Cao, Jenny

Abstract Pathogenic variants in cardiomyopathy genes confer substantial disease risk, yet clinical penetrance varies widely. The population-level prevalence, age-specific penetrance, and the extent to which polygenic susceptibility modifies disease risk across diverse ancestries remain poorly defined. This population-based cohort study leveraged genome sequencing and linked electronic health record data from the All of Us Research Program (n=414,830). This study found that P/LP variants in cardiomyopathy-associated genes were present in 0.91% of participants (95% CI, 0.88%–0.94%), with similar prevalence across ancestry groups. Compared with non-carriers, variant carriers had significantly higher odds of all-cause heart failure (ACHF, OR, 2.58; 95% CI, 2.31–2.89), non-ischemic heart failure (NIHF, OR, 2.74; 95% CI, 2.42–3.10), and non-ischemic cardiomyopathy (NICM, OR, 4.99; 95% CI, 4.44–5.63). Among carriers, by age 50 years, 24.5% (95% CI, 14.5%–33.4%) developed ACHF, 17.2% (95% CI, 8.8%–24.8%) developed NIHF, and 30.1% (95% CI, 19.5%–40.2%) developed NICM. Higher polygenic risk for heart failure was independently associated with increased risk of ACHF (OR, 1.81; 95% CI, 1.74–1.89), NIHF (OR, 1.66; 95% CI, 1.58–1.75), and NICM (OR, 1.69; 95% CI, 1.59–1.80). Among carriers with elevated polygenic risk, odds of disease were substantially higher than among non-carriers at average polygenic risk (ACHF: OR, 4.71; 95% CI, 4.17–5.32; NIHF: OR, 4.56; 95% CI, 3.99–5.22; NICM: OR, 8.51; 95% CI, 7.44–9.73). Results showed that P/LP variants in cardiomyopathy genes were relatively common in this large, ancestrally diverse cohort, and conferred increased risk of cardiomyopathy and HF, with incomplete but clinically meaningful penetrance. Polygenic risk for HF independently and additively increased disease risk across ancestries. Integrating both may improve risk stratification and enable more precise, equitable care.

Abstract Background The Rochester Epidemiology Project (REP) has been used to examine numerous infectious and non-infectious entities in a population-based approach in Olmsted County, Minnesota. To further investigate patterns of enterococcal bloodstream infection (BSI), we used the Expanded Rochester Epidemiology Project (E-REP) to include additional surrounding counties to conduct a retrospective population-based study of adult patients who developed enterococcal BSI, with or without infective endocarditis (IE). Methods The E-REP population under study included eight counties in southeastern Minnesota (including Olmsted County), representing a total population of over 250,000 individuals. Adults (age ≥ 18 years) diagnosed with an initial episode of enterococcal BSI with or without enterococcal IE between January 1, 2018 and December 31, 2022 were included; patients with either polymicrobial BSI with enterococci or a previous bout of enterococcal BSI before the study period were excluded. Cases of enterococcal BSI and IE were identified using ICD-10 codes and underwent complete medical record review. Patient characteristics, microbiology, antibiotic regimens, infectious complications, and outcomes were collected. Results A total of 113 cases of enterococcal BSI were identified over the five-year study period. The age- and sex-adjusted incidence rate of enterococcal BSI was 6.9 per 100,000 person-years, with a significantly higher rate among males than females (Figure 1). BSI incidence rate varied by age, with patients 80 years or older having the highest incidence rate (Figures 1 and 2). Twenty-two cases of enterococcal IE were identified, yielding an overall IE prevalence of 20.8% (Figure 3). The cumulative mortality rate at 12 months was high at 41.7% (Figure 3). Five patients (4.4%) had a relapse of enterococcal BSI, defined as recurrence of BSI after negative follow-up blood cultures and within 12 weeks of the initial BSI. Conclusion This is the first population-based investigation that has focused on the epidemiology and clinical profile of patients with enterococcal BSI and complicating IE in a US population. This included an IE prevalence of 20.8%, which should be considered when evaluating and managing patients with enterococcal BSI. Disclosures Larry M. Baddour, MD, UpToDate, Inc.: Royalty payments (authorship duties).