Anemia is associated with a poor prognosis in heart failure with preserved ejection fraction (HFpEF), but the reasons underlying this association are unclear. Previous studies have reported an association between anemia and diastolic dysfunction. However, these studies used volume- and flow-dependent indexes of diastolic dysfunction. We hypothesized that in HFpEF, anemia is more closely associated with volume status and not markers of intrinsic myocardial dysfunction. We prospectively studied 419 outpatients in a systematic HFpEF program, all of whom underwent hemoglobin measurement and comprehensive echocardiography. Longitudinal, radial, and circumferential strain were also measured in 311 patients. We defined anemia as hemoglobin <12g/dL in women and <13g/dL in men. Linear and Cox regression analyses were used to determine the association between anemia and echocardiographic/strain variables and adverse outcomes, respectively. Over half (224/419 [53%]) of the HFpEF patients had anemia. Anemia was associated with volume (preload)-dependent markers of diastolic dysfunction including echocardiographic E/A (p = 0.004) and E/e' ratio (p = 0.014) and elevated right heart pressures such as right atrial pressure (p = 0.002) and pulmonary artery systolic pressure (p<0.001). Anemia was not associated with markers of intrinsic myocardial dysfunction such as lateral e' (p = 0.16) and septal e' (p = 0.65) velocities or echocardiographic strain parameters (p > 0.05 for all comparisons). Anemia was associated with the combined outcome of cardiovascular hospitalization or death (hazard ratio = 1.50 [95% confidence interval 1.20, 1.88]; p < 0.001). In conclusion, anemia in HFpEF is associated with markers of volume status and not intrinsic markers of myocardial dysfunction.
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