Author + information
- Alexander C. Egbe, MD, MPH∗ ( and )
- Carole A. Warnes, MD
- ↵∗Division of Cardiovascular Diseases, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905
There are limited data about outcomes after aortic valve replacement (AVR) in patients with mixed aortic valve disease (MAVD) (1). We conducted a retrospective review of all adults with moderate-to-severe MAVD who underwent AVR at Mayo Clinic from January 1, 1994 to December 31, 2014 to determine the occurrence of cardiovascular adverse events (CAE). Moderate-to-severe MAVD was defined as the combination of greater than or moderate aortic stenosis and greater than or moderate aortic regurgitation.
We defined CAE as ischemic stroke (ischemic or hemorrhagic cerebrovascular events documented on brain imaging); heart failure hospitalization (hospitalization for worsening heart failure symptoms requiring intravenous diuretics); severe left ventricular (LV) dysfunction (LV ejection fraction <35%) or cardiac death (death directly related to cardiac pathology such as congestive heart failure, myocardial infarction, or sudden death).
There were 283 patients (age 67 ± 5 years; 206 men, 73%) who met the inclusion criteria for this study. A bicuspid/unicuspid was present in 107 participants (38%), coronary artery disease in 89 (31%), and 62 (22%) had LV ejection fraction <50% at the time of AVR. The indication for surgery was symptoms of angina or dyspnea (n = 252, 89%), abnormal exercise test (n = 27, 10%), and unknown (n = 4, 1%). A bioprosthetic valve was implanted in 151 participants (57%), and concomitant aorta replacement and coronary artery bypass grafting were performed in 75 (27%) and 89 (31%), respectively. There were 5 perioperative deaths.
The following CAE occurring during a mean follow-up of 9 ± 3 years: ischemic stroke (22 patients, 8%); heart failure hospitalization (28 patients, 10%); severe LV dysfunction (46 patients, 16%); and late cardiac death (26 patients, 9%). For CAE analysis, only the first adverse event was counted per patient. CAE occurred in 69 patients (24%). The rate of CAE was 13%, 25%, and 42% at 3, 5, and 8 years, respectively. The rate of CAE was significantly higher in the patients with relative wall thickness (RWT) >0.46, 38% versus 8% at 5 years (p < 0.001) and in the patients with left ventricular mass index >160 g/m2, 37% versus 10% at 5 years (p < 0.001). The difference in CAE rate was less profound in patients with LV ejection fraction <50% compared with those with normal LV function, 31% versus 20% (p = 0.04) (Figure 1). The multivariable predictors of CAE were RWT >0.46 (hazard ratio [HR]: 3.24; 95% confidence interval [CI]: 1.25 to 5.33; p = 0.001), left ventricular mass index >180 g/m2 (HR: 1.79; 95% CI: 1.32 to 2.63; p = 0.02), and pre-operative LV ejection fraction <50% (HR: 1.48; 95% CI: 1.11 to 2.59; p = 0.02). The presence of RWT >0.46 reliably predicted post-operative CAE with sensitivity of 78% and specificity of 88%.
This study shows that the strongest risk factor for CAE after AVR in this population is the severity of pre-operative LV hypertrophy. Although concentric LV hypertrophy is a well-known independent risk factor CAE in patients with isolated aortic stenosis, very little is known about its prognostic role in the MAVD population (2). The recommendations for AVR, in patients with isolated aortic stenosis or aortic regurgitation, in the current guidelines are based on LV ejection fraction and LV end-systolic dimensions (3). The current study shows that concentric LV hypertrophy is a better predictor of outcome after AVR compared with LV ejection fraction and LV dimensions in the patients with MAVD.
Experimental studies from genetically altered mouse models show that although adaptive LV hypertrophy resulted in normalization of wall stress, severe LV hypertrophy was maladaptive and resulted in deterioration of cardiac function despite normal wall stress (4). Perhaps the hemodynamic burden of combined pressure and volume load results in maladaptive LV hypertrophy and subclinical LV dysfunction.
Our data show that patients with severe LV hypertrophy remain at an increased risk of CAE event after undergoing AVR. Perhaps assessment of LV hypertrophy should be considered as a prognostic tool in determining the timing of AVR in this population.
Please note: Both authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- American College of Cardiology Foundation
- Egbe A.C.,
- Luis S.A.,
- Padang R.,
- Warnes C.A.
- Cioffi G.,
- Faggiano P.,
- Vizzardi E.,
- et al.
- Nishimura R.A.,
- Otto C.M.,
- Bonow R.O.,
- et al.
- Esposito G.,
- Rapacciuolo A.,
- Naga Prasad S.V.,
- et al.