Featured science studies simultaneously published in JACC and presented at AHA 2025 looked at artificial intelligence applied to an electrocardiogram (ECG-AI) for heart failure (HF) risk, treatment of Chagas disease, early aspirin withdrawal in STEMI and non-ST-segment elevation acute coronary syndrome (NSTE-ACS), and safety of the pentaspline pulsed-field ablation (PFA) catheter.

ECG-AI For HF Risk
One study found that, paired with the PREVENT-HF equation, ECG-AI improved discrimination of near-term HF risk. Among the 14,126 participants, positive screening rates were 2.9% for ECG-AI LEF (which detects systolic dysfunction), 11.1% for ECG-AI DD (which detects diastolic dysfunction), 11.9% for a composite of the two, 25.1% for PREVENT-HF score ≥10% and 5.8% for PREVENT-HF score ≥20%. Participants with positive ECG-AI screens had a 10-20 fold greater risk of developing HF compared to those with negative. At one, three, five, and 10 years, adding ECG-AI to PREVENT-HF led to net reclassification improvements of 0.086 to 0.125 with PREVENT-HF score ≥10% and 0.327 to 0.403 with PREVENT-HF score ≥20%. "Although many risk factors for incident [HF] including age and sex are known to be encoded in ECG-AI signals, the incremental contribution of ECG-AI to risk stratification above and beyond PREVENT-HF suggests that these models may be identifying other features including subclinical structural heart disease," write study authors Akshay S. Desai, MD, FACC, et al.

ANSWER-HF: Sacubitril-Valsartan vs. Enalapril in Chagas Disease
In the ANSWER-HF study by Vagner Madrini Junior, MD et al., sacubitril-valsartan did not lead to significant improvements in left ventricular ejection fraction (LVEF) at six months compared to enalapril in patients with chronic Chagas cardiomyopathy (CCC) and non-ischemic HF with reduced ejection fraction (HFrEF) – but did lead to a greater reduction in NT-proBNP. The study randomized 190 Brazilian patients (mean age 61 years; 40% women; 69% Black or mixed race; baseline mean LVEF, 30.1%) with CCC and HFrEF 1:1 to six months of either sacubitril-valsartan or enalapril therapy. Results at six months showed a mean LVEF increase of 2.1% in the sacubitril-valsartan arm compared to 1.2% in the enalapril arm (p=0.36). Sacubitril-valsartan led to a greater NT-proBNP reduction (geometric mean ratio, 0.68; p<0.001) and higher total wins (win ratio, 1.80) with both treatments being well-tolerated among patients. "Patients with this neglected disease remain largely absent from contemporary HF trials, leaving clinicians with little guidance on the applicability of established therapies to this high-risk population," write the authors. "These findings highlight the biological activity of sacubitril/valsartan in Chagas cardiomyopathy, but their clinical implications remain uncertain and require confirmation in larger, adequately powered, and longer-term studies."

NEO-MINDSET: Monotherapy vs. DAPT in STEMI vs. NSTE-ACS
Early aspirin withdrawal may be harmful and increase risk of ischemic events in PCI patients with STEMI, according to a prespecified analysis of the NEO-MINDSET trial. However, P2Y12 inhibitor monotherapy may instead be a viable option in NSTE-ACS, with ischemic events comparable and bleeding reduced compared to standard dual antiplatelet therapy (DAPT). Among 3,410 patients (62.1% with STEMI, 37.9% with NSTE-ACS) randomized to twelve months either potent P2Y12 inhibitor monotherapy or DAPT (aspirin + a potent P2Y12 inhibitor), results showed that monotherapy in STEMI patients was associated with higher rate of an ischemic composite outcome of all-cause death, MI, stroke or urgent target vessel revascularization compared with DAPT (8.2% vs. 5.2%; hazard ratio [HR], 1.60). Conversely, in those with NSTE-ACS, ischemic events were similar between both arms (5.1% vs. 6.0%; HR, 0.84; p=0.030). Additionally, bleeding outcomes were lower with monotherapy compared with DAPT in both STEMI (HR, 0.37) and NSTE-ACS (HR, 0.45) arms. "Taken together, our findings suggest that very early aspirin withdrawal may not be advised in STEMI, but this strategy does not appear to confer an excessive ischemic risk in NSTE-ACS," write study authors Caio A.M. Tavares MD, PhD, et al. "This hypothesis warrants careful exploration in a prospective setting."

MANIFEST-US: Is the Pentaspline PFA Catheter Safe?
PFA had a safety profile consistent with preferentiality to functional myocardial tissue ablation without evidence of esophageal fistula or pulmonary veins (PV) stenosis, with a major complication rate ~0.6% driven mostly by vascular adverse events and pericardial tamponade, according to a retrospective analysis of the MANIFEST-US trial. In the analysis of 41,968 patients undergoing PFA with the pentaspline catheter (median age, 68 years; 44% women; 73% first-time ablation) from 102 U.S. centers, results showed that major adverse events only occurred in 0.63%, with cardiac tamponade in 0.16%, vascular injury requiring intervention in 0.18% and stroke in 0.10%. There were no cases of esophageal fistula, persistent phrenic nerve paralysis or PV stenosis captured, and mortality at 30 days was low at 0.04%. "The overall favorable rate of [adverse events] in MANIFEST-US, and in particular, the absence of some of the most serious energy-related complications of ablation such as atrio-esophageal fistula, indicate that this pentaspline PFA catheter remains a very safe [atrial fibrillation] ablation technology," conclude authors Mohit K. Turagam, MD, FACC, et al.

In a related editorial comment, Sanket S. Dhruva, MD, MHS, FACC, et al., said "Turagam and colleagues have provided physicians and patients with much-needed safety data about PFA – but their landmark effort also highlights the important needs and opportunities to build enduring mechanisms for generation of patient safety data ... we can and should aspire to a higher standard and settle for no less."

Click here to read all the AHA 2025 articles simultaneously published in JACC Journals.

Clinical Topics: Heart Failure and Cardiomyopathies, Prevention, Acute Heart Failure

Keywords: AHA Annual Scientific Sessions, AHA25, Heart Failure, Secondary Prevention, Care Team