New Indications for Aortic Valve Replacement in Chronic Aortic Regurgitation
May 1, 2025
By Michael H. Crawford, MD, Editor
Synopsis: A retrospective observational study of asymptomatic patients with isolated moderate to severe or severe aortic valve regurgitation by echocardiography has shown that left ventricular (LV) ejection fraction (EF) < 60%, LV end systolic volume index > 45 mL/m², or global longitudinal strain less than -15% is associated with all-cause mortality, but mortality is highest when current guideline recommendations are present. This suggests that there is a survival penalty with the sole use of the current guidelines.
Source: Anand V, Michelena HI, Scott CG, et al. Echocardiographic markers of early left ventricular dysfunction in asymptomatic aortic regurgitation: Is it time to change the guidelines? JACC Cardiovasc Imaging. 2025;18(3):266-274.
Several recent studies have suggested that newer measures of left ventricular (LV) performance and new cut points of the guideline-recommended measures may be superior for determining when to intervene in patients with chronic aortic regurgitation (AR). However, the prevalence and significance of these new measures with respect to outcomes are not known. Thus, these investigators from the Mayo Clinic conducted a retrospective observational study of consecutive asymptomatic patients with moderate to severe or severe AR from 2004 until 2019. They excluded those with acute AR as the result of aortic dissection or infective endocarditis, moderate or more other left heart valve disease, prior aortic or mitral valve surgery, ischemic cardiomyopathy, prior coronary bypass surgery, hypertrophic cardiomyopathy, or cardiac amyloid.
The severity of AR was determined by quantitative echocardiography in 85% of subjects, where moderate to severe was defined as a regurgitant volume of 45 mL to 60 mL and severe as > 60 mL. They identified 673 such patients in their database (mean age 57 years, 14% women). The primary endpoint was survival under medical surveillance. Secondary endpoints were a comparison of new early markers of LV dysfunction to the class I and IIa guideline-recommended LV markers (ejection fraction [EF] < 55% and end-systolic dimension > 50 mm or > 25 mm/m²). The early markers studied were left ventricular ejection fraction (LVEF) < 60%, LV end-systolic volume index (ESVi) ≥ 45 mL/m², and LV global longitudinal strain (GLS) worse than -15%.
After a median follow-up of 2.5 years, 10% of study subjects had died and 281 had surgical aortic valve replacement. Mortality was highest in those who met guideline criteria for surgery (adjusted hazard ratio [HR], 4.22; 95% confidence interval [CI], 2.15 to 8.29; P < 0.001). Using no early markers of LV dysfunction as the reference, mortality also was increased in the presence of one or more of the new early markers of LV dysfunction (HR, 2.18; 95% CI, 1.21 to 3.92; P = 0.009). In the absence of guideline class I/IIa criteria, the presence of one of the new LV dysfunction markers was not significantly associated with higher mortality, but the presence of two (HR, 3.39; 95% CI, 1.72 to 6.68; P < 0.001) or all three (HR, 5.46; 95% CI, 2.51 to 11.90; P < 0.001) were.
The authors concluded that using the current guidelines to identify patients with significant chronic AR who would benefit from surgical valve replacement incurs a mortality cost that could be ameliorated by using newer measures of LV dysfunction.
Commentary
Significant chronic AR often is surprisingly well-tolerated, and it can take a decade or more before symptoms or LV dysfunction occurs. In fact, I have seen patients who could perform impressive athletic feats with moderate to severe AR. On the other hand, I have seen many cases where I believe we waited too long to recommend surgery, because the patient never fully regained normal LV function afterward.
In the pursuit of better indicators of the need for surgery in asymptomatic AR patients, several small studies have suggested that different cutoffs for LVEF (< 60%) or newer measures of LV function (ESVi and GLS) may perform better for identifying patients who would benefit from surgery. Thus, this larger study from Mayo Clinic is of interest.
The Mayo Clinic study showed that only 20% of their patients over a 2.5-year median follow-up ever met class I/IIa criteria for AV replacement. However, 42% of the patients developed one or more of the new early markers of LV dysfunction. Thus, early markers often are present in the absence of guideline criteria. Also, the presence of two or more of the new measures was associated with mortality. Therefore, this study supports the concept that a substantial proportion of patients may benefit from surgery before the current guideline criteria are met.
There are limitations to this study. It is retrospective and observational, which means that it is hypothesis-generating and would require a prospective, randomized trial to confirm the conclusions. The response to surgery was not included in the analysis and could affect the conclusions. Since it was conducted at one Midwestern referral hospital, racial and ethnic diversity was limited. Only 72% of the patients had the new measures of LV dysfunction performed. There was no cardiac magnetic resonance imaging data, which is gaining ground as an alternative to echocardiography. Finally, there were surprisingly few women (14%) in the study population, for which the authors had no explanation, but which certainly introduces a referral bias.
The main deterrent to such a change in practice is that AR still requires surgery, which has a mortality and morbidity penalty as well. However, surgery and anesthesia techniques, prosthetic valves, and post-surgical care have improved in this century. Also, the Ross procedure is making a comeback, AV repair also is possible in selected cases, and techniques for dealing with proximal aorta issues have improved. So, perhaps it is time to reevaluate the guidelines.
Michael H. Crawford, MD, is Professor Emeritus of Medicine and Consulting Cardiologist, UCSF Health, San Francisco.
A retrospective observational study of asymptomatic patients with isolated moderate to severe or severe aortic valve regurgitation by echocardiography has shown that left ventricular (LV) ejection fraction (EF) < 60%, LV end systolic volume index > 45 mL/m², or global longitudinal strain less than -15% is associated with all-cause mortality, but mortality is highest when current guideline recommendations are present. This suggests that there is a survival penalty with the sole use of the current guidelines.
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