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

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I Catheter Based Fibrinolysis of Pulmonary Embolism –Hi PEITHO

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

II PRO-TAVI trial

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

III ORBITA CTO Sham vs PCI for Angina Relief

• Tightly Blinded Trial Confirms PCI Reduces Angina in Obstructive Occlusion https://www.medscape.com/viewarticle/tightly-blinded-trial-confirms-pci-reduces-angina-2026a10009ob

• A Randomized, Placebo-Controlled Trial of Chronic Total Occlusion Percutaneous Coronary Intervention in Stable Angina - ORBITA-CTO https://www.jacc.org/doi/10.1016/j.jacc.2026.03.027
• ORBITA 1 10.1016/S0140-6736(17)32714-9 External Link
• ORBITA 2 https://www.nejm.org/doi/full/10.1056/NEJMoa2310610
• DECISION CTO https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.118.031313
• EuroCTO https://doi.org/10.1093/eurheartj/ehy220

IV CHIPS BCIS3 Impella Supported High-Risk PCI

• Adoption Before Evidence: CHIP-BCIS3 Humbles Impella https://www.medscape.com/viewarticle/adoption-before-evidence-chip-bcis3-humbles-impella-2026a10009jh

• Left Ventricular Unloading in High-Risk PCI (CHIP BCIS3) https://www.nejm.org/doi/full/10.1056/NEJMoa2515704
• Microaxial Flow Pump or Standard Care in Infarct-Related Cardiogenic Shock (DanGer Shock) https://www.nejm.org/doi/full/10.1056/NEJMoa2312572

V CHAMPION AF – Watchman vs DOAC in Patients With AF

• CHAMPION-AF Trial Finds LAAC an Alternative for NOAC in Lower-Risk Patients https://www.medscape.com/viewarticle/champion-af-trial-finds-laac-alternative-noac-lower-risk-2026a10009ij
• Six Reasons Why CHAMPION-AF Should Not Change Practice https://www.medscape.com/viewarticle/six-reasons-why-champion-af-should-not-change-practice-2026a10009i7

• Left Atrial Appendage Closure or Anticoagulation for Atrial Fibrillation (CHAMPION AF) https://www.nejm.org/doi/full/10.1056/NEJMoa2517213
• Left Atrial Appendage Closure or Medical Therapy in Atrial Fibrillation (CLOSURE AF) https://www.nejm.org/doi/full/10.1056/NEJMoa2513310

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

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.

To read a partial transcript or to comment, visit:

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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.

To read a partial transcript or to comment, visit:

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I Listener Feedback

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

II Beta-blocker in Non-obstructive HCM

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

III Apixaban vs Rivaroxaban for Bleeding Risk

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

IV Diltiazem vs Metoprolol When Combined with DOAC

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

V Actual Clinical Use of Smart Watches

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

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

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I Urgent AF ablations

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

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

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

III Loop Recorders

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

IV Heart Failure Therapy when there is Cancer

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

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

This podcast is intended for healthcare professionals only.

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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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