JACC Global

Can we make reliable PCI decisions based on coronary angiography alone? Host Mitsuaki Sawano, MD, welcomes Toru Tanigaki, MD (Gifu Heart Center), Takuya Mizukami, MD, PhD (Showa Medical University), and Hitoshi Matsuo, MD, PhD (Gifu Heart Center) to discuss their recent JACC: Cardiovascular Interventions study. The investigator-initiated PROVISION trial randomised 401 patients across 13 Japanese centres to angiography-derived FFR (FFRangio) or conventional pressure wire-based FFR. Revascularisation rates were 41.4% versus 37.9%, meeting the prespecified noninferiority criterion, with no significant difference in 1-year clinical events. We discuss whether angiography-derived FFR is ready for clinical decision-making, the challenges of conducting an independent RCT, and how computational physiology and AI could transform coronary assessment.

Is immune checkpoint inhibitor (ICI)-associated myocarditis the same disease when it occurs early versus months after starting cancer therapy? Host Mitsuaki Sawano, MD, and co-host Shun Kohsaka, MD, welcome Kazuaki Maruyama, MD (Mie University), Shiro Nakamori, MD (Mie University), and Yuichi Tamura, MD (International University of Health and Welfare) to discuss their recent JACC: CardioOncology study examining inflammatory cell profiles in early- and late-manifestation ICI myocarditis. Using endomyocardial biopsy specimens from 35 patients across 11 Japanese centers, the investigators found substantially greater T-cell and macrophage infiltration in early cases, while late-manifestation cases showed less myocardial inflammation despite similar fibrosis and LVEF. We discuss whether timing may identify different inflammatory phenotypes, why clinical severity does not necessarily reflect the degree of myocardial inflammation, and the difficult clinical question of whether ICI therapy should always be permanently discontinued after suspected myocarditis. Finally, we explore how Japan’s unique experience with myocardial biopsy helped uncover these differences and whether carefully selected patients with late, milder presentations might eventually be considered for ICI rechallenge, while recognizing the hypothesis-generating nature of these findings.

Is immune checkpoint inhibitor (ICI)-associated myocarditis the same disease when it occurs early versus months after starting cancer therapy? Host Mitsuaki Sawano, MD, and co-host Shun Kohsaka, MD, welcome Kazuaki Maruyama, MD (Mie University), Shiro Nakamori, MD (Mie University), and Yuichi Tamura, MD (International University of Health and Welfare) to discuss their recent JACC: CardioOncology study examining inflammatory cell profiles in early- and late-manifestation ICI myocarditis. Using endomyocardial biopsy specimens from 35 patients across 11 Japanese centers, the investigators found substantially greater T-cell and macrophage infiltration in early cases, while late-manifestation cases showed less myocardial inflammation despite similar fibrosis and LVEF. We discuss whether timing may identify different inflammatory phenotypes, why clinical severity does not necessarily reflect the degree of myocardial inflammation, and the difficult clinical question of whether ICI therapy should always be permanently discontinued after suspected myocarditis. Finally, we explore how Japan’s unique experience with myocardial biopsy helped uncover these differences and whether carefully selected patients with late, milder presentations might eventually be considered for ICI rechallenge, while recognizing the hypothesis-generating nature of these findings.

Does pulsed field ablation (PFA) for pulmonary vein isolation affect structures beyond the pulmonary veins? Host Mitsuaki Sawano, MD, welcomes Yosuke Nakatani, MD (Gunma University) to discuss his recent JACC: Clinical Electrophysiology study examining the effects of PFA on the vein of Marshall (VoM). In this prospective study of 72 patients undergoing PFA using three different systems, a microelectrode catheter was positioned within the VoM to continuously record electrograms during ablation. PFA acutely altered VoM electrograms in 44% of patients, including complete elimination in 22%, but persistent VoM modification remained in only 14% by the end of the procedure. Importantly, the effect was strongly related to the distance between the PFA electrode and the VoM, suggesting that catheter geometry and proximity may matter more than energy strength alone. We discuss what these findings reveal about the unintended collateral effects of PFA, why most acute VoM effects rapidly recover, whether PFA could ever replace ethanol infusion for VoM ablation, and how a research idea conceived during Dr. Nakatani’s fellowship in Bordeaux ultimately became a first-in-human mechanistic study in Japan.

Could sirolimus-coated balloons change how we treat femoropopliteal peripheral artery disease? Host Mitsuaki Sawano, MD, welcomes Yoshimitsu Soga, MD, PhD (Kokura Memorial Hospital) to discuss the 3-year results of the SELUTION SFA Japan study, a prospective multicenter study of 134 patients with symptomatic femoropopliteal disease treated with a novel sirolimus-eluting balloon. Despite relatively complex lesions, the study showed encouraging long-term outcomes, with particularly few additional restenosis and target lesion revascularization events after the first year. We discuss why sirolimus may offer an alternative to paclitaxel, how sustained drug delivery makes a sirolimus-coated balloon possible, and what the recently published SIRONA randomized trial adds to the evolving evidence comparing sirolimus- and paclitaxel-coated balloons. Finally, we look ahead to whether sirolimus DCBs could reshape PAD intervention and what the peripheral experience might eventually teach us about coronary DCB therapy.

Which of the thousands of biomarkers associated with cardiovascular disease could actually become a useful drug target? Host Mitsuaki Sawano, MD, and co-host Nobuhiro Ikemura, MD, welcome Satoshi Yoshiji, MD, PhD (McGill University) to discuss a recent JACC study tackling this question in ischemic heart disease. Starting with 9,520 circulating proteins, the investigators used human genetics to move beyond association toward stronger evidence for causality, combining Mendelian randomization, genetic colocalization, multiple proteomic platforms, and cross-ancestry validation to narrow thousands of signals to a small group of potential therapeutic targets. We break down what these methods actually mean for clinicians: what cis-pQTLs tell us, why MR alone is not enough, what colocalization adds, and why validation across platforms and populations matters. The episode explores how this emerging approach could help determine which biological targets are worth pursuing in drug development and ultimately testing in clinical trials.

Hosts Mitsuaki Sawano, MD, Satoshi Shoji, MD, and Kentaro Ejiri, MD, welcome Yoshito Kadoya, MD, PhD (University of British Columbia / St. Paul’s Hospital) to discuss his JACC: Cardiovascular Imaging study, “PET-Based Coronary Microvascular Dysfunction Phenotypes and Outcomes in Patients With Normal Myocardial Perfusion.” Among 3,317 patients with normal relative perfusion on cardiac PET, the study examined four phenotypes defined by myocardial flow reserve and stress myocardial blood flow. Both classical CMD and endogen CMD were associated with higher long-term cardiovascular risk, suggesting that reduced MFR may remain clinically meaningful even when stress myocardial blood flow is preserved. The episode explores how PET can phenotype coronary microvascular dysfunction, differences between invasive and noninvasive approaches to CMD, and Dr. Kadoya’s cardiac imaging training and career in Canada.

Host Mitsuaki Sawano, MD, welcomes Shuhei Nomura, PhD (Tohoku University), Lisa Yamasaki, MD (Harvard T.H. Chan School of Public Health), and Haruka Sakamoto, MD, PhD (St. Luke’s International Hospital) to discuss two policy reviews published in The Lancet Regional Health – Western Pacific. Fifteen years after the 2011 Lancet Japan Series, Japan faces population aging, rising long-term care needs, workforce shortages, financial pressures, and a rapidly changing global health environment. The episode explores how Japan can shift from hospital-centered care toward prevention and community-based care while also rethinking its role in global health. The guests discuss why domestic reform and international collaboration must increasingly move together, and what Japan can learn from its neighbors as it prepares for 2040.

Hosts Mitsuaki Sawano, MD, and Hiroyuki Sato, MD, welcome Kazutaka Nakasone, MD (Kobe University) to discuss his JACC: Clinical Electrophysiology study on atrial tachycardia (AT) after pulsed field ablation (PFA) for atrial fibrillation. In a 5-center European registry of 4,144 patients, 76 (1.8%) underwent repeat ablation for AT. Most ATs were left atrial macroreentrant tachycardias, with approximately 86% involving dual-loop circuits. The episode explores why comprehensive left atrial mapping may be key to selecting the optimal ablation line, the impact of PVI versus posterior wall isolation, and the potential role of 3D mapping. Dr. Nakasone also shares how the study grew from his fellowship in Brussels and his experience training in Belgium.

Hosts Mitsuaki Sawano, MD, and Satoshi Shoji, MD, welcome Misato Chimura, MD, PhD (University of Glasgow) to discuss her ESC SimPub paper in JACC, “Low-normal hemoglobin concentrations and clinical outcomes in heart failure.” Using individual participant-level data from 11 randomized trials including 42,213 patients across the full LVEF spectrum, the study examined the continuous relationship between hemoglobin and clinical outcomes. Risk was lowest around 14 g/dL in women and 15 g/dL in men, while even patients just above the WHO anemia threshold had higher event rates. The episode explores why “normal” may not always mean low risk in heart failure, the role of iron deficiency, how these findings should and should not influence clinical practice, and the research environment behind the study at the University of Glasgow.