JACC: Associate Editor Michelle M. Kittleson, MD, PhD, FACC, and JACC: CardioOncology Deputy Editor Ronald Witteles, MD, FACC, discuss the current findings on the impact of vutrisiran in patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM). This study on HELIOS-B comprises details on cardiovascular (CV) events and provides updated mortality analyses from a later data cut than the primary analysis. Risk of ACM and CV events, including CV hospitalizations and heart failure events, was reduced with vutrisiran versus placebo in the overall population, with consistent trends regardless of baseline tafamidis use. These findings reinforce the balanced benefit on mortality and CV events demonstrated in the primary analysis of HELIOS-B.

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.

Join JACC Editor in Chief Harlan Krumholz, MD, SM, as he speaks about this ACC.25 presentation published in JACC. This fascinating study by Rohan Khera et al independently analyzed patient-level data from the SURMOUNT trials of tirzepatide for obesity. The study revealed striking individual variability in weight loss and metabolic response, even to a highly effective therapy—an insight powerfully illustrated through waterfall plots. Reviewers praised the transparent, sponsor-independent approach and the study’s contribution to precision medicine, though they noted it was descriptive rather than predictive, underscoring the need for future research to identify what drives differential treatment response.

This special lipid-themed issue of JACC emphasizes the importance of innovative research in lipid disorders to reduce cardiovascular risk, highlighting studies that extend our understanding of lipid biology and evaluate new treatments. Key reviews and original investigations explore novel lipid-modifying therapies, such as RNA interference and antibody therapies, demonstrating their potential in managing complex lipid disorders. The issue also includes editorials and case studies that provide critical context and underscore the need for personalized and mechanism-driven approaches in lipid management.

In this special issue of the JACC, Dr. Valentin Fuster explores the latest findings in lipid research, covering groundbreaking therapies aimed at tackling cardiovascular risks tied to lipid disorders. Key highlights include innovative approaches to lowering triglyceride-rich lipoproteins using angiopoietin-like protein 3 inhibitors and other novel treatments, with promising data on reducing cardiovascular risk through targeted therapies.

Hosts Mitsuaki Sawano, MD, and co-host Satoshi Shoji, MD, welcome regional associate editor Kentaro 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.

In a Deep Dive in our May 13 issue, Editor-in-Chief Harlan Krumholz, MD, SM, FACC, discusses a study led by Barry Borlaug that investigates whether excess weight or metabolic dysfunction has a greater impact on heart failure with preserved ejection fraction (HFpEF). The findings showed that obesity—more than insulin resistance—was strongly associated with worse hemodynamic and functional outcomes. Reviewers praised the study's nuanced approach and use of invasive measures, while editorialists emphasized the ongoing importance of addressing both adiposity and metabolic health in HFpEF management.

This JACC Deep Dive in our May 13 issue highlights new findings from the SUMMIT CKD study, showing that terzepatide improves symptoms, function, and weight in patients with HFpEF and obesity—regardless of kidney function. The analysis also underscores the importance of using both creatinine and cystatin C to better assess kidney health. Reviewers praised the study’s methodological rigor and dual focus, while noting the need for larger, long-term trials to confirm renal outcomes.