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.