Exercise Echocardiography for Risk Stratification in Unexplained Dyspnea: The Incremental Value of the Mean Pulmonary Artery Pressure/Slope

Abstract

Background Patients with unexplained dyspnea and an elevated mean pulmonary artery pressure (mPAP)/cardiac output (CO) slope on invasive hemodynamic assessment during exercise have worse clinical outcomes. The aim of this study was to evaluate the incremental prognostic value of the noninvasive mPAP/CO slope in addition to heart failure with preserved ejection fraction (HFpEF) probability scores and diastolic stress testing in patients with unexplained dyspnea. Methods In a multicenter cohort study involving six Belgian dyspnea clinics, patients with unexplained dyspnea underwent exercise echocardiography for mPAP/CO slope assessment. Positive HFpEF scores were defined as HFA-PEFF (Heart Failure Association pretest probability echocardiography, functional testing, final diagnosis) score >= 5 and H2FPEF (heavy, hypertensive, atrial fibrillation, pulmonary hypertension, elder, filling pressure) score >= 6. The outcome evaluated was a composite of all-cause mortality or heart failure hospitalization. Results Among 2,452 patients (mean age, 63 +/- 15 years; 53% women), mPAP/CO slope > 3.5 mm Hg <middle dot> L-1 <middle dot> min(-1) best predicted adverse outcomes. The prognostic value of the mPAP/CO slope was greater in patients with negative HFpEF scores than in those with positive scores (interaction P = .02). The mPAP/CO slope remained independently prognostic after adjustment for N-terminal pro-B-type natriuretic peptide (hazard ratio [HR], 2.26; 95% CI, 1.33-3.82) and for HFpEF scores and diastolic stress testing (HR, 1.99; 95% CI, 1.37-2.88), whereas exercise tricuspid regurgitant velocity did not. Both HFpEF score-negative patients with slope > 3.5 mm Hg <middle dot> L-1 <middle dot> min(-1) (HR, 2.99; 95% CI, 1.81-4.95) and HFpEF score-positive patients (HR, 6.29; 95% CI, 4.25-9.31) showed significantly higher risk compared with HFpEF score-negative patients with slope <= 3.5 mm Hg <middle dot> L-1 <middle dot> min(-1). Conclusions The mPAP/CO slope, unlike exercise tricuspid regurgitant velocity, adds prognostic value beyond natriuretic peptides, HFpEF scores, and diastolic stress testing, identifying high-risk patients with exercise-induced hemodynamic abnormalities who may benefit from invasive confirmation and closer follow-up.