Masaru Obokata1, Garvan C Kane1, Yogesh N V Reddy1, Thomas P Olson1, Vojtech Melenovsky1, Barry A Borlaug2. 1. From Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic Rochester, MN (M.O., G.C.K., Y.N.V.R., T.P.O., B.A.B.); and IKEM - Institute for Clinical and Experimental Medicine, Department of Cardiology, Prague, Czech Republic (V.M.). 2. From Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic Rochester, MN (M.O., G.C.K., Y.N.V.R., T.P.O., B.A.B.); and IKEM - Institute for Clinical and Experimental Medicine, Department of Cardiology, Prague, Czech Republic (V.M.). borlaug.barry@mayo.edu.
Abstract
BACKGROUND: Diagnosis of heart failure with preserved ejection fraction (HFpEF) is challenging and relies largely on demonstration of elevated cardiac filling pressures (pulmonary capillary wedge pressure). Current guidelines recommend use of natriuretic peptides (N-terminal pro-B type natriuretic peptide) and rest/exercise echocardiography (E/e' ratio) to make this determination. Data to support this practice are 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: N-Terminal pro-B type natriuretic peptide 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 pulmonary capillary wedge pressure at rest (r=0.63, P<0.0001) and during exercise (r=0.57, P<0.0001). Although specific, current guidelines were poorly sensitive, identifying only 34% to 60% of subjects with invasively proven HFpEF on the basis of 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 on the basis of 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 on the basis of 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: URL: http://www.clinicaltrials.gov. Unique Identifier: NCT01418248.
BACKGROUND: Diagnosis of heart failure with preserved ejection fraction (HFpEF) is challenging and relies largely on demonstration of elevated cardiac filling pressures (pulmonary capillary wedge pressure). Current guidelines recommend use of natriuretic peptides (N-terminal pro-B type natriuretic peptide) and rest/exercise echocardiography (E/e' ratio) to make this determination. Data to support this practice are 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: N-Terminal pro-B type natriuretic peptide 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 pulmonary capillary wedge pressure at rest (r=0.63, P<0.0001) and during exercise (r=0.57, P<0.0001). Although specific, current guidelines were poorly sensitive, identifying only 34% to 60% of subjects with invasively proven HFpEF on the basis of 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 on the basis of 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 on the basis of 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: URL: http://www.clinicaltrials.gov. Unique Identifier: NCT01418248.
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