insulin resistance and altered energy metabolism is common in non-alcoholic fatty liver disease (nAfLD) and appears to also be associated with myocardial dysfunction. We aimed to evaluate prevalence, staging and clinical features correlated with nAfLD among patients with heart failure with preserved ejection fraction (Hfpef). Adults with Hfpef were prospectively enrolled. Demographic and clinical data were collected. NAFLD was defined based on liver biopsy, abdominal imaging or icD-coding and the absence of other liver diseases. Descriptive, bivariate and multivariable analyses were performed. 181 patients were analyzed. The median age was 70 with 89% white, 59% female, median BMI 35.1, and 48% with diabetes. NAFLD was present in 27% of the full cohort and 50% of those with imaging. In patients with imaging, multivariable analysis identified diabetes (OR 3.38, 95% CI 1.29-8.88) and BMI (OR 1.11, 95% CI 1.04-1.19) as independent correlates of NAFLD. 54% of NAFLD patients had a NAFLD fibrosis score consistent with advanced fibrosis. Cirrhosis was present in 6.6% of patients overall and 11.5% with imaging. NAFLD patients had a higher frequency of advanced heart failure (75% vs 55%, p 0.01). NAFLD has a twofold higher prevalence in HFpEF compared to the general population and is independently associated with BMi and diabetes. patients with HFpEF and NAFLD also appeared to have more advanced fibrosis including cirrhosis suggesting a potential synergistic effect of cardiac dysfunction on fibrosis risk in NAFLD. This data supports consideration for evaluation of underlying liver disease in Hfpef patients.

Background: Since coronavirus disease 2019 (COVID-19) was first identified in Wuhan, China, in December 2019, the number of cases has risen exponentially. Clinical characteristics and outcomes among patients with orthotopic heart transplant (OHT) with COVID-19 remain poorly described. Methods: We performed a retrospective case series of patients with OHT with COVID-19 admitted to 1 of 2 hospitals in Southeastern Michigan between March 21 and April 22, 2020. Clinical data were obtained through review of the electronic medical record. Final date of follow-up was May 7, 2020. Demographic, clinical, laboratory, radiologic, treatment, and mortality data were collected and analyzed. Results: We identified 13 patients with OHT admitted with COVID-19. The mean age of patients was 61 § 12 years, 100% were black males, and symptoms began 6 § 4 days before admission. The most common symptoms included subjective fever (92%), shortness of breath (85%), and cough (77%). Six patients (46%) required admission to the intensive care unit. Two patients (15%) died during hospitalization. Conclusions: Black men may be at increased risk for COVID-19 among patients with OHT. Presenting signs and symptoms in this cohort are similar to those in the general population. Elevated inflammatory markers on presentation appear to be associated with more severe illness.

Heart failure with preserved ejection fraction (HFpEF) is a prevalent but incompletely understood syndrome. Traditional models of HFpEF pathophysiology revolve around systemic HTN and other causes of increased left ventricular afterload leading to left ventricular hypertrophy (LVH) and diastolic dysfunction. However, emerging models attribute the development of HFpEF to systemic proinflammatory changes secondary to common comorbidities which include HTN. Alterations in passive ventricular stiffness, ventricular-arterial coupling, peripheral microvascular function, systolic reserve, and chronotropic response occur. As a result, HFpEF is heterogeneous in nature, making it difficult to prescribe uniform therapies to all patients. Nonetheless, treating systemic HTN remains a cornerstone of HFpEF management. Antihypertensive therapies have been linked to LVH regression and improvement in diastolic dysfunction. However, to date, no therapies have definitive mortality benefit in HFpEF. Non-pharmacologic management for HTN, including dietary modification, exercise, and treating sleep disordered breathing, may provide some morbidity benefit in the HFpEF population. Future research is need to identify effective treatments, perhaps in more specific subgroups, and focus may need to shift from reducing mortality to improving exercise capacity and symptoms. Tailoring antihypertensive therapies to specific phenotypes of HFpEF may be an important component of this strategy.

Identifying individuals at high risk of heart failure during precursor stages could allow for earlier initiation of treatments to modify disease progression. We performed a GWAS meta-analysis to generate a heart failure (HF) polygenic risk score (PRS) then tested the association with phenotypic subtypes (reduced ejection fraction [HFrEF] and preserved ejection fraction [HFpEF]) to evaluate the value of polygenic risk prediction. Results from the European-ancestry analysis showed that an ancestry-matched PRS, calculated from GBMI meta-analysis outperformed the previous HF GWAS (HERMES), yielding an adjusted odds ratio (aOR) of 2.27 (95% CI: 2.05-2.51; p: 1.76x10-56) from GBMI compared to 1.30 (95% CI: 1.18-1.44; p: 1.42x10-7) from HERMES, and 1.49 (95% CI: 1.33-1.66; p: 8.38x10-13) compared to 1.17 (95% CI: 1.05-1.31; p: 0.004) for HFrEF and HFpEF, respectively. Next, we evaluated the performance differences between ancestry-matched and multi-ancestry PRS in the African American cohort. The GBMI multi-ancestry GWAS-based PRS had a significant aOR of 1.49 (p: 0.006). Findings suggest that a PRS for heart failure derived from the GBMI multi-ancestry study is useful in predicting HFrEF, but less powerful in predicting HFpEF in an independent cohort. The difficulty in predicting HFpEF could result from the GBMI HF phenotype, preferencing HFrEF over HFpEF, and/or greater genetic heterogeneity in the HFpEF phenotype.

Lower extremity function, as measured by the SPPB, independently predicts hospitalization burden in outpatients with HFpEF. Additional studies are warranted to explore shared mechanisms and treatment implications of frailty in HFpEF.