Response by Ailawadi et al to Letter Regarding Article, “One-Year Outcomes After MitraClip for Functional Mitral Regurgitation.”
Paul A. Grayburn M.D.
Ailawadi, G., D. S. Lim and P. A. Grayburn (2019). “Response by Ailawadi et al to Letter Regarding Article, ‘One-Year Outcomes After MitraClip for Functional Mitral Regurgitation.’” Circulation 140(5): e175-e176.
We thank Gul and Haseeb for the thoughtful insights into our report that documented 1-year outcomes after MitraClip implantation for functional mitral regurgitation (FMR) for patients enrolled in the EVEREST II study (Endovascular Valve Edge-to-Edge Repair Study). Gul and Haseeb note that left ventricular dyssynchrony occurs in the setting of ventricular remodeling, which can lead to mitral regurgitation (MR). They note that cardiac resynchronization therapy (CRT) as part of an aggressive optimal medical management strategy can improve MR and should be first-line therapy. Our study spanned the early experience with MitraClip in the United States from 2007 to 2013 and included >600 patients with functional MR, many of whom were not surgical candidates. Our understanding of the role of CRT has evolved during the last decade. Therefore, our study did not capture nor did it require CRT before enrollment. With greater understanding of optimal medical therapy, the COAPT study (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) did require CRT in appropriate patients before assessment of MR severity as part of optimal medical therapy. More than 35% of patients who were in COAPT had CRT placed previously yet still had significant MR. Although the denominator of patients who were referred for treatment of their FMR in COAPT and were then treated and responded to CRT is unknown, other studies have evaluated the impact of CRT on FMR. Van der Bijl and colleagues3 reported the effect of FMR on outcomes after CRT. Of 518 patients with grade 2 to 4+ FMR, only 40% had improvement following CRT, whereas the remaining 60% had no improvement in their MR severity. Nonresponse to CRT was independently associated with mortality (hazard ratio, 1.77; P<0.001). Moreover, other studies have documented a worsening of MR severity after CRT in 10% to 15% of patients. Data such as these have called into question which therapy, MitraClip or CRT, should be first-line therapy for significant functional MR even in patients who meet criteria for CRT. According to Kienemund and colleagues, roughly one-third of patients with an indication for CRT have moderate to severe FMR, which can be caused by altered ventricular geometry/size or the dyssynchrony itself. Some have suggested that MitraClip may be a preferred approach over CRT in selected patients.4 Because current guidelines support the use of CRT as first-line treatment before evaluation for FMR, limited data remain. Unfortunately, the ongoing trial of MitraClip versus medical therapy for nonresponders to CRT to which Gul and Haseeb refer will not answer the important question of which should be first-line treatment: MitraClip or CRT for FMR. (Text of response to a comment about author’s article, Ailawadi G, Lim DS, Mack MJ, Trento A, Kar S, Grayburn PA, Glower DD, Wang A, Foster E, Qasim A, et al.; EVEREST II Investigators. One-year outcomes after MitraClip for functional mitral regurgitation. Circulation. 2019; 139:37–47.)