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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BACKGROUND Aortic stiffening and reduced nitric oxide (NO) availability may contribute to the pathophysiology of heart failure with preserved ejection fraction (HFpEF). OBJECTIVES We assessed indices of arterial stiffness at rest and during exercise in subjects with HFpEF and hypertensive controls, to examine their relationship to cardiac hemodynamics and determine whether exertional arterial stiffening can be mitigated by inorganic nitrite. METHODS Twenty-two hypertensive controls and 98 HFpEF subjects underwent hemodynamic exercise testing with simultaneous expired gas analysis. Invasively measured radial artery pressure waveforms were converted to central aortic waveforms by transfer function to assess integrated measures of pulsatile aortic load, including arterial compliance, resistance, elastance, and wave reflection. RESULTS Arterial load and wave reflections were similar in HFpEF and controls at rest. During submaximal exercise, HFpEF subjects displayed reduced total arterial compliance and higher effective arterial elastance despite similar mean arterial pressures to controls. This was directly correlated with higher ventricular filling pressures and depressed cardiac output reserve (both p <0.0001). With peak exercise, increased wave reflections impaired compliance, resistance and elastance were observed. A subset of HFpEF subjects (n = 52) received sodium nitrite or placebo in a 1:1 double blind, randomized fashion. Compared to placebo, nitrite decreased aortic wave reflections at rest and improved arterial compliance, elastance, and improved central hemodynamics during exercise. CONCLUSION Abnormal pulsatile aortic loading during exercise occurs in HFpEF independent of hypertension, and is correlated with classical hemodynamic derangements that develop with stress. Inorganic nitrite mitigates arterial stiffening with exercise and improves hemodynamics, indicating that arterial stiffening with exercise is at least partially reversible. Further study is required to test effects of agents that target the NO pathway in reducing arterial stiffness in HFpEF.

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Aims Left atrial (LA) function is impaired in heart failure with preserved ejection fraction (HFpEF) and predicts disease severity and risk of adverse outcome. We sought to evaluate whether LA strain could enhance diagnosis of HFpEF. Methods and results Consecutive patients with unexplained exertional dyspnoea and image quality suitable for measuring LA strain underwent invasive cardiopulmonary exercise testing to ascertain the presence of HFpEF or non‐cardiac causes of dyspnoea (NCD). LA reservoir strain was measured in all patients, while LA conduit and booster strain were measured in patients with sinus rhythm. LA strain was measurable in 363 of 378 examinations (96.5%; HFpEF: 238, NCD: 125). LA reservoir strain (29 ± 16% vs. 40 ± 13%, P < 0.0001) and conduit strain (18 ± 10% vs. 22 ± 10%, P = 0.0001) were significantly impaired in HFpEF compared to NCD. Of all echocardiographic indices, LA reservoir strain best discriminated HFpEF from NCD [area under the curve (AUC) 0.719, P < 0.0001], outperforming E/e' (AUC difference +0.117, P < 0.0001), LA enlargement (+0.090, P = 0.001), tricuspid regurgitation velocity > 2.8 m/s (+0.082, P = 0.0085), left ventricular hypertrophy (+0.0159, P < 0.0001) and left ventricular global longitudinal strain (+0.0198, P < 0.0001). Indexing LA reservoir strain to estimated LA pressure (E/e') as a surrogate for LA compliance further improved diagnostic performance (AUC 0.772, P < 0.0001; +0.053 compared to LA reservoir strain alone, P = 0.003). Conclusion Left atrial reservoir strain may provide enhanced diagnostic accuracy beyond conventional echocardiographic measures to discriminate HFpEF from NCD. Further study is required to verify the diagnostic utility of LA strain.

This study provides the first evidence linking altered exercise haemodynamics to pulmonary abnormalities and symptoms of dyspnoea in patients with HFpEF. Further study is required to identify the mechanisms by which haemodynamic derangements affect lung function and symptoms and to test novel therapies targeting exercise haemodynamics in HFpEF.