Quantitative Echocardiographic Determinants of Clinical Outcome in Asymptomatic Patients With Aortic Regurgitation. A Prospective Study

Objectives: The purpose of this study was to define the link between aortic regurgitation (AR) quantitation and clinical outcome in asymptomatic patients with AR. Background: Quantitative American Society of Echocardiography (QASE) thresholds are recommended for AR assessment, but impact on clinical outcome is unknown. Methods: We prospectively enrolled (1991 to 2003) 251 asymptomatic patients (age 60 ± 17 years) with isolated AR and ejection fraction ≥50% with quantified AR and left ventricular (LV) volumes using Doppler-echocardiography. Results: Survival under medical management was independently determined by baseline regurgitant volume (RVol) (adjusted hazard ratio [HR] 1.22 [95% confidence interval (CI) 1.08 to 1.35] per 10 ml/beat, p = 0.002) and effective regurgitant orifice (ERO) (adjusted HR 1.52 [95% CI 1.19 to 1.91] per 10 mm², p = 0.002), which superseded traditional AR grading. Patients with QASE-severe AR (RVol ≥60 ml/beat or ERO ≥30 mm²) versus QASE-mild AR (RVol <30 ml and ERO <10 mm²) had lower survival (10 years: 69 ± 9% vs. 92 ± 4%, p = 0.05) independently of all clinical characteristics (adjusted HR 4.1 [95% CI 1.4 to 14.1], p = 0.01) and lower survival free of surgery for AR (10 years: 20 ± 5% vs. 92 ± 4%, p < 0.001, adjusted HR 12.9 [95% CI 5.4 to 38.5]). Cardiac events were considerably more frequent with QASE-severe versus -moderate or -mild AR (10 years: 63 ± 8% vs. 34 ± 6% and 21 ± 8%, p < 0.0001). Independent determinants of cardiac events were quantitative AR grading (QASE-severe adjusted HR 5.2 [95% CI 2.2 to 14.8], p < 0.001; QASE-moderate adjusted HR 2.4 [95% CI 1.06 to 6.6], p = 0.035), which superseded traditional AR assessment (p < 0.001) and LV end-systolic volume index (ESVI) (adjusted HR 1.09 [95% CI 1.03 to 1.14 per 10 ml/m²], p = 0.002), which superseded LV M-mode diameters. In QASE-severe AR, patients with ESVI ≥45 versus <45 ml/m² had higher cardiac event rates (10 years: 87 ± 8% vs. 40 ± 10%, p < 0.001). Cardiac surgery for AR reduced cardiac events in patients with QASE-severe AR (adjusted HR 0.23 [95% CI 0.09 to 0.57], p = 0.002). Conclusions: Echocardiographic quantitation of AR severity and ESVI provides independent and superior predictors of clinical outcome in asymptomatic patients with AR and ejection fraction ≥50% and should be widely clinically applied. Patients with QASE-severe AR and ESVI ≥45 ml/m² should be carefully considered for cardiac surgery, which reduces cardiac events risk.