The HFPEF score, which relies on simple clinical characteristics and echocardiography, enables discrimination of HFpEF from noncardiac causes of dyspnea and can assist in determination of the need for further diagnostic testing in the evaluation of patients with unexplained exertional dyspnea.
Background Heart failure (HF) with preserved ejection fraction (HFpEF) is a heterogeneous syndrome. Phenotyping patients into pathophysiologically homogenous groups may enable better targeting of treatment. Obesity is common in HFpEF and has many cardiovascular effects, suggesting it may be a viable candidate for phenotyping. We compared cardiovascular structure, function, and reserve capacity in subjects with obese HFpEF, non-obese HFpEF, and controls. Methods Subjects with obese HFpEF (BMI≥35kg/m2, n=99), non-obese HFpEF (BMI<30kg/m2, n=96), and non-obese controls free of HF (n=71) underwent detailed clinical assessment, echocardiography and invasive hemodynamic exercise testing. Results Compared to both non-obese HFpEF and controls, subjects with obese HFpEF displayed increased plasma volume (3907 [3563,4333] vs. 2772 [2555,3133] and 2680 [2380,3006] ml, p<0.0001), more concentric left ventricular remodeling, greater right ventricular dilatation (base 34±7 vs. 31±6 and 30±6 mm, p=0.0005; length 66±7 vs. 61±7 and 61±7 mm, p<0.0001), more right ventricular dysfunction, increased epicardial fat thickness (10±2 vs. 7±2 and 6±2 mm, p<0.0001), and greater total epicardial heart volume (945 [831,1105] vs. 797 [643,979] and 632 [517,768] ml, p<0.0001), despite lower NT-proBNP levels. Pulmonary capillary wedge pressure was correlated with body mass and plasma volume in obese HFpEF (r=0.22 and 0.27, both p<0.05), but not in non-obese HFpEF (p≥0.3). The increase in heart volumes in obese HFpEF was associated with greater pericardial restraint and heightened ventricular interdependence, reflected by increased ratio of right to left heart filling pressures (0.64±0.17 vs. 0.56±0.19 and 0.53±0.20, p=0.0004), higher pulmonary venous pressure relative to left ventricular transmural pressure, and greater left ventricular eccentricity index (1.10±0.19 vs 0.99±0.06 and 0.97±0.12, p<0.0001). Interdependence was enhanced as pulmonary artery pressure load increased (interaction p<0.05). As compared to non-obese HFpEF and controls, obese HFpEF subjects displayed worse exercise capacity (peak oxygen consumption 7.7±2.3 vs. 10.0±3.4 and12.9±4.0 ml/min*kg, p<0.0001), higher biventricular filling pressures with exercise and depressed pulmonary artery vasodilator reserve. Conclusions Obesity-related HFpEF is a genuine form of cardiac failure and a clinically relevant phenotype that may require specific treatments.
Background Diagnosis of heart failure (HF) with preserved ejection fraction (HFpEF) is challenging and relies largely on demonstration of elevated cardiac filling pressures (pulmonary capillary wedge pressure, PCWP). Current guidelines recommend use of natriuretic peptides (NT-proBNP) and rest/exercise echocardiography (E/e’ ratio) to make this determination. Data to support this practice is conflicting. Methods Simultaneous echocardiographic-catheterization studies were prospectively conducted at rest and during exercise in subjects with invasively-proven HFpEF (n=50) and participants with dyspnea but no identifiable cardiac pathology (n=24). Results NT-proBNP levels were below the level considered to exclude disease (≤125 pg/ml) in 18% of subjects with HFpEF. E/e’ ratio was correlated with directly measured PCWP at rest (r=0.63, p<0.0001) and during exercise (r=0.57, p<0.0001). While specific, current guidelines were poorly sensitive, identifying only 34–60% of subjects with invasively-proven HFpEF based upon resting echocardiographic data alone. Addition of exercise echocardiographic data (E/e’ ratio>14) improved sensitivity (to 90%) and thus negative predictive value, but decreased specificity (71%). Conclusions Currently proposed HFpEF diagnostic guidelines based upon resting data are poorly sensitive. Adding exercise E/e’ data improves sensitivity and negative predictive value but compromises specificity, suggesting that exercise echocardiography may help rule out HFpEF. These results question the accuracy of current approaches to exclude HFpEF based upon resting data alone and reinforce the value of exercise testing using invasive and noninvasive hemodynamic assessments to definitively confirm or refute the diagnosis of HFpEF. Clinical trial registration NCT01418248 https://clinicaltrials.gov/ct2/results?term=NCT01418248&Search=Search
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