Background: The prevalence and clinical significance of right ventricular (RV) systolic dysfunction (RVD) in patients with heart failure and preserved EF (HFpEF) are not well characterized. Methods and Results: Consecutive, prospectively identified HFpEF (Framingham HF criteria, EF ≥50%) patients (N=562) from Olmsted County, Minnesota underwent echocardiography at HF diagnosis and follow-up for cause specific mortality and HF hospitalization. RV function was categorized by tertiles of tricuspid annular plane systolic excursion (TAPSE) and by semi-quantitative (normal, mild RVD or moderate-severe RVD) 2D assessment. Whether RVD was defined by semi-quantitative assessment or TAPSE ≤ 15 mm, HFpEF patients with RVD were more likely to have atrial fibrillation, pacemakers and chronic diuretic therapy. At echo, patients with RVD had slightly lower LVEF, worse diastolic dysfunction, lower blood pressure and cardiac output, higher pulmonary artery systolic pressure (PASP), and more severe RV enlargement and tricuspid valve regurgitation. Adjusting for age, sex, PASP and comorbidities, the presence of any RVD by semi-quantitative assessment was associated with higher all-cause (hazard ratio (HR) = 1.35 (1.03-1.77; p=0.03)) and cardiovascular (HR=1.85 (1.20-2.80; p=0.006)) mortality and higher first (HR=1.99 (1.35-2.90; p=0.0006) and multiple (HR=1.81 (1.18-2.78; p=0.007) HF hospitalization rates. RVD defined by TAPSE values showed similar but weaker associations with mortality and HF hospitalizations. Conclusions: In the community, RVD is common in HFpEF patients, associated with clinical and echocardiographic evidence of more advanced HF and predictive of poorer outcomes.

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IMPORTANCE Heart failure (HF) with preserved ejection fraction (HFpEF) is common, is frequently associated with ventricular wall thickening, and has no effective therapy. Transthyretin amyloid cardiomyopathy (ATTR-CM) can cause the HFpEF clinical phenotype, has highly effective therapy, and is believed to be underrecognized. OBJECTIVE To examine the prevalence of ATTR-CM without and with systematic screening in patients with HFpEF and ventricular wall thickening. DESIGN, SETTING, AND PARTICIPANTS This population-based cohort study assessed ATTR-CM prevalence in 1235 consecutive patients in southeastern Minnesota with HFpEF both without (prospectively identified cohort study) and with (consenting subset of cohort study, n = 286) systematic screening. Key entry criteria included validated HF diagnosis, age of 60 years or older, ejection fraction of 40% or greater, and ventricular wall thickness of 12 mm or greater. In this community cohort of 1235 patients, 884 had no known ATTR-CM, contraindication to technetium Tc 99m pyrophosphate scanning, or other barriers to participation in the screening study. Of these 884 patients, 295 consented and 286 underwent scanning between October 5, 2017, and March 9, 2020 (community screening cohort). EXPOSURES Medical record review or technetium Tc 99m pyrophosphate scintigraphy and reflex testing for ATTR-CM diagnosis. MAIN OUTCOMES AND MEASURESThe ATTR-CM prevalence by strategy (clinical diagnosis or systematic screening), age, and sex.RESULTS A total of 1235 patients participated in the study, including a community cohort (median age, 80 years; interquartile range, 72-87 years; 630 [51%] male) and a community screening cohort (n = 286; median age, 78 years; interquartile range, 71-84 years; 149 [52%] male). In the 1235 patients in the community cohort without screening group, 16 patients (1.3%; 95% CI, 0.7%-2.1%) had clinically recognized ATTR-CM. The prevalence was 2.5% (95% CI, 1.4%-4.0%) in men and 0% (95% CI, 0.0%-0.6%) in women. In the 286 patients in the community screening cohort, 18 patients (6.3%; 95% CI, 3.8%-9.8%) had ATTR-CM. Prevalence increased with age from 0% in patients 60 to 69 years of age to 21% in patients 90 years and older (P < .001). Adjusting for age, ATTR-CM prevalence differed by sex, with 15 of 149 men (10.1%; 95% CI, 5.7%-16.1%) and 3 of 137 women (2.2%; 95% CI, 0.4%-6.3%) having ATTR-CM (P = .002). CONCLUSIONS AND RELEVANCEIn this cohort study based in a community-based setting, ATTR-CM was present in a substantial number of cases of HFpEF with ventricular wall thickening, particularly in older men. These results suggest that systematic evaluation can increase the diagnosis of ATTR-CM, thereby providing therapeutically relevant phenotyping of HFpEF.

Background Readmission or death following heart failure (HF) hospitalization is a consequential and closely scrutinized outcome, but risk factors may vary by population. We characterized the risk factors for post-discharge readmission/death in subjects treated for acute heart failure (AHF). Methods and Results A post hoc analysis was performed on data from 744 subjects enrolled in three AHF trials conducted within the Heart Failure Network (HFN): Diuretic Optimization Strategies Evaluation in Acute Heart Failure (DOSE-AHF), CARdiorenal REScue Study in Acute Decompensated Heart Failure (CARRESS-HF), and Renal Optimization Strategies Evaluation in Acute Heart Failure (ROSE-AHF). All-cause readmission/death occurred in 26% and in 38% of subjects within 30- and 60-days of discharge, respectively. Non-HF cardiovascular causes of readmission were more common in the ≤ 30 day timeframe vs. the 31-60 day timeframe (23% vs. 10%, p=0.016). In a Cox proportional hazards model adjusting a priori for LVEF < 50% and trial, the risk factors for all-cause readmission/death included: elevated baseline BUN, ACEI/ARB non-use, lower baseline sodium, non-white race, elevated baseline bicarbonate, lower SBP at discharge/day 7, depression, increased length of stay, and male sex. Conclusions In an AHF population with prominent congestion and prevalent renal dysfunction, early readmissions were more likely to be due to non-HF cardiovascular causes compared to later readmissions. The association between use of ACEI/ARB and lower all-cause readmission/death in Cox proportional hazards model suggests a role for these drugs to improve post-discharge outcomes in AHF.