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.

This podcast is intended for healthcare professionals only.

To read a partial transcript or to comment, visit:

https://www.medscape.com/twic

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.

This podcast is intended for healthcare professionals only.

To read a partial transcript or to comment, visit:

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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

This podcast is intended for healthcare professionals only.

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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.

This podcast is intended for healthcare professionals only.

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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.

This podcast is intended for healthcare professionals only.

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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.

This podcast is intended for healthcare professionals only.

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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.

This podcast is intended for healthcare professionals only.

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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.

This podcast is intended for healthcare professionals only.

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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.

This podcast is intended for healthcare professionals only.

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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.

This podcast is intended for healthcare professionals only.

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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.

To read a partial transcript or to comment, visit:

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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.

To read a partial transcript or to comment, visit:

https://www.medscape.com/twic

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:

https://www.medscape.com/twic

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.

To read a partial transcript or to comment, visit:

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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.

To read a partial transcript or to comment, visit:

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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.

To read a partial transcript or to comment, visit:

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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.

To read a partial transcript or to comment, visit:

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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.

To read a partial transcript or to comment, visit:

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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.

To read a partial transcript or to comment, visit:

https://www.medscape.com/twic

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 ? 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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The big beta-blocker story from ESC, dual pathway therapy with aspirin and OAC, stopping OAC after successful AF ablation, and DANCAVAS II trial are the topics John Mandrola, MD, discusses on 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 Listener Feedback

This Week in Cardiology Podcast ? August 29 https://www.medscape.com/viewarticle/1002877

II The Big Beta-blocker Story from ESC

Beta-Blockers Post-MI: A Clear Clinical Message https://www.medscape.com/viewarticle/beta-blockers-post-mi-clear-clinical-message-2025a1000mz0

REBOOT https://www.nejm.org/doi/full/10.1056/NEJMoa2504735 BETAMI-DANBLOCK https://www.nejm.org/doi/abs/10.1056/NEJMoa2505985 REDUCE AMI https://www.nejm.org/doi/10.1056/NEJMoa2401479 CAPITAL RCT https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0199347 Post Hoc Analysis From REBOOT Trial https://eurointervention.pcronline.com/article/effect-of-beta-blocker-withholding-or-withdrawal-after-myocardial-infarction-without-reduced-ejection-fraction-on-ischaemic-events-a-post-hoc-analysis-from-the-reboot-trial Beta-Blockers After MI With Mildly Reduced Ejection Fraction https://doi.org/10.1016/S0140-6736(25)01592-2 CAPRICORN 10.1016/S0140-6736(00)04560-8 External Link BHAT https://jamanetwork.com/journals/jama/fullarticle/370103 ISIS 1 https://pubmed.ncbi.nlm.nih.gov/2873379/

III Aspirin and OAC Combination Clearly Dangerous

Aspirin Plus Oral Anticoagulants Raises Mortality, Bleeding https://www.medscape.com/viewarticle/aspirin-plus-oral-anticoagulants-raises-mortality-bleeding-2025a1000nam

AQUATIC https://www.nejm.org/doi/full/10.1056/NEJMoa2507532 AFIRE https://www.nejm.org/doi/full/10.1056/NEJMoa1904143 EPIC CAD https://www.nejm.org/doi/10.1056/NEJMoa2407362 OAC-ALONE  https://pubmed.ncbi.nlm.nih.gov/30586700/

IV Stop or Continue OAC after Successful AF Ablation

ALONE-AF https://jamanetwork.com/journals/jama/fullarticle/2838294 OCEAN trial protocol https://doi.org/10.1016/j.ahj.2017.12.007

V DANCAVAS II Trial

DANCAVAS II https://doi.org/10.1093/eurheartj/ehaf704 DANCAVAS I https://www.nejm.org/doi/full/10.1056/NEJMoa2208681

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CAC 0 takes a gut punch, ICD therapies cannot be surrogates for benefit, and two important trials from ESC 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 CAC 0

LDL-C and CVD Risk With CAC Score 0 https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehaf497/8228645

II ICD Therapies

Contemporary ICD Benefit https://www.jacc.org/doi/10.1016/j.jacep.2025.06.028 PROFID Trial https://profid-project.eu/profid-ehra-trial/ MADIT-RIT Trial https://www.nejm.org/doi/full/10.1056/NEJMoa1211107 Declining Risk of Sudden Death in HF https://www.nejm.org/doi/full/10.1056/NEJMoa1609758

III Digit-HF

DIGIT-HF Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2415471 Digoxin?Mortality: Comparison in the DIG trial https://academic.oup.com/eurheartj/article/40/40/3336/5520008

IV POTCAST

POTCAST trial https://www.nejm.org/doi/full/10.1056/NEJMoa2509542

ESC Preview

IV HTN Guidelines

New Blood Pressure Guidelines: 4 Things I Like and 2 Concerns  https://www.medscape.com/viewarticle/new-blood-pressure-guidelines-4-thing-i-and-2-concerns-2025a1000m1x

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John Mandrola discusses conduction system pacing vs standard pacing, withdrawing HF meds when AF is corrected and patient selection in LAAO.

This podcast is intended for healthcare professionals only.

To read a partial transcript or to comment, visit:

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I Conduction System Pacing

CSPACE trial https://doi.org/10.1016/j.jacc.2025.06.043 BLOCK HF trial https://www.nejm.org/doi/full/10.1056/NEJMoa1210356 BioPace trial https://doi.org/10.1093/europace/euaf029

II  Withdrawing Meds After AF Corrected

WITHDRAW AF https://doi.org/10.1093/eurheartj/ehaf563 TRED HF https://pubmed.ncbi.nlm.nih.gov/30429050/

III Patient Selection in Left Atrial Appendage Occlusion

Long-Term Outcomes Following LAAO in Medicare Beneficiaries: Outcomes From the National Cardiovascular Data Registry https://www.ahajournals.org/doi/10.1161/JAHA.124.039780

ESC Preview

IV HTN Guidelines

New Blood Pressure Guidelines: 4 Things I Like and 2 Concerns https://www.medscape.com/viewarticle/new-blood-pressure-guidelines-4-thing-i-and-2-concerns-2025a1000m1x

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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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Big new hypertension guidelines, ultraprocessed foods, coronary sinus reduction and evidence-based medicine, and more news on pulsed field ablation 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 HTN Guidelines

BP Meds Should Begin Promptly, New ACC/AHA Guidelines Say

https://www.medscape.com/viewarticle/bp-meds-should-begin-promptly-new-acc-aha-guidelines-say-2025a1000lms

Guideline for Management of High Blood Pressure https://www.ahajournals.org/doi/10.1161/CIR.0000000000001356 BPROAD trial https://www.nejm.org/doi/full/10.1056/NEJMoa2412006 Trial Score Framework https://pmc.ncbi.nlm.nih.gov/articles/PMC6459598/

II UltraProcessed Foods

AHA statement on Ultraprocessed Foods and Cardiometabolic Health https://www.ahajournals.org/doi/full/10.1161/CIR.0000000000001365

III Refractory Angina and the Coronary Sinus Reducer ? A Lesson in EBM

Coronary Sinus Reducer Shows Promise, With Caveats https://www.medscape.com/viewarticle/coronary-sinus-reducer-shows-promise-caveats-2025a1000l76 Coronary Sinus Reducer ? Meta-analysis https://www.jacc.org/doi/10.1016/j.jcin.2025.06.012 COSIRA II Trial https://clinicaltrials.gov/study/NCT05102019

IV Pulsed Field Ablation Still Looking Strong

Management of OACs After PFA 10.1016/j.hrthm.2025.03.1952 External Link

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Listener feedback on SURPASS CVOT, AF ablation and the limits of meta-analyses, a Watchman alert from FDA, and oral anticoagulation choices in elderly patients are discussed by John Mandola, MD, in this week's podcast.

This podcast is intended for healthcare professionals only.

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I SURPASS CVOT

This Week in Cardiology Podcast, August 1 https://www.medscape.com/viewarticle/1002781 Mounjaro Appears More Heart Protective Than Trulicity in Trial Of Eli Lilly Diabetes Drugs

https://www.medscape.com/s/viewarticle/mounjaro-proves-more-heart-protective-than-trulicity-trial-2025a1000kct

II Catheter and Surgical AF ablation

Catheter and Surgical Ablation for AF: Meta-Analysis https://www.acpjournals.org/doi/10.7326/ANNALS-25-00253

III Watchman Air Embolism Alerts

Looming Pay Cut to LAAO Triggers Objection From Card Groups

https://www.medscape.com/viewarticle/looming-pay-cut-laao-triggers-objection-card-groups-2025a1000l0j

FDA Alert https://www.fda.gov/medical-devices/medical-device-recalls/early-alert-watchman-access-system-issue-boston-scientific

IV Switching Oral Anticoagulants in Frail Older Adults Patients

FRAIL AF Trial https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.123.066485 COMBINE AF Substudy https://doi.org/10.1016/j.jacc.2025.05.060 The Most Important Study From ESC: FRAIL-AF https://www.medscape.com/viewarticle/996063

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Exercise and CV outcomes, aldosterone modulation, AI for ECG reading, GLP-1 comparisons, end-of-life decisions, and another well-meaning policy that caused harm in veterans are discussed by John Mandrola, MD, in this week's podcast.

This podcast is intended for healthcare professionals only.

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I Exercise and CV outcomes

II Aldosterone Modulation in Cardio-Kidney Disease

Aldosterone and Aldosterone Modulation https://doi.org/10.1016/j.jacc.2025.06.012 Randomized Aldactone Evaluation Study https://www.nejm.org/doi/full/10.1056/NEJM199909023411001

III AI vs MD ECG-Reading for Cath Lab Activation

Accuracy of Cath Lab Activation Decisions https://doi.org/10.1016/j.ajem.2025.07.061

IV Tirzepatide vs Dulaglutide - SURPASS CVOT Study

Eli Lilly Press Release https://investor.lilly.com/news-releases/news-release-details/lillys-mounjaro-tirzepatide-gipglp-1-dual-agonist-demonstrated REWIND Study 10.1016/S0140-6736(19)31149-3 External Link

V End-of-Life Decisions

Doctors' Own End-of-Life Choices Defy Common Medical Practice

https://www.medscape.com/viewarticle/doctors-own-end-life-choices-defy-common-medical-practice-2025a1000k01

Physicians' Preferences for Their Own End of Life https://jme.bmj.com/content/early/2025/06/05/jme-2024-110192 How US Doctors Die: A Cohort Study https://agsjournals.onlinelibrary.wiley.com/doi/full/10.1111/jgs.14112

VI Well-Meaning Policies That Make Sense
 

The Mission Act and Cardiovascular Procedures https://jamanetwork.com/journals/jama/fullarticle/2837067

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The VENTOUX study of endurance athletes, the 10,000 step myth was not busted, rate vs rhythm control for AF, and GLP1 drugs and observational studies 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 Endurance Athletes and Arrhythmia (again)

VENTOUX trial

https://www.ahajournals.org/doi/10.1161/CIRCIMAGING.125.018470

II Daily Step Count and Health ? no myths were busted.

Lancet Public Health: https://doi.org/10.1016/S2468-2667(25)00164-1

III Rate vs Rhythm Control of AF

Medscape: Everyone Deserves a Shot at the American Dream: Sinus Rhythm

https://www.medscape.com/viewarticle/everyone-deserves-shot-american-dream-sinus-rhythm-2025a1000jle

This Week in Cardiology, July 11, 2025 https://www.medscape.com/viewarticle/1002704 AFFIRM trial https://www.nejm.org/doi/full/10.1056/NEJMoa021328 AFFIRM substudy https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/486560

IV GLP-1 Drugs and Observational Studies

Neurodegeneration and Stroke After Semaglutide and Tirzepatide

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2836412

SUSTAIN-6 https://www.nejm.org/doi/full/10.1056/NEJMoa1607141 SELECT Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2307563

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Finerenone, what not to consider when choosing treatment of AS, brain health after atrial fibrillation ablation, early rhythm control for AF, and Watchman reimbursement cuts are discussed by John Mandrola, MD, in this week's podcast.

This podcast is intended for healthcare professionals only.

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I Finerenone
FDA Widens Indication of Finerenone for Heart Failure Patients

https://www.medscape.com/viewarticle/fda-widens-indication-finerenone-heart-failure-patients-2025a1000ive

FDA finerenone approval https://bayer2019tf.q4web.com/news/news-details/2025/U-S--FDA-Approves-KERENDIA-finerenone-to-Treat-Patients-With-Heart-Failure-With-Left-Ventricular-Ejection-Fraction-40-Following-Priority-Review/default.aspx FINEARTS-HF trial https://www.nejm.org/doi/full/10.1056/NEJMoa2407107

II Choosing TAVI or Surgical AVR

Carbon Emission when treating AS

EHJ study https://doi.org/10.1093/eurheartj/ehaf379

III Brain Lesions and Visual Migraine After Left-Sided Ablations
Post-Ablation Visual Auras a Sign of Transient Brain Injury?https://www.medscape.com/viewarticle/post-ablation-visual-auras-sign-transient-brain-injury-2025a1000iro

TRAVERSE Trial https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.124.071352 TRAVERSE Migraine Substudy https://doi.org/10.1016/j.hrthm.2025.06.035

IV Early Rhythm Control for AF

EHJ Rapid Communication https://doi.org/10.1093/eurheartj/ehaf397 EAST-AFNET 4 Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2019422

V Watchman Cuts

CMS Reduces LAAO Value in Proposed Fee Schedule https://www.acc.org/Latest-in-Cardiology/Articles/2025/07/15/20/08/CMS-Reduces-LAAO-Value-in-Proposed-2026

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Approval of first-generation devices, the ticagrelor controversy, ICD longevity, the PRAGUE-25 trial (one of the most important trials of the year), and some thoughts on the end of EP as a profession 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 More Ticagrelor Controversy

BMJ Investigation Finds More Concerns in Ticagrelor Trials https://www.medscape.com/viewarticle/investigation-bmj-raises-more-concerns-about-ticagrelor-2025a1000gh3 Ticagrelor PLATO study https://www.bmj.com/content/389/bmj.r1201 Ticagrelor vs Clopidogrel https://www.nejm.org/doi/full/10.1056/NEJMoa0904327 Review of the Ticagrelor Trials Evidence Base https://www.ahajournals.org/doi/10.1161/JAHA.123.031606 The Plato Trial: Do you believe in magic? https://doi.org/10.1093/eurheartj/ehp545 ONSET/OFFSET Antiplatelet Effects https://www.ahajournals.org/doi/10.1161/circulationaha.109.912550 RESPOND Study https://www.ahajournals.org/doi/10.1161/circulationaha.109.919456

II ICD Battery Longevity

Variability in ICD Battery Longevity https://doi.org/10.1016/j.hrthm.2025.05.031

PRAGUE-25 Trial of AF Ablation vs LFM

PRAGUE-25 Trial https://www.jacc.org/doi/10.1016/j.jacc.2025.04.042

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FDA approves triple-drug polypill, a change of opinion, a deep dive into invasive pulmonary embolism therapies, heart disease trends, and diabetes care is on fire 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 FDA News in HTN

FDA announcement https://george-medicines.com/george-medicines-announces-fda-approval-of-widaplik-telmisartan-amlodipine-and-indapamide-a-new-single-pill-combination-treatment-for-hypertension-in-adults-including-initial-treatment/ Lancet Study https://doi.org/10.1016/S0140-6736(24)01744-6 JACC study vs placebo https://www.jacc.org/doi/abs/10.1016/j.jacc.2024.08.025 JAMA Cardiology Meta-analysis https://jamanetwork.com/journals/jamacardiology/fullarticle/2804313

II Invasive PE Therapy

EHJ-Open review: https://academic.oup.com/ehjopen/article/5/3/oeaf071/8156689 PEITHO Trial https://www.nejm.org/doi/10.1056/NEJMoa1302097 REAL PE Observational Study https://pmc.ncbi.nlm.nih.gov/articles/PMC11308131/

III Heart Disease Trends

King et al https://www.ahajournals.org/doi/10.1161/JAHA.124.038644

IV Diabetes Coverage

Medscape Link https://www.medscape.com/viewcollection/37830

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A big, deep dive into CTA and fractional flow reserve CT, and a sobering report on the new EVOQUE valve are discussed by John Mandrola, MD, in this week's podcast.

This podcast is intended for healthcare professionals only.

To read a partial transcript or to comment, visit:

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I Listener Feedback and Correction

CRAAFT HF https://clinicaltrials.gov/study/NCT06505798

II Imaging and Behavior Change

SCOT HEART 1 https://www.nejm.org/doi/full/10.1056/NEJMoa1805971 Five Reasons I Don't Believe an Imaging Test Improves Outcomes https://www.medscape.com/viewarticle/901204 SCOT HEART 2 https://www.jacc.org/doi/10.1016/j.jcmg.2024.05.016

III. More on Imaging and CT FFR
Symptoms Don't Always Indicate the Severity of Coronary Artery Disease https://www.medscape.com/viewarticle/symptoms-dont-always-indicate-severity-coronary-artery-2025a1000ge6

ADVANCE Registry Protocol https://www.journalofcardiovascularct.com/article/S1934-5925(16)30288-X/abstract Research Letter JACC CV Imaging  https://doi.org/10.1016/j.jcmg.2025.05.002 ADVANCE Registry Paper 2018 https://doi.org/10.1093/eurheartj/ehy530 Cook et al JAMA Card https://jamanetwork.com/journals/jamacardiology/fullarticle/2629072 Low diagnostic yield Patel paper NEJM https://www.nejm.org/doi/full/10.1056/NEJMoa0907272 Venk Murthy thread https://x.com/venkmurthy/status/1033379922679660544

IV EVOQUE Real World Data

JACC has published a sobering research letter on the Transcatheter Tricuspid Valve Replacement called EVOQUE valve.

Lupu et al JACC IV https://doi.org/10.1016/j.jcin.2025.03.019 TRISCEND II https://www.nejm.org/doi/full/10.1056/NEJMoa2401918

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Listener feedback on cardiac sarcoidosis, SA node ablation, surgical AF ablation, chronic kidney disease protection, and recruiting for clinical trials 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

EHJ paper Mathijssen et al https://doi.org/10.1093/eurheartj/ehaf338 Nordenswan et al https://www.ahajournals.org/doi/full/10.1161/CIRCEP.117.006145#tab-contributors

II IST

HR Case Reports https://doi.org/10.1016/j.hrcr.2025.05.017 Lakkireddy et al https://doi.org/10.1016/j.hrthm.2021.07.010

III Survival After Surgical AF ablation during CABG

McClure et al https://doi.org/10.1093/europace/eux336 Schaffer et al https://doi.org/10.1016/j.athoracsur.2025.03.044

IV Finerenone with Empagliflozin in CKD and DM

The Confidence Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2410659

V Recruiting for Important Trials and the Stature of EP as a Profession

Two UK Cardiology Trials Struggle to Recruit Patients

https://www.medscape.com/viewarticle/two-uk-cardiology-trials-struggle-recruit-patients-2025a1000ffs

CRAFT HF https://clinicaltrials.gov/study/NCT06505798 BRITISH https://doi.org/10.1016/j.ahj.2023.09.008 PROFID https://profid-project.eu/profid-ehra-trial/

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Listener feedback on cardiac sarcoidosis, out-of-hospital cardiac arrest, less is more when it comes to post-stent antiplatelets, lipoprotein(a), and atrial fibrillation in HFpEF are discussed by John Mandrola, MD, in this week's podcast.

This podcast is intended for healthcare professionals only.

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I Listener Feedback

Mathijssen https://doi.org/10.1093/eurheartj/ehaf338 Poyhonen https://doi.org/10.1161/CIRCEP.124.013239

II News in out of hospital cardiac arrest

AHA Press Release https://newsroom.heart.org/news/nfl-safety-justin-reid-expands-cpr-education-for-youth-through-summer-program Chan et al https://www.ahajournals.org/doi/abs/10.1161/CIRCOUTCOMES.124.011799

III Post-Stent Antiplatelet

4D ACS trial https://eurointervention.pcronline.com/article/one-month-dual-antiplatelet-therapy-followed-by-prasugrel-monotherapy-at-a-reduced-dose-the-4d-acs-randomised-trial

IV Lp(a) and the new PREVENT equation for Predicting cardiac events

Aug 02, 2024 This Week in Cardiology Podcast https://www.medscape.com/viewarticle/1001429 Bhatia et al https://jamanetwork.com/journals/jamacardiology/fullarticle/2835022

V AF in HFpEF

Saksena et al https://doi.org/10.1093/europace/euad095

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Listener feedback, CRT vs CSP, important clues on the ECG, beta-blocker interruption after myocardial infarction, novel approaches to LDL-C lowering, and ICD decisions in cardiac sarcoidosis 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

II CRT vs CSP ? CONSYST-CRT

? Trial JACC EP https://doi.org/10.1016/j.jacep.2025.03.024

III The Important QRS

? Kewcharoen et al https://www.ahajournals.org/doi/10.1161/CIRCEP.125.013809

IV ABYSS Trial of BB Interruption after MI Continues to be Mis-interpreted

? ABYSS Main https://www.nejm.org/doi/full/10.1056/NEJMoa2404204

? ABYSS substudy https://doi.org/10.1093/eurheartj/ehaf170

? REDUCE AMI https://www.nejm.org/doi/full/10.1056/NEJMoa2401479

V Oral PCSK9i and the PURSUIT Trial

? Koren et al https://www.jacc.org/doi/10.1016/j.jacc.2025.03.499

? Editorial https://doi.org/10.1016/j.jacc.2025.03.518

? Is Lifelong LDL-C Lowering Within Reach? The heart-1 Gene-Editing Trial https://www.medscape.com/viewarticle/998162

? Heart-1 Gene Therapy Trial Pauses Enrollment https://www.medscape.com/viewarticle/998162

? EHJ coverage VERVE https://academic.oup.com/ehjcvp/article/10/2/87/7455877

VI Cardiac Sarcoidosis and Risk of VT

? EHJ paper Mathijssen et al https://doi.org/10.1093/eurheartj/ehaf338

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Listener feedback on sports "disqualification," big digoxin news, Brugada syndrome, another positive finerenone study, and unblinded transcatheter trials are discussed by John Mandrola, MD, in this week's podcast.

This podcast is intended for healthcare professionals only.

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I Listener Feedback

JACC EP Paper https://www.jacc.org/doi/10.1016/j.jacep.2025.03.013

II Digoxin News

DIGIT HF Baseline Characteristics paper https://doi.org/10.1002/ejhf.3679 DIGIT HF Rationale paper https://pmc.ncbi.nlm.nih.gov/articles/PMC6607489/ Dig trial https://www.nejm.org/doi/full/10.1056/NEJM199702203360801 DECISION trial https://onlinelibrary.wiley.com/doi/full/10.1002/ejhf.3428 Ziff et al BMJ meta-analysis https://www.bmj.com/content/351/bmj.h4451

III Brugada Syndrome

Gomes et al https://doi.org/10.1093/europace/euaf091

IV Another Finerenone Substudy Published

FINEARTS-HF trial substudy, Bhatt, A et al https://doi.org/10.1016/j.cardfail.2025.05.006 FINEARTS HF Main paper https://www.nejm.org/doi/full/10.1056/NEJMoa2407107 TOPCAT https://www.nejm.org/doi/full/10.1056/NEJMoa1313731 TOPCAT regional variation Circ paper https://www.ahajournals.org/doi/10.1161/circulationaha.114.013255

V Another Opinion on Unblinded Transcatheter Intervention Trials

Kaul https://eurointervention.pcronline.com/article/unblinded-trials-of-transcatheter-interventions-with-subjective-endpoints-what-are-the-implications

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The BedMed trial of nighttime BP meds, SURMOUNT-5, Troponin URL, gene tests in patients with no disease, and guideline-directed medical therapy for HF are the topics John Mandrola, MD, discusses in this week's podcast.

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I Timing of BP Meds ? The BedMed RCT

MAPEC https://doi.org/10.3109/07420528.2010.510230 Hygia https://doi.org/10.1093/eurheartj/ehz754 Turgeon et al https://www.ahajournals.org/doi/10.1161/HYPERTENSIONAHA.121.16501 TIME trial https://doi.org/10.1016/S0140-6736(22)01786-X BedMed https://jamanetwork.com/journals/jama/fullarticle/2833860 Time Antihypertensives Taken Doesn't Matter: New Trials https://www.medscape.com/viewarticle/time-antihypertensives-taken-doesnt-matter-new-trials-2024a1000g3z Timing of BP Dosing Doesn't Matter: BedMed and BedMed-Frail https://www.medscape.com/viewarticle/timing-blood-pressure-dosing-doesnt-matter-again-bedmed-and-2024a1000fz2 Timing of Blood Pressure Meds Doesn't Affect Outcomes: BedMed in Print https://www.medscape.com/viewarticle/timing-blood-pressure-meds-doesnt-affect-outcomes-bedmed-2025a1000cdm

II Tirzepatide vs Semaglutide

SURMOUNT 5 https://www.nejm.org/doi/full/10.1056/NEJMoa2416394

III Age-specific Troponins

Coyle and McEvoy https://doi.org/10.1093/eurheartj/ehaf308 Mandrola/Foy JAMA-IM https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2777967

IV Return to Play for Gene Positive Phenotype Negative athletes

Martinez et al https://doi.org/10.1016/j.jacep.2025.03.013

V Rapid Titration of GDMT in HF

STRONG HF: More Beats Less After Discharge for Heart Failure https://www.medscape.com/viewarticle/983698

JACC-HF Substudy https://doi.org/10.1016/j.jchf.2025.02.020 STRONG HF https://doi.org/10.1016/S0140-6736(22)02076-1 AVID https://www.nejm.org/doi/full/10.1056/NEJMoa013474 EAST https://www.nejm.org/doi/full/10.1056/NEJMoa013474

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

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I The KETO-CTA Study

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

II Subclinical AF ? Anticoagulate or Not?

Anticoagulation in Subclinical AF May Offer Little Benefit

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

Treat AFib 'Diagnosed' by Smartwatch

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

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

III GLP1a for Treatment of Fatty Liver Disease

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

Features

CABG Still Superior to Stents Despite FAME 3 Endpoint Swap

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

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

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I  FDA announces approval for TAVR in pts with asymptomatic AS

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

II PPG that Can Distinguish source of Tachycardia

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

III PRAETORIAN -XL trial

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

IV Stroke in Young People

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

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

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I Help with ECGs in the ED

AI Shows Promise for Rapid NSTEMI Diagnosis

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

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

II A Novel way to Treat HTN

A Pacemaker to Control BP Gets FDA Breakthrough Designation

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

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

III Type of PFA may matter for Silent Cerebral Lesions

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

IV Accountability coming to US AF ablation

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

V Pacing in Patients with Undergoing Transcatheter Tricuspid Valve Replacement

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

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

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I FAME 3 at Five Years

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

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

II TAVR in Low-Risk Patients at 5 years

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

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

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

III The Matter of Pacemakers After TAVI

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

IV Mavacamten Looks to Have Specific Indications

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

FINAL THOUGHTS

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

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

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

I TAP IT 

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

II STRIDE

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

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

III FRESH UP

No Need to Restrict Fluids in Stable Heart Failure

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

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

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

IV PFA for AF ablation

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

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

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

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

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