Comparative evaluation of atrial and ventricular function using advanced echocardiography in patients with exercise-induced pulmonary hypertension with or without positive diastolic stress test

Abstract Background Diastolic stress echocardiography (DSE) is recommended for the non-invasive assessment of exertional LV filling pressures in suspected heart failure with preserved ejection fraction (HFpEF). A positive DSE is defined by an exercise-induced increase in both mitral inflow to septal mitral annular velocity ratio (E/e′ ≥ 14) and tricuspid regurgitation velocity (TRV > 2.8 m/s) in patients (pts) with exertional dyspnoea and grade I diastolic dysfunction (DD) at rest. Since some of these pts exhibits an isolated increase in TRV, we aimed to compare advanced echocardiographic parameters of atrial and ventricular function in pts with exercise-induced pulmonary hypertension (PH) with and without a positive DSE. We hypothesised that although exercise-induced TRV elevation may reflect a flow-mediated increase in pulmonary artery pressure (PAP), some of these pts may still have a HFpEF physiology. Methods Patients with exertional dyspnoea, preserved LVEF, and grade I DD at rest were prospectively enrolled and evaluated by echocardiography at rest and during exercise using semi-supine bicycle DSE. Patients with non-sinus rhythm, coronary artery disease, moderate-to-severe valvular disease, or resting PH were excluded. Based on exertional TRV and DSE results, 3 groups were formed: Group 1: No exercise-induced PH (TRV ≤ 2.8 m/s) Group 2: TRV > 2.8 m/s and negative DSE Group 3: Positive DSE In addition to conventional echocardiographic measures, we assessed peak left atrial reservoir strain (LARS) at rest and during exercise, global longitudinal strain (GLS), and myocardial work indices using speckle tracking echocardiography. ANOVA and ANCOVA were used to evaluate intra- and intergroup differences. Results The study included 46 pts (74% men, 64.2 ± 11 years). Significant differences were observed between groups in terms of age (p < 0.001), resting LARS (Group 1: 35.1 ± 7.3% vs Group 2: 30.5 ± 12.1% vs Group 3: 22.1 ± 9.1%, p = 0.016), and exercise LARS (Group 1: 48.0 ± 7.6% vs Group 2: 39.1 ± 20.0% vs Group 3: 24.1 ± 8.7%, p = 0.019). Post hoc analysis revealed a significant difference between Group 1 and Group 3 (p = 0.004 and 0.026), and a marginally significant difference between Group 2 and Group 3 (p = 0.084 and 0.064) for both resting and exercise LARS, suggesting a decline in both atrial function and functional reserve from Group 1 to Group 3. No significant differences were observed between groups for NT-proBNP (p = 0.63), indexed LA volume (p = 0.056), GLS (p = 0.252), TAPSE (p = 0.93), or myocardial work indices. Conclusion In patients with exertional dyspnoea and preserved LVEF, an exercise-induced increase in PAP, even with a negative DSE, may indicate an impaired hemodynamic adaptation and reduced atrial functional reserve. These findings highlight the importance of DSE in the diagnostic evaluation of HFpEF, and suggest the existence of a clinically relevant "intermediate phenotype" within the HFpEF spectrum.LARS ANOVA across groups Group comparison using ANOVA