Pre-TAVI aortic regurgitation aids survival post-TAVI in mixed aortic valve disease patients

Samir Kapadia, corresponding author

Patients who have mixed aortic valve disease with pre-existing aortic regurgitation have better survival rates following transcatheter aortic valve implantation (TAVI) than those who have aortic stenosis alone. Writing in JACC: Cardiovascular Interventions, Johnny Chahine (Cleveland Clinic, Cleveland, USA) et al say better outcomes among mixed disease patients with aortic regurgitation after the procedure account for the findings, due to left ventricular adaptation to aortic regurgitation before TAVI.

They say. “We hypothesise that in MAVD [mixed aortic valve disease] patients with pre-existing AR [aortic regurgitation], the left ventricle has already been accustomed and has likely remodelled due to volume overload, making it easier for these patients to tolerate post TAVI AR. On the contrary, in patients with pure AS [aortic stenosis], the ventricle is hypertrophied, with reduced compliance, making it less likely to tolerate post TAVI AR. This could explain the better outcomes observed in patients with MAVD who developed post-TAVI AR, which was not seen in patients with MAVD who did not develop post-TAVI AR.”

In an accompanying editorial, David Hildick Smith (Royal Sussex County Hospital, Brighton, UK) described the findings as a “relief”. He said: “Correlating post-TAVI mild AR with pre-procedural AR is clinically important. The message from the current study is clear. While we all do our best to make sure a patient leaves the lab without any aortic regurgitation, one factor that can be taken into consideration in deciding how vigorously to try to eradicate AR is the degree of pre-existing AR.”

However, as Samir Kapadia (Cleveland Clinic, Cleveland, USA), the corresponding author of the study, pointed out to Cardiovascular News: “We strive to achieve no aortic regurgitation for all patients, with careful attention to procedural details including valve size selection and optimal positioning.”

The investigators aimed to compare outcomes after TAVI in patients with pure aortic stenosis (no aortic regurgitation or trivial associated aortic regurgitation) to those with aortic stenosis and mild or more severe aortic regurgitation (mixed aortic valve disease) and to determine the impact of pre-existing aortic regurgitation.

Chahine et al explain: “Many of the landmark trials that studied the role of TAVI in high or intermediate surgical risk patients with severe AS did not include MAVD subjects, and hence it has been challenging to extrapolate the excellent outcomes of TAVI to this particular group. Moreover, the incidence of MAVD is also expected to increase due to an overall ageing population and an associated increase in the incidence of degenerative heart valve conditions. The natural course of these patients is considered to be worse than those with either pure AS or AR.”

The single centre, retrospective, observational study included 1,133 patients who underwent TAVI between January 2014 and December 2017. The primary outcome was all-cause mortality. Secondary clinical endpoints included bleeding and vascular complications, stroke, kidney injury, valve dysfunction, and a composite endpoint of early safety (within 30 days of TAVI) and clinical efficacy (after 30 days).

Patients were excluded if they had a previous history of surgical or aortic valve replacement, no aortic stenosis, and if TAVI was performed via a non-transfemoral route. They were then divided into the two groups based on the presence of pre-TAVI aortic regurgitation. All patients had echocardiography before TAVI, and the vast majority had another one following the procedure. Aortic stenosis and regurgitation before and after TAVI were graded as mild, moderate, or severe according to guidelines. Variables were compared using Mann-Whitney, Chi-square, and Fisher exact tests, and Kaplan−Meier analyses were used to compare survivals.

After exclusions, 1,133 patients remained, and median follow up was 27 months (interquartile range [IQR] 18–38). In all, 688 patients (61%) had mixed aortic valve disease (median age 83 years, 43% female); of these, 17% developed mild, 2% moderate, and <1% severe post-TAVI aortic regurgitation.

Chahine and colleagues found that patients with mixed aortic valve disease had better survival than patients with pure aortic stenosis (p=0.03), a benefit sustained after both propensity score matching and multivariable logistic regression. In addition, among those who developed post-TAVI aortic regurgitation, patients in the mixed disease group had better survival (p=0.04), but pre-TAVI aortic regurgitation did not improve survival in patients who did not develop post-TAVI aortic regurgitation (p=0.11). The three-year mortality rate was decreased in patients with mixed aortic valve disease both overall (p=0.02), and when post-TAVI aortic regurgitation occurred (p=0.03).

There were no statistically significant differences in secondary outcomes between the two groups. Readmission for congestive heart failure or valve related symptoms 30 days post-procedure was slightly higher in the pure AS group, but was not significant (10.3 vs. 14.2, p=0.051). Major or life-threatening bleeding occurred in 17.9% of cases, overall, with no statistically significant difference between groups (17.4% in the MAVD group vs. 18.7% in the pure AS group, p=0.6). The composite endpoints (early safety within 30 days of TAVI and clinical efficacy 30 days post-TAVI) were not different among the groups (p=0.12 and p=0.21, respectively).

Limitations of the study include that it was a single centre retrospective observational study, and that mortality data may be underestimated “since we relied on our electronic medical record as well as a commercial obituary service”.

Speaking to Cardiovascular News, Kapadia cautioned: “It is important to realise that the study does not prove a cause–effect relationship of aortic regurgitation to mortality; it is also possible that other unmeasured confounding variables exist. One such variable is the timing of TAVI in relation to disease progression. It is possible that MAVD patients present earlier compared to pure AS patients, and hence have better outcomes.”

The authors highlight the need for “further large prospective, randomised controlled, multicentre trials … to validate our findings and investigate whether a similar relationship exists in SAVR [surgical aortic valve repair] and aortic valve repair for mixed aortic valvular disease”.


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