This Week in Cardiology

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

This podcast is intended for healthcare professionals only.

To read a partial transcript or to comment, visit:

https://www.medscape.com/twic

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

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

II Yet another GLP-1 Drug Announced this Week

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

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

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

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

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

IV Lipid Guideline News

Lipid Guidelines: Four Major Concerns

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

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

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

This podcast is intended for healthcare professionals only.

To read a partial transcript or to comment, visit:

https://www.medscape.com/twic

I Digoxin in Rheumatic Heart Disease

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

II The Physiologic Threshold for Angina

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

III Prediction in Hypertrophic Cardiomyopathy

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

IV TAVR Trends in Young Patients

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

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

This podcast is intended for healthcare professionals only.

To read a partial transcript or to comment, visit:

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I Listener Feedback

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

II Immediate Complete vs Staged Revascularization in STEMI

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

III Polygenic Risk Scores for Prediction

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

IV Practice Improvement Policies Undergo the Proper Test – Randomization

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

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

This podcast is intended for healthcare professionals only.

To read a partial transcript or to comment, visit:

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I Time to Quadruple Therapy in HFrEF

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

II AVANT GUARD

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

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

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

III Speaking of Scary News on PFA – The TIFFANY Study

• Abstract - The TIFFANY Study https://www.heartrhythmjournal.com/article/S1547-5271(26)01747-9/fulltext

• Delayed Myocardial Ischemia and Malignant Arrhythmias After PFA https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.125.077983
• Alberto Alfie Comment https://x.com/ALFIEEP1/status/2050029151315189774?s=20

IV TREAT PVC Trial

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

V NSTEMI In Frail Older Patients

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

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PCSK9 inhibitors in high-risk diabetes without ASCVD, the CAAN-AF trial, conduction system pacing vs biventricular pacing, PFA and stroke, and therapeutic fashion infects expert consensus are the topics John Mandrola, MD, discusses in this week's podcast.

This podcast is intended for healthcare professionals only.

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I VESALIUS-CV

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

II How Best to Maximize CRT Benefit in Patients with AF

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

III Stroke Rates in PFA vs Thermal Ablation

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

IV Five New CSP Studies Presented and Published

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

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

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

V New EP Training Document Published

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

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

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I ACC: SPIRIT-HF Trial

• FINEARTS-HF Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2407107
• TOPCAT Trial https://www.nejm.org/doi/full/10.1056/NEJMoa1313731

• TOPCAT Americas Trial https://www.ahajournals.org/doi/10.1161/circulationaha.114.013255

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

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

III Drug-Coated Balloons Looked Quite Good in PAD interventions

Sirolimus-Coated Balloon Reduces Amputation Risk in Peripheral Artery Disease

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

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

IV Another Vascular Story from the European Heart Rhythm Association

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

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

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

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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:

https://www.medscape.com/twic

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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