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.