Takahama, Hiroyuki

Background: The Acute Decompensated Heart Failure National Registry (ADHERE) risk levels are a validated tool to assess the risk of in-hospital mortality in patients with acute decompensated heart failure (ADHF). The objective of this study is to determine if the risk levels predict 60-day outcomes in well-defined ADHF patients from NIH Heart Failure Clinical Research Network (HFCRN) trials. Methods: Our study cohort included 835 unique patients with ADHF enrolled in 3 NIH HFCRN trials: Diuretic Optimization Strategies Evaluation (DOSE), CARdiorenal REScue Study in Acute Decompensated Heart Failure (CARRESS-HF), and Renal Optimization Strategies Evaluation (ROSE). ADHERE risk level was assigned, as previously described, by baseline BUN (<43 vs. ≥43 mg/dL), Cr (<2.2 vs. ≥2.2, a modification from 2.75 mg/dL used in ADHERE due the Cr distribution in our study population), and systolic BP (≥ 115 vs < 115 mmHg). Baseline characteristics and outcomes were compared between risk levels. Results: Of the 835 patients enrolled in DOSE (308), CARRESS-HF (188), and ROSE (360), an ADHERE risk level could be assigned to 830, with 62 (8%) high, 521 (63%) intermediate, 247 (30%) low risk. Baseline characteristics (Table 1) and outcomes (Table 2), including combined 60-day death and re-hospitalization (hazard ratio 1.94, high risk versus low risk, p<0.01), varied by ADHERE risk level. Conclusion: ADHERE risk levels predict 60-day death and re-hospitalization rates in patients with ADHF. These results extend the utility of the ADHERE risk levels, by informing longer-term clinical decisions regarding advanced heart failure treatment, care transition strategies and clinical trial design.

Background— Left atrial (LA) compliance and contractility influence left ventricular stroke volume. We hypothesized that diminished LA compliance and contractile function occur early during the development of heart failure with preserved ejection fraction (HFpEF) and impair overall cardiac performance. Methods and Results— Cardiac magnetic resonance imaging, echocardiography, left ventricular and LA pressure-volume studies, and tissue analyses were performed in a model of early HFpEF (elderly dogs, renal wrap-induced hypertension, exogenous aldosterone; n=9) and young control dogs (sham surgery; n=13). Early HFpEF was associated with LA enlargement, cardiomyocyte hypertrophy, and enhanced LA contractile function (median active emptying fraction 16% [95% confidence interval, 13–24]% versus 12 [10–14]%, P =0.008; end-systolic pressure-volume relationship slope 2.4 [1.9–3.2]mm Hg/mL HFpEF versus 1.5 [1.2–2.2]mm Hg/mL controls, P =0.01). However, atrioventricular coupling was impaired and the curvilinear LA end-reservoir pressure-volume relationship was shifted upward/leftward in HFpEF (LA stiffness constant [β LA ] 0.16 [0.11–0.18]mm Hg/mL versus 0.06 [0.04–0.10]mm Hg/mL controls; P =0.002), indicating reduced LA compliance. Impaired atrioventricular coupling and lower LA compliance correlated with lower left ventricular stroke volume. Total fibrosis and titin isoform composition were similar between groups; however, titin was hyperphosphorylated in HFpEF and correlated with β LA . LA microvascular reactivity was diminished in HFpEF versus controls. LA microvascular density tended to be lower in HFpEF and inversely correlated with β LA . Conclusions— In early-stage hypertensive HFpEF, LA cardiomyocyte hypertrophy, titin hyperphosphorylation, and microvascular dysfunction occur in association with increased systolic and diastolic LA chamber stiffness, impaired atrioventricular coupling, and decreased left ventricular stroke volume. These data indicate that maladaptive LA remodeling occurs early during HFpEF development, supporting a concept of global myocardial remodeling.

Background— The prevalence and clinical significance of right ventricular (RV) systolic dysfunction (RVD) in patients with heart failure and preserved ejection fraction (HFpEF) are not well characterized. Methods and Results— Consecutive, prospectively identified HFpEF (Framingham HF criteria, ejection fraction ≥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 and by semiquantitative (normal, mild RVD, or moderate to severe RVD) 2-dimensional assessment. Whether RVD was defined by semiquantitative assessment or tricuspid annular plane systolic excursion ≤15 mm, HFpEF patients with RVD were more likely to have atrial fibrillation, pacemakers, and chronic diuretic therapy. At echocardiography, patients with RVD had slightly lower left ventricular ejection fraction, worse diastolic dysfunction, lower blood pressure and cardiac output, higher pulmonary artery systolic pressure, and more severe RV enlargement and tricuspid valve regurgitation. After adjustment for age, sex, pulmonary artery systolic pressure, and comorbidities, the presence of any RVD by semiquantitative assessment was associated with higher all-cause (hazard ratio=1.35; 95% confidence interval, 1.03–1.77; P =0.03) and cardiovascular (hazard ratio=1.85; 95% confidence interval, 1.20–2.80; P =0.006) mortality and higher first (hazard ratio=1.99; 95% confidence interval, 1.35–2.90; P =0.0006) and multiple (hazard ratio=1.81; 95% confidence interval, 1.18–2.78; P =0.007) HF hospitalization rates. RVD defined by tricuspid annular plane systolic excursion values showed similar but weaker associations with mortality and HF hospitalizations. Conclusions— In the community, RVD is common in HFpEF patients, is associated with clinical and echocardiographic evidence of more advanced HF, and is predictive of poorer outcomes.