The ASPIRED syncope RCT, two studies in coronary artery calcium scoring, and the LEAP-Block trial of CSP vs RV pacing 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 Syncope

• ASPIRED Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2605812
• REMOSYNCED Trial https://clinicaltrials.gov/study/NCT05066347

II TWO CAC Studies

• Atherosclerosis in Young Adults and Risk of Mortality Over 30 Years https://jamanetwork.com/journals/jamacardiology/fullarticle/2855732
• Predictive Utility of CAC Score Added to PREVENT Score https://jamanetwork.com/journals/jama/fullarticle/2853347

III Conduction System Pacing vs Standard RV Pacing for AV block

• LEAP-Block Trial https://jamanetwork.com/journals/jama/fullarticle/2855975
• Meta-analysis: CSP vs RV Pacing in Preserved or Mildly Reduced EF https://doi.org/10.1016/j.cjca.2026.04.009

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Listener feedback on the nonobstructive HCM trials, AI-enhanced visits, timing of non-culprit PCI in STEMI, new tricuspid valve intervention, and EP at a crossroads 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

Koelemen meta-analysis https://www.medrxiv.org/content/10.64898/2026.09.08.26362195v1.full.pdf

Improving SCD Risk Stratification in HCM https://pmc.ncbi.nlm.nih.gov/articles/PMC11026183/

II More on Nonobstructive HCM

Communication on Post-Hoc Analysis of ODYSSEY (mavacamten)

Mavacamten in Nonobstructive HCM 10.1016/j.jacc.2025.12.092

III Complete vs Staged PCI in STEMI With Multivessel Disease

Immediate vs Staged CR in Multivessel Disease and STEMI: Meta-Analysis https://doi.org/10.1016/j.jcin.2026.07.033

Timing of Nonculprit PCI for STEMI and Multivessel Disease: Editorial https://doi.org/10.1016/j.jcin.2026.08.009

COMPLETE Trial https://www.nejm.org/doi/full/10.1056/NEJMoa1907775

FLOWER MI Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2104650

FRAME AMI Trial https://doi.org/10.1093/eurheartj/ehac763

iMODERN Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2512918

COCUA Trial https://doi.org/10.1016/j.ahj.2023.01.020

MULTISTARS Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2307823

OPTION STEMI Trial 10.1016/S0140-6736(25)01529-6 External Link

CULPRIT SHOCK Trial https://www.nejm.org/doi/full/10.1056/NEJMoa1710261

BioVasc Trial Substudy https://eurointervention.pcronline.com/article/immediate-versus-staged-complete-revascularisation-in-patients-presenting-with-stemi-and-multivessel-disease

Main BioVasc Trial 10.1016/S0140-6736(23)00351-3 External Link

FULL REVASC Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2314149

IV A Call to Action for Electrophysiologists

Twenty Years at the Crossroads 10.1016/j.jacep.2026.09.023

EP at a Crossroads - Josephson 2007 https://doi.org/10.1016/j.hrthm.2006.12.045

EP at a Crossroads: A Revisit - Josephson 2016 https://doi.org/10.1016/j.hrthm.2016.07.024

V FDA Approves Another Tricuspid Valve Repair System

Press release https://www.edwards.com/newsroom/news/2026-10-21-fda-approval-of-edwards-lifesciences--pascal-preci

TRIC I HF Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2606934

CLASP II TR Trial https://pubmed.ncbi.nlm.nih.gov/42855029/

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Some promising studies in amyloidosis, aficamten in nonobstructive HCM, costs of the microaxial flow pump in cardiogenic shock, and more on the VESALIUS trial of evolocumab 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 Light Chain Amyloidosis – A Potentially Helpful Drug

Anselamimab Does Not Reduce Light-Chain Amyloidosis Deaths

https://www.medscape.com/viewarticle/anselamimab-does-not-reduce-light-chain-amyloidosis-deaths-2026a1000z79

II Aficamten in Nonobstructive HCM: The ACACIA trial

III Microaxial Flow Pump Cost Analysis of Danger Shock

IV More on Evolocumab at ESC: Vesalius Trial Substudies

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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Listener feedback on POET II, sham control trials in atrial fibrillation, ICDs in HCM, and agenda laundering 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

POET II Response-Tailored or Standard-Duration ABX for Infectious Endocarditis

• POET I Trial https://www.nejm.org/doi/10.1056/NEJMoa1808312
• POET II Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2607887

II PVI-SHAM-AF trial Back in the News

• GAP-AF Trial https://www.ahajournals.org/doi/10.1161/circep.115.003337
• PVI-SHAM-AF Trial 10.1016/S0140-6736(26)01558-8 External Link
• Why Sham Studies Are a Sham in 2026 10.1016/j.hrthm.2026.09.056 External Link
• The Indispensable Role of Sham Controls in Evaluating Interventional Therapies 10.1016/j.hrthm.2026.10.001 External Link

III ICDs in HCM

• I CDs for the Prevention of SCD in High-Risk Patients with HCM https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.125.078597
• ICDs in HCM: Editorial https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.126.079687

IV Agenda Laundering

• How Commercial “Agenda Laundering” Shapes Critical Care https://www.bmj.com/content/395/bmj-2026-100963

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Listener feedback on DANISH-CRT, the POET II trial, a mechanistic study in obesity and AF, the DANCODE trial of slowing CAC progression, and more on GLP-1 drugs 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

• DANISH-CRT Trial 10.1016/S0140-6736(26)01597-7
• Identifying LV Posterior Wall Delay in RBBB Using Lead V8 https://doi.org/10.1016/j.jacep.2026.03.009
• Using Lead V8 as a Tool to Improve Patient Selection in CRT https://doi.org/10.1093/europace/euaf194

II POET II Response-Tailored or Standard-Duration Antibiotics for Endocarditis

• POET I https://www.nejm.org/doi/10.1056/NEJMoa1808312
• POET II https://www.nejm.org/doi/full/10.1056/NEJMoa2607887

III Obesity and AF – A Neat Study from the Team in Prague

• LA Remodeling and Functional Maladaptations in Obesity https://www.ahajournals.org/doi/10.1161/CIRCHEARTFAILURE.126.014509

IV Reducing CAC: The DANCODE Trial

• DANCODE Trial https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.126.082363

V Two Big RCTs of New GLP-1 Drugs

• TRIUMPH-1 Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2604169
• SYNCHRONIZE-2 Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2607219

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Listener feedback, pulmonary embolism intervention, simple vs complex in BiV pacing, exercise in AF, and TAVR for paradoxical low-flow, low-gradient aortic stenosis 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 LBBP ICD Lead

• LEADR LBBAP Trial https://pubmed.ncbi.nlm.nih.gov/41110529/

TRIC-I-HF trial

• TRIC-I-HF Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2606934
• Growth of Tricuspid Interventions in Germany https://www.jacc.org/doi/10.1016/j.jcin.2025.05.030

II Treatment of Acute Intermediate-High Risk PE – the PRAGUE-26 Trial

• PRAGUE-26 Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2608012

III Targeting CS leads in CRT devices – DANISH-CRT Trial

• DANISH-CRT Trial 10.1016/S0140-6736(26)01597-7

IV Exercise for AF, Especially When There Is LA Disease

• Physical Activity and Risk of Incident AF in Atrial Cardiomyopathy https://www.jacc.org/doi/10.1016/j.jacadv.2026.102999

V Paradoxical Low-Flow, Low-Gradient AS – REBOOT-PARADOX

• REBOOT-PARADOX trial 10.1016/j.jacc.2026.08.017
• ROTAS Trial https://heart.bmj.com/content/110/20/1223

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Another ESC recap, listener feedback on two trials, and a paper on GLP-1 effects on inflammation from the SELECT trial 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 Correction on PROFID Trial

II Listener Feedback

III Fifth Universal Definition of MI

• Fifth Universal Definition of MI https://doi.org/10.1093/eurheartj/ehag101
• Foy/Mandrola Editorial on Troponin Use and Interpretation https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2777967

IV New ESC HF Guidelines

• ESC Guidelines for Management of HF https://doi.org/10.1093/eurheartj/ehag100
• Sanjay Kaul on X https://x.com/kaulcsmc/status/2094959683215958158?s=20
• Geographic Disparities in TOPCAT https://pmc.ncbi.nlm.nih.gov/articles/PMC5065247/

V AIR STEMI Trial

• AIR-STEMI Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2605373
• CR Strategies After MI https://www.jacc.org/doi/10.1016/j.jacc.2024.04.051
• 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

VI GLP-1 News – A SELECT Trial Secondary Analysis

• Semaglutide and hsCRP in Patients with CVD and Obesity https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.125.074482

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A second ESC recap plus two breaking stories on the failure of an investigational Lp(a) reducing drug and a new FDA approval of an AI-ECG app are covered by John Mandrola, MD

This podcast is intended for healthcare professionals only.

To read a partial transcript or to comment, visit:

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I Lp(a) Disappointment

• HORIZON https://clinicaltrials.gov/study/NCT04023552
• Press Release https://www.novartis.com/news/media-releases/novartis-announces-lpahorizon-phase-iii-topline-results-pelacarsen-patients-elevated-lpa-and-established-cardiovascular-disease-cvd
• Rationale paper https://doi.org/10.1016/j.ahj.2025.03.019

II FDA Clears AI-ECG for Acute MI Detection

• Accuracy of cath lab activation decisions for STEMI-equivalent and mimic ECGs: Physicians vs. AI (Queen of Hearts by PMcardio) 10.1016/j.ajem.2025.07.061
• AI-Enabled ECG Analysis Improves Diagnostic Accuracy and Reduces False STEMI Activations: A Multicenter U.S. Registry https://www.jacc.org/doi/10.1016/j.jcin.2025.10.018
• Queen of Hearts™ AI ECG App https://www.powerfulmedical.com/pmcardio-stemi/

III TARGET CTCA Trial

• Targeted Use of Computed Tomographic Coronary Angiography in Acute Chest Pain https://www.nejm.org/doi/10.1056/NEJMoa2608903

IV CorCal trial

• Press release https://www.escardio.org/news/press/press-releases/new-data-presented-on-the-use-of-coronary-artery-calcium-for-cardiovascular-risk-assessment/
• CorCal Outcomes: A randomized trial using the pooled cohort equation or coronary artery calcium to select statin therapy in primary prevention patients. Study design and baseline characteristics https://doi.org/10.1016/j.ahj.2026.107473

V AMUNDSEN Trial

• LDL Cholesterol Lowering With Evolocumab Before Percutaneous Coronary Intervention for Acute Myocardial InfarctionThe AMUNDSEN Randomized Clinical Trial https://jamanetwork.com/journals/jama/fullarticle/2853274

VI TRIC-I-HF trial

• Tricuspid Repair Cuts Death, HF Hospitalization in Severe TR https://www.medscape.com/viewarticle/tricuspid-repair-cuts-death-hf-hospitalization-severe-tr-2026a1000wvk
• Tricuspid-Valve Intervention in Heart Failure https://www.nejm.org/doi/full/10.1056/NEJMoa2606934

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