI GLP-1 News – A SELECT Trial Secondary Analysis

Semaglutide and hsCRP in Patients with CVD and Obesity https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.125.074482

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

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A second ESC recap plus two breaking stories on the failure of an investigational Lp(a) reducing drug and a new FDA approval of an AI-ECG app are covered by John Mandrola, MD

This podcast is intended for healthcare professionals only.

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I Lp(a) Disappointment

HORIZON https://clinicaltrials.gov/study/NCT04023552 Press Release https://www.novartis.com/news/media-releases/novartis-announces-lpahorizon-phase-iii-topline-results-pelacarsen-patients-elevated-lpa-and-established-cardiovascular-disease-cvd Rationale paper https://doi.org/10.1016/j.ahj.2025.03.019

II FDA Clears AI-ECG for Acute MI Detection

Accuracy of cath lab activation decisions for STEMI-equivalent and mimic ECGs: Physicians vs. AI (Queen of Hearts by PMcardio) 10.1016/j.ajem.2025.07.061 AI-Enabled ECG Analysis Improves Diagnostic Accuracy and Reduces False STEMI Activations: A Multicenter U.S. Registry https://www.jacc.org/doi/10.1016/j.jcin.2025.10.018 Queen of Hearts™ AI ECG App https://www.powerfulmedical.com/pmcardio-stemi/

III TARGET CTCA Trial

Targeted Use of Computed Tomographic Coronary Angiography in Acute Chest Pain https://www.nejm.org/doi/10.1056/NEJMoa2608903

IV CorCal trial

Press release https://www.escardio.org/news/press/press-releases/new-data-presented-on-the-use-of-coronary-artery-calcium-for-cardiovascular-risk-assessment/ CorCal Outcomes: A randomized trial using the pooled cohort equation or coronary artery calcium to select statin therapy in primary prevention patients. Study design and baseline characteristics https://doi.org/10.1016/j.ahj.2026.107473

V AMUNDSEN Trial

LDL Cholesterol Lowering With Evolocumab Before Percutaneous Coronary Intervention for Acute Myocardial InfarctionThe AMUNDSEN Randomized Clinical Trial https://jamanetwork.com/journals/jama/fullarticle/2853274

VI TRIC-I-HF trial

Tricuspid Repair Cuts Death, HF Hospitalization in Severe TR https://www.medscape.com/viewarticle/tricuspid-repair-cuts-death-hf-hospitalization-severe-tr-2026a1000wvk Tricuspid-Valve Intervention in Heart Failure https://www.nejm.org/doi/full/10.1056/NEJMoa2606934

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ESC recaps on the SINGLE-AF trial, CMR Guide trial, two ATTR studies, PVI-SHAM-AF, STAREE, and an observational study of ICD benefit over the past decades are the topics John Mandrola, MD, discusses in this week's podcast.

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I SINGLE-AF Trial

To Anticoagulate or Not in Intermediate-Risk AF: The SINGLE-AF Trial https://www.medscape.com/viewarticle/anticoagulate-or-not-intermediate-risk-af-single-af-trial-2026a1000uko

SINGLE-AF https://www.nejm.org/doi/10.1056/NEJMoa2607978

II Scar as an ICD risk stratifier

Is Scar on CMR an Indication for ICD? CMR Guide Leaves Doubts

https://www.medscape.com/viewarticle/scar-cmr-indication-icd-cmr-guide-leaves-doubts-2026a1000ukq

CMTR GUIDE Trial https://jamanetwork.com/journals/jama/fullarticle/2853395 MADIT II Trial https://www.nejm.org/doi/full/10.1056/NEJMoa013474

III Single vs Dual Therapy in ATTR-CM

HELIOS-B Trial Sub-analysis https://www.sciencedirect.com/science/article/pii/S0735109726072086 HELIOS-B Sub-analysis Editorial https://www.sciencedirect.com/science/article/pii/S0735109726073766#bib8 HELIOS-B main trial https://www.nejm.org/doi/10.1056/NEJMoa2409134 CARDIO-TTRansform Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2608510

IV A Stunning Result of another Sham-controlled AF ablation trial

Does AF Ablation Work? That's in Question After PVI-SHAM-AF https://www.medscape.com/viewarticle/does-af-ablation-work-s-question-after-sham-pvi-af-2026a1000uli

PVI-SHAM-AF Trial 10.1016/S0140-6736(26)01558-8 External Link SHAM-PVI Trial https://jamanetwork.com/journals/jama/fullarticle/2823283 PFA-Sham Trial https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.126.079484

V Should Older Adults Take Statins: The STAREE trial.

STAREE Strengthens Case for Over-the-Counter Statins https://www.medscape.com/viewarticle/staree-strengthens-case-over-counter-statins-2026a1000vrw

STAREE Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2607314

VII Declining ICD Benefit After MI

Mortality Reduction with ICD for Prevention of SCD Post-MI https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehag706/8768943 CONTEMP-ICD Trial https://clinicaltrials.gov/study/NCT06543446 PROFID-EHRA Trial https://profid-project.eu/profid-ehra-trial/

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

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Listener feedback on mechanical CPR devices, PFA and stroke, the Lindy effect in adopting new technology, and an ESC preview 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 Listener Feedback on Mechanical Compression Devices for OHCA

Mechanical CPR Device Use and Cardiac Arrest Survival

https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.126.079272

PARAMEDIC trial https://www.thelancet.com/article/S0140-6736(14)61886-9/fulltext CIRC trial https://www.resuscitationjournal.com/article/S0300-9572(14)00128-2/fulltext LINC trial https://jamanetwork.com/journals/jama/fullarticle/1774037 Cochrane Review – Mechanical vs Manual Chest Compressions for Cardiac Arrest https://pmc.ncbi.nlm.nih.gov/articles/PMC6953326/

II PFA and Stroke

Risk of Stroke and TIA With PFA vs RF Ablation https://www.ahajournals.org/doi/epub/10.1161/CIRCULATIONAHA.126.081092 AVANT GUARD Trial https://www.nejm.org/do/10.1056/NEJMdo008538/full/ EMBOL-AF Registry https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehag217/8566008

III A New ICD Lead

LEADR LBBAP Trial https://doi.org/10.1016/j.hrthm.2026.08.030

IV ESC Preview

Mandrola's Preview of the European Society of Cardiology 2026 https://www.medscape.com/viewarticle/mandrolas-preview-european-society-cardiology-2026-2026a1000tfi

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Mechanical CPR devices, the dangers of AF performance measures, two scholarly articles on CLOSURE and CHAMPION, and a little ESC preview 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 Mechanical Compression Devices for OHCA

· Mechanical CPR Device Use Cardiac Arrest Survival

https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.126.079272

· PARAMEDIC Trial https://www.thelancet.com/article/S0140-6736(14)61886-9/fulltext

· CIRC Trial https://www.resuscitationjournal.com/article/S0300-9572(14)00128-2/fulltext

· LINC trial https://jamanetwork.com/journals/jama/fullarticle/1774037

· Cochrane Review of Mechanical vs Manual Chest Compressions for Cardiac Arrest https://pmc.ncbi.nlm.nih.gov/articles/PMC6953326/

II ACC AF Performance Measures

· 2026 AHA/ACC Clinical Performance for Patients With AF https://www.jacc.org/doi/10.1016/j.jacc.2026.05.032#sec-3

III Two Critical Appraisals of the recent LAAC trials

· Reappraising CHAMPION-AF 10.1016/j.hrthm.2026.07.048 External Link

· CHAMPION and CLOSURE: Reconciling Contrast Results https://doi.org/10.1093/eurheartj/ehag608

ESC Early Preview

· CMR Guide trial https://pmc.ncbi.nlm.nih.gov/articles/PMC6931571/

· SINGLE AF Trial 10.1016/j.hroo.2025.12.008 External Link

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Listener feedback, the ZEUS trial fails, a fascinating statin trial, more on GLP-1 drugs, and radiation safety in the EP lab 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 ZEUS Fails

Rethinking Inflammation and ASCVD: Four Lessons From the ZEUS Trial

https://www.medscape.com/viewarticle/rethinking-inflammation-and-ascvd-four-lessons-zeus-trial-2026a1000rlm

ZEUS Trial https://doi.org/10.1001/jamacardio.2025.4491

II Statins and the Elderly

SAGA/SITE trial 10.1016/j.lanhl.2026.100884 External Link

III GLP-1 and CV Risk

SURMOUNT-1 Trial https://www.nejm.org/doi/10.1056/NEJMoa2206038 SURMOUNT-1 Post Hoc Analysis https://www.jacc.org/doi/10.1016/j.jacc.2026.04.044 Reframing GLP-1s as Cardiometabolic Health Drugs: Editorial https://www.jacc.org/doi/10.1016/j.jacc.2026.06.039

IV Radiation Exposure to the Uterus in the EP Lab

Occupational Radiation Safety in EP During Pregnancy https://www.ahajournals.org/doi/epub/10.1161/CIRCULATIONAHA.126.080556 Survey: Working in Cath Lab During Pregnancy https://www.surveymonkey.com/share/d5c1edf7-6d99-49d4-a9fa-e9168f63ab55

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Another failure of LA posterior wall isolation, first-line AF ablation, a revelation on EAST-AFNET 4 trial, an LAAC meta-analysis, and preventing AKI post-cardiac surgery are the topics John Mandrola, MD, discusses in this week's podcast.

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I Listener Feedback

DAPT-MVD Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2517588

II Another Failure of Posterior Wall Isolation

CORNERSTONE-AF Trial https://doi.org/10.1093/eurheartj/ehag486 CAPLA Trial https://jamanetwork.com/journals/jama/fullarticle/2800186 PVIOTAL IDE Trial 10.1016/j.hrthm.2025.08.018 External Link

III First Line AF ablation – One new study and a discovery about a second one

Catheter Ablation vs AAD for First-line Treatment of AF 10.1016/j.hrthm.2025.07.061 External Link EAST-AFNET 4 Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2019422 Cardiology Trials Substack https://cardiologytrials.substack.com/p/summary-and-discussion-of-east-afnet

IV Left Atrial Appendage Closure Meta-analysis

Long-Term Efficacy and Safety of LAAC vs OAC -- Meta-analysis https://academic.oup.com/europace/article/28/7/euag159/8739567

V Prevention of AKI after Cardiac Surgery: MERCURI-2

MERCURI-2 Study https://jamanetwork.com/journals/jama/fullarticle/2852324

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The first oral PCSK9 inhibitor, another study finding safe MRI scanning in patients with nonconditional CIEDs, the PFA-SHAM trial, and the curious case of orthopedic injuries in cardiology are the topics John Mandrola, MD, discusses in this week's podcast.

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I Enlicitide Approved

First Oral PCSK9 Inhibitor Welcomed for Potential Primary Care Impact https://www.medscape.com/viewarticle/first-oral-pcsk9-inhibitor-welcomed-potential-primary-care-2026a1000own

Dr Gregory Katz Substack https://gregorykatz.substack.com/p/are-we-sure-mercks-new-cholesterol CORALreef Lipids Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2511002 CORALreef HeFH Trial https://jamanetwork.com/journals/jama/fullarticle/2841258 CORALreef Outcomes Trial https://clinicaltrials.gov/study/NCT06008756

II MRI Scans in Non-conditional CIEDs

Specialized Nurse Practitioners Safely Manage MRI in Patients With Cardiac Implantable Devices https://www.medscape.com/viewarticle/specialized-nurse-practitioners-safely-manage-mri-patients-2026a1000ozt

Nurse Practitioner-Led CIED Monitoring During MRI 10.1016/j.hroo.2026.04.031 External Link MRI in Nonconditional Pacemakers and ICDs https://academic.oup.com/europace/article/22/2/288/5717383 Heart Rhythm Society Consensus Document 10.1016/j.hrthm.2017.04.025 External Link

III PFA-SHAM trial

PFA-SHAM Trial https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.126.079484 SHAM-PVI Trial https://jamanetwork.com/journals/jama/fullarticle/2823283

IV Orthopedic Injuries in Cardiology

What Will It Take to Make Fluoroscopy Labs Safer?

https://www.medscape.com/viewarticle/what-will-it-take-make-fluoroscopy-labs-safer-2026a1000ox6

Expert Consensus Statement on Enhanced Radiation Protection https://www.jacc.org/doi/10.1016/j.jcin.2026.06.011 'Shed the Lead' and the Injuries. Should Cath Labs Go Lead-Free? https://www.medscape.com/viewarticle/shed-lead-and-injuries-should-cath-labs-go-lead-free-2024a1000hnb Health Hazards of Working in the Interventional Laboratory https://doi.org/10.1016/j.jacc.2014.11.056

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DAPT back in the news, a practice-changing trial in VTE therapy, new knowledge in sudden cardiac death, heart failure definitions updated, and a dumb decision by NICE in the UK are the topics discussed by John Mandrola, MD, in this week's podcast.

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I Antiplatelet Therapy After Stenting

DAPT-MVD Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2517588 HOST-EXAM Trial at 2 years https://pubmed.ncbi.nlm.nih.gov/34010616/ HOST-EXAM Trial at 10 years 10.1016/S0140-6736(26)00422-8 External Link Nick Kurzen on X https://x.com/ncurzen/status/2077676739463922151

II Aspirin Proves Its Mettle After Hip and Knee Replacement

EPCAT III Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2603649 CRISTAL Trial https://jamanetwork.com/journals/jama/fullarticle/2795528

III New (and old) Knowledge in Sudden Cardiac Death

Sudden Cardiac Death and its Relation to Cardiac Disease at Autopsy https://doi.org/10.1016/j.jacc.2026.01.029 Sudden Cardiac Death Due to MI With Obstructive and Nonobstructive Coronary Arteries https://doi.org/10.1016/j.jacc.2026.01.030 Frequency of Sudden Cardiac Death and Profiles of Risk https://www.ajconline.org/article/S0002-9149(97)00477-3/fulltext

IV Heart Failure Diagnosis

AHA/ACC/ESC/WHF Expert Consensus Document http://jacc.org/doi/10.1016/j.jacc.2026.05.036

V NICE Makes a Dumb Decision

NICE Recommends New Nonsteroidal MRA for Heart Failure

https://www.medscape.com/viewarticle/nice-recommends-new-nonsteroidal-mra-heart-failure-2026a1000nzv

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Listener feedback on ICE vs TEE in AF ablation, fractional flow reserve without a wire or catheter, more bad news for ticagrelor, the POLY-HF trial, and oxygen targets after cardiac arrest are the topics John Mandrola, MD, discusses in this week's podcast.

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I Listener Feedback

Oct 10, 2025 This Week in Cardiology Podcast

https://www.medscape.com/viewarticle/1002990

ICE vs TEE in Atrial Fibrillation Ablation https://jamanetwork.com/journals/jamacardiology/fullarticle/2839370

II FFR Without the Wire – Angiography-Derived FFR to Guide PCI

ALL-RISE Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2600949 FAST III Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2601841 FAVOR III Trial 10.1016/S0140-6736(24)02175-5 External Link FAME 2 Trial https://www.nejm.org/doi/full/10.1056/NEJMoa1205361 Venk Murthy on X https://x.com/venkmurthy/status/2074849421452329456?s=20

III More Bad News for Ticagrelor

Jul 11, 2025 This Week in Cardiology Podcast https://www.medscape.com/viewarticle/1002704

Prasugel, Ticagrelor, or Clopidogrel After PCI https://jamanetwork.com/journals/jamacardiology/fullarticle/2849614

IV The Polypill in Heart Failure

POLY-HF trial https://www.nature.com/articles/s41591-026-04504-5

V Oxygen Targets After Cardiac Arrest

LOGICAL Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2513814 ICU-ROX Trial https://link.springer.com/article/10.1007/s00134-020-06196-y Secondary Analysis of the PILOT Trial https://journal.chestnet.org/article/S0012-3692(25)00553-7/fulltext Oxygen Targets in Comatose Survivors of Cardiac Arrest https://www.nejm.org/doi/10.1056/NEJMoa2208686

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Listener feedback on valvular heart disease, statins and frailty, left atrial posterior wall ablation fails again, interpreting medical tests and AI ECG reading are the topics John Mandrola, MD, discusses in this week's podcast.

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I Listener Feedback

PREVUE-VALVE Study https://www.jacc.org/doi/10.1016/j.jacc.2026.02.5137

II Statins and Frailty

Statin Initiation Tied to Lower Frailty Risk in Older Adults https://www.medscape.com/viewarticle/statin-initiation-tied-lower-frailty-risk-older-adults-2026a1000lec

Statins and Survival Free of Incident Frailty https://doi.org/10.1093/eurheartj/ehag451

III LA Posterior Wall Isolation Fails Again

CORNERSTONE Trial https://doi.org/10.1093/eurheartj/ehag486 CAPLA Trial https://jamanetwork.com/journals/jama/fullarticle/2800186

IV Does the Display of Test Results Improve Clinical Decisions?

Interval Likelihood Ratios for Clinical Decsion-Making https://evidence.nejm.org/doi/full/10.1056/EVIDoa2500249 Making Sense of Health Statistics https://journals.sagepub.com/doi/full/10.1111/j.1539-6053.2008.00033.x

V AI and the ECG and Saving Doctors

Case Report — AI-Enhanced Diagnostics https://www.nature.com/articles/s41591-026-04454-y The New York Times article https://www.nytimes.com/2026/06/22/health/artificial-intelligence-heart-damage.html

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Listener feedback, more long-term data on the TAVR/SAVR question, population prevalence of valvular heart disease in the US, and a CMS proposal to expand TAVR coverage are the topics John Mandrola, MD, discusses in this week's podcast.

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I Listener Feedback

ICD Trends and Outcomes: 15-Year Analysis https://doi.org/10.1093/europace/euag110 MADIT-RIT https://www.nejm.org/doi/full/10.1056/NEJMoa1211107

II More Long Term Data on TAVR vs SAVR

PARTNER 2 Trial https://www.jacc.org/doi/10.1016/j.jacc.2026.03.169 10-Year Outcomes of SAPIEN 3 TAVR or SAVR in Intermediate-Risk Patients https://doi.org/10.1016/j.jacc.2026.03.170 TAVR at a Decade: Editorial https://doi.org/10.1016/j.jacc.2026.04.042 EVOLUT Trial https://www.jacc.org/doi/10.1016/j.jacc.2026.02.5063 Updated 5-year Outcomes of TAVR vs SAVR in AS https://heart.bmj.com/content/early/2026/02/11/heartjnl-2025-327092 NOTION Trial https://doi.org/10.1093/eurheartj/ehae043 PARTNER 3 Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2509766 NOTION 2 Trial https://academic.oup.com/eurheartj/article/45/37/3804/7673297 TAVR vs SAVR Editorial : https://academic.oup.com/eurheartj/advance-article-abstract/doi/10.1093/eurheartj/ehag407/8708044

III The PREVUE-VALVE Study

PREVUE-VALVE Study https://www.jacc.org/doi/10.1016/j.jacc.2026.02.5137

IV CMS has Proposed New Coverage for TAVR

CMS Proposal Document https://www.cms.gov/medicare-coverage-database/view/ncacal-decision-memo.aspx?proposed=Y&ncaId=321

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Listener feedback, transcatheter tricuspid valve replacement, a new metabolic disease called CKM, the ARISE-FLUIDS Trial, the BIHCA trial, and temporal trends in ICD therapies are the topics John Mandrola, MD, discusses in this week's podcast.

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I Listener Feedback

LOSE-AF Trial https://jamanetwork.com/journals/jama/fullarticle/2849335 ARREST-AF Trial https://jamanetwork.com/journals/jamacardiology/fullarticle/2840225 POP-AF Trial https://doi.org/10.1093/eurheartj/ehaf689 PRAGUE-25 Trial https://www.jacc.org/doi/10.1016/j.jacc.2025.04.042

II Transcatheter Tricuspid Valve Replacement

TRISCEND Cost Study https://doi.org/10.1016/j.shj.2026.101049 TRISCEND II Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2401918

III More Disease Creation – the CKM Syndrome

ACC/AHA Release First-Ever Guideline for CKM Syndrome https://www.medscape.com/viewarticle/acc-aha-release-first-ever-guideline-ckm-syndrome-2026a1000jbs

CKM Guideline in Circulation https://www.ahajournals.org/doi/10.1161/CIR.0000000000001447

IV Two Trials That Teach Important EBM Lessons

ARISE-FLUIDS Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2516225 Dr Josh Farkas Post on X https://x.com/PulmCrit/status/2065064796270022845?s=20

V Bicarbonate for Inpatient Cardiac Arrest –The BIHCA trial

BIHCA Trial https://jamanetwork.com/journals/jama/fullarticle/2850405

VI The Decline of VT in Heart Failure

Trends and Outcomes in ICD Recipients: 15-Year Analysis https://doi.org/10.1093/europace/euag110 Declining Risk of Sudden Death in HF https://www.nejm.org/doi/full/10.1056/NEJMoa1609758

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Chemical cardioversion in the ED, HF monitoring, weight loss in AF, and surgical LAA excision are the topics John Mandrola, MD, discusses in this week's podcast.

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I Chemical Cardioversion of AF in the ED: The FLECA-ED Trial

FLECA-ED Rationale paper https://pmc.ncbi.nlm.nih.gov/articles/PMC10299428/ FLECA-ED ESC Slides https://esc365.escardio.org/presentation/321209 Review on Flecainide Use Despite CAST https://doi.org/10.1016/j.hrthm.2025.08.034 RACE 7 ACWAS Trial https://www.nejm.org/doi/full/10.1056/NEJMoa1900353

II Heart Failure Monitoring – The ALLEVIATE-HF Trial

ALLEVIATE-HF Trial https://doi.org/10.1016/j.jacc.2026.03.075 CHAMPION Trial https://doi.org/10.1016/S0140-6736(11)60101-3 GUIDE HF Trial https://doi.org/10.1016/S0140-6736(21)01754-2 ALLEVIATE-HF Editorial: Alerts Are Not Treatment https://doi.org/10.1016/j.jacc.2026.04.014 Steve Stiles Medscape report on CHAMPION https://www.medscape.com/viewarticle/755189

III A Negative Weight Loss Study in AF

LOSE-AF Trial https://jamanetwork.com/journals/jama/fullarticle/2849335

IV Surgical LAA Excision

OPINION Trial https://doi.org/10.1093/eurheartj/ehaf674 LAAOS 3 trial https://www.nejm.org/doi/full/10.1056/NEJMoa2101897

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A life-long treatment for high LDL, a VESALIUS subanalysis, tirzepatide beats semaglutide again, arrhythmia burden in cardiac amyloidosis, and a lipid guideline rebuttal are the topics John Mandrola, MD, discusses in this week's podcast.

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I Permanent Lipid Lowering therapy

Verve 102 Therapy for FH https://www.nejm.org/doi/full/10.1056/NEJMoa2601283

II Vesalius Substudy on PCSK9i Use in Patients With Previous PCI

VESALIUS Subgroup Analysis https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.126.080616 VESALIUS Study - NEJM https://www.nejm.org/doi/full/10.1056/NEJMoa2514428

III Tirzepatide looking to be best again

SURPASS-EARLY Trial https://www.acpjournals.org/doi/10.7326/ANNALS-25-05602 SURMOUNT-5 Trial https://www.nejm.org/doi/abs/10.1056/NEJMoa2416394

IV Arrhythmias in Cardiac Amyloidosis

Loop Recorders Reveal Arrhythmias in Cardiac Amyloidosis https://www.medscape.com/viewarticle/loop-recorders-reveal-arrhythmias-cardiac-amyloidosis-2026a1000gq9

EXCALIBUR Study https://www.jacc.org/doi/10.1016/j.jacc.2026.04.030

V Lipid Guidelines

· In Defense of the 2026 Dyslipidemia Guideline https://www.medscape.com/viewarticle/defense-2026-dyslipidemia-guideline-2026a1000hd0

Lipid Guidelines: Four Major Concerns https://www.medscape.com/viewarticle/lipid-guidelines-four-major-concerns-2026a1000fim

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Three more digoxin trials, yet another GLP-1 drug on the horizon, vagal nerve stimulation, trial inside baseball, and more on lipid guidelines are the topics John Mandrola, MD, discusses in this week's podcast.

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I More About Low-dose Digoxin in HF — The DECISION Trial(s)

DECISION Trial https://www.nature.com/articles/s41591-026-04406-6 Digitalis Glycosides in HF — JAMA Meta-Analysis https://jamanetwork.com/journals/jama/fullarticle/2848972 DIGIT-HF Trial https://www.nejm.org/doi/10.1056/NEJMoa2415471 RADIANCE Trial (1993) https://www.nejm.org/doi/full/10.1056/NEJM199307013290101 DECISION Withdrawal Study https://doi.org/10.1093/eurheartj/ehag385 Digoxin Discontinuation vs Continuation in Chronic HF https://doi.org/10.1016/j.amjcard.2007.02.099

II Yet another GLP-1 Drug Announced this Week

Lillly News Release on Retatrutide https://investor.lilly.com/news-releases/news-release-details/lillys-triple-agonist-retatrutide-delivered-powerful-weight-loss

III A Big Story in HF Science – Vagal Nerve Stimulation in HFrEF

ANTHEM HFrEF trial https://doi.org/10.1016/j.jacc.2026.03.040 Editorials

An Unfinished ANTHEM https://doi.org/10.1016/j.jacc.2026.04.033

When Trials Stop Prematurely https://doi.org/10.1016/j.jacc.2026.03.039

IV Lipid Guideline News

Lipid Guidelines: Four Major Concerns

https://www.medscape.com/viewarticle/lipid-guidelines-four-major-concerns-2026a1000fim

Editorial: Time to Move Beyond the Statin Nocebo Effect https://www.jacc.org/doi/10.1016/j.jacc.2026.04.002 Correspondence: SAMSON N-of-1 Trial of Statin, Placebo, or No Treatment https://www.nejm.org/doi/full/10.1056/NEJMc2031173

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Another positive digoxin trial, another classic coronary physiology study from Imperial College London (ORBITA-FIRE), news in hypertrophic cardiomyopathy, and TAVR done in the wrong patients are the topics John Mandrola, MD, discusses in this week's podcast.

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I Digoxin in Rheumatic Heart Disease

Dig-RHD Trial https://jamanetwork.com/journals/jama/fullarticle/2848973 Safety and Efficacy of Digoxin: Meta-Analysis https://www.bmj.com/content/351/bmj.h4451.long DIGIT-HF Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2415471 DIG Trial https://www.nejm.org/doi/full/10.1056/NEJM199702203360801 RADIANCE Trial https://www.nejm.org/doi/full/10.1056/NEJM199307013290101

II The Physiologic Threshold for Angina

ORBITA-FIRE Trial https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.125.078738

III Prediction in Hypertrophic Cardiomyopathy

Predictors of Long-Term Outcomes in HCM https://jamanetwork.com/journals/jama/fullarticle/2848800#250998713

IV TAVR Trends in Young Patients

Temporal Trends in AVR for Aortic Stenosis in Patients Wall Street Journal article https://www.wsj.com/health/healthcare/heart-valve-tavr-surgery-aorta-1e0eda70

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Listener feedback from the DanGer Shock investigators, complete vs staged revascularization, polygenic risk scores, and quality improvement failure in an RCT are the topics John Mandrola, MD, discusses in this week's podcast.

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I Listener Feedback

DanGer Shock Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2312572 CHIP-BCIS 3 Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2515704

II Immediate Complete vs Staged Revascularization in STEMI

Meta-analysis: Timing of Complete Revasc in Patients with STEMI and Multivessel Disease https://www.ahajournals.org/doi/10.1161/CIRCINTERVENTIONS.126.016601 COMPLETE Trial https://www.nejm.org/doi/full/10.1056/NEJMoa1907775 FULL REVASC Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2314149 iMODERN Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2512918

III Polygenic Risk Scores for Prediction

Polygenic Risk Report in US-Based Hospitals for 8 CV Conditions https://www.jacc.org/doi/10.1016/j.jacc.2026.03.035

IV Practice Improvement Policies Undergo the Proper Test – Randomization

Quality Improvement on Hospitalizations and Health Outcomes for People with CHD https://www.ahajournals.org/doi/10.1161/CIRCOUTCOMES.125.012904

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Time to quadruple therapy, the disappointing AVANT GUARD trial, PFA risks, the TREAT-PVC trial, and NSTEMI care in the frail elderly are the topics John Mandrola, MD, discusses in this week's podcast.

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I Time to Quadruple Therapy in HFrEF

Time to Quadruple Therapy After Diagnosis of HFrEF https://jamanetwork.com/journals/jamacardiology/fullarticle/2846899

II AVANT GUARD

PFA Bests Meds as First-Line Treatment for Persistent AF in Randomized Trial https://www.medscape.com/viewarticle/pulsed-field-ablation-bests-meds-first-line-treatment-2026a1000dsm

Pulsed Field Ablation of AF Disappoints in Setup for Success: AVANT GUARD https://www.medscape.com/viewarticle/pulsed-field-ablation-af-disappoints-setup-success-avant-2026a1000ddt

AVANT GUARD Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2600929 Persistent AF: Meta-analysis of Invasive Strategies 10.1016/j.ijcard.2018.11.127 External Link

III Speaking of Scary News on PFA – The TIFFANY Study

Abstract - The TIFFANY Study https://www.heartrhythmjournal.com/article/S1547-5271(26)01747-9/fulltext Delayed Myocardial Ischemia and Malignant Arrhythmias After PFA https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.125.077983 Alberto Alfie Comment https://x.com/ALFIEEP1/status/2050029151315189774?s=20

IV TREAT PVC Trial

TREAT-PVC Trial https://doi.org/10.1016/j.jacep.2026.01.011 TREAT-AF Study 2020 https://doi.org/10.1016/j.jacep.2019.11.008

V NSTEMI In Frail Older Patients

SENIOR-RITA Trial https://www.nejm.org/doi/10.1056/NEJMoa2407791 Subanalysis of Senior RITA Trial https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2847995 Timing of Invasive Strategy in Patients With Non-ST-Elevation Acute Coronary Syndrome -- Meta-analysis https://doi.org/10.1016/S0140-6736(17)31490-3

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PCSK9 inhibitors in high-risk diabetes without ASCVD, the CAAN-AF trial, conduction system pacing vs biventricular pacing, PFA and stroke, and therapeutic fashion infects expert consensus 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 VESALIUS-CV

VESALIUS-CV Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2514428 JAMA Substudy https://jamanetwork.com/journals/jama/fullarticle/2847162

II How Best to Maximize CRT Benefit in Patients with AF

CAAN-AF Trial https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehag206/8654625?searchresult=1 Role of AV Node Ablation: Meta-analysis of Observational Studies https://www.jacc.org/doi/10.1016/j.jacc.2011.10.891

III Stroke Rates in PFA vs Thermal Ablation

Comparative Safety of RF versus PFA for AF in a High-Volume US Medical Center https://esc365.escardio.org/Ehra-congress/sessions/18281

IV Five New CSP Studies Presented and Published

HeartSync-LBBP Trial https://jamanetwork.com/journals/jamacardiology/fullarticle/2845803 PhysioSync-HF Trial

https://jamanetwork.com/journals/jamacardiology/fullarticle/2845802

LEFT-BUNDLE-CRT Trial https://doi.org/10.1093/eurheartj/ehag225 Long-Term Follow-up of His-Alternative I Trial https://www.jacc.org/doi/10.1016/j.jacep.2026.02.016 LECART Trial https://esc365.escardio.org/Ehra-congress/sessions/17140

V New EP Training Document Published

Advanced Training Statement on Clinical Cardiac Electrophysiology https://www.jacc.org/doi/10.1016/j.jacc.2026.01.074

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SPIRIT-HF, another spironolactone trial in HFpEF; the ESSENCE imaging study of the drug olezarsen; the SirPAD trial in peripheral artery disease; and ultrasound-guided femoral venous access are the topics John Mandrola, MD, discusses in this week's podcast.

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I ACC: SPIRIT-HF Trial

FINEARTS-HF Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2407107 TOPCAT Trial https://www.nejm.org/doi/full/10.1056/NEJMoa1313731 TOPCAT Americas Trial https://www.ahajournals.org/doi/10.1161/circulationaha.114.013255

II A New Class of Lipid Lowering Drug Has a Dubious Debut At ACC

ESSENCE-TIMI 73b Imaging Study https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.126.080012 ESSENCE-TIMI 73b Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2507227 IMPROVE IT Trial https://www.nejm.org/doi/full/10.1056/NEJMoa1410489

III Drug-Coated Balloons Looked Quite Good in PAD interventions

Sirolimus-Coated Balloon Reduces Amputation Risk in Peripheral Artery Disease

https://www.medscape.com/viewarticle/sirolimus-coated-balloon-reduces-amputation-risk-peripheral-2026a1000a83

SirPAD trial https://www.nejm.org/doi/full/10.1056/NEJMoa2600360

IV Another Vascular Story from the European Heart Rhythm Association

ULYSSES Trial https://doi.org/10.1093/eurheartj/ehag291 ULTRA-FAST Trial https://doi.org/10.1093/europace/eux175

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Three imaging-guided PCI trials (two with surprising results), LDL targets, an oral PCSK9 inhibitor, and another beta-blocker withdrawal trial are the topics John Mandrola, MD, discusses in this week's podcast.

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I IVUS-Guided PCI

OPTIMAL Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2600440 IVUS-CHIP Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2601521 ILUMIEN IV Trial https://www.nejm.org/doi/10.1056/NEJMoa2305861 DKCRUSH VIII Trial https://doi.org/10.1016/j.jacc.2026.01.081

II Ez-PAVE Trial — Low vs Very Low LDL-targets

Does Ez-PAVE Support 'Lower Is Better' for LDL-C? https://www.medscape.com/viewarticle/does-ez-pave-support-lower-better-ldl-c-2026a1000akx

Ez-PAVE Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2600283 2026 ACC/AHA Lipid Guidelines https://www.ahajournals.org/doi/10.1161/CIR.0000000000001423

III CORALreef AddOn

CORALreef AddOn Trial https://www.jacc.org/doi/abs/10.1016/j.jacc.2026.03.036 This Week in Caardiology 2-6-26 https://www.medscape.com/viewarticle/1003240 CORALreef Lipids Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2511002

IV Another Post-MI Beta-blocker Withdrawal Study: SMART-DECISION

SMART-DECISION Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2601005 ABYSS Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2404204

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John Mandrola offers an ACC recap of 5 big trials—Hi-PEITHO, PROTAVI, ORBITA-CTO, CHIPS-BCIS3 and CHAMPION AF

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I Catheter Based Fibrinolysis of Pulmonary Embolism –Hi PEITHO

Fibrinolysis Treatment Validated in Large Trial for Acute Intermediate-Risk PE https://www.medscape.com/viewarticle/fibrinolysis-treatment-validated-large-trial-acute-2026a10009im Ultrasound-Facilitated, Catheter-Directed Fibrinolysis for Acute Pulmonary Embolism (HI PEITHO) https://www.nejm.org/doi/full/10.1056/NEJMoa2516567 National Early Warning Score (NEWS) https://www.england.nhs.uk/ourwork/clinical-policy/sepsis/nationalearlywarningscore/

II PRO-TAVI trial

Deferral of percutaneous coronary intervention in patients undergoing transcatheter aortic valve implantation (PRO-TAVI) 10.1016/S0140-6736(26)00308-9 External Link PCI in Patients Undergoing Transcatheter Aortic-Valve Implantation (Notion 3) https://www.nejm.org/doi/full/10.1056/NEJMoa2401513

III ORBITA CTO Sham vs PCI for Angina Relief

Tightly Blinded Trial Confirms PCI Reduces Angina in Obstructive Occlusion https://www.medscape.com/viewarticle/tightly-blinded-trial-confirms-pci-reduces-angina-2026a10009ob A Randomized, Placebo-Controlled Trial of Chronic Total Occlusion Percutaneous Coronary Intervention in Stable Angina - ORBITA-CTO https://www.jacc.org/doi/10.1016/j.jacc.2026.03.027 ORBITA 1 10.1016/S0140-6736(17)32714-9 External Link ORBITA 2 https://www.nejm.org/doi/full/10.1056/NEJMoa2310610 DECISION CTO https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.118.031313 EuroCTO https://doi.org/10.1093/eurheartj/ehy220

IV CHIPS BCIS3 Impella Supported High-Risk PCI

Adoption Before Evidence: CHIP-BCIS3 Humbles Impella https://www.medscape.com/viewarticle/adoption-before-evidence-chip-bcis3-humbles-impella-2026a10009jh Left Ventricular Unloading in High-Risk PCI (CHIP BCIS3) https://www.nejm.org/doi/full/10.1056/NEJMoa2515704 Microaxial Flow Pump or Standard Care in Infarct-Related Cardiogenic Shock (DanGer Shock) https://www.nejm.org/doi/full/10.1056/NEJMoa2312572

V CHAMPION AF – Watchman vs DOAC in Patients With AF

CHAMPION-AF Trial Finds LAAC an Alternative for NOAC in Lower-Risk Patients https://www.medscape.com/viewarticle/champion-af-trial-finds-laac-alternative-noac-lower-risk-2026a10009ij Six Reasons Why CHAMPION-AF Should Not Change Practice https://www.medscape.com/viewarticle/six-reasons-why-champion-af-should-not-change-practice-2026a10009i7 Left Atrial Appendage Closure or Anticoagulation for Atrial Fibrillation (CHAMPION AF) https://www.nejm.org/doi/full/10.1056/NEJMoa2517213 Left Atrial Appendage Closure or Medical Therapy in Atrial Fibrillation (CLOSURE AF) https://www.nejm.org/doi/full/10.1056/NEJMoa2513310

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Early aortic valve replacement in aortic stenosis, left atrial appendage occlusion in JAMA Cardiology, and a big preview of the upcoming American College of Cardiology meeting are the topics John Mandrola, MD, discusses in this week's podcast.

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I Early AVR

RECOVERY Trial at 10 Years https://www.nejm.org/doi/full/10.1056/NEJMoa2511920

II Major Bleeding with Amulet and Watchman in JAMA Cardiology

Amulet IDE Trial https://jamanetwork.com/journals/jamacardiology/fullarticle/2847047 5-year Results From Amulet IDE https://www.jacc.org/doi/10.1016/j.jacc.2024.10.101

III ACC Preview

Mandrola's Top 4 Trials from ACC 2026: Details Matter

https://www.medscape.com/viewarticle/mandrolas-top-4-trials-acc-2026-details-matter-2026a10008ti

CHIB-BCIS3 Trial https://www.ahajournals.org/doi/10.1161/CIRCINTERVENTIONS.123.013367 Champion-AF Protocol https://doi.org/10.1016/j.ahj.2023.05.022 ORBITA-CTO Protocol Paper https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2023.1172763/full SPIRIT-HF Clinical Trials.gov https://clinicaltrials.gov/study/NCT04727073

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Listener feedback, the huge CLOSURE-AF trial of LAAC vs best medical therapy, previews of CHAMPION AF, and the controversial ACC/AHA lipid treatment guidelines are the topics John Mandrola, MD, discusses in this week's podcast.

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I Listener Feedback

COBRRA Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2510703

Closure AF published in NEJM

CLOSURE-AF Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2513310 CHAMPION AF Rationale - Watchman FLX vs DOACs in Patients With AF https://pubmed.ncbi.nlm.nih.gov/37279840/

LIPID Guidelines

ACC/AHA Joint Committee Guideline on Management of Dyslipidemia https://www.jacc.org/doi/10.1016/j.jacc.2025.11.016

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Beta-blocker in non-obstructive hypertrophic cardiomyopathy, a head-to-head apixaban vs rivaroxaban RCT, diltiazem vs metoprolol combined with DOAC, and the accuracy of smart watches for AF are the topics John Mandrola, MD, discusses in this week's podcast.

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I Listener Feedback

EMPATICC trial https://academic.oup.com/eurheartj/article/47/9/1034/8242490

II Beta-blocker in Non-obstructive HCM

BB vs Calcium Channel Blocker in Non-obstructive HCM https://doi.org/10.1016/j.jacc.2025.11.028 RCT of Metoprolol in Patients With Obstructive HCM https://doi.org/10.1016/j.jacc.2021.07.065

III Apixaban vs Rivaroxaban for Bleeding Risk

COBRRA Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2510703 AMPLIFY Trial (Apixaban) https://www.nejm.org/doi/10.1056/NEJMoa1302507 EINSTEIN Trial (Rivaroxaban) https://www.nejm.org/doi/full/10.1056/NEJMoa1007903

IV Diltiazem vs Metoprolol When Combined with DOAC

Risk for Bleeding in AF Patients Using Apixaban or Rivaroxaban With Diltiazem https://www.acpjournals.org/doi/10.7326/ANNALS-25-01408

V Actual Clinical Use of Smart Watches

CIRCA-DOSE Original Trial https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.119.042622 Wearable Smartwatches for AF Detection After Ablation https://doi.org/10.1093/europace/euaf280

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Listener feedback, urgent AF ablation, AF ablation as a stroke-reducing therapy, implantable loop recorder accuracy, and HF management in the setting of serious disease are the topics John Mandrola, MD, discusses in this week's podcast.

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I Urgent AF ablations

Urgent vs Elective AF Ablation in the US https://www.jacc.org/doi/10.1016/j.jacep.2025.12.030

II AF Ablation Is Not Likely a Good Therapy for Stroke Reduction

STABLED Trial https://jamanetwork.com/journals/jamaneurology/fullarticle/2845745 Catheter Ablation for AF Associated With Lower Incidence of Stroke https://doi.org/10.1093/eurheartj/ehw087

III Loop Recorders

ILR Accuracy - Multicenter, Multidevice Comparison https://doi.org/10.1016/j.jacep.2025.12.039

IV Heart Failure Therapy when there is Cancer

EMPATICC Trial https://doi.org/10.1093/eurheartj/ehaf705

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A superb note on CPR and DNR orders, patients' vs doctors' preferences for statins, more on GLP-1s, another LAAC story, and some closing cautionary notes on PFA are the topics John Mandrola, MD, discusses in this week's podcast.

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I Listener Feedback

Addressing Inadequate Documentation of Unilateral DNR https://jamanetwork.com/journals/jama/fullarticle/2829203 Video: Can We Talk About CPR? https://www.youtube.com/watch?v=yTCRfY3ETvI Personal Reminiscences of CPR's Origin https://www.ajconline.org/article/S0002-9149(03)00977-9/pdf

II Public Preferences for Statin Therapy

Measuring Public Preferences for Statin Therapy https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2844660

III GLP-1 RA News

ACHIEVE Trial https://doi.org/10.1016/S0140-6736(26)00202-3

IV New Trial in GLP-1 for Patients with AF

Seminal-AF Trial https://clinicaltrials.gov/study/NCT06499857

V Relationship between Spontaneous Echo Contrast and LAAC Outcomes

OCEAN-LAAC Trial https://doi.org/10.1016/j.jacep.2025.09.028 News Release on Upcoming LAAOS-4 trial https://www.phri.ca/watchman/ Reading the "Smoke" -- Editorial on OCEAN-LAAC https://www.jacc.org/doi/10.1016/j.jacep.2025.10.029

VI Concluding Remarks on My Talk at Western AF

Delayed Myocardial Ischemia and Malignant Arrhythmias After PFA https://www.ahajournals.org/doi/abs/10.1161/CIRCULATIONAHA.125.077983

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EVOLUT Low Risk data, a provocative meta-analysis, DNR orders, targeted hypothermia, good news in HFpEF evidence, and GLP-1s as AF drugs are the topics John Mandrola, MD, discusses in this week's podcast.

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I EVOLUT Low Risk 6-year Results and a 5-year Meta-Analysis of TAVR vs SAVR

6-Year Outcomes of TAVR vs SAVR https://www.jacc.org/doi/10.1016/j.jacc.2026.02.5063 EVOLUT Low Risk Trial at 2 years https://www.nejm.org/doi/full/10.1056/NEJMoa1816885 EVOLUT Low Risk Trial at 3 years https://www.jacc.org/doi/10.1016/j.jacc.2023.02.017 EVOLUT Low Risk Trial at 4 years https://www.jacc.org/doi/10.1016/j.jacc.2023.09.813 Nonproportional Hazards for Time-to-Event Outcomes in Clinical Trials https://www.jacc.org/doi/10.1016/j.jacc.2019.08.1034 TAVR vs SAVR 5-Year Outcomes - Systematic Review https://heart.bmj.com/content/early/2026/02/11/heartjnl-2025-327092 TAVR vs SAVR Updated Meta-Analysis of RCTs https://www.jacc.org/doi/10.1016/j.jacc.2024.12.031 UK TAVI Trial https://jamanetwork.com/journals/jama/fullarticle/2792251 Dr David Cohen on X https://x.com/djc795/status/2023556582030852172?s=46&t=zXMCUoVjSsdyemzWlzeBjA

II DNR in the Hospital

Inadequate Documentation of Unilateral DNR Orders https://jamanetwork.com/journals/jama/fullarticle/2829203 GeriPal Blog Unilateral DNR Orders https://geripal.org/unilateral-dnr-gina-piscitello-erin-demartino-will-parker/

III Yet another failure of Targeted Hypothermia

2-Year Follow-Up of TTM2 Trial https://jamanetwork.com/journals/jamaneurology/fullarticle/2845193 TTM2 Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2100591

IV Good news in HFpEF Evidence

ALT-FLOW II Trial https://doi.org/10.1093/ejhf/xuaf016

V GLP-1 as AF drugs

Semaglutide as Adjunctive Therapy in Obesity-Related PAF https://doi.org/10.1093/europace/euag018

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Ticagrelor vs prasugrel, a new LAAC device, pulsed field ablation AF results, lifestyle intervention in AF, the term "provider" vs "doctor," and coffee are the topics John Mandrola, MD, discusses in this week's podcast.

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I TUXEDO-2 Trial

TUXEDO-2 Trial https://jamanetwork.com/journals/jamacardiology/fullarticle/2844869 ISAR-REACT 5 Trial https://www.nejm.org/doi/full/10.1056/NEJMoa1908973

II VERITAS Study of Dual-Seal LAAO

VERITAS Study https://doi.org/10.1016/j.jacep.2026.01.021

III PFA vs RF over 4 years

Advent-LTO study https://www.nature.com/articles/s41591-026-04246-4 ADVENT Study https://www.nejm.org/doi/full/10.1056/NEJMoa2307291 SPHERE PER-AF Study https://www.nature.com/articles/s41591-024-03022-6 SINGLE SHOT CHAMPION Study https://www.nejm.org/doi/full/10.1056/NEJMoa2502280 BEAT PAROX-AF Trial https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehaf1115/8436829

IV What's in a Name — Use of the Term "Provider"

Physicians Are Not Providers: The Ethical Significance of Names https://www.acpjournals.org/doi/10.7326/ANNALS-25-03852

V Coffee and Dementia Risk

Coffee/Tea Intake and Dementia Risk https://jamanetwork.com/journals/jama/fullarticle/2844764 Mandrola Commentary: Enough With the Coffee Research and Other Distractions https://www.medscape.com/viewarticle/883709

VI Lifestyle interventions Post AF ablation

Improving Outcomes of AF by Lifestyle Interventions https://academic.oup.com/eurheartj/article/47/6/669/8243674

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Problems with the PREVENT score, a breakthrough in lipid-lowering therapy, a surprising benefit in stroke care, and more thoughts on statins and preventive care of heart disease are the topics John Mandrola, MD, discusses in this week's podcast.

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I PREVENT Score

PREVENT Equations in Young Adults https://doi.org/10.1016/j.jacc.2025.12.019 Hospital Readmission Reduction Program for HF

https://pmc.ncbi.nlm.nih.gov/articles/PMC7664458/

II A New Breakthrough in LDL-C Management With an Oral PCSK9 Inhibitor

https://www.medscape.com/viewarticle/time-overcome-pcsk9i-inertia-new-data-future-options-2025a1000wf8

CORALreef Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2511002 CORALreef Outcomes Trial https://clinicaltrials.gov/study/NCT06008756

III A Win for the Factor XI Inhibitor Asundexian – OCEANIC Stroke Trial

https://www.medscape.com/viewarticle/first-clear-win-factor-xia-inhibitors-stroke-reduced-2026a10003t0

OCEANIC-STROKE Slide deck https://clinicaltrialresults.org/wp-content/uploads/2026/02/26-02-02_ISC_OCEANIC-STROKE-primary.pdf OCEANIC-AF Study Stopped Early https://www.bayer.com/media/en-us/oceanic-af-study-stopped-early-due-to-lack-of-efficacy/

IV Statin Side Effects

Assessment of AEs Attributed to Statins -- Meta-analysis https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(25)01578-8/fulltext N-of-1 Trial to Assess AEs of Statins https://www.nejm.org/doi/full/10.1056/NEJMc2031173 When to Start a Statin Is a Decision About Preference -- Editorial https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.117.029808

V Heart Disease Statistics

CV Statistics in the US, 2026 https://www.jacc.org/doi/10.1016/j.jacc.2025.12.027

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Listener feedback, huge news in the rapidly expanding world of PFA AF Ablation, obesity, and a beautiful trial studying an AI-enhanced diagnostic tool in the office are the topics discussed by John Mandrola, MD, in this week's podcast.

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I Listener Feedback

Risk-Based TEE Omission in PVI 10.1016/j.hrthm.2025.04.056 External Link

II PFA News

BEAT PAROX-AF trial https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehaf1115/8436829 Life-Threatening Delayed Myocardial Ischemia and Malignant Arrhythmias Occurring After PFA https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.125.077983 Heart Rhythm TV: Life-Threatening Delayed Myocardial Ischemia and Malignant Arrhythmias https://www.youtube.com/watch?v=M-npoLKmRa4 MAUDE Adverse Event report https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfmaude/detail.cfm?mdrfoi__id=23733351&pc=QZI

III Obesity trends

US State-Level Obesity Trends 1990-2022 and Forecasted to 2035 https://jamanetwork.com/journals/jama/fullarticle/2844495

IV New Tools in the Office

TRICORDER Trial https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(25)02156-7/fulltext

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Listener feedback, the value of procedural volume for TAVR and MTEER, ventricular arrhythmia in older athletes, and the Goldilocks time horizon for predicting and modifying CV risk 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 Procedural Volume and Outcomes for TAVI and M-TEER

Operator Procedural Volumes and Outcomes for TAVR and MTEER https://jamanetwork.com/journals/jamacardiology/fullarticle/2843740

II Ventricular Arrhythmia in Older Male Endurance Athletes

Myocardial Fibrosis May Raise Arrhythmia Risk in Older Male Endurance Athletes

https://www.medscape.com/viewarticle/myocardial-fibrosis-may-raise-arrhythmia-risk-older-male-2026a10001y0

Timing and Relationship of VA With Exercise Patterns in Older Male Endurance Athletes https://doi.org/10.1093/eurjpc/zwag021

III Predicting Cardiac Risk and Statin Use

30-Year ASCVD Risk Among US Adults Aged 30-59 https://www.ahajournals.org/doi/10.1161/CIRCOUTCOMES.125.012348

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Some great listener feedback, one of the best studies of the year in atrial fibrillation and heart failure, imaging to exclude left atrial thrombus, and a truly amazing first cardiac procedure 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 Listener Feedback

On Fish Oil and AF

Links between omega-3 fatty acids and AF https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.121.058596 Omega-3 and risk of AF https://doi.org/10.1016/j.pcad.2024.11.003 DHA vs EPA in reducing vulnerability to AF https://www.ahajournals.org/doi/10.1161/CIRCEP.112.971515

II Withdrawal of HF Therapy AF rhythm control

The AF is Gone, the EF Is Up. Can You Stop the HF Meds?

https://www.medscape.com/viewarticle/af-gone-ef-can-you-stop-hf-meds-2024a1000h6o

Effect of beta-blockers in patient with HF plus AF -- meta-analysis https://pubmed.ncbi.nlm.nih.gov/25193873/ TRED HF Trial 10.1016/S0140-6736(18)32484-X External Link WITHDRAW-AF Trial https://academic.oup.com/eurheartj/article/47/2/250/8238240

III ICE or TEE Before AF Ablation

ICE vs TEE in Atrial Fibrillation Ablation https://jamanetwork.com/journals/jamacardiology/fullarticle/2839370

IV The Vector Procedure

Percutaneous Aorto-Coronary Bypass Graft: the VECTOR procedure https://www.ahajournals.org/doi/10.1161/CIRCINTERVENTIONS.125.016130

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The limits of knowing coronary artery disease anatomy, fish oil and AF risk, a new drug for PSVT, and maybe I was wrong about a drug for AF conversion (the RAFF4 trial). These 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 Prediction of CAD is hard — even if you have anatomy

CCTA in Prediction of First Coronary Events https://jamanetwork.com/journals/jama/fullarticle/2841255

II Fish Oil and AF (and as a bonus we learn again about analytic flexibility)

Are Fish Oils on the Hook for AF Risk?

https://www.medscape.com/viewarticle/995290

Omega-3 and Fish Oil Use With Risk of AF https://www.ahajournals.org/doi/full/10.1161/JAHA.125.043031 Effect of Long-Term Marine Omega-3 Fatty Acids on the Risk of AF https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.121.055654 RESPECT-EPA Trial https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.123.065520 Association Between Omega-3 Fatty Acids and AF: Meta Analysis https://link.springer.com/article/10.1007/s10557-021-07204-z Fish Oil Supplements and Risk of AF https://academic.oup.com/eurjpc/article/29/14/1911/6679610 Editorial: Fish Oil Supplements and AF Risk https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.121.057464

III A New Drug for PSVT

FDA Approval https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-drug-type-abnormally-fast-heart-rhythm RAPID trial https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)00776-6/fulltext

IV AF Conversion with Vernakalant

RAFF4 Trial https://www.bmj.com/content/391/bmj-2025-085632.long Editorial: Rapid Cardioversion for Acute AF https://www.bmj.com/content/391/bmj.r2264

VI A Quick Note on HFpEF

Med Op-Ed: Avalanche Survival, HFpEF Skepticism, and More

https://www.medscape.com/viewarticle/med-op-ed-avalanche-survival-hfpef-skepticism-and-more-2026a1000012

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The MI paradox of risk scores, the CELEBRATE trial of a new subcutaneous glycoprotein IIb/IIIA inhibitor (with its funny endpoint), the SURPASS CVOT trial, and the bad story of andexanet alfa 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 What do risk scores mean for individuals? Or perhaps a better question: Is a first MI preventable?

Limitations of Screening in Predicting First MI https://www.jacc.org/doi/10.1016/j.jacadv.2025.102361 Sudden Death Due to Cardiac Arrhythmias https://www.nejm.org/doi/abs/10.1056/NEJMra000650 UMC Amsterdam group (EHJ) https://academic.oup.com/eurheartj/article/46/38/3762/8181058

II CELEBRATE Trial

CELEBRATE Trial https://evidence.nejm.org/doi/full/10.1056/EVIDoa2500268

III SURPASS CVOT Trial Published

Aug 01, 2025 This Week in Cardiology Podcast

https://www.medscape.com/viewarticle/1002781

SURPASS-CVOT Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2505928 REWIND Trial 10.1016/S0140-6736(19)31149-3 External Link

IV FDA Pulls Andexanet Alfa From the Market

ANNEXA 4 https://www.nejm.org/doi/10.1056/NEJMoa1814051 ANNEXA I https://www.nejm.org/doi/full/10.1056/NEJMoa2313040 Richard Buka Tweet https://x.com/richardbuka/status/2001045834050216327?s=20

V Mandrola's Top Cardiovascular Stories of 2025

https://www.medscape.com/viewarticle/mandrolas-top-10-cardiovascular-stories-2025-2025a1000yuh

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An elegant study in post-TAVI atrioventricular block, a PSA for my structural colleagues, revascularization in women, and a CTO PCI trial 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 AV Block After TAVR

Heart Blocks During vs After TAVR Show Distinct Patterns

https://www.medscape.com/viewarticle/heart-blocks-during-vs-after-tavr-show-distinct-patterns-2025a1000ypp

Mechanisms Underlying Alterations in Cardiac Conduction After TAVR https://jamanetwork.com/journals/jamacardiology/fullarticle/2842748

II Related PSA Announcement to My Structural Colleagues

III Revascularization Strategies in Women with Severe Chronic CAD

Women With Chronic Severe CAD Fare Better With CABG vs PCI

https://www.medscape.com/viewarticle/women-chronic-severe-cad-fare-better-cabg-vs-pci-2025a1000ygd

PCI vs CABG in Women With Chronic CAD https://doi.org/10.1093/eurheartj/ehaf806 PCI vs CABG - Meta-Analysis of 4 RCTs https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02334-5/abstract CABG vs Drug-Eluting Stent Implantation for CAD - Meta-Analysis https://www.jacc.org/doi/10.1016/j.jcin.2016.10.008 RECHARGE trial https://therechargetrial.com/

IV A CTO PCI RCT – But don't get your hopes up

Early vs Late-Staged PCI After Subintimal Tracking and Re-entry for CTO https://doi.org/10.1016/j.jacc.2025.09.1598 DECISION CTO trial https://pubmed.ncbi.nlm.nih.gov/30813758/ National Inpatient Sample Database PCI CTO Associated With Higher Mortality https://pubmed.ncbi.nlm.nih.gov/37356643/

V Mandrola's Top 10 Stories

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Less is more after PCI, the TARGET-FIRST trial, a negative blood pressure trial that is actually positive, aspirin vs OAC for bleeding, AEDs, and Factor XI is not dead yet are the topics discussed by John Mandrola, MD, on this week's podcast.

This podcast is intended for healthcare professionals only.

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I Less is More: TARGET-FIRST

TARGET-FIRST Trial https://www.nejm.org/doi/10.1056/NEJMoa2508808 STOPDAPT-2 ACS Trial https://jamanetwork.com/journals/jamacardiology/fullarticle/2789701

II A Negative Trial That Is Actually Positive

The RETREAT-FRAIL Study https://www.nejm.org/doi/full/10.1056/NEJMoa2508157

III Major Bleeding With Aspirin vs Apixaban

Subanalysis of ARTESiA https://jamanetwork.com/journals/jamacardiology/fullarticle/2841075 ARTESiA Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2310234 AVERROES Trial https://www.nejm.org/doi/full/10.1056/NEJMoa1007432

IV High Value Interventions – The AED

Experts Call for AED Placement on All Commercial Aircraft https://www.medscape.com/viewarticle/experts-call-aed-placement-all-commercial-aircraft-2025a1000xzf In-Flight Sudden Cardiac Arrest and AED Use 10.1016/j.cjca.2025.10.010 External Link

V Factor XI Inhibitors – OCEANIC STROKE trial

Bayer Press Release on Asundexian https://www.bayer.com/en/us/news-stories/oceanic-stroke

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Listener feedback, huge news in the world of carotid disease with the CREST-2 publication, prasugrel beats ticagrelor again, and a big coffee trial 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

Complete Revascularization for Acute MI Meta-analysis https://doi.org/10.1016/S0140-6736(25)02170-1

II A Sea Change in the Treatment of Carotid Artery Disease — CREST-2 Published

ECST-2 https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(25)00107-3/fulltext SPACE-2 https://pubmed.ncbi.nlm.nih.gov/36115360/ CREST-2 Trial www.nejm.org/doi/full/10.1056/NEJMoa2508800 CREST Protocol paper https://pmc.ncbi.nlm.nih.gov/articles/PMC5987521/

III Prasugrel Beats Ticagrelor in High-Risk Patients With Diabetes After PCI https://www.medscape.com/viewarticle/prasugrel-beats-ticagrelor-high-risk-patients-diabetes-after-2025a1000wbt

PLATO trial https://www.nejm.org/doi/full/10.1056/NEJMoa0904327 Ticagrelor or prasugrel vs clopidogrel in PCI https://eurointervention.pcronline.com/article/ticagrelor-or-prasugrel-versus-clopidogrel-in-patients-undergoing-percutaneous-coronary-intervention-for-chronic-coronary-syndromes ISAR-REACT 5 trial https://www.nejm.org/doi/full/10.1056/NEJMoa1908973

IV Another Coffee and AF study

Can Coffee Cut the Risk for Atrial Fibrillation?

https://www.medscape.com/viewarticle/can-coffee-cut-risk-atrial-fibrillation-2025a1000w11

A Coffee a Day to Keep the AFib Away? The DECAF Trial Discussed https://www.medscape.com/viewarticle/coffee-day-keep-afib-away-decaf-trial-discussed-2025a1000v5z

DECAF trial https://jamanetwork.com/journals/jama/fullarticle/2841253

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Listener feedback on the PISCES trial, AHA news (including a big PCSK9i trial), beta-blockers post MI, LAAC, and post-AF ablation OAC use 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

Why I Believe Fish Oil's Big CV Benefit in Dialysis Patients https://www.medscape.com/viewarticle/why-i-believe-fish-oils-big-cv-benefit-dialysis-patients-2025a1000uzg

PISCES trial https://www.nejm.org/doi/full/10.1056/NEJMoa2513032

II PCSK9 Inhibitor News

In Global Trial, PCSK9 Inhibitor Provides Major Protection Against First CV Event https://www.medscape.com/viewarticle/global-trial-pcsk9-inhibitor-provides-major-protection-2025a1000uzp

VESALIUS-CV trial https://www.nejm.org/doi/full/10.1056/NEJMoa2514428 ODYSSEY trial https://www.nejm.org/doi/full/10.1056/NEJMoa1801174 FOURIER https://www.nejm.org/doi/full/10.1056/NEJMoa1615664 Anish Koka Tweet on LDL-lowering https://x.com/anish_koka/status/1987280506937909326?s=20

III Beta-Blockers After MI and John Cleland

Beta-Blockers after MI with normal EF https://www.nejm.org/doi/full/10.1056/NEJMoa2512686 REBOOT-CNIC trial https://www.nejm.org/doi/full/10.1056/NEJMoa2504735 REDUCE AMI trial https://academic.oup.com/ehjcvp/article/9/2/192/6895544?login=false ABYSS trial https://www.nejm.org/doi/full/10.1056/NEJMoa2404204 CAPITAL RCT trial https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0199347 Beta-Blockers after MI with mildly reduced EF https://pubmed.ncbi.nlm.nih.gov/40897190/ John Cleland Clinical Outlook https://www.nature.com/articles/s41569-025-01228-w

IV Left Atrial Appendage Closure – The CLOSURE-AF trial

Percutaneous LAAC in AF Falls Short Again in CLOSURE-AF https://www.medscape.com/viewarticle/percutaneous-left-atrial-appendage-closure-af-falls-short-2025a1000uzu

Prague-17 Trial https://www.jacc.org/doi/10.1016/j.jacc.2020.04.067 OPTION trial https://www.nejm.org/doi/full/10.1056/NEJMoa2408308

V Oral AC after AF ablation – the OCEAN Trial

Anticoagulation After AF Ablation: The OCEAN Trial Still Leaves Questions https://www.medscape.com/viewarticle/anticoagulation-after-af-ablation-ocean-trial-still-leaves-2025a1000v4t

OCEAN Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2509688 ALONE-AF trial https://jamanetwork.com/journals/jama/fullarticle/2838294

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Listener feedback on non-culprit PCI in STEMI, a major cardiac result in patients on hemodialysis, news on GLP-1 agonists, a dubious stroke trial, and an AHA preview 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

Meta-analysis of MI as a surrogate https://pubmed.ncbi.nlm.nih.gov/34694318/ Compare Acute Trial https://www.nejm.org/doi/full/10.1056/NEJMoa1701067 DANAMI-3–PRIMULTI 10.1016/S0140-6736(15)60648-1 External Link CULPRIT-SHOCK https://www.nejm.org/doi/full/10.1056/NEJMoa1710261

II Huge Cardiac News for Patients with ESRD PISCES article EMBARGOED Till 1130 AM EST

PISCES Trial www.nejm.org/doi/full/10.1056/NEJMoa2513032 REDUCE-IT Trial https://www.nejm.org/doi/full/10.1056/NEJMoa1812792 STRENGTH Trial https://jamanetwork.com/journals/jama/fullarticle/2773120 FISH trial https://jamanetwork.com/journals/jama/fullarticle/1150094

III Obesity Agents

White House announces deal with Lilly and Novo on GLP-1 drugs https://www.reuters.com/business/healthcare-pharmaceuticals/novo-lilly-shares-rise-trump-obesity-drug-deal-nears-2025-11-06/

Amylin Agonists

Amylin Analog Eloralintide Reduces Weight in Phase 2 Trial

https://www.medscape.com/viewarticle/amylin-analog-eloralintide-reduces-weight-phase-2-trial-2025a1000uqf

Eloralintide Phase 2 Study https://doi.org/10.1016/S0140-6736(25)02155-5

GLP-1 Comparisons

SURMOUNT-5 Trial https://www.nejm.org/doi/10.1056/NEJMoa2416394 Tirzepatide vs Semaglutide in 10-year CVD Risk Reduction https://doi.org/10.1093/ehjopen/oeaf117

IV A Problematic Trial in Stroke Care

LAMP trial https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2840370

V AHA Preview

AHA 2025: Mandrola's Four Trials to Look For https://www.medscape.com/viewarticle/aha-2025-mandrolas-four-trials-look-2025a1000u80

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Four pillars of cardiology today, stable coronary artery disease, severe aortic stenosis, the evaluation of chest pain, and best therapies for atrial fibrillation 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 Stable CAD Complete vs culprit-only revascularization at time of STEMI

iMODERN Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2512918 PRAMI Trial https://www.nejm.org/doi/full/10.1056/NEJMoa1305520 COMPLETE Trial https://www.nejm.org/doi/full/10.1056/NEJMoa1907775 FULL REVASC Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2314149 PCI Revascularization Strategies After MI https://www.jacc.org/doi/10.1016/j.jacc.2024.04.051 CULPRIT SHOCK Trial https://www.nejm.org/doi/full/10.1056/NEJMoa1710261 How a Meta-Analysis Can Mislead https://www.sensible-med.com/p/how-a-meta-analysis-can-misleadthe

II SEVERE Aortic Senosis

7-Year PARTNER 3 Results – TAVI vs SAVR

7-year results PARTNER 3 https://www.nejm.org/doi/full/10.1056/NEJMoa2509766 PARTNER 3 at 1 year https://www.nejm.org/doi/10.1056/NEJMoa1814052 PARTNER 3 at 5 years https://www.nejm.org/doi/10.1056/NEJMoa2307447

III Functional vs Anatomic Assessment in Suspected CAD

10-year follow-up of PROMISE trial https://jamanetwork.com/journals/jamacardiology/fullarticle/2838118 PROMISE Trial https://www.nejm.org/doi/10.1056/NEJMoa1415516 CCTA vs Functional Stress Test – Meta-Analysis https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2655243

IV ARREST AF

ARREST AF trial https://jamanetwork.com/journals/jamacardiology/fullarticle/2840225

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The PREVENT score in hypertension, GLP-1 mechanism of action in cardiovascular disease, CAD type and statin benefit, and the problem with hospitalization endpoints in HF 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 Is the PREVENT Calculator Best for Determining CVD Risk? Insights From a Post Hoc Analysis of SPRINT Trial

https://www.medscape.com/viewarticle/prevent-calculator-best-determining-cvd-risk-insights-post-2025a1000svo

PREVENT Calculator https://doi.org/10.1016/j.jacc.2025.07.037 SPRINT Trial https://www.nejm.org/doi/full/10.1056/NEJMoa1511939

II GLP-1 Mechanism of Action in CV Disease

Analysis of SELECT Trial 10.1016/S0140-6736(25)01375-3 External Link SELECT trial https://www.nejm.org/doi/full/10.1056/NEJMoa2307563

III Statins and CAD Phenotype on CTA and Outcomes

Interactions Between Statin Use, CAD Phenotypes on CTA https://www.jacc.org/doi/10.1016/j.jcmg.2025.05.018 Statin Use for Primary Prevention of CVD https://jamanetwork.com/journals/jama/fullarticle/2795522

IV HHF Endpoints in Heart Failure Trials

The Problem with Hospitalization Endpoints in HF Trials https://onlinelibrary.wiley.com/doi/10.1002/ejhf.70070

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