Biomedical subjects

Anjali T Owens

Publications and source records attributed to Anjali T Owens.

3 recordsLinked to original sources

PubMed2026

Social Determinants of Health and Clinical Outcomes in Hypertrophic Cardiomyopathy.

IMPORTANCE: Area-based indicators of social determinants of health (SDOH) are associated with higher risk for acquired heart disease, but their impact on conditions with a strong genetic etiology, such as hypertrophic cardiomyopathy (HCM), is not well understood. OBJECTIVE: To determine the association of area-based SDOH with clinical outcomes in patients with HCM. DESIGN, SETTING, AND PARTICIPANTS: This multicenter, prospective cohort study was conducted among US adult patients with HCM from 5 sites in the Sarcomeric Human Cardiomyopathy Registry (a multicenter prospective registry of patients with HCM) who were followed up for a median (IQR) period of 2.15 (0.15-5.82) years. Data were entered from 2015 to March 2024, and data analysis was completed from March 2024 to June 2025. EXPOSURES: Patients' residential addresses were geocoded at the zip code level and linked to the American Communities Survey to estimate area-based (1) median household income and (2) social deprivation index (SDI), which ranges from 0 to 100, with higher scores indicating a more deprived area. MAIN OUTCOMES AND MEASURES: Multivariate models, adjusting for age at diagnosis, body mass index, hypertension, and sex, were used to estimate the independent association of area-based median household income and SDI with heart failure (HF), ventricular arrhythmias (VA), and an overall composite outcome (VA, HF, atrial fibrillation, stroke, and death). RESULTS: Among 4431 US adult patients with HCM, median (IQR) age at HCM diagnosis was 51.3 (38.9-61.6) years, and 1862 patients (42.0%) were female. Median (IQR) area-based household income was $80 000 ($60 000-$110 000), and median (IQR) SDI was 25 (10-55). Adjusted hazard ratios comparing the lowest income group to the highest income group were 2.07 (95% CI, 1.77-2.42; P < .001) for HF, 1.31 (95% CI, 0.97-1.78; P = .08) for VA, and 1.52 (95% CI, 1.36-1.69; P < .001) for the overall composite outcome. Adjusted hazard ratios comparing the highest SDI (ie, more deprived) group to the lowest SDI group were 1.48 (95% CI, 1.29-1.70; P < .001) for HF, 1.55 (95% CI, 1.15-2.09; P = .004) for VA, and 1.36 (95% CI, 1.22-1.50; P < .001) for the overall composite outcome. CONCLUSIONS AND RELEVANCE: In this multicenter cohort study, residing in an area with lower median household income or worse SDI were each independently associated with adverse clinical outcomes in patients with HCM. These findings suggest that despite the genetically determined nature of HCM, place of residence is associated with patient outcomes.

Humans↗

PubMed2024

Bidirectional Risk Modulator and Modifier Variant of Dilated and Hypertrophic Cardiomyopathy in BAG3.

IMPORTANCE: The genetic factors that modulate the reduced penetrance and variable expressivity of heritable dilated cardiomyopathy (DCM) are largely unknown. BAG3 genetic variants have been implicated in both DCM and hypertrophic cardiomyopathy (HCM), nominating BAG3 as a gene that harbors potential modifier variants in DCM. OBJECTIVE: To interrogate the clinical traits and diseases associated with BAG3 coding variation. DESIGN, SETTING, AND PARTICIPANTS: This was a cross-sectional study in the Penn Medicine BioBank (PMBB) enrolling patients of the University of Pennsylvania Health System's clinical practice sites from 2014 to 2023. Whole-exome sequencing (WES) was linked to electronic health record (EHR) data to associate BAG3 coding variants with EHR phenotypes. This was a health care population-based study including individuals of European and African genetic ancestry in the PMBB with WES linked to EHR phenotypes, with replication studies in BioVU, UK Biobank, MyCode, and DCM Precision Medicine Study. EXPOSURES: Carrier status for BAG3 coding variants. MAIN OUTCOMES AND MEASURES: Association of BAG3 coding variation with clinical diagnoses, echocardiographic traits, and longitudinal outcomes. RESULTS: In PMBB (n = 43 731; median [IQR] age, 65 [50-76] years; 21 907 female [50.1%]), among 30 324 European and 11 198 African individuals, the common C151R variant was associated with decreased risk for DCM (odds ratio [OR], 0.85; 95% CI, 0.78-0.92) and simultaneous increased risk for HCM (OR, 1.59; 95% CI, 1.25-2.02), which was confirmed in the replication cohorts. C151R carriers exhibited improved longitudinal outcomes compared with noncarriers as assessed by age at death (hazard ratio [HR], 0.85; 95% CI, 0.74-0.96; median [IQR] age, 71.8 [63.1-80.7] in carriers and 70.3 [61.6-79.2] in noncarriers) and heart transplant (HR, 0.81; 95% CI, 0.66-0.99; median [IQR] age, 56.7 [46.1-63.1] in carriers and 55.6 [45.2-62.9] in noncarriers). C151R was associated with reduced risk of DCM (OR, 0.42; 95% CI, 0.24-0.74) and heart failure (OR, 0.27; 95% CI, 0.14-0.50) among individuals harboring truncating TTN variants in exons with high cardiac expression (n = 358). CONCLUSIONS AND RELEVANCE: BAG3 C151R was identified as a bidirectional modulator of risk along the DCM-HCM spectrum, as well as an important genetic modifier variant in TTN-mediated DCM. This work expands on the understanding of the etiology and penetrance of DCM, suggesting that BAG3 C151R is an important genetic modifier variant contributing to the variable expressivity of DCM, warranting further exploration of its mechanisms and of genetic modifiers in DCM more broadly.

Humans↗

PubMed2024

Aficamten and Cardiopulmonary Exercise Test Performance: A Substudy of the SEQUOIA-HCM Randomized Clinical Trial.

IMPORTANCE: Impaired exercise capacity is a cardinal manifestation of obstructive hypertrophic cardiomyopathy (HCM). The Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic Obstructive HCM (SEQUOIA-HCM) is a pivotal study characterizing the treatment effect of aficamten, a next-in-class cardiac myosin inhibitor, on a comprehensive set of exercise performance and clinical measures. OBJECTIVE: To evaluate the effect of aficamten on exercise performance using cardiopulmonary exercise testing with a novel integrated measure of maximal and submaximal exercise performance and evaluate other exercise measures and clinical correlates. DESIGN, SETTING, AND PARTICIPANTS: This was a prespecified analysis from SEQUOIA-HCM, a double-blind, placebo-controlled, randomized clinical trial. Patients were recruited from 101 sites in 14 countries (North America, Europe, Israel, and China). Individuals with symptomatic obstructive HCM with objective exertional intolerance (peak oxygen uptake [pVO2] ≤90% predicted) were included in the analysis. Data were analyzed from January to March 2024. INTERVENTIONS: Randomized 1:1 to aficamten (5-20 mg daily) or matching placebo for 24 weeks. MAIN OUTCOMES AND MEASURES: The primary outcome was change from baseline to week 24 in integrated exercise performance, defined as the 2-component z score of pVO2 and ventilatory efficiency throughout exercise (minute ventilation [VE]/carbon dioxide output [VCO2] slope). Response rates for achieving clinically meaningful thresholds for change in pVO2 and correlations with clinical measures of treatment effect (health status, echocardiographic/cardiac biomarkers) were also assessed. RESULTS: Among 282 randomized patients (mean [SD] age, 59.1 [12.9] years; 115 female [40.8%], 167 male [59.2%]), 263 (93.3%) had core laboratory-validated exercise testing at baseline and week 24. Integrated composite exercise performance improved in the aficamten group (mean [SD] z score, 0.17 [0.51]) from baseline to week 24, whereas the placebo group deteriorated (mean [SD] z score, -0.19 [0.45]), yielding a placebo-corrected improvement of 0.35 (95% CI, 0.25-0.46; P <.001). Further, aficamten treatment demonstrated significant improvements in total workload, circulatory power, exercise duration, heart rate reserve, peak heart rate, ventilatory efficiency, ventilatory power, and anaerobic threshold (all P <.001). In the aficamten group, large improvements (≥3.0 mL/kg per minute) in pVO2 were more common than large reductions (32% and 2%, respectively) compared with placebo (16% and 11%, respectively). Improvements in both components of the primary outcome, pVO2 and VE/VCO2 slope throughout exercise, were significantly correlated with improvements in symptom burden and hemodynamics (all P <.05). CONCLUSIONS AND RELEVANCE: This prespecified analysis of the SEQUOIA-HCM randomized clinical trial found that aficamten treatment improved a broad range of exercise performance measures. These findings offer valuable insight into the therapeutic effects of aficamten. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05186818.

Humans↗