Prognostic Significance of Elevated Left Ventricular Filling Pressures with Exercise: Insights from a Cohort of 14,338 Patients

Abstract

Exercise echocardiography can assess for cardiovascular causes of dyspnea other than coronary artery disease. However, the prevalence and prognostic significance of elevated left ventricular (LV) filling pressures with exercise is understudied. We evaluated 14,338 patients referred for maximal symptom-limited treadmill echocardiography. In addition to assessment of LV regional wall motion abnormalities (RWMAs), we measured patients' early diastolic mitral inflow (E), septal mitral annulus relaxation (e'), and peak tricuspid regurgitation velocity before and immediately after exercise. Over a mean follow-up of 3.3±3.4years, patients with E/e' ≥15 with exercise (n=1,323; 9.2%) had lower exercise capacity (7.3±2.1 vs 9.1±2.4 metabolic equivalents, P<.0001) and were more likely to have resting or inducible RWMAs (38% vs 18%, P<.0001). Approximately 6% (n=837) had elevated LV filling pressures without RWMAs. Patients with a poststress E/e' ≥15 had a 2.71-fold increased mortality rate (2.28-3.21, P<.0001) compared with those with poststress E/e' ≤ 8. Those with an E/e' of 9 to 14, while at lower risk than the E/e' ≥15 cohort (hazard ratio [HR]= 0.58 [0.48-0.69]; P<.0001), had higher risk than if E/e' ≤8 (HR= 1.56 [1.37-1.78], P<.0001). On multivariable analysis, adjusting for age, sex, exercise capacity, LV ejection fraction, and presence of pulmonary hypertension with stress, patients with E/e' ≥15 had a 1.39-fold (95% CI, 1.18-1.65, P<.0001) increased risk of all-cause mortality compared with patients without elevated LV filling pressures. Compared with patients with E/e' ≤ 15 after exercise, patients with E/e' ≤15 at rest but elevated after exercise had a higher risk of cardiovascular death (HR= 8.99 [4.7-17.3], P<.0001). Patients with elevated LV filling pressures are at increased risk of death, irrespective of myocardial ischemia or LV systolic dysfunction. These findings support the routine incorporation of LV filling pressure assessment, both before and immediately following stress, into the evaluation of patients referred for exercise echocardiography.