Left Ventricular Size and Outcomes in Aortic Regurgitation

By Michael H. Crawford, MD, Editor

Synopsis: A multinational, retrospective, observational registry study of patients with significant aortic valve regurgitation has shown that left ventricular end-systolic dimension and volume measurements are valuable for risk-stratifying such patients and should be incorporated into the guidelines for when to intervene.

Source: Santi PL, Bernard J, Fortuni F, et al. Left ventricular dilatation in patients with significant aortic regurgitation: Association with outcome. Eur Heart J. 2025;26(8):1466-1474.

Current guidelines recommend aortic valve replacement in patients with chronic severe aortic regurgitation (AR) if they become symptomatic, or if they develop a left ventricular ejection fraction (LVEF) < 55%, a left ventricular (LV) end-systolic diameter (ESD) > 50 mm or an ESD index (ESDi) > 25 mm/m² (class I indications). However, recent studies have shown that an ESDi of > 20 mm/m² may be better. Also, LV volumes are believed by some to be better predictors of adverse outcomes than dimensions. Thus, a retrospective, observational, multicenter, international registry study was conducted to determine if integrating volume measurements with dimensions would improve risk stratification in such patients.

From the registry, 1,070 adult patients with significant AR (moderate or more) on their first echocardiogram who were enrolled between 2003 and 2022 were selected. The researchers excluded patients with acute AR, more than mild aortic valve (AV) stenosis, significant mitral valve disease, or previous valve procedures. There were 485 patients (45%) with ESDi < 20 mm/m² and end-systolic volume index (ESVi) < 45 mL/m² (nondilated group), 279 patients (26%) with one measure exceeding these thresholds and one measure not exceeding the threshold (discordant group), and 306 patients (28%) with both measures above the cutoff (concordant group).

After a 7.4-year median follow-up, 16% of the patients had died and 45% had surgical AV replacement. Of the latter patients, 16% also had aortic root surgery and 4% had coronary bypasses, and there were six patients who died within 30 days of surgery. Adjusted 10-year survival was worse in those patients with concordant enlarged systolic values (P < 0.001). Adjusted multivariable Cox regression analysis showed that the discordant values group and the concordant values group were independently associated with all-cause mortality: discordant hazard ratio (HR), 2.07 (95% confidence interval [CI], 1.30 to 3.30; P = 0.002) and concordant HR, 2.76 (95% CI, 1.62 to 4.71; P < 0.001).

Subgroup analysis of those with LVEF > 55% and asymptomatic patients showed similar results, confirming the independent predictive association between the LV volume groups and the observed outcomes. The authors concluded that in patients with significant AR, an ESDi > 20 mm/m² or an ESVi > 45 mL/m² or both were associated with an approximately two-fold increase in all-cause mortality and were supportive of including these LV volumetric and linear measurements in the decision on when to intervene in such patients.

Commentary

Despite serious concerns about the potential for errors in using echocardiographic LV chamber diameter as a criterion for deciding when to intervene on patients with severe AR, they still are the preferred LV size measurements in the guidelines. Also, studies have shown that LV volumes may be more accurate predictors. In addition, several studies have pointed out the potential inaccuracies in using Doppler echocardiography to quantitate AR severity. Accordingly, some have shown the superior potential for cardiac magnetic resonance imaging for quantitating AR severity, and LV size and function. Given the ubiquity of echocardiography and the vast experience with it now, this study, which pursues finding a superior way to use echocardiography for assessing the risk of mortality in chronic AR, is of interest.

First, the researchers included patients with moderate AR or worse in their definition of significant AR. Second, they added ESVi to the mix with ESDi and found that an increased end-systolic LV size by either measure or more potently with both increased, is associated with all-cause mortality, and might be better criteria for intervening. Basically, the authors concluded that, using echocardiography, LV size is more important than the severity of AR if it is at least moderate.

There are limitations to this registry study to be considered. It is retrospective and observational, so there may be unmeasured confounders, and direct cause and effect cannot be assured. Data on the patients’ progress during the follow-up period was not available. No information on the cause of death other than during the 30 days post-surgery (for those undergoing surgery) was provided. The decision for surgery was up to each patient’s physician. The class II indications of LV end-diastolic diameter > 65 mm or > 70 mm were not evaluated. Finally, the authors did not specify whether ESDi or ESVi was the superior measure.

Although this study adds significantly to our thinking on this topic, randomized controlled trials still are necessary to achieve certainty with this important decision. Finally, percutaneous techniques for replacing the aortic valve in AR patients are being tested and may change the whole dynamic in the way transcutaneous therapy for aortic stenosis did.

Michael H. Crawford, MD, is Professor Emeritus of Medicine and Consulting Cardiologist, UCSF Health, San Francisco.