Individual patient data meta‐analysis of the effects of the CARILLON® mitral contour system

Abstract

Aims Functional mitral regurgitation (MR) (FMR) is common in heart failure with reduced ejection fraction and worsens morbidity and mortality, even when mild. The CARILLON® mitral contour system (Cardiac Dimensions, Kirkland, WA, USA), a mitral annuloplasty device delivered percutaneously to the coronary sinus, is designed to reduce the mitral annular dimension by virtue of the close anatomic relationship between the coronary sinus and the posterior mitral annulus. We performed a comprehensive individual patient data meta‐analysis of all studies that used CARILLON® device vs. control that have measured mitral regurgitation severity, left ventricular (LV) remodelling, functional status, and heart failure‐related outcomes in heart failure with reduced ejection fraction patients. Methods and results The Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE were searched in July 2020. Primary outcomes of interest were measures of MR severity, LV remodelling, New York Heart Association functional class and heart failure‐related outcomes [mortality and heart failure hospitalization (HFH) during follow up]. All data were received as individual patient and individual time point data‐points. Mean differences and 95% confidence intervals (CIs) were calculated for continuous data using a fixed‐effects model. Three studies (REDUCE FMR, TITAN and TITAN II) enrolling 209 participants were identified and included. Pooled analysis showed that, compared with control, CARILLON® device significantly improved both MR volume (mean difference MD ‐9.20, 95% C.I. −16.11 to −2.29 mL, P = 0.009) and MR grade (MD ‐1.12, 95% CI −1.36 to −0.88, P < 0.00001) and this was associated with a significant reduction in LA volume, MD −7.54 mL, 95% CI −14.90 to − 0.18, P = 0.04. Significant LV reverse remodelling was also seen in terms of EDV (MD −16.53, 95% CI −28.61 to −44.4 mL, P = 0.007), and a trend in ESV (MD −8.68, 95% CI −18.69 to −1.34 mL, P = 0.09) but no significant effect on LVEF (MD 0.88, 95% CI −1.52% to 2.38%, P = 0.47), due presumably to the greater residual MR in the control patients falsely elevating the LVEF. In addition, the CARILLON® device significantly improved New York Heart Association functional Class (MD −0.22, 95% CI −0.24 to −0.16, P < 0.00001), associated with a lower rate of HFH compared with controls (45.3% vs. 64%, respectively, P = 0.04). As a sensitivity analysis we also restricted the analyses to those patients with Class 3+/4+ MR at baseline. In this cohort, the echocardiographic results were similar, and the reduction in HFH rates was even more marked (43.9% vs. 82.9%, respectively, P = 0.04). Conclusions This comprehensive meta‐analysis of individual patient data has shown that CARILLON® device provides statistically significant and clinically meaningful benefits on MR severity, LA and LV volumes, and remodelling and rates of subsequent heart failure hospitalization

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“…A sham‐controlled randomized trial testing a transcatheter indirect mitral annuloplasty device met its primary endpoint of mitral regurgitant volume reduction with reverse LV and LA remodelling at 12 months 619 . Further studies confirmed favourable results on LA volumes and LV remodelling with trends towards improvement in mean 6MWT distance and symptoms and a reduction in HF hospitalizations in an IPD meta‐analysis 620–623 . Transcatheter mitral valve replacement is also emerging as a possible alternative option, but randomized trials are still lacking 624 …”

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“…Even a small mitral effective regurgitant orifice area contributes to LA remodelling on top of traditional systolic and diastolic parameters 180 . Percutaneous mitral valve annuloplasty may also effectively reduce mitral valve annulus and have favourable effects on LV remodelling and patients' symptoms 181,182 . Tricuspid regurgitation is highly prevalent in HF patients.…”

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