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

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

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

II Transcatheter Tricuspid Valve Replacement

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

III More Disease Creation – the CKM Syndrome

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

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

IV Two Trials That Teach Important EBM Lessons

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

V Bicarbonate for Inpatient Cardiac Arrest –The BIHCA trial

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

VI The Decline of VT in Heart Failure

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

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

This podcast is intended for healthcare professionals only.

To read a partial transcript or to comment, visit:

https://www.medscape.com/twic

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

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

II Heart Failure Monitoring – The ALLEVIATE-HF Trial

• ALLEVIATE-HF Trial https://doi.org/10.1016/j.jacc.2026.03.075
• CHAMPION Trial https://doi.org/10.1016/S0140-6736(11)60101-3
• GUIDE HF Trial https://doi.org/10.1016/S0140-6736(21)01754-2
• ALLEVIATE-HF Editorial: Alerts Are Not Treatment https://doi.org/10.1016/j.jacc.2026.04.014

• Steve Stiles Medscape report on CHAMPION https://www.medscape.com/viewarticle/755189

III A Negative Weight Loss Study in AF

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

IV Surgical LAA Excision

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

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

This podcast is intended for healthcare professionals only. To read a partial transcript or to comment, visit:

https://www.medscape.com/twic

I Permanent Lipid Lowering therapy

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

II Vesalius Substudy on PCSK9i Use in Patients With Previous PCI

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

III Tirzepatide looking to be best again

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

IV Arrhythmias in Cardiac Amyloidosis

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

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

V Lipid Guidelines

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

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

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

This podcast is intended for healthcare professionals only.

To read a partial transcript or to comment, visit:

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

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

II Yet another GLP-1 Drug Announced this Week

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

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

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

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

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

IV Lipid Guideline News

Lipid Guidelines: Four Major Concerns

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

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

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

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 < 65 https://www.ahajournals.org/doi/10.1161/CIRCINTERVENTIONS.126.016826
• 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.

To read a partial transcript or to comment, visit:

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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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