Exercise echocardiography of left ventricular diastolic function in patients with different clinical conditions and cardiovascular risk factors: functional significance and prognostic impact

Background Pulmonary vascular pressures are flow-dependent, with invasively determined upper limits of normal pulmonary artery wedge pressure (PAWP) defined by a PAWP–cardiac output (CO) relationship of approximately 2 mmHg/L/min. Accordingly, flow-corrected indices such as the ratio of mitral Doppler E to tissue Doppler e' waves (E/e’) to CO slope during exercise Doppler echocardiography (ex-TTE) may better discriminate normal from abnormal left ventricle (LV) diastolic response to exercise. Purpose To investigate the functional significance and the prognostic impact of the ex-TTE derived E/e′–CO slope in patients with different clinical conditions and cardiovascular risk factors. Methods The study population included 478 patients (mean age±SD = 61 ± 13 years; 236 females) with different clinical conditions and cardiovascular risk factors enrolled in the RIGHT-NET registry (Table 1). All participants underwent resting and ex-TTE using a semi-recumbent cycle ergometer with incremental workloads of 25 Watts every 2 minutes until maximal tolerated effort. LV diastolic measurements were obtained at rest and during mid-level exercise (heart rate ≤110 bpm), prior to E and A wave fusion. The E/e′ ratio was calculated using the average of septal and lateral e′ velocities. CO was derived from left ventricular outflow tract diameter and Doppler flow-velocity measurements. The E/e′–CO slope was calculated from the change in E/e′ relative to the change in CO between rest and exercise. An abnormal E/e′–CO slope was defined as ≥0.6, based on prior validation. Results An abnormal E/e′–CO slope ≥0.6 (Group 1) was present in 125 patients, while 353 patients had a normal slope <0.6 (Group 2). Compared with Group 2, Group 1 patients were older, more frequently female, and had a higher prevalence of heart failure and atrial fibrillation. They also exhibited lower hemoglobin levels, higher creatinine, more elevated NT-proBNP or BNP concentrations and pronounced cardiac structural, functional, and hemodynamic abnormalities at rest and at peak exercise (Table 1). During a median follow-up of 2544 days, 29 deaths and 16 hospitalizations occurred among 446 patients with available follow-up data. The cumulative incidence of the combined endpoint of death or hospitalization was significantly higher in Group 1 than in Group 2 (16.2% [19/117] vs. 7.0% [23/329], p = 0.006). Patients with an E/e′–CO slope ≥0.6 demonstrated significantly higher hospitalization rates and reduced survival (Figure 1). Conclusions In patients with different clinical conditions and cardiovascular risk factors, exercise-induced LV diastolic dysfunction, defined by an abnormal ex-TTE derived E/e′–CO slope, is associated with a poorer clinical phenotype, more severe cardiac structural, functional, and hemodynamic impairment, and an adverse prognosis, with higher rates of death and hospitalization.