By Michael H. Crawford, MD, Editor

SOURCE: Kodali S, 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 2015;36:449-456.

Moderate or severe paravalvular regurgitation (PVR) has been reported in up to one-quarter of patients following transcatheter aortic valve replacement (TAVR) and has been associated with a higher 1-year mortality. Whether PVR is the cause of increased mortality or is simply associated with mortality is unclear. Thus, these investigators from the PARTNER trial of the Edwards SAPIEN catheter mounted valve sought to characterize the anatomic and physiologic impact of PVR by echocardiography and its relationship to the observed mortality. The patients in this analysis included 496 from the randomized trial: 40 from the randomized post trial continued access phase and 1979 from the non-randomized post commercial approval registry. From these 2515 patients, 81 were excluded because of missing echocardiograms, resulting in a total population of 2434. In these patients, 53% had no or trace PVR, 38% mild, and 9% were graded moderate to severe. There were differences in baseline echocardiographic parameters between these three groups. Despite similar aortic valve areas, left ventricular (LV) size was larger with increasing PVR severity; LV ejection fraction (EF) was lower; annulus diameter was larger; and there was more mitral and aortic regurgitation pre-procedure. Also, PVR was observed less with the transapical approach and with the 23 mm valve vs the 26 mm valve.

Thirty-day outcomes were not different in the three groups, but at 1-year all cause mortality, cardiac mortality, and rehospitalization were progressively higher as PVR severity increased. In a multivariate model that considered multiple clinical and echocardiographic variables, moderate-to-severe PVR (HR, 2.2; 95% CI, 1.7-3.4; P < 0.0001) and mild PVR (HR, 1.4; 1.1-1.9, P = 0.012) were independent predictors of 1-year mortality. Despite similar post procedure aortic valve areas and increases in LVEF in all three groups, LV end diastolic dimension decreased in the none to trace and mild PVR groups, but increased in the moderate-to-severe PVR group. The latter group exhibited less decrease in LV mass as well. The authors concluded that baseline differences in patients with PVR post-transcatheter aortic valve replacement (TAVR) may increase the risk of this complication, which is associated with higher one year mortality.

COMMENTARY

This is the largest systematic study of the impact of PVR following TAVR, and it confirms the results of some smaller studies that even mild PVR is associated with increased 1-year mortality. Also, this study shows that PVR is associated with larger LV diastolic volumes and less LV mass regression after TAVR. However, despite controlling for this reduced LV remodeling benefit of TAVR, mild or more PVR is still an independent predictor of 1-year mortality. PVR does not change 30-day mortality, which suggests that there is some delayed effect that decreases survival.

Interestingly, there were baseline echocardiographic differences in the 3 severity of PVR groups. Most provocative is the observation that the more severe PVR group had more baseline aortic regurgitation and larger LVs. Thus, there may be structural changes in the LV that make TAVR less successful. Of note, baseline aortic annulus and outflow tract diameters were larger in the more severe PVR patients. Also, use of the larger 26 mm valve was associated with more PVR. This suggests that valve sizing may be more difficult in larger LVs and this leads to more PVR, which in turn retards the remodeling of these larger LVs and increases long term mortality.