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By Michael H. Crawford, MD, Editor
SYNOPSIS: A large database observational study of patients with chronic aortic mild or moderate regurgitation (AR) largely due to bicuspid aortic valve or aortic root dilatation showed that it was largely an indolent disease, with only 20% progressing to moderately severe AR in five years.
SOURCES: Yang LT, Enrizquez-Sarano M, Michelena HI, et al. Predictors of progression in patients with stage B aortic regurgitation. J Am Coll Cardiol 2019;74:2480-2492.
Vanoverschelde JL, Vancraeynest D. Progression of aortic regurgitation: The missing link between disease severity and clinical complications. J Am Coll Cardiol 2019;74:2493-2495.
Little is known about the progression of mild, asymptomatic aortic valve regurgitation (AR) to severe AR. Investigators from the Mayo Clinic examined their echocardiographic database for patients with any degree of AR short of severe from 2004 to 2017 who met the following criteria: baseline echo with the severity of AR quantitated and at least one other such echo ≥ 3 months hence.
Yang et al excluded those with moderate or more aortic stenosis or mitral valve disease and other cardiac conditions such as complex congenital heart disease. Patients who progressed to moderately severe AR as defined by the American Society of Echocardiography criteria were considered progressors. The primary outcome considered was all-cause mortality. The authors identified 1,077 patients (mean age, 66 years), of whom 18% had trivial or mild AR, 43% had mild to moderate AR, and 39% had moderate AR. Median time to the second echo was 19.5 months. Progression to moderately severe AR in these three severity groups at four years was 4.2, 4.4, and three years, respectively. In total, 21% of study patients progressed over a median of four years; at 10 years, it was 36%.
In a multivariate analysis, aortic root size (annulus and sinotubular junction) and effective regurgitation orifice area (EROA) were strongly associated with progression, but not sinus of Valsalva or ascending aorta size, blood pressure, or medications. Overall survival at five and 10 years was 83% and 67%, respectively. Strong multivariate predictors of survival were age, comorbidities, functional class, resting heart rate, and left ventricular ejection fraction (LVEF). LV end-systolic diameter index was only predictive of survival in those with progression to moderately severe AR. The authors concluded that based on the progression of AR severity observed in their population, echoes performed at five-, three-, and one-year intervals for trivial/mild, mild to moderate, or moderate AR, respectively, should be adequate to detect clinically significant changes in AR parameters such as EROA, regurgitant volume, and annulus and sinotubular junction aortic diameter.
The most important finding of this study is that chronic mild or moderate AR is an indolent condition over five to 10 years. In contrast, aortic stenosis is uniformly progressive over this time. About 20% of patients progressed to moderately severe AR in five years and 36% at 10 years.
Since severe AR is considered significant regarding surgical decision-making, Yang et al wanted to set this degree of AR as their endpoint, but had to select moderately severe to observe enough patients who progressed to create a robust analysis of factors leading to progression. The major organization guidelines do not recognize the moderately severe category, but the American Society of Echocardiography guidelines do. Also, the authors confirmed older data that show most patients maintain a normal LVEF, and a low EF is an uncommon indication for surgery.
Yang et al did not directly address indications for surgery, but rather sought to determine factors that predict progression. In their multivariate analysis, the authors found the severity of AR by echo, aortic root size, and New York Heart Association class predicted progression. These results are hardly surprising, but do confirm the importance of echocardiography for following chronic AR patients. The authors proposed a follow-up sequence based on AR severity that is different from major guidelines.
However, they confined their study population to those whose echo permitted an advanced quantitative assessment of AR severity. This and other exclusion criteria eliminated 70% of patients with AR in their database. Quantitation of AR by Doppler echo often is challenging, especially with eccentric jets such as those frequently found in bicuspid aortic valves. Also, all the quantitation measures feature significant shortcomings so that an overall gestalt based on several measures is used to arrive at the severity classification, which is not ideal.
Also of interest is the finding that neither a history of hypertension or elevated systolic blood pressure were related to progression. However, about two-thirds of these patients were on an angiotensin modulator or a calcium blocker. In addition, the importance of diastolic LV size was predictive only in relation to severity of AR, but not as an independent factor. LV end-systolic volume index was predictive only of outcomes in patients with moderately severe or worse AR. In the end, the most reliable predictor of progression may be symptoms; however, symptoms can be difficult to assess since other comorbidities are common in these patients, and the patients age over time.
There were several weaknesses to this study, besides its retrospective design. Yang et al required adequate echoes for quantitation, which limited the sample size. At least two echoes were performed, which would bias the study toward those with more comorbidities. Also, the timing of repeat echoes was variable and inconsistent.
In addition, the authors did not consider the etiology of AR, but two-thirds of their patients featured a dilated aortic root or a bicuspid valve. Thus, applicability to other etiologies of AR may be limited.
Financial Disclosure: Clinical Cardiology Alert’s Physician Editor Michael H. Crawford, MD, Peer Reviewer Susan Zhao, MD, Nurse Planner Aurelia Macabasco-O’Connell, PhD, ACNP-BC, RN, PHN, FAHA, Editor Jonathan Springston, Editor Jason Schneider, Editorial Group Manager Leslie Coplin, and Accreditations Manager Amy M. Johnson, MSN, RN, CPN, report no financial relationships relevant to this field of study.