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Even mild paravalvular regurgitation following transcatheter aortic valve replacement (TAVR) with a balloon-expandable device increases mortality risk at 1 year, according to a substudy of the PARTNER trial published online October 1, 2014, ahead of print in the European Heart Journal. The risk, which increases in proportion to the degree of leakage, remained after adjustment for differences in baseline characteristics.

Differences in Outcome Appear at 1 Year

Patients undergoing valve implantation via the transapical approach compared with the transfemoral approach had less paravalvular leakage (P < .0001). In addition, those with moderate/severe regurgitation were more likely to have received the larger, 26-mm bioprosthesis and had a lower cover index—reflecting a lower degree of oversizing of the prosthesis—than those with less leakage. 

Rates of 30-day mortality and stroke were similar in patients with none/trace, mild, and moderate/severe regurgitation (3.1% vs 3.4% vs 4.5%; P = .06 and 3.4% vs. 3.7% vs. 2.3%; P = .59, respectively). However, 1-year rates of all-cause death, cardiac death, and rehospitalization rose in proportion to worsening regurgitation (table 1).

Table 1. One-Year Outcomes by Grade of Paravalvular Regurgitation^a

^a Log-rank P value < .0001 for all outcomes.

In addition, at 6 months patients with moderate/severe regurgitation were less likely to have  improved more than 1 NYHA class compared with those with none/trace or mild leakage (P = .0001 and P < .01, respectively). 

Following TAVR, indexed effective orifice area improved over baseline similarly in all patients. At 1 year there was a decrease in LV end-systolic and end-diastolic volumes in the none/trace and mild regurgitation groups but no change in LV end-systolic volume and a trend toward increased LV end-diastolic volume in the moderate/severe group (P = .06). LV ejection fraction and mass index improved significantly over time across all groups. However, the reduction in LV mass index was attenuated in the moderate/severe group (-8.4 ± 26.6 g/m²) compared with the none/trace (-19.6 ± 32.8 g/m²; P = .001) and mild groups (-17.3 ± 33.0 g/m²;P = .010).

On multivariable analysis, both moderate/severe (HR 2.18; 95% CI 1.69-3.35) and mild (HR 1.37; 95% CI 1.14-1.90) regurgitation predicted higher 1-year mortality, as did several clinical and anatomical characteristics, including major arrhythmia, renal disease, and larger annulus diameter.

Regurgitation Assessment Often Problematic

In a telephone interview with TCTMD, Samir R. Kapadia, MD, of the Cleveland Clinic (Cleveland, OH), said the paper is important because “very few [TAVR] studies have this kind of rigorous core lab analysis, and the quality of these data is as good as it gets.” A key contributor to controversy over the prognostic significance of leakage has been that “we don’t have a gold standard for assessing the severity of paravalvular leak,” he explained. “Grading regurgitation is tricky.”

The authors agree, suggesting that “a standardized and comprehensive system for assessing [regurgitation], including quantitative assessment as proposed by the recently published VARC-2 guidelines, may help elucidate the true impact of varying severities of [regurgitation].”

To those who question the role of leakage in compromising outcomes, pointing instead to the influence of baseline characteristics, Dr. Kapadia makes 2 points: regurgitation develops acutely—ie, patients who previously did not have the condition suddenly do—and moderate leakage is often misclassified as mild. This study should write “end of story” to the doubters’ line of thinking, he added.

Dr. Kapadia expressed skepticism regarding suggestions that leakage may be device-specific, explaining that discrepant findings in the CoreValve (Medtronic, Minneapolis, MN) trials and other literature are probably attributable to variations in regurgitation measurement and definitions.

The current study shows the impact of paravalvular leakage not only on mortality but also on hemodynamics and need for rehospitalization—factors that affect patients’ quality of life, Dr. Kapadia observed. This underscores the need to minimize the condition by optimizing annulus sizing with 3D imaging and improving procedural technique, he added. Newer-generation valves are already targeting the problem of regurgitation and assessing it as an endpoint in studies, he reported.

“Paravalvular regurgitation is a complication we cannot live with if we are going to offer this therapy to younger people and those at lower risk for surgery,” he said. “But we are getting ahead of the curve.”

Note: Dr. Kodali and several study co-authors are faculty members of the Cardiovascular Research Foundation, which owns and operates TCTMD.

Source:
Kodali S, Pibarot P, Douglas PS, et al. Paravalvular regurgitation after transcatheter aortic valve replacement with the Edwards Sapien valve in the PARTNER trial: characterizing patients and impact on outcomes. Eur Heart J. 2014;Epub ahead of print.

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