Prognostic value of the cardiac damage staging system and CPETecho in patients with heart failure with preserved ejection fraction

Abstract Background The cardiac damage staging system was designed to capture the progressive structural impact of aortic stenosis and has proven prognostic value in valvular heart disease. The prognostic value of the cardiac damage staging system in patients with heart failure with preserved ejection fraction (HFpEF) is unknown. Purpose To evaluate the prognostic value of the cardiac damage staging system and the integrated use of cardiopulmonary exercise testing and echocardiography (CPET-echo) in patients with HFpEF. Methods In a multicenter cohort study, a total of 429 patients (65% female; 74years) with HFpEF underwent CPETecho. On the basis of a cardiac damage staging scheme recently proposed by Généreux et al., patients were categorized into five independent stages: Stage 0 – no other cardiac damage detected; Stage 1 – LV damage (LV hypertrophy, diastolic or systolic dysfunction); Stage 2 – LA or mitral valve damage (enlarged LA; presence of atrial fibrillation or ≥moderate functional mitral regurgitation); Stage 3 – pulmonary hypertension or ≥moderate tricuspid regurgitation (TR) and Stage 4 – RV damage. They were subsequently evaluated for the occurrence of the combined endpoint heart failure (HF) death and HF hospitalizations. Results Cardiac damage was identified in 78% of patients, with 20% exhibiting left ventricular damage (Stage 1), 27% showing left atrial or mitral valve damage (Stage 2), and 42% presenting with right ventricular damage (Stage 4); no patients were classified with pulmonary vasculature or tricuspid valve damage (Stage 3). Over a median follow-up of 27 months IQR 16–39, 120 patients reached the primary endpoint. Among them, 79% had ≥Stage 2 cardiac damage. In the multivariable Cox regression, age; cardiac damage stage (≥2 versus 2); diastolic stress test (septal E/e' 15 versus septal E/e' ≤15) and cardiorespiratory fitness (%-predicted peak VO2 80 versus ≥80) were independently associated with the adverse outcome (Figure 1). When added to the model NTproBNP (660 versus ≤600ng/L, for patients in atrial fibrillation and 220 versus ≤220ng/L, for patients in sinus rhythm) was not independently associated with the outcome. Incorporating cardiac damage and CPETecho derived parameters (diastolic stress test and cardiorespiratory fitness) significantly improved event prediction beyond sex and age: likelihood χ2=25.6, p 0.01 and AUC 0.538 versus 0.642, p0.001 (Figure 1). Figure 2 depicts event-free survival at 36 months. Conclusions More advanced cardiac damage stages are strongly associated with poor outcomes in HFpEF. CPET-echo further enhances risk stratification and may guide individualized management.