Hosts Mitsuaki Sawano, MD, welcome Dr. Yuki Kawashima, MD and Dr. Ryo Inuzuka, MD (The University of Tokyo) to discuss their JACC study on how genetic variants in FBN1 can predict the timing and risk of mitral valve surgery in Marfan syndrome. Using one of the world's largest longitudinal Marfan cohorts, the study shows that not all mutations carry equal risk: specific in-frame variants within the DNCD region are associated with earlier and higher surgical risk, while other variants follow distinct age-dependent trajectories. This episode highlights a key shift—from uniform surveillance to genotype-driven precision care, where genetics can inform who to follow more closely, and when intervention may be needed.

Hosts Mitsuaki Sawano, MD, Shun Kohsaka, MD, and Nobuhiro Ikemura, MD welcome Dr. Yuichi J. Shimada (Columbia University) to discuss his ACC presentation on plasma microRNA profiling in hypertrophic cardiomyopathy (HCM). In this episode, we explore how transcriptomic analysis of 1,600+ circulating microRNAs in 280 patients identified three distinct molecular subtypes of HCM, each associated with different risks of major adverse cardiovascular events. Moving beyond traditional phenotyping, this work highlights the biological heterogeneity of HCM and the potential of molecular stratification to refine risk prediction and guide future therapies. From early ACC experiences to building a research career across the U.S., Dr. Shimada also shares insights into the evolving landscape of HCM—from current therapies to the future promise of gene-based approaches.

Hosts Mitsuaki Sawano, MD, Shun Kohsaka, MD, and Nobuhiro Ikemura, MD welcome Dr. Ryohei Ono, MD, PhD (University of Glasgow / Chiba University) to discuss his simultaneously published JACC study analyzing over 23,000 patients from global HFrEF trials. Once considered regional, Chagas cardiomyopathy is now a global concern. This episode highlights its consistently higher risks of cardiovascular death, heart failure hospitalization, and stroke compared with other etiologies, and explores how etiology should shape prognosis, trial design, and future heart failure care.

Hosts Mitsuaki Sawano, MD, Kentaro Ejiri, MD, and Nobuhiro Ikemura, MD welcome Dr. Kanna Nakamura, MD and Dr. Yugo Yamashita, MD (Kyoto University) to discuss their Late Breaking Clinical Cohort presented at the 2026 JCS in Fukuoka, exploring venous thromboembolism (VTE) risk prediction in cancer patients using comprehensive genomic profiling. In a cohort of patients undergoing cancer genomic panel testing, 14.3% developed VTE over a median follow-up of ~2 years. Specific gene mutations—including KRAS, CDKN2A, and TP53—were associated with higher VTE risk, suggesting that genomic data may complement traditional clinical scores such as the Khorana score. This episode highlights a key shift in cardio-oncology: moving beyond conventional risk models toward precision risk stratification, where tumor genomics may help identify patients truly at risk for thrombotic complications and guide preventive strategies.

Hosts Mitsuaki Sawano, MD, and Kentaro Ejiri, MD welcome Dr. Yusuke Watanabe, MD (Teikyo University) to discuss his study from the OCEAN-TAVI Registry, examining the long-term impact of mild paravalvular regurgitation (PVR) after TAVR. In over 5,000 patients with up to 9 years of follow-up, mild PVR—traditionally considered clinically acceptable—was associated with higher risks of all-cause mortality and bioprosthetic valve failure (BVF). Even modest regurgitation appeared to have cumulative effects over time, potentially contributing to volume overload, progressive valve degeneration, and adverse clinical outcomes. The episode challenges a long-held assumption in structural heart interventions: is "mild" PVR truly benign, or does it carry meaningful long-term consequences—especially as TAVR expands to younger, lower-risk populations?

Hosts Mitsuaki Sawano, MD, Nobuhiro Ikemura, MD, and Satoshi Shoji, MD welcome Dr. Ryohei Ono, MD, PhD (BHF Cardiovascular Research Centre, University of Glasgow / Chiba University) to discuss his JACC: Heart Failure study, "Lactate Dehydrogenase and Outcomes in Patients With HFrEF: Insights From GALACTIC-HF." The episode explores how LDH—one of the most commonly measured laboratory tests—may be a hidden gem for prognostication, reflecting systemic hypoperfusion and multiorgan stress in patients with advanced HFrEF and offering additional context beyond traditional cardiac biomarkers.

Hosts Mitsuaki Sawano, MD, and colleagues welcome Dr. Yusuke Kobari, MD, PhD (Heart Center, Copenhagen) to discuss his recent publication in JACC: Cardiovascular Interventions, "Clinical Application of Guideline-Directed Medical Therapy in TAVR Patients With Heart Failure and Reduced Ejection Fraction." Among 336 patients with LVEF ≤40%, most were eligible for quadruple HF therapy, yet only 27% received it by 3 months. Patients on more complete GDMT had lower 2-year rates of cardiovascular death or heart failure hospitalization, while those on fewer agents had higher event rates. This episode explores an essential message: TAVR is not the endpoint of care in patients with HFrEF. Even in the structural heart era, optimization of foundational HF pharmacotherapy remains a central consideration—raising important questions about how we integrate procedural success with longitudinal medical management.

Hosts Mitsuaki Sawano, MD, Nobu Ikemura, MD, and Satoshi Shoji, MD welcome Dr. Shingo Matsumoto, MD (Toho University) and Dr. Yohei Ohno, MD (Tokai University) to discuss their JACC: Cardiovascular Interventions study, "Atrial Fibrillation and Tricuspid Regurgitation in Patients Undergoing Mitral Valve Transcatheter Edge-to-Edge Repair." Building on prior evidence that residual tricuspid regurgitation (TR) influences outcomes after M-TEER, this analysis examines how atrial fibrillation (AF) interacts with TR progression and right ventricular remodeling. In a large OCEAN-Mitral cohort, AF was associated with greater TR persistence and progression after M-TEER, distinct patterns of right ventricular dysfunction, and amplified risk of cardiovascular death or heart failure hospitalization when moderate-or-greater TR remained post-procedure. The discussion reframes post–M-TEER management beyond the mitral valve alone, highlighting the importance of right-heart assessment, TR surveillance, and the evolving role of AF in shaping structural heart outcomes.