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.

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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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Another knock against the antiplatelet/anticoagulant combo, polypills in HF, the physical exam of the future, and the problem of underpowered trials that even Bayesian analyses cannot rescue 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

• Trends Study https://www.heartrhythmjournal.com/article/S1547-5271(11)00496-6/fulltext

II Another knock against the Antiplatelet/Anticoagulation combination

"Antiplatelet Plus Oral Anticoagulant Lowers Stroke, Raises Bleeding Risk" https://www.medscape.com/viewarticle/antiplatelet-plus-oral-anticoagulant-lowers-stroke-raises-2025a1000re0

• ATIS-NVAF Trial https://jamanetwork.com/journals/jamaneurology/fullarticle/2839511
• AQUATIC trial https://www.nejm.org/doi/abs/10.1056/NEJMoa2507532

III Polypill for HFrEF

• A Multilevel Polypill for Patients With HFrEF https://www.jacc.org/doi/10.1016/j.jacadv.2025.102195

IV The Physical Exam of the Future

• Point-of-Care Ultrasound https://doi.org/10.1016/j.jchf.2025.102707

V More on Underpowered Trials – GA vs Moderate Sedation in IV stroke

• SEGA Trial https://jamanetwork.com/journals/jamaneurology/fullarticle/2839838
• Bayesian Analyses of CV Trials https://doi.org/10.1016/j.cjca.2021.03.014

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GLP-1 use in HFrEF, left atrial posterior wall isolation during AF ablation, peri-device leaks for LAAO, new findings in post-cardiac surgery AF, and imaging before AF ablation 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

HYPERION trial https://www.nejm.org/doi/10.1056/NEJMoa2508170

ZENITH trial https://www.nejm.org/doi/full/10.1056/NEJMoa2415160

II GLP1 Use in HFrEF

Effects of GLP-1s in Patients With HFrEF https://doi.org/10.1016/j.jchf.2025.102573

FIGHT Study https://jamanetwork.com/journals/jama/fullarticle/2540402

FIGHT Study Post-hoc Analysis https://dom-pubs.pericles-prod.literatumonline.com/doi/10.1111/dom.14862

Substudy of EXSCEL Trial https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.119.041659

III LA Posterior Wall Isolation Saga

Failure of PW Wall Isolation by PFA with Epicardial Mapping https://doi.org/10.1016/j.jacep.2025.08.017

IV Peridevice Leaks After LAAO

IMPRESSION LAAC Study https://doi.org/10.1016/j.jacep.2025.08.014

V Post Cardiac Surgery AF

Monitoring of New-Onset AF After CABG https://jamanetwork.com/journals/jama/fullarticle/2839710

PACES trial https://clinicaltrials.gov/study/NCT04045665

VI TEE vs ICE Before AF ablation

ICE vs TEE Study https://jamanetwork.com/journals/jamacardiology/fullarticle/2839370

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Two great stories of translation science leading to beneficial drugs in terrible diseases of the heart and the Sisyphean task of predicting the need for pacing after TAVI 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 Sotatercept

• HYPERION Trial https://www.nejm.org/doi/10.1056/NEJMoa2508170
• ZENITH Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2415160
• Evidence report on treatment for PAH https://icer.org/news-insights/press-releases/icer-publishes-final-evidence-report-on-treatment-for-pulmonary-arterial-hypertension/
• PAH Sotatercept Editorial https://www.nejm.org/doi/full/10.1056/NEJMe2503944

II Acoramidis and ATTR Cardiomyopathy

• ATTRIBUTE-CM Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2305434?logout=true
• ATTRIBUTE-CM Analysis - Substudy https://www.jacc.org/doi/10.1016/j.jacc.2025.09.013
• Tafamadis Trial https://www.nejm.org/doi/full/10.1056/NEJMoa1805689

III Pacing After TAVI

• Prophylactic pacemaker after TAVI https://www.jacc.org/doi/10.1016/j.jacep.2025.07.028
• PROMOTE study https://doi.org/10.1016/j.hrthm.2024.12.019
• Evaluation of ESC criteria on RBBB patients undergoing TAVI https://doi.org/10.1016/j.hrthm.2024.11.030
• Editorial on Heart Rhythm journal papers https://www.heartrhythmjournal.com/article/S1547-5271(25)00114-6/abstract

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A bold trial in valvular heart disease, a CV prevention trial whose message is humility, VTE dogma challenged, more news on oral GLP-1 agonists, and a few public service announcements 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 DOUBLE-CHOICE: Minimalist Approach to TAVI May Be as Good as Standard of Care https://www.medscape.com/viewarticle/double-choice-minimalist-approach-tavi-may-be-good-standard-2025a1000pp7

• Patient & Physician Perspectives on CV Risk https://www.ahajournals.org/doi/10.1161/CIRCOUTCOMES.124.011837

II KP Vaccinate Trial

• KP Vaccinate Trial https://evidence.nejm.org/doi/full/10.1056/EVIDoa2500208
• IAMI trial https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.121.057042
• Increasing Flu Vaccinations in Patients With Chronic Disease https://jamanetwork.com/journals/jama/fullarticle/2824956
• MI FREEE Trial https://www.nejm.org/doi/full/10.1056/NEJMsa1107913

III Hi PRO Trial

• Apixaban for Extended Treatment of VTE https://www.nejm.org/doi/full/10.1056/NEJMoa2509426
• Recurrent VTE in Patients with Provoked VTE https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/226140

IV Oral GLP-1 Agonists

• ATTAIN 1 Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2511774

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More trials at ESC, including PARACHUTE HF, DAPA ACT HF-TIMI 68, AMALFI, and a super-interesting modeling study of when to start oral anticoagulants in AF, 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 PARACHUTE HF

First Evidence of Treatment Benefit in Chagas Heart Failure

https://www.medscape.com/viewarticle/first-evidence-treatment-benefit-chagas-heart-failure-2025a1000oem

• PARACHUTE-HF https://www.jacc.org/doi/10.1016/j.jchf.2024.05.021

II SGLT2i Early Initiation — DAPA ACT HF-TIMI 68 Trial

Trial Data Support In-Hospital Initiation of SGLT2 Inhibitors for Heart Failure https://www.medscape.com/viewarticle/trial-data-support-hospital-initiation-sglt2-inhibitors-2025a1000o5q

• DAPA ACT HF-TIMI 68

https://www.ahajournals.org/doi/abs/10.1161/CIRCULATIONAHA.125.076575

III AMALFI Trial of AF Screening

Remote ECG Screening Ups Atrial Fibrillation Detection 'Modestly' https://www.medscape.com/viewarticle/remote-ecg-screening-ups-atrial-fibrillation-detection-2025a1000myx

• AMALFI Trial https://jamanetwork.com/journals/jama/article-abstract/2838482
• STROKESTOP Trial https://www.thelancet.com/article/S0140-6736(21)01637-8/fulltext
• LOOP Trial 10.1016/S0140-6736(21)01698-6 External Link

IV Finding that Sweet Spot of Stroke Risk Threshold for Starting DOAC therapy

• Stroke Risk Threshold for non-Vitamin K Antagonist OAC in AF https://www.ahajournals.org/doi/10.1161/CIRCOUTCOMES.125.012090
• Variations in Rates of Stroke Across Patients With AF https://www.ahajournals.org/doi/10.1161/circulationaha.116.024057

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More from ESC including: Valvular HD guidelines, a new drug class for HTN, myosin inhibition in HCM, vericiguat, and digoxin are the topic discussed by John Mandrola, MD.

This podcast is intended for healthcare professionals only.

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I New European Valvular Heart Disease Guidelines

• 2025 ESC/EACTS Guidelines for the management of valvular heart disease https://doi.org/10.1093/eurheartj/ehaf194
• Debate: Does Asymptomatic Aortic Stenosis Warrant Early Intervention? https://exp.medscape.com/debates/does-asymptomatic-aortic-stenosis-warrant-early-intervention/
• Surgical Ablation of Atrial Fibrillation during Mitral-Valve Surgery https://www.nejm.org/doi/full/10.1056/NEJMoa1500528
• Surgical ablation of atrial fibrillation: a systematic review and meta-analysis https://doi.org/10.1093/europace/eux336

II New Drug for Resistant HTN

• Baxdrostat: A 'Game Changer' for Hypertension? https://www.medscape.com/viewarticle/baxdrostat-game-changer-hypertension-2025a1000mz7

• Efficacy and Safety of Baxdrostat in Uncontrolled and Resistant Hypertension https://www.nejm.org/doi/full/10.1056/NEJMoa2507109
• Lorundrostat Efficacy and Safety in Patients with Uncontrolled Hypertension https://www.nejm.org/doi/10.1056/NEJMoa2501440

III HCM News at ESC

• New Trials Clarify Role of Myosin Inhibitors for Hypertrophic Cardiomyopathy https://www.medscape.com/viewarticle/new-trials-clarify-role-myosin-inhibitors-hypertrophic-2025a1000myv

• MAPLE HCM https://www.nejm.org/doi/full/10.1056/NEJMoa2504654
• SEQUOIA HCM https://www.nejm.org/doi/10.1056/NEJMoa2401424
• ODYSSEY HCM https://www.nejm.org/doi/full/10.1056/NEJMoa2505927

IV Vericiguat at ESC

• New Data Said to Support Vericiguat as Standard Therapy for Heart Failurehttps://www.medscape.com/viewarticle/new-data-said-support-vericiguat-standard-therapy-heart-2025a1000mz9

• VICTOR https://doi.org/10.1016/S0140-6736(25)01665-4
• VICTORIA https://www.nejm.org/doi/full/10.1056/NEJMoa1915928
• An individual participant data analysis of the VICTORIA and VICTOR trials https://doi.org/10.1016/S0140-6736(25)01682-4

V More on Digoxin

• RATE AF substudy https://doi.org/10.1002/ejhf.70022
• Main RATE-AF trial https://jamanetwork.com/journals/jama/fullarticle/2774407
• Efficacy of β blockers in patients with heart failure plus atrial fibrillation: an individual-patient data meta-analysis https://doi.org/10.1016/S0140-6736(14)61373-8

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