In this special JACC lipid-focused issue, Dr. Valentin Fuster explores groundbreaking global research on lipoprotein(a), its complex role in cardiovascular disease across populations, and the promising future of targeted therapies. From massive Chinese cohort studies to a novel oral PCSK9 inhibitor trial, this episode highlights the frontlines of lipid science shaping tomorrow's heart health.

JACC focuses in again on Lipids in our June 3 issue, bringing critical insights into emerging targeted therapies. In the June 3 Deep Dive, editor-in-chief Harlan M. Krumholz, MD, SM, FACC, reviews the INTERASPIRE study by Ray et al, reviewing implications, key findings, and a thoughtful summary and analysis of the reviewer findings.

In the latest JACC offering from EuroPCR, JACC Associate Editor Celina M. Yong, MD, FACC, interviews Dr. Ashkan Eftekhari, PhD, to discuss insights into his study, Biolimus-Eluting Biomatrix Stent Versus a Dual-Therapy Sirolimus-Eluting Stent in PCI: SORT OUT XI Randomized Trial. The biolimus A9-eluting BioMatrix Alpha stent (BES), has not been compared with another contemporary drug eluting stent. This study compared one-year target lesion failure (TLF) in BES versus the dual-therapy sirolimus-eluting Combo stent (DTS) in an all-comer population undergoing PCI. A total of 3,136 patients were randomized 1:1 to either BES or DTS. The primary result showed that BES was non-inferior to DTS. Additionally, there was a significantly higher rate of definite stent thrombosis in the BES arm. In conclusion, BES was non-inferior to DTS at one-year follow-up with respect to the primary endpoint, TLF.

Hosts Mitsuaki Sawano, MD, and Nobuhiro Ikemura, MD, welcome Yoshitaka Kimura, MD, PhD, of Leiden University Medical Center, to discuss proactive ablation strategies in patients with repaired Tetralogy of Fallot (rTOF). Dr. Kimura presents data from a long-term, single-center study evaluating electroanatomical mapping and preventive ablation of slow-conducting anatomical isthmuses (SCAI) in rTOF patients without prior ventricular tachycardia (VT). The findings show that identifying and successfully ablating SCAI significantly reduced VT incidence, with all VT events occurring in patients where ablation failed. Moreover, this approach reduced the proportion of patients qualifying for ICD implantation from 25–51% under current guidelines to just 11%. Dr. Kimura underscores a paradigm shift in congenital heart disease management—from treating VT reactively to preventing it proactively—highlighting the value of data-driven, tailored care strategies that avoid unnecessary device implantation and better target high-risk individuals.

Go behind the scenes with JACC as editor-in-chief Harlan M. Krumholz, MD, SM, FACC, talks about what 's caught his attention in the latest JACC issue on amyloid. In this paper by Sheikh et al, the authors did a pre-specified exploratory analysis from the HELIOS-B trial, evaluating vutrisiran in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). The study showed that vutrisiran helped preserve or improve functional capacity and quality of life over 30 months, with consistent benefits across both monotherapy and tefamidis-treated patients. Waterfall plots illustrated the full spectrum of individual patient responses, revealing meaningful improvements in many while underscoring variability in outcomes. The analysis emphasized this heterogeneity, supporting a move toward precision care in amyloidosis.

In this special issue of JACC, Dr. Valentin Fuster presents groundbreaking advances in the understanding and treatment of transthyretin amyloid cardiomyopathy, a once-fatal disease now facing a wave of therapeutic innovation. Highlighting seven key presentations, the episode explores novel biomarkers, gene editing, stabilizers, silencers, and real-world clinical outcomes that signal a new era of hope for patients.

JACC Executive Associate Editor Karthik Murugiah, MD, FACC, speaks with author Jasmine M. Marquard, MD, PhD, on her study published in JACC and presented at EuroPCR. The discussion focuses on 10-year outcomes, including repeated events, of fractional flow reserve (FFR)-guided complete revascularization versus treatment of the infarct-related artery only in ST-segment elevation myocardial infarction. As the original trial, the primary outcome was a composite of all-cause mortality, recurrent myocardial infarction, or any revascularization. Complete revascularization reduced the risk of the primary outcome by 24%. Complete re-vascularization showed an absolute reduction of 13 events (-1 to 28 events) per 100 persons after 10 years. FFR-guided complete revascularization reduced future and repeated events after 10 years, primarily by reducing revascularization rates, without reducing myocardial infarctions or death.

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.