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.