Association of Echocardiographic Left Ventricular End-Systolic Volume and Volume-Derived Ejection Fraction With Outcome in Asymptomatic Chronic Aortic Regurgitation

Li-Tan Yang, MD1,2Vidhu Anand, MBBS1Elena I. Zambito, RDCS1Patricia A. Pellikka, MD1Christopher G. Scott, MS3Prabin Thapa, MS3Ratnasari Padang, MBBS, PhD1Masaaki Takeuchi, MD4Rick A. Nishimura, MD1Maurice Enriquez-Sarano, MD1Hector I. Michelena, MD1

JAMA Cardiol. 2021;6(2):189-198. doi:10.1001/jamacardio.2020.5268

Key Points

Question  Are disk-summation method–derived left ventricular (LV) end-systolic volume index and LV ejection fraction (LVEF) associated with mortality in asymptomatic patients with hemodynamically significant chronic aortic regurgitation?

Findings  In this cohort study of 492 asymptomatic patients with moderately severe to severe aortic regurgitation, besides conventional linear LVEF and LV end-systolic dimension index, LV end-systolic volume index and volume-derived LVEF were robust independent factors associated with mortality. Thresholds of increased mortality risk for linear LVEF and volume-derived LVEF were 60%, and for LV end-systolic dimension index and volume index, 21 to 22 mm/m2 and 40 to 45 mL/m2, respectively; previously reported LV end-systolic volume index threshold of 45 mL/m2 was a robust marker of increased risk of death.

Meaning  In asymptomatic low-risk patients with aortic regurgitation, LV end-systolic volume index and volume-derived LVEF provided similar risk-stratifying power as conventional linear LVEF and LV end-systolic dimension index.


Importance  Volumetric measurements by transthoracic echocardiogram may better reflect left ventricular (LV) remodeling than conventional linear LV dimensions. However, the association of LV volumes with mortality in patients with chronic hemodynamically significant aortic regurgitation (AR) is unknown.

Objective  To assess whether LV volumes and volume-derived LV ejection fraction (Vol-LVEF) are determinants of mortality in AR.

Design, Setting, and Participants  This cohort study included consecutive asymptomatic patients with chronic moderately severe to severe AR from a tertiary referral center (January 2004 through April 2019).

Exposures  Clinical and echocardiographic data were analyzed retrospectively. Aortic regurgitation severity was graded by comprehensive integrated approach. De novo disk-summation method was used to derive LV volumes and Vol-LVEF.

Main Outcome and Measures  Associations between all-cause mortality under medical surveillance and the following LV indexes: linear LV end-systolic dimension index (LVESDi), linear LVEF, LV end-systolic volume index (LVESVi), and Vol-LVEF.

Results  Of 492 asymptomatic patients (mean [SD] age, 60 [17] years; 425 men [86%]), ischemic heart disease prevalence was low (41 [9%]), and 453 (92.1%) had preserved linear LVEF (≥50%) with mean (SD) LVESVi of 41 (15) mL/m2. At a median (interquartile range) of 5.4 (2.5-10.1) years, 66 patients (13.4%) died under medical surveillance; overall survival was not different than the age- and sex-matched general population (P = .55). Separate multivariate models, adjusted for age, sex, Charlson Comorbidity Index, and AR severity, demonstrated that in addition to linear LVEF and LVESDi, LVESVi and Vol-LVEF were independently associated with mortality under surveillance (all P < .046) with similar C statistics (range, 0.83-0.84). Spline curves showed that continuous risks of death started to rise for both linear LVEF and Vol-LVEF less than 60%, LVESVi more than 40 to 45 mL/m2, and LVESDi above 21 to 22 mm/m2. As dichotomized variables, patients with LVESVi more than 45 mL/m2 exhibited increased relative death risk (hazard ratio, 1.93; 95% CI, 1.10-3.38; P = .02) while LVESDi more than 20 mm/m2 did not (P = .32). LVESVi more than 45 mL/m2 showed a decreased survival trend compared with expected population survival.

Conclusions and Relevance  In this large asymptomatic cohort of patients with hemodynamically significant AR, LVESVi and Vol-LVEF worked equally as well as LVESDi and linear LVEF in risk discriminating patients with excess mortality. A LVESVi threshold of 45 mL/m2 or greater was significantly associated with an increased mortality risk.

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