By Michael Crawford, MD, Editor

SYNOPSIS: Asymptomatic patients suffering from moderate aortic stenosis and regurgitation with preserved left ventricular function have the same prognosis as asymptomatic patients with severe aortic stenosis and normal left ventricular function and should be followed closely for the development of symptoms.

SOURCES: Egbe AC, Luis SA, Padang R, Warnes CA. Outcomes in moderate mixed aortic valve disease: Is it time for a paradigm shift? J Am Coll Cardiol 2016;67:2321-2329.

Parker MW, Aurigemma GP. The simple arithmetic of mixed aortic valve disease: LVH + volume load = trouble. J Am Coll Cardiol 2016;67:2330-2333.

There are few guidelines and little data on the management of mixed aortic valve disease. Investigators from the Mayo Clinic performed a retrospective observational study of 251 patients with moderate aortic stenosis and moderate aortic regurgitation for an average follow-up of nine years. Inclusion criteria were age > 18 years, asymptomatic, normal left ventricular (LV) ejection fraction (> 50%), and at least two years of follow-up. Exclusion criteria included radiation valve disease, prior endocarditis, prior aortic valve intervention, and concomitant moderate or more disease of other valves. The mixed aortic valve disease patients were compared to three matched control groups: isolated moderate aortic regurgitation, isolated moderate aortic stenosis, and isolated severe aortic stenosis. All the control groups also were asymptomatic and presented with normal LV systolic function. After matching for age and sex, there were 117 patients in each group for comparative analysis. Bicuspid valves made up 31% of the mixed group and 18-32% of the other three groups. The primary endpoint was composite adverse events: New York Heart Association class III-IV symptoms, aortic valve replacement, or cardiac death. The mean age of the mixed patients was 63 years, 73% were men, 38% featured a bicuspid valve, and 16% suffered from coronary artery disease. During follow-up, the composite endpoint occurred in 77% of patients. Sixty-nine percent developed symptoms, 62% underwent aortic valve replacement, and 4% died. At the time of aortic valve replacement, 75% had progressed to severe aortic stenosis and 14% had progressed to severe aortic regurgitation. The composite adverse event rate in the mixed group was similar to the severe aortic stenosis group (71% vs. 68% at five years), but higher than the moderate aortic stenosis group (31%) and the moderate regurgitation group (22%, both P < 0.0001). The authors concluded that moderate asymptomatic mixed aortic valve disease with preserved LV function has a similar prognosis as asymptomatic severe aortic stenosis with preserved LV function. Additionally, the authors noted that these patients should be monitored closely for the development of symptoms.


One of my clinical mentors told me that in valve disease two moderates equaled severe, and that is how you manage mixed valve disease. At that time, this was largely based on clinical experience, but sometimes clinical observations prove to be correct, and it is nice to see this one validated by a large observational study. In this study, the prognosis of moderate mixed aortic valve disease was similar to that of severe aortic stenosis. This knowledge should inform our management of those patients. The authors recommended close follow-up to detect the onset of symptoms. This seems straightforward enough, but are there objective criteria for valve replacement that would trump symptom development? Unfortunately, this study does not answer the question definitively, and there are no existing guidelines to help. However, this study suggests some parameters worth considering in borderline cases.

During follow-up, 19 patients in the mixed group developed symptoms without any change in the measured severity of aortic stenosis or regurgitation. These patients presented with advanced diastolic dysfunction and concentric LV hypertrophy. Interestingly, mixed patients demonstrated the largest measured LV mass of all four groups (138 g/m2) compared to moderate aortic regurgitation (94 g/m2), moderate stenosis (103 g/m2), and severe stenosis (123 g/m2, all P < 0.02). Also, the mixed group produced the highest prevalence of advance diastolic dysfunction (32% vs. 5% vs. 12% vs. 22%, respectively, all P < 0.03). Thus, the combination of a pressure and volume load results in a markedly hypertrophied left ventricle, which often develops diastolic dysfunction. The latter may result in symptoms before the individual valve lesions have progressed to severe. In the multivariate analysis, only age and relative wall thickness > 0.42 (thickness/diameter), which reflects mass and concentric hypertrophy, predicted adverse events. Also, among those in the group with progressive regurgitation leading to symptoms, none reached an end-systolic dimension of 50 mL, which is a replacement criterion for aortic regurgitation in the guidelines. Thus, LV dimensions may not be useful for decision-making in mixed patients.

Most patients who developed symptoms progressed to severe aortic stenosis, so the valve area by the continuity equation should be useful to follow. However, peak velocity alone may not be, as regurgitation can increase it as well. Ejection fraction decreased modestly during follow-up in patients who underwent valve replacement, but still was largely in the normal range, so it doesn’t appear to be useful in this group either.

Follow closely asymptomatic patients with moderate mixed aortic valve disease and monitor them for symptom development. Pay special attention to those with marked increases in LV mass, concentric hypertrophy, and advanced diastolic dysfunction.