Background: Women with obstructive hypertrophic cardiomyopathy (oHCM) often present with a greater burden of disease and worse prognosis. Whether there are sex-related differences in response to aficamten is unknown. Methods: We performed a pre-specified subgroup analysis of sex differences in the doubleblind, randomized-controlled SEQUOIA-HCM trial of aficamten versus placebo in patients with oHCM. Baseline characteristics were compared using t-test for continuous variables and C2 test for categorical variables. Prespecified primary (change in peak oxygen uptake, pVO2) and secondary end points from baseline to end of treatment (week 24) were analyzed using linear regression models, adjusted for baseline values, beta-blocker use, and exercise mode. Results: Of the 282 participants, women (n=115) were older (64 years-old in women vs. 56 years-old in men), had lower Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS), higher NT-proBNP levels, and lower pVO2 at baseline. Women had smaller left ventricular (LV) chamber sizes, higher E/e' ratios, and higher LV outflow tract (LVOT) gradients. At 24 weeks, there was a significant treatment-related increase in pVO2 in women (+1.5, [+0.7 to +2.4] and men (+2.0 [+0.9 to +3.0])). Both women and men had significant treatment-related decreases in LVOT gradients at rest and with Valsalva, with no sex-bytreatment interaction at week 24 (p-interaction ³ 0.13). There was a significant improvement in KCCQ-CSS in women (11 [6 to 15]) and men (6 [2 to 9], p-interaction = 0.08). Women had a greater reduction in lateral E/e' ratio (p-interaction = 0.01). The geometric mean proportional reduction in NT-proBNP were similar in women and men (p-interaction = 0.10). Conclusions: Women enrolled in SEQUOIA-HCM were older with worse baseline health status, higher NT-proBNP, and higher LVOT gradients compared to men. Despite these differences, both men and women derived significant benefits in the primary and secondary end points following treatment with aficamten.

Background: Targeted, digital recruitment strategies like tailored websites using motivational themes may improve recruitment in clinical trials, but their effectiveness remains unclear. We hypothesized that themes emphasizing community well-being, personal health benefits, or access to perks would increase engagement and pre-screening sign-ups compared to a standard contribution to science message in a clinical trial focused on Black adults. Methods: We implemented A/B testing of website themes for recruitment in GoFresh, a randomized trial testing the DASH diet intervention on blood pressure among Black adults. Website themes were derived from pre-developed motivational categories and included: (1) contribution to science (control group), (2) community well-being, (3) personal blood pressure improvement (4) access to perks (groceries or cash). A/B randomization directed visitors to a theme randomly between June and December 2024. Using an open-source web analytics platform, we captured data on two primary outcomes: 1) sign-up rate defined as the proportion of unique visitors who completed the trial's pre-screening form; and 2) engagement defined as (a) mean pageviews per session and (b) mean time spent on site per session. We compared themes using Welch's t-tests with statistical significance assessed as two-tailed p<0.05. Results: Among 11,484 visitors over 6 months, the themes of community well-being (13.8%), personal blood pressure improvement (14.1%), and access to perks (13.1%) all attracted higher sign-up rates than contribution to science (11.1%) (p<0.05 for all comparisons). All alternative themes also led to significantly higher mean pageviews compared to the contribution to science theme (p<0.05 for all comparisons) while mean time on site was similar across all themes (range: 52 to 55 seconds with p>0.05 for all comparisons). There were no statistical differences noted across the three alternative motivational themes for these outcomes. Conclusions: Tailored websites with digital messages emphasizing community well-being, personal health benefits, and access to perks significantly improved engagement and prescreening sign-up rates, demonstrating that they may enhance recruitment within cardiovascular research. Registration: Unique Identifiers: NCT05393232, NCT05121337; URL: https://clinicaltrials.gov.

Proteins linked to heritable coronary heart disease (CHD) could uncover new pathophysiological mechanisms of atherosclerosis. We report on the protein profile associated with a family history of early-onset CHD and whether the relation between proteins and coronary atherosclerotic burden differs according to family history status, as well as inferences from Mendelian randomization.

Current guidelines recommend a stepwise strategy to achieve low-density lipoprotein cholesterol (LDL-C) goals after acute coronary syndrome (ACS). Earlier intensive strategies based on a combination of lipid-lowering therapies (LLTs) could be useful from the onset of ACS. However, the role of bempedoic acid in ACS, particularly when combined with high-intensity statins and ezetimibe, remains uncertain. The aim of ES-BempeDACS (Efficacy and Security of Bempedoic Acid in Acute Coronary Syndrome) was to compare the efficacy and safety of triple LLT (high-dose, high-intensity statin+ezetimibe+bempedoic acid) versus standard of care (high-dose, high-intensity statin+ezetimibe) after ACS.

Congenital long-QT syndrome is most often associated with pathogenic variants in KCNQ1 encoding the pore-forming voltage-gated potassium channel subunit of the slow delayed rectifier current (IKs). Generation of IKs requires assembly of KCNQ1 with an auxiliary subunit encoded by KCNE1, which is also associated with long-QT syndrome, but the causality of autosomal dominant disease is disputed. By contrast, KCNE1 is an accepted cause of recessive Jervell and Lange-Nielson syndrome type 2 (JLN2). The functional consequences of most KCNE1 variants have not been determined, and the population prevalence of JLN2 is unknown.

Lp(a) (lipoprotein [a]) and coronary artery calcium score (CACS) are independently associated with atherosclerotic cardiovascular disease (ASCVD) risk. This study aimed to investigate sex-specific prognostic differences between Lp(a) and CACS in ASCVD risk.

Calmodulinopathies are very rare genetic disorders associated with a high risk for sudden cardiac death. Disease-causing variants in 1 of the 3 identical CALM genes cause severe forms of long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, or idiopathic ventricular fibrillation, and there are many open questions concerning management and underlying mechanisms. What is currently known depends largely on the initial publications from the International Calmodulinopathy Registry. However, progress is delayed because the accrual of patients in the International Calmodulinopathy Registry is slow. As we did long ago for long QT syndrome, this is a call for action, requesting doctors all over the world to enroll even their isolated cases in the registry. This is the only way to obtain, for an adequate number of patients, the data necessary to define the spectrum of clinical manifestations and the genotype-phenotype correlation essential for an improved risk stratification and best therapeutic management. If you are willing to contribute, please contact us.

Assessment of the systemic right ventricle (RV) is critical for patients with hypoplastic left heart syndrome (HLHS). Traditional imaging metrics fail to capture the RV's complex geometry and remodeling in HLHS, limiting risk stratification. We aimed to apply statistical shape modeling to a large multicenter cohort of cardiac magnetic resonance data sets to define RV shape variants and evaluate associations with clinical outcomes.

Atherosclerosis is a pathophysiological process common to a range of cardiovascular diseases. We reasoned that considering clinical presentations of atherosclerosis across the coronary, peripheral, and cerebrovasculature as a single entity would enhance statistical power to identify rare genetic variation driving pathological processes across multiple vascular beds.

The Helix Research Network program is a large population genomics initiative that screens an all-comers population of patients for Centers for Disease Control and Prevention Tier 1 genetic conditions, including familial hypercholesterolemia (FH). We evaluated changes in clinical management and low-density lipoprotein cholesterol (LDL-C) levels among patients we identified to have FH.

Although chronic obstructive pulmonary disease (COPD) and heart failure with preserved ejection fraction often coexist with overlapping clinical features, they are usually studied separately. The SPIROMICS HF (Subpopulations and Intermediate Outcome Measures in COPD and Heart Failure Study) is testing hypotheses that new computed tomography emphysema subtypes are associated with specific cardiovascular phenotypes (eg, cor pulmonale, cor pulmonale parvus), common airway branch variants are associated with right heart dysfunction, and symptomatic tobacco-exposed people with preserved spirometry have signs of increased left ventricular afterload.

People with chronic limb-threatening ischemia lack Food and Drug Administration-approved therapies for wound healing, creating an unmet need for novel approaches. Prior studies of biologics in chronic limb-threatening ischemia have largely targeted end-stage patients with amputation-free survival as the primary outcome. This trial evaluated the efficacy of intramuscular administration of AMG0001, a plasmid encoding human HGF (hepatocyte growth factor), to promote ulcer healing in patients with chronic limb-threatening ischemia and neuroischemic ulcers.

Patients with intermediate-high risk pulmonary embolism (PE) have an elevated right-to-left-ventricular (RV/LV) diameter ratio and are at risk of early clinical decompensation and mortality. Reperfusion therapy aims to rapidly relieve acute RV pressure overload and normalize hemodynamics. STORM-PE is the first reported randomized controlled trial (RCT) to test the efficacy and evaluate the safety of mechanical thrombectomy (MT), specifically computer assisted vacuum thrombectomy (CAVT) with anticoagulation (AC) compared to AC alone.