Conduction system pacing (CSP) is a promising and potentially cost-effective alternative to biventricular pacing (BiVP) in patients with heart failure with reduced ejection fraction (HFrEF) and left bundle-branch block (LBBB), but its impact on heart failure (HF) outcomes remains uncertain. To compare CSP vs BiVP on an HF-related outcome in patients with HFrEF and LBBB. PhysioSync-HF (Conduction System Pacing Versus Biventricular Resynchronization in Patients With Chronic Heart Failure) was an investigator-initiated, multicenter, noninferiority randomized clinical trial enrolling participants from November 2022 to December 2023 with 12 months of follow-up at 14 hospitals across all regions of Brazil. Adults with symptomatic HFrEF (New York Heart Association NYHA] classes II through III), left ventricular ejection fraction (LVEF) of 35% or less, and LBBB (QRS duration ≥130 milliseconds) were eligible for inclusion. Data were analyzed from May to August 2025. Patients were randomized 1:1 to either CSP (preferentially left bundle-branch area pacing) or BiVP. The primary outcome was a hierarchical composite of death, HF hospitalizations, urgent HF visits, and change in LVEF at 12 months. The prespecified noninferiority margin for the odds ratio (OR) was 1.2. A total of 173 patients (median [IQR] age, 62 years [56-68]; 86 female patients [49.7%]; 115 (66.5%) with dilated cardiomyopathy; median [IQR] LVEF, 26% [22%-31%]; median [IQR] QRS, 180 milliseconds [170-200]) were included. At 12 months, CSP failed to meet noninferiority and was inferior to BiVP for the primary end point (OR, 2.36; 95% CI, 1.37-4.06; P = .99 for noninferiority; P = .002 for between-group difference). The time-to-event composite of death, HF hospitalizations, or urgent HF visits was higher in CSP (hazard ratio, 2.35; 95% CI, 0.99-5.61). Mean (SD) LVEF increased to 35% (12%) with CSP and 39% (12%) with BiVP (mean difference, 3.8%; 95% CI, 0.3%-7.3%). Relative to baseline, both groups had comparable improvements in QRS duration, Kansas City Cardiomyopathy Questionnaire Overall Summary Score, NYHA class, and natriuretic peptide levels. Total direct medical cost related to the procedure and heart failure care was the equivalent of $7090 (95% CI, $5779-$8648) lower in patients randomized to CSP at 12 months. In patients with HFrEF and LBBB, CSP was inferior to BiVP for a composite of death, HF hospitalizations, urgent HF visits, and change in LVEF at 12 months. These findings do not support the routine use of CSP as the first-line resynchronization strategy in this population. ClinicalTrials.gov Identifier: NCT05572736.

Left bundle-branch pacing (LBBP) has been proposed as an alternative to biventricular pacing (BiVP) for patients with heart failure with left bundle-branch block (LBBB). However, robust clinical evidence from randomized clinical trials is lacking. To evaluate the long-term clinical outcomes of LBBP and BiVP. This multicenter, prospective, randomized clinical trial enrolled 200 patients at 6 centers in China with a left ventricular ejection fraction (LVEF) of 35% or less and LBBB from October 2020 to March 2022. This study was took place from October 2020 to September 2024. These data were analyzed September 2024 to December 2024. Patients were randomly assigned in a 1:1 ratio to receive either LBBP or BiVP. The primary end point was the time to death from any cause or heart failure hospitalization (HFH). The secondary end points included all-cause death, HFH, echocardiographic response (absolute increase in LVEF ≥5%), and super response (absolute increase in LVEF ≥15% or improvement of LVEF to ≥50%) rates. Of the 200 included patients, 136 were male and 64 were female. The success rate was 98% in the LBBP group and 94% in the BiVP group (P = .28). The median follow-up duration was 36 (range, 33-39) months. The primary end point of time to death or HFH was significantly lower in the LBBP group compared with BiVP (8% vs 28%; hazard ratio [HR], 0.26; 95% CI, 0.12-0.57; P < .001). There was no significant difference in all-cause mortality between the groups (2.0% vs 5.0%; HR, 0.40; 95% CI, 0.08-2.04; P = .25). However, LBBP significantly reduced the risk of HFH (7.0% vs 28.0%; HR, 0.23; 95% CI, 0.10-0.52; P < .001). The echocardiographic response rates were similar in both groups (86.0% vs 81.0%; P = .34) but the super-response rate was higher in the LBBP group (55.0% vs 36.0%; P < .007). In this study, LBBP was superior to BiVP in reducing the risk of death or HFH in patients with LBBB and severely reduced LVEF. Further trials are warranted in this patient population. Chinese Clinical Trial Registry identifier: ChiCTR2000036554.

Mounting evidence suggests that renin-independent aldosteronism is common and often underrecognized. Yet, whether aldosteronism across this broader spectrum is associated with incident cardiovascular disease (CVD) has not, to the authors' knowledge, been comprehensively evaluated. To determine whether aldosterone measures are associated with incident CVD events in community-dwelling older adults. This prospective cohort analysis included participants from the Atherosclerosis Risk in Communities (ARIC) study with serum aldosterone and renin levels measured in 2011 to 2013. Longitudinal analyses were conducted in March to September 2025 using Cox regression to assess associations between aldosterone parameters and incident CVD among participants free of heart failure (HF), myocardial infarction (MI), stroke, and potassium-sparing diuretic use at ARIC visit 5 (2011-2013). Serum aldosterone level and aldosterone-renin ratio (ARR). Incident HF hospitalization, atrial fibrillation (AF), ischemic stroke, MI, and a composite of these events plus all-cause death. Among 3477 individuals free of baseline CVD (mean [SD] age, 74.8 [4.9] years; 2139 female [61.5%]), the median (IQR) aldosterone level was 5.1 (3.0-8.3) ng/dL (to convert to picomoles per liter, multiply by 27.74), renin activity was 0.78 (0.41-1.90) ng/mL per hour, and ARR was 5.9 (2.2-12.3) ng/dL per ng/mL/h. Over 9 years of follow-up, higher ARR was associated with the composite outcome (adjusted hazard ratio [aHR], 1.04; 95% CI, 1.01-1.08 per doubling), stroke (aHR, 1.13; 95% CI, 1.02-1.26), and AF (aHR, 1.10; 95% CI, 1.05-1.15) but not with incident HF hospitalization (aHR, 1.02; 95% CI, 0.96-1.07) or MI (aHR, 1.01; 95% CI, 0.92-1.12). The findings of this cohort study underscore a spectrum of primary aldosteronism, in which higher ARR was independently associated with increased risks of AF and ischemic stroke among older adults, supporting the aldosterone pathway as a potential target for CVD prevention.

Familial hypercholesterolemia (FH) is a common genetic condition that causes hypercholesterolemia and increased risk for premature atherosclerotic cardiovascular disease (ASCVD). The prevalence, management, and consequences of genetically confirmed FH across the US are poorly understood. To identify genotype-positive FH in a national US cohort and describe its prevalence, consequences, and lipid-lowering management. In the All of Us (AoU) cohort study, whole-genome sequencing and phenotypic data from US adult participants enrolled between May 2018 and July 2022 were analyzed to identify and study genotype-positive FH. Data were analyzed between May 2024 and May 2025. FH variants (pathogenic or likely pathogenic) in LDLR, APOB, and PCSK9 genes were manually classified with standard criteria. The primary outcomes were demographic characteristics, lipid measurements, ASCVD, and prevalence of FH and noncarriers in AoU. Lipid management was then characterized among individuals with FH through lipid-lowering therapy (LLT) documentation and guideline-based low-density lipoprotein cholesterol (LDL-C) targets. A total of 245 388 participants were included, with mean (SD) age of 56.5 (16.9) years and 145 563 female participants (59.3%). Genotype-positive FH was identified in 865 participants (prevalence, 0.35%; 95% CI, 0.33%-0.38%; 1 in 287 participants). Among individuals with genotype-positive FH, 349 (40%) were prescribed statins, and 332 (38.4%) had LDL-C measured. Coronary artery disease, peripheral artery disease, and transient ischemic attack or stroke were significantly more common in genotype-positive FH carriers compared to noncarriers (coronary artery disease: odds ratio [OR], 2.91; 95% CI, 2.34-3.58; peripheral artery disease: OR, 1.51; 95% CI, 1.16-1.96; and transient ischemic attack or stroke: OR, 1.54; 95% CI, 1.11-2.09). Only 30.1% of participants positive for FH variants had LDL-C less than 100 mg/dL at their most recent result compared to 48.2% of noncarriers (P < .001). Of the total participants with ASCVD and LLT prescription, significantly fewer individuals with FH met the secondary prevention LDL-C target (<70 mg/dL; 19.33% vs 43.12%; P < .001) compared to noncarriers. This cohort study finds a prevalence of genotype-positive FH in All of Us participants of 0.35% (95% CI, 0.33%-0.38%), with state-level variation. A minority of individuals with genotype-positive FH met guideline-recommended LDL-C targets and had increased rates of ASCVD.