Survival After TAVR Better in Patients with Mixed Aortic Valve Disease Vs. Pure Aortic Stenosis

Survival following transcatheter aortic valve replacement (TAVR) appears to be better in patients with mixed aortic valve disease — i.e., both aortic stenosis and aortic regurgitation — than in those with pure aortic stenosis, according to the largest study of the question reported to date.

The survival advantage was greatest among patients who developed residual aortic regurgitation following TAVR, found the retrospective investigation, which was conducted at Cleveland Clinic and published in JACC: Cardiovascular Interventions (2019;12:2299-2306).

“The trials that supported approval of TAVR for patients with severe aortic stenosis at high or intermediate surgical risk largely excluded patients with significant mixed aortic valve disease,” says the study’s senior and corresponding author, Samir Kapadia, MD, Chair of Cardiovascular Medicine at Cleveland Clinic. “Guidelines from major societies address TAVR for mixed aortic valve disease only by recommending that decisions be based on whichever lesion is predominant. We conducted this analysis to get a better understanding of TAVR outcomes in the setting of mixed aortic valve disease, especially since it is believed to have a more aggressive natural history than pure aortic stenosis.”

Study design and results

The study compared outcomes among all patients who underwent TAVR at Cleveland Clinic from 2014 through 2017 according to whether they had isolated aortic stenosis (AS) (i.e., no or trivial aortic regurgitation) or mixed aortic valve disease (MAVD) (AS with associated aortic regurgitation that was mild, moderate or severe). The primary endpoint was all-cause mortality.

After exclusion of patients with prior AVR or whose TAVR was done via a non-transfemoral route, 1,133 patients were included in the study — 445 with pure AS and 688 with MAVD. The patient groups were comparable except for a significantly higher median body mass index and higher rates of diabetes mellitus and atrial fibrillation in the pure AS arm and a significantly higher rate of prior stroke or transient ischemic attack in the MAVD arm.

Over median follow-up of 27 months, the following key outcome findings emerged:

• Cumulative long-term survival was greater in the MAVD group than in the pure AS group (P = 0.03), including after propensity score matching and multivariate logistic regression. Three-year survival was also significantly higher in the MAVD group.
• Post-TAVR aortic regurgitation developed at a higher rate in the MAVD group (22.1%) than in the pure AS group (14.4%) (P = 0.001). In both groups, the large majority of post-TAVR aortic regurgitation was mild.
• Among patients who developed post-TAVR aortic regurgitation, survival was greater in the MAVD group (P = 0.04), but among those who did not develop post-TAVR aortic regurgitation, survival was comparable between the two patient groups (P = 0.11).
• Secondary outcomes — which consisted of various safety and clinical efficacy measures within 30 days after TAVR — were comparable between the two patient groups.

Making sense of the findings

“These findings suggest that hearts that were previously exposed to aortic regurgitation — in the form of mixed aortic valve disease — before TAVR may be better able to tolerate mild aortic regurgitation after TAVR, which could explain our observation of better survival in the patients with mixed disease, which notably extended specifically to those who had post-procedural regurgitation,” says Dr. Kapadia.

He hypothesizes that this could be due to remodeling of the left ventricle resulting from volume overload related to the prior aortic regurgitation. In contrast, the ventricle is apt to be hypertrophied and have minimal compliance in patients with pure AS, reducing its tolerance of aortic regurgitation following TAVR.

“In any case,” Dr. Kapadia notes, “these findings should not be used to support tolerating any degree of post-TAVR paravalvular regurgitation, in view of the demonstrated deleterious effect of regurgitation on patient outcomes.”

What about surgical AVR?

“It’s worth noting that similarly mixed results have been observed in studies of survival among patients with mixed aortic valve disease following surgical AVR,” says James Yun, MD, a Cleveland Clinic cardiothoracic surgeon who was not involved in the current analysis.

He adds, however, that whether the current findings extend to surgical AVR remains to be determined. “Large, prospective, randomized trials are needed to ultimately validate these interesting findings with regard to TAVR for mixed aortic valve disease, and certainly with regard to surgical AVR or aortic valve repair in the setting of mixed disease,” Dr. Yun observes.

“The incidence of mixed aortic valve disease is projected to rise due continued aging of the population and a parallel increase in degenerative valve disease,” concludes Dr. Kapadia. “So this will be a growing research priority.”