JACC Global

Hosts Mitsuaki Sawano, MD, Satoshi Shoji, MD, Nobuhiro Ikemura, MD, and Hiroyuki Sato, MD welcome Dr. Tasuku Yamamoto, MD (Cleveland Clinic) to discuss his JACC: Clinical Electrophysiology study, “Neurocognitive Function, Cerebral Blood Flow, and Hippocampal Volume After Catheter Ablation of Atrial Fibrillation.” Using detailed digital cognitive testing with CANTAB alongside brain MRI in a prospective cohort, the study explores whether AF ablation is associated with changes in cognition, cerebral blood flow, and hippocampal volume. While the primary cognitive endpoints were neutral, ablation was linked to increased cerebral blood flow and greater hippocampal volume change—both correlating with improvements in memory-related measures. This episode delves into the mechanistic implications, highlighting how AF-related cognitive decline may extend beyond overt stroke, and how rhythm control, brain perfusion, and antiarrhythmic drug exposure may collectively shape long-term neurocognitive outcomes.

Hosts Mitsuaki Sawano, MD, and Shun Kohsaka, MD, welcome Dr. Yugo Yamashita, MD (Kyoto University) to discuss the newly released 2026 AHA/ACC Guideline for Acute Pulmonary Embolism and its accompanying JACC commentary from an Asia-Pacific perspective. This special episode first breaks down the major updates in the guideline, including the new A-to-E clinical classification, outpatient management of selected low-risk patients, evolving use of advanced therapies such as mechanical thrombectomy, and practical questions around anticoagulation duration. The discussion then turns to regional realities across Asia-Pacific, highlighting differences in epidemiology, imaging practices, drug availability, thrombolytic strategies, and guideline implementation. Through this lens, the episode explores why pulmonary embolism care cannot simply be imported from Western practice, and what evidence is still needed to build more precise, regionally relevant management strategies for acute PE.

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.

Hosts Mitsuaki Sawano, MD, and Satoshi Shoji, MD welcome Dr. Tomonari Harada, MD, PhD (Mayo Clinic / Gunma University) with commentary from Dr. Masaru Obokata, MD (Gunma University) to discuss their JACC study, “Echocardiographic Diastolic Function Grading in HFpEF: Testing the Updated 2025 ASE Criteria.” This investigation applies the newly updated 2025 ASE diastolic function grading algorithm to invasively confirmed HFpEF cohorts and examines how frequently patients may be classified as “Normal” or “Grade 1” despite established disease. Across compensated outpatient HFpEF, acute decompensated admissions, and external validation cohorts, the study highlights substantial false-negative classifications, limited discrimination from noncardiac dyspnea, and dynamic grade shifts with changes in congestion status. The episode explores the clinical implications: why diastolic grade alone should not be used to exclude HFpEF, how exercise criteria perform in real-world cohorts, and why integrating pre-test probability and HFpEF-specific frameworks remains essential in contemporary heart failure evaluation.

Hosts Mitsuaki Sawano, MD, and Kentaro Ejiri, MD, welcome Dr. Yusuke Nakashima, MD (Yamaguchi University) and Prof. Shigeki Kobayashi , MD(Yamaguchi University) to discuss their study published in JACC: Cardiovascular Imaging, exploring prognostic markers in patients with cardiac sarcoidosis following steroid therapy. Focusing on a condition in which clinical stability does not always equate to low risk, this episode examines how residual myocardial inflammation on FDG-PET and oxidative stress assessed by urinary 8-OHdG can help stratify future risk of major adverse cardiovascular events after treatment initiation. Through a detailed walk-through of imaging, biomarkers, and longitudinal outcomes, the conversation highlights how combining post-treatment functional imaging with biochemical markers may refine risk assessment, guide follow-up intensity, and move cardiac sarcoidosis management beyond symptom control toward more precise, individualized prognostic evaluation.

Hosts Mitsuaki Sawano, MD, and Satoshi Shoji, MD welcome Dr. Shun Kohsaka, MD (Keio University School of Medicine) and Prof. Noboru Motomura, MD (Toho University Sakura Medical Center) to discuss their JACC study examining nationwide trends in coronary revascularization across Japan. Using two of the country’s largest all-Japan registries—the J-PCI registry and the JCVSD—this analysis tracks how PCI and CABG volumes evolved from a steady decline to a post-2020 plateau, amid major external influences including ISCHEMIA trial results, reimbursement policy changes, and the COVID-19 pandemic. The conversation highlights how evidence, health policy, and clinical practice interact at a national level, offering rare insight into why revascularization patterns in stable coronary disease did not continue to fall despite shifting evidence, and what this means for the future of ischemic heart disease care in Japan.

Host Mitsuaki Sawano welcomes Dr. Sachiyo Ono, MD (Department of Cardiology, Kurashiki Central Hospital; Minneapolis Heart Institute Foundation International Scholar) to discuss her JACC: Clinical Electrophysiology study from the OCEAN-LAAC registry. Focusing on patients undergoing Left Atrial Appendage Closure, this episode explores how Spontaneous Echo Contrast (SEC)—particularly when combined with persistent atrial fibrillation—relates to thromboembolic events and device-related thrombosis after LAAC. The conversation highlights practical implications for peri-procedural assessment, post-procedural risk stratification, and future considerations in antithrombotic management, while emphasizing how left atrial pathology may continue to matter even after appendage closure.

Hosts Mitsuaki Sawano, MD, Kentaro Ejiri, MD, Nobu Ikemura, MD, and Satoshi Shoji, MD welcome Dr. Shu Hirata, MD (Department of Cardiology, Nihon University Itabashi Hospital), with guest commentary from Dr. Hiroyuki Sato, MD (Tohoku University), to discuss the REHEALTH-AF Study published in JACC: Clinical Electrophysiology. Focusing on patients aged 80 years and older with atrial fibrillation—a group often underrepresented in research and less frequently considered for catheter ablation in routine practice—this prospective multicenter registry enrolled 703 clinically eligible patients (ablation n=249; non-ablation n=454) and compares ablation and non-ablation strategies with respect to symptom burden, quality of life, frailty trajectories, cognitive function, and cardiac biomarkers over one year.

Hosts Mitsuaki Sawano, MD, Shun Kohsaka, MD, and Satoshi Shoji, MD welcome Prof. Tomonori Okamura, MD, and Dr. Aya Hirata, MPH, PhD (Department of Preventive Medicine and Public Health, Keio University School of Medicine) to discuss their JACC Viewpoint, “Current Status of Cardiovascular Disease in Japan: Prevention Strategies, Future Challenges, and Fundamental Lessons.” Building on the Global Burden of Disease (GBD) 2023 analysis featured in Epi 40, this episode explores why Japan has achieved one of the world’s lowest cardiovascular DALY and mortality rates, highlighting decades of population-wide hypertension control, universal health insurance, and nationwide health checkups. The conversation then turns to emerging challenges—including super-aging, metabolic risk, and heart failure—and asks a key question: how can Japan move beyond single–risk-factor success toward personalized, sustainable prevention strategies for the next era of cardiovascular health? #jaccbaran

Hosts Mitsuaki Sawano, MD, and Satoshi Shoji, MD welcome Dr. Hiroshi Tsunamoto to discuss his JACC study from the OCEAN-Mitral Registry, examining how transmitral pressure gradients (TMPG) and residual mitral regurgitation (MR) jointly determine outcomes after transcatheter edge-to-edge repair (M-TEER) for functional MR. In over 2,300 patients, higher postprocedural TMPG (≥5 mmHg) was consistently associated with worse 2-year outcomes, regardless of residual MR severity, while patients achieving MR ≤ mild with TMPG <5 mmHg had the best prognosis. This episode highlights a practical, nuanced concept for M-TEER success—optimizing the balance between MR reduction and mitral gradient, rather than focusing on MR alone.

Hosts Mitsuaki Sawano, MD, and Satoshi Shoji, MD welcome Prof. Kosuke Inoue (Kyoto University) and Dr. Yuichiro Mori (Kyoto University) to discuss their JACC Brief Report, “Evaluation of the PREVENT Equations in a Nationwide Cohort of 7.7 Million Korean Adults.” Using one of the world’s largest national health databases, the study externally validates the AHA-developed PREVENT risk equations in an East Asian population, showing good discrimination and calibration for ASCVD, outperforming the traditional Pooled Cohort Equations, while highlighting persistent overestimation of heart failure risk, particularly in men. This episode explores why risk prediction models often behave differently across regions, what PREVENT gets right in East Asia, where recalibration may still be needed, and how global collaboration is reshaping cardiovascular risk assessment.

Hosts Mitsuaki Sawano, MD, Kentaro Ejiri, MD, welcome Dr. Takahiro Suzuki to discuss his JACC paper, “Blood Pressure After Changes in Light-to-Moderate Alcohol Consumption in Women and Men: Longitudinal Japanese Annual Checkup Analysis.” Using a two-cohort design—cessation among habitual drinkers and initiation among nondrinkers—the study demonstrates dose-dependent blood pressure effects when alcohol intake is reduced or begun, and importantly fills a major evidence gap for women and for light-to-moderate drinking, areas long underrepresented in prior research. These timely findings challenge assumptions about “safe” drinking levels and inform evolving hypertension guidelines and lifestyle counseling.

Hosts Mitsuaki Sawano, MD, Kentaro Ejiri, MD, and Satoshi Shoji, MD welcome Dr. Keishi Ichikawa, MD (Lundquist Institute at Harbor–UCLA) to discuss his JACC: Cardiovascular Imaging study from the Miami Heart Study, defining the population norms of coronary plaque using AI-based coronary CT angiography. In 2,301 asymptomatic adults, AI detected plaque in nearly 9 out of 10 individuals —providing age- and sex-specific nomograms for calcified and noncalcified plaque. The episode explores how these data move beyond calcium scoring, reveal “hidden” plaque burden, and lay the groundwork for future preventive strategies and risk stratification in truly asymptomatic populations.

Hosts Mitsuaki Sawano, MD, Nobuhiro Ikemura, MD, and Satoshi Shoji, MD welcome Prof. Yoshinobu Onuma (University of Galway)—Last Author of the ARC Position Statement—along with guest commentators Prof. Ken Kozuma (Teikyo University) and Dr. Taku Asano (St. Luke’s International Hospital) to discuss the evolving role of drug-coated balloons (DCBs) in coronary intervention. The conversation highlights key insights from the ARC document, including DCB technology classifications, drug and coating differences, and the essential role of optimal lesion preparation, while outlining evidence-based indications across ISR, de novo lesions, bifurcations, ACS, diabetes, and high-bleeding-risk patients. The episode underscores why DCBs are not a class effect and how “leave nothing behind” strategies may shape the future of PCI.

Hosts Mitsuaki Sawano, MD, and Satoshi Shoji, MD welcome Prof. Shuhei Nomura, PhD (Tohoku University) for an in-depth discussion of the landmark JACC Global Burden of Cardiovascular Diseases and Risk Factors, 1990–2023 analysis, covering data from 204 countries and territories. Dr. Nomura, a leading member of the Global Burden of Disease (GBD) collaboration, explains how cardiovascular disease—still largely preventable—now accounts for an increasing share of global health loss, with metabolic risks such as high blood pressure, elevated glucose, high BMI, and unhealthy diet offsetting gains from reduced smoking and infection control. The conversation also highlights Japan’s slowing health-improvement pace, the rise of diabetes and overweight/obesity, and the urgent need to narrow regional disparities.

Hosts Mitsuaki Sawano, MD, and Nobuhiro Ikemura, MD, welcome Dr. Taisuke Nakade (Juntendo University) and Dr. Yuya Matsue (Juntendo University) to discuss how a simple Clinical Frailty Scale (CFS) captures multidimensional vulnerability and predicts outcomes in heart failure. Drawing on 3,905 patients (mean age 73 years) from the nationwide JROAD-HF NEXT registry, the JACC study (Frailty Scale Captures Multidimensional Vulnerability and Predicts Mortality in Heart Failure, 2025; doi:10.1016/j.jacc.2025.09.1590*) showed that higher CFS scores correlated stepwise with poorer physical and cognitive function and a marked rise in 2-year mortality (HR up to 6.6 for CFS 7-9). Adding CFS to standard risk models significantly improved prognostic discrimination, underscoring that bedside frailty assessment can efficiently identify high-risk patients and guide multidisciplinary heart-failure care.

Hosts Mitsuaki Sawano, MD, Kentaro Ejiri, MD, Nobuhiro Ikemura and Satoshi Shoji, MD, welcome Naohiko Sahara, MD (Toho University Ohashi Medical Center) to discuss his JACC: Clinical Electrophysiology study on intracardiac echocardiography (ICE) for detecting periaortic ventricular tachycardia substrate. In a multimodality core lab analysis, Dr. Sahara showed that ICE outperformed cardiac MRI in identifying arrhythmogenic scars, with wall thinning <0.6 cm predicting substrate even when no LGE was seen on MRI. The study highlights ICE’s growing role as a diagnostic bridge between imaging and electrophysiology in VT ablation.

Hosts Mitsuaki Sawano, MD, Kentaro Ejiri, MD, and Nobuhiro Ikemura, MD, highlight JACC Simultaneous Publications from the AHA 2025 Scientific Sessions, featuring three impactful clinical trials: (1) Effect of Aficamten vs. Metoprolol on Patient-Reported Health Status in Obstructive Hypertrophic Cardiomyopathy, (2) Sacubitril/Valsartan vs. Enalapril in Heart Failure Due to Chagas Disease (ANSWER-HF Trial), and (3) Behavioral Economics and Medication Adherence for Hypertension. These SimPub studies showcase the spectrum of innovation—from precision therapy and global heart failure management to behavioral science—defining the next chapter of cardiovascular medicine.

Host Mitsuaki Sawano, MD, welcome Dr. Shinnosuke Kikuchi, MD of Yokohama City University Medical Center to discuss how closure time–ADP (CT-ADP) refines bleeding risk after TAVR beyond VARC-HBR criteria. Based on data from 884 patients in the Strasbourg TAVR registry, the study (JACC: Cardiovasc Interv. 2025; doi:10.1016/j.jcin.2025.08.011) showed that CT-ADP >180 s independently predicted both periprocedural and late major bleeding, even among patients already classified as high risk.

Hosts Dr. Mitsuaki Sawano, Dr. Kentaro Ejiri, and Dr. Satoshi Shoji welcome Dr. Nobuyuki Kagiyama of Juntendo University and Dr. Shinichi Goto of Tokai University to discuss PRIME 2.0: An Update to the Proposed Requirements for Cardiovascular Imaging–Related Machine Learning Evaluation Checklist, recently published in JACC. Building on the original 2020 PRIME framework, this global collaboration revises the checklist to keep pace with rapid advances in AI—from deep learning and multimodal data fusion to the emergence of generative models. Drs. Kagiyama and Goto share insights into the modified Delphi process that united clinicians and engineers to establish seven key domains spanning the AI research lifecycle, aiming to enhance transparency, reproducibility, and responsible clinical translation in cardiovascular imaging research.

Hosts Mitsuaki Sawano, MD, Kentaro Ejiri, MD, and Satoshi Shoji, MD, welcome Drs. Kensuke Ueno (The University of Tokyo), Kentaro Kamiya (Kitasato University), and Tetsuya Takahashi (Juntendo University) to discuss the role of frailty in shaping cardiovascular versus noncardiovascular mortality across left ventricular ejection fraction (LVEF) subtypes. They provide expert commentary on the recent JACC: Heart Failure publication (Frailty Phenotype and Cardiovascular vs Noncardiovascular Mortality: Differences Across Left Ventricular Ejection Fraction Subtypes, Ueno K, Kamiya K, et al., 2025; doi:10.1016/j.jchf.2025.102654), which analyzed 5,777 patients aged ≥65 years from the nationwide J-Proof HF registry. The study found frailty prevalence exceeded 60% across all LVEF groups, but its prognostic significance diverged—frailty was linked to cardiovascular mortality in HFrEF, and to noncardiovascular mortality in HFpEF. These findings highlight how frailty cuts across heart failure phenotypes yet carries distinct risks, underscoring the need for tailored management strategies in older adults with HF.

Hosts Mitsuaki Sawano, MD, Shun Kohsaka, MD, Kentaro Ejiri, MD, and Satoshi Shoji, MD, welcome Dr. Nobuhiro Ikemura of Tachikawa Hospital, formerly of Saint Luke’s Mid America Heart Institute to discuss trajectories of angina following initial invasive versus conservative strategies for chronic coronary disease. Dr. Ikemura provides expert commentary on the recent JACC publication (Trajectories of Angina After Initial Invasive vs Conservative Strategy for Chronic Coronary Disease, ISCHEMIA Research Group), which analyzed 2,977 patients with baseline angina from the ISCHEMIA trial using latent class trajectory modeling to identify six distinct symptom patterns over two years. The study revealed that an invasive approach more often produced rapid or early improvement, while many conservatively managed patients had persistent angina, especially women and smokers. These findings highlight how capturing the “patient journey” beyond averages can inform shared decision-making, guide follow-up, and shape individualized treatment strategies in chronic coronary disease.

Hosts Mitsuaki Sawano, MD, Kentaro Ejiri, MD, Satoshi Shoji, MD, and Nobuhiro Ikemura, MD, welcome Dr. Yuki Sahashi of Cedars-Sinai Medical Center and the Ouyang Lab to discuss artificial intelligence automation of echocardiographic measurements and its cardiovascular implications. Dr. Sahashi provides expert commentary on the recent JACC publication (J Am Coll Cardiol. 2025; doi:10.1016/j.jacc.2025.07.053), which developed and validated 18 open-source deep learning models using 877,983 echocardiographic measurements from 155,215 studies across diverse datasets. This work demonstrates how AI can (1) reduce measurement variability, (2) improve efficiency, and (3) enable high-throughput cardiovascular research, while also raising critical questions around (1) clinical integration, (2) bias reduction, (3) regulatory standards, and (4) building trust in AI systems.

Hosts Dr. Mitsuaki Sawano, Dr. Kentaro Ejiri, and Dr. Satoshi Shoji welcome Dr. Takeshi Kitai and Dr. Koshiro Kanaoka of the National Cerebral and Cardiovascular Center to discuss their JACC study, Heart Failure in the Oldest-Old: A Growing Clinical and Economic Burden in Aging Japan. Drawing on over 730,000 HF hospitalizations from the JROAD-DPC registry (2016–2022), they reveal how the proportion of patients ≥85 years rose to nearly half of all admissions, with associated costs surging from $870M to $1.03B. Despite lower per-admission costs, the sheer growth in cases has intensified the national burden, underscoring the urgent need for rethinking care models, from palliative care and goal setting to balancing home- and facility-based management in Japan’s rapidly aging society.

Hosts Mitsuaki Sawano, MD, Kentaro Ejiri, MD, and Satoshi Shoji, MD, welcome Dr. Shunsuke Inoue of The University of Tokyo to discuss clonal hematopoiesis of indeterminate potential (CHIP) and its cardiovascular implications. Dr. Inoue provides expert commentary on two recent JACC publications: a Women’s Health Initiative analysis linking CHIP mutations such as TET2, ASXL1, and JAK2 with distinct cardiovascular outcomes in older women, and an exploratory substudy of the LoDoCo2 trial examining whether low-dose colchicine modifies CHIP clone dynamics. Together, these studies highlight the complexity of CHIP as both a biomarker and a potential therapeutic target, raising new questions about how age, mutation subtype, and anti-inflammatory strategies intersect in cardiovascular risk.

Hosts Mitsuaki Sawano, MD, and colleagues welcome Dr. Jun Yasuhara (Center for Cardiovascular Research and Heart Center, Nationwide Children’s Hospital) and Dr. Toshiomi Katsuki (Saitama City Hospital) for a Basic to Translational Science special. Dr. Jun Yasuhara presents his mouse model study on congenital aortic valve disease, showing how disruption of NOTCH1 and GATA5 produces a highly penetrant, clinically relevant bicuspid aortic valve and progressive aortic stenosis phenotype. Dr. Toshiomi Katsuki highlights his work on Scarb1 in endothelial cells, revealing how this receptor mediates maladaptive crosstalk with fibroblasts under pressure overload. Using single-cell RNA sequencing and spatial transcriptomics, his team mapped pathogenic signaling networks and demonstrated that knocking out Scarb1 or pharmacologically inhibiting it attenuates heart failure progression, positioning endothelial cells as a novel therapeutic target.

Hosts Mitsuaki Sawano, MD, Kentaro Ejiri, MD, and Satoshi Shoji, MD, welcome Dr. Shunsuke Uetake of Nippon Medical School Chiba Hokusoh Hospital to discuss the clinical presentation and long-term outcomes of late-onset symptomatic arrhythmogenic right ventricular cardiomyopathy (ARVC), based on a retrospective cohort study recently published in JACC: Clinical Electrophysiology. Dr. Uetake reviews findings from 76 probands with definite ARVC by 2010 Task Force criteria who presented with symptomatic ventricular arrhythmias between 2004 and 2024. Patients were divided into early-onset (≤40 years) and late-onset (>40 years) groups. Compared with early-onset disease, late-onset ARVC was associated with less severe initial presentation (palpitations more common, fewer syncope or cardiac arrest cases), slower ventricular tachycardia cycle length, and fewer arrhythmic events and heart failure progression during long-term follow-up, despite similar structural substrate on electroanatomical mapping. These results highlight that age of onset, even within the same genetic background, may shape the arrhythmic burden and clinical trajectory of ARVC, raising new questions about risk stratification and management in this rare but high-stakes cardiomyopathy.

Mitsuaki Sawano, MD, with Nobuhiro Ikemura, MD highlight two JACC papers simultaneously published at ESC 2025. “Comparison of Extended Cryoballoon Ablation, Standard Cryoballoon Ablation, and Radiofrequency Catheter Ablation in Patients with Persistent AF (EXCAPE-AF Trial)” – In persistent AF, extended CB with posterior wall isolation offered no benefit over standard CB or RF, underscoring PVI as central. 2nd paper titled “Impact of Obicetrapib on Major Adverse Cardiovascular Events in High-Risk Patients: A Pooled Analysis” – This next-gen CETP inhibitor produced robust lipid lowering and a signal for coronary event reduction, reviving interest after prior CETP concerns.

Hosts Mitsuaki Sawano, MD, Shun Kohsaka, MD, and Satoshi Shoji, MD, highlight two JACC papers simultaneously published at ESC 2025. Computed Tomography Angiography or Standard of Care after Left Main PCI? The PULSE Trial tested routine CCTA follow-up versus symptom- or ischemia-driven management after LM PCI. While the primary composite outcome showed no difference, CCTA reduced spontaneous MI but increased imaging-driven revascularization. The Adipokine Hypothesis of Heart Failure With a Preserved Ejection Fraction: A Novel Framework to Explain Pathogenesis and Guide Treatment by Dr. Milton Packer proposes that HFpEF is driven by visceral adiposity–mediated adipokine imbalance, leading to systemic inflammation, hypertrophy, and fibrosis, offering a unifying framework for pathogenesis and therapeutic strategies.

Hosts Mitsuaki Sawano, MD, Shun Kohsaka, MD, and Satoshi Shoji, MD, highlight two JACC papers simultaneously published at ESC 2025. Twice-A-Day Clopidogrel vs Ticagrelor to Reduce Short-Term MACE after Primary PCI: The TADCLOT Trial tested whether ticagrelor is superior to high-dose clopidogrel in reducing 30-day MACE after primary PCI for STEMI. While no difference was observed at 30 days, ticagrelor showed a signal for early ischemic protection at 7 and 14 days without excess bleeding. Personalized or Standard Duration of Dual Antiplatelet Therapy after PCI: The PARTHENOPE Trial compared risk score–guided DAPT durations (3, 6, or 24 months) against the standard 12-month strategy in over 2,000 PCI patients. Personalized therapy reduced NACE at 24 months, driven by fewer ischemic events, with no excess in bleeding.

Hosts Mitsuaki Sawano, MD, and Kentaro Ejiri, MD, highlight two JACC papers simultaneously published at ESC 2025. Prediction of Aortic Stenosis Progression Using Artificial Intelligence: A Machine Learning Model reports an interpretable algorithm using echo parameters alone to forecast AS progression within 5 years. Mechanistic Basis for Differential Effects of Interatrial Shunt Treatment in HFrEF vs HFpEF: The RELIEVE-HF Trial examines structural and hemodynamic differences explaining why shunt therapy reduced LV volumes in HFrEF but increased PASP and RA area in HFpEF.

Hosts Mitsuaki Sawano, MD, Shun Kohsaka, MD, Nobuhiro Ikemura, MD, and Satoshi Shoji, MD, welcome Dr. Hidenori Yaku to discuss orthostatic pulse pressure (OPP) as a marker of preload insufficiency in HFpEF, based on a prespecified analysis from the PRESERVED-HF trial. Dr. Yaku reviews findings from 324 patients with HFpEF randomized to dapagliflozin or placebo. Across groups with high, intermediate, or low OPP, dapagliflozin improved health status as measured by the Kansas City Cardiomyopathy Questionnaire and increased six-minute walk distance, with no significant interaction by OPP level. However, fluid depletion–related adverse events, although infrequent overall, were observed more often in patients with the lowest OPP. These results suggest that simple measurement of OPP may help identify patients at higher risk for volume depletion events, while the symptomatic and functional benefits of SGLT2 inhibition are preserved across the spectrum of OPP.

Hosts Mitsuaki Sawano, MD, Kentaro Ejiri, MD, and Satoshi Shoji, MD, welcome Dr. Masatake Kobayashi of Tokyo Medical University to explore the interaction between aldosterone and mineralocorticoid receptor antagonists (MRAs) in a post hoc analysis of the EPHESUS trial. Dr. Kobayashi reviews findings from a cohort of post–myocardial infarction patients with left ventricular dysfunction or heart failure in whom aldosterone levels were measured. In the placebo group, higher baseline aldosterone or an increase over one month was associated with cardiovascular death or heart failure hospitalization, whereas these associations were not observed in the eplerenone group. The analysis offers descriptive evidence on how MRA therapy may modify the relationship between aldosterone and outcomes, even in a population with relatively low aldosterone levels compared to prior studies. The discussion extends to implications for GDMT optimization in Japan, as well as distinctions among spironolactone, eplerenone, and the emerging non-steroidal MRA, finerenone.

Hosts Mitsuaki Sawano, MD, and Nobuhiro Ikemura, MD, welcome Dr. Atsushi Sugiura to discuss transcatheter edge-to-edge repair (TEER) for primary tricuspid regurgitation (TR). Dr. Sugiura reviews findings from a retrospective, international, multicenter cohort study of 114 high-surgical-risk patients with primary TR who underwent TEER. In this cohort, TR was graded as moderate or less at discharge in 83% of patients, with an in-hospital mortality rate of 1.8%. At one year, most patients continued to have TR at moderate or less, along with observed changes in right heart dimensions and NYHA functional class. One-year mortality and heart failure rehospitalization rates were similar to those observed in a surgical repair cohort. These results describe procedural and clinical outcomes of TEER in a high-risk primary TR population across centers in Germany, Switzerland, and the United States.

Hosts Mitsuaki Sawano, MD, Kentaro Ejiri, MD, welcome Dr. Yuka Oda of the Tokyo Heart Rhythm Hospital to discuss the clinical impact of high-intensity targeted ablation in scar-related ventricular tachycardia (VT). Dr. Oda shares insights from a multicenter retrospective study investigating the use of targeted ablation of rotational activation patterns (RAP) in patients with scar-related VT. Among patients where RAP could be identified and adequately ablated, the one-year VT-free survival rate reached 83%, underscoring the potential benefit of functional, high-density ablation strategies.

In this Chinese-language interview, JACC: Asia Deputy Editor Dong Zhao, MD, and author Liang Chen, MD, PhD, discuss Dr. Chen’s work on a national multi-center cohort registry in China focused on arrhythmogenic cardiomyopathy (ACM). The study highlights the genetic differences in ACM between Asian and Western populations, the importance of genotype-phenotype correlation, and the use of machine learning to enhance diagnosis and risk stratification.

In this episode, host Mitsuaki Sawano, MD, is joined by Dr. Shoichiro Yatsu, MD, to discuss his sub-analysis of the ADVENT-HF trial, recently published in JACC: Heart Failure. The study investigates the effects of peak-flow-triggered adaptive servo-ventilation (ASVPF) on left ventricular (LV) structure and function in patients with heart failure and sleep-disordered breathing (SDB). Compared to earlier studies using different ASV algorithms, ADVENT-HF highlights the safety and clinical value of ASVPF, showing meaningful improvements in sleep quality, symptoms, and quality of life. Dr. Yatsu also shares insights from managing legacy trial data collected over more than a decade.

In this episode, hosts Mitsuaki Sawano, MD, Nobuhiro Ikemura, MD, and Satoshi Shoji, MD, are joined by Dr. Yoichiro Sugizaki, MD, for an in-depth discussion on his landmark OCT-based study investigating chronic stent recoil (CSR) and its impact on target lesion revascularization (TLR) in the contemporary era of thin-strut, second-generation drug-eluting stents (DES). Together, they delve into the frequency, mechanisms, and clinical relevance of CSR—an underappreciated phenomenon increasingly observed in heavily calcified or eccentric lesions despite technological advancements in stent design. The conversation underscores why recognizing CSR is essential for interventional cardiologists and explores practical strategies to mitigate its impact.

Hosts Mitsuaki Sawano, MD, and co-hosts Kentaro Ejiri, MD, and Satoshi Shoji, MD, are joined by HFpEF expert Hidenori Yaku, MD, from Northwestern University, for a deep dive into early treatment response to acoramidis, an amyloid stabilizer recently approved in Japan. They discuss its impact on serum transthyretin (sTTR) levels and the emerging role of sTTR as a dynamic biomarker of treatment efficacy. The episode explores the clinical relevance of early sTTR elevation, key insights from the ATTRibute-CM trial—including mediation and logistic regression analyses—and the use of waterfall plots to visualize treatment response. The team also compares acoramidis with tafamidis and vutrisiran, and looks ahead to the evolving therapeutic landscape of ATTR-CM, including gene editing and amyloid removal strategies. This paper was the topic of the recent JACC Journal Club: https://www.jacc.org/journal-club

Hosts Mitsuaki Sawano, MD, and Nobuhiro Ikemura, MD, welcome Yoshitaka Kimura, MD, PhD, of Leiden University Medical Center, to discuss proactive ablation strategies in patients with repaired Tetralogy of Fallot (rTOF). Dr. Kimura presents data from a long-term, single-center study evaluating electroanatomical mapping and preventive ablation of slow-conducting anatomical isthmuses (SCAI) in rTOF patients without prior ventricular tachycardia (VT). The findings show that identifying and successfully ablating SCAI significantly reduced VT incidence, with all VT events occurring in patients where ablation failed. Moreover, this approach reduced the proportion of patients qualifying for ICD implantation from 25–51% under current guidelines to just 11%. Dr. Kimura underscores a paradigm shift in congenital heart disease management—from treating VT reactively to preventing it proactively—highlighting the value of data-driven, tailored care strategies that avoid unnecessary device implantation and better target high-risk individuals.

Hosts Mitsuaki Sawano, MD, co-host Nobuhiro Ikemura, MD, welcome Kentaro Kamiya, PhD, from Kitasato University, to discuss the ACTIVE-ADHF trial, a landmark multicenter RCT on early cardiac rehabilitation in acute decompensated heart failure. The study found that initiating exercise-based rehab during hospitalization significantly improved physical function, quality of life, and activity levels at discharge—even in non-frail patients—without increasing adverse events. Dr. Kamiya emphasizes that early rehab can prevent functional decline and support recovery, challenging assumptions about who benefits from acute-phase intervention and offering globally relevant evidence grounded in Japan’s unique clinical setting.

Ejiri, MD, for his debut appearance on the JACC: Baran Journal Club. Dr. Ejiri presents insights on the Altshock-2 trial, a pivotal randomized controlled trial evaluating early intra-aortic balloon pump (IABP) support in heart failure-related cardiogenic shock (HF-CS). The discussion covers the trial’s clinical relevance, key challenges, and the implications of its findings within the Japanese healthcare context. The episode also delves into evolving definitions of cardiogenic shock, trial methodology, and the potential for Altshock-2 to inform more individualized treatment approaches in Japan.

Hosts Mitsuaki Sawano, MD, co-host Shun Kohsaka, MD, and Nobuhiro Ikemura, MD, welcome Tomohiko Taniguchi, MD, from Kobe City Medical Center General Hospital, to discuss findings from the CURRENT AS Registry-2 on low-gradient severe aortic stenosis (AS). Based on data from over 3,300 patients across 21 Japanese centers, the study categorized AS into four hemodynamic subtypes, revealing that low-gradient AS with reduced LVEF had the poorest prognosis, paradoxical LFLG AS was associated with high rates of atrial fibrillation and advanced cardiac damage despite low valve calcification, and normal-flow LG AS frequently exceeded guideline-based calcification thresholds despite being labeled as moderate. Dr. Taniguchi emphasizes the need to revise conventional illustrations of AS subtypes by incorporating cardiac damage and frailty and underscores the importance of proper statistical interpretation in subgroup analyses.