Mixed Aortic Valve Disease and Predictors of Adverse Events

Study Questions:

What is the freedom of adverse effects (AEs) in patients with mixed aortic valve stenosis and regurgitation?


Mixed aortic valve disease (MAVD) was defined as combined moderate regurgitation and moderate stenosis, or a combination of severe aortic stenosis or severe aortic regurgitation, with the second lesion being moderate. Moderate aortic stenosis was defined as a peak velocity of 3.0-3.9 m/s and aortic valve area 1.0-1.5 cm2. Moderate AR was defined on the basis of multiple echocardiographic and Doppler parameters. Patients were retrospectively identified and followed from 1994 to 2013 for a composite AE endpoint of developing New York Heart Association (NYHA) class III/IV symptoms, requiring aortic valve replacement (AVR) or death. At the time of entry, all patients were NYHA class I (asymptomatic) and had normal left ventricular systolic function (ejection fraction ≥50%), a trileaflet aortic valve, and all were free of concurrent, moderate, or greater mitral tricuspid or pulmonary valve disease.


A total of 213 patients with MAVD were followed. At the beginning of this study, the age was 69 ± 11 years and 67% were male. The mean follow-up duration was 10.1 ± 3 years. Of the 213 patients, 152 (71%) had combined moderate aortic stenosis and aortic regurgitation at the time of presentation. The composite endpoint was reached in 172 (81%) patients. NYHA class III/IV symptoms developed in 143 patients (67%), 126 of whom underwent an AVR. Freedom from symptoms was 47% and 43% at 3 and 5 years. At an average follow-up duration of 2.9 ± 2.1 years, 152 patients underwent AVR, 126 for development of symptoms. On follow-up, there were two cardiac, two noncardiac, and two unknown deaths in the AVR group, and three deaths in patients who had not undergone AVR. On follow-up, the composite AE endpoint was reached in 172 patients. Freedom from composite AE endpoint was 42% and 30% at 3 and 5 years. Freedom from AEs was worse in the subset with aortic valve peak velocity ≥5 m/s, least in the subgroup with aortic valve velocity of 3.0-3.9 m/s, and intermediate otherwise. Freedom from AEs was also significantly worse in patients with severe stenosis or regurgitation compared to patients with mixed moderate stenosis or regurgitation. Compared to historical controls and nonsimultaneous published cohorts, patients with moderate/severe MAVD had event rates comparable to patients with isolated severe aortic stenosis. Multivariable analysis identified patients with severe lesions (hazard ratio, 2.58; p = 0.001) and peak velocity (per 1 m/s difference; HR, 2.73; p < 0.0001) as predictors of an adverse outcome.


Moderate MAVD has a high rate of AEs, which is comparable to outcomes seen in severe isolated aortic stenosis, and these patients should be followed in a similar manner.


Current valvular heart disease guidelines provide useful well-validated parameters for following patients with isolated valvular heart disease, but are limited in that little data have existed regarding the outcomes and the appropriate follow-up of patients with combined stenotic and regurgitant valve lesions. The study presented here nicely approaches the issue of MAVD, defined as moderate stenosis in combination with moderate regurgitation, and as with a small number of prior studies, demonstrated that these patients have outcomes equivalent to that of patients with isolated severe aortic stenosis. Similar to prior studies, a peak aortic valve velocity >4 m/s conferred a worse prognosis compared to peak velocity below that threshold. In isolated aortic stenosis, the peak gradient is directly proportional to the severity of stenosis, whereas in mixed lesions, the Doppler velocity will be impacted by the magnitude of regurgitation as well. The authors nicely point out the extra hemodynamic burden that a regurgitant lesion places on the pressure overload of aortic stenosis, and it appears that the simple parameter of aortic valve peak velocity provides discriminatory value with respect to prognosis in these patients. Based on this study as well as several smaller studies with virtual identical results, patients with MAVD require the same level of clinical surveillance given to patients with isolated aortic stenosis, and prophylactic AVR needs to be considered based not just on apparent severity of the isolated lesion, but the overall hemodynamic burden, which appears to be reflected by the peak aortic valve gradient.

Clinical Topics: Cardiac Surgery, Congenital Heart Disease and Pediatric Cardiology, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Valvular Heart Disease, Aortic Surgery, Cardiac Surgery and CHD & Pediatrics, Cardiac Surgery and VHD, Congenital Heart Disease, CHD & Pediatrics and Imaging, CHD & Pediatrics and Interventions, Interventions and Imaging, Interventions and Structural Heart Disease, Echocardiography/Ultrasound

Keywords: Aortic Valve Insufficiency, Aortic Valve Stenosis, Cardiac Surgical Procedures, Constriction, Pathologic, Diagnostic Imaging, Echocardiography, Heart Defects, Congenital, Heart Valve Diseases, Heart Valve Prosthesis, Transcatheter Aortic Valve Replacement, Tricuspid Valve

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