Transcatheter Mitral Valve Repair (MitraClip) and the Kidney

Transcatheter mitral valve repair (TMVR) is a minimally invasive procedure used as a treatment option for patients with symptomatic chronic moderate to severe, or severe mitral regurgitation (MR). The MitraClip is an edge-to-edge leaflet repair device and is currently the only device approved by the U.S. Food and Drug Administration for TMVR. MR is one of the most common valve lesions. Patients with chronic kidney disease (CKD) and MR usually have multiple comorbidities, increasing their surgical risk for valve replacement and making them possible candidates for TMVR by use of the MitraClip. The interaction between MR and the kidney is complex: MR can lead to abnormalities in hemodynamics and congestive heart failure, which may lead to or worsen CKD. Repair of the mitral valve may therefore be expected to have a favorable impact on kidney function in some patients. Conversely, kidney function plays an important role in cardiovascular disease, and it is well known that the outcomes of many procedures such as transcatheter aortic valve replacement (TAVR) are worse in patients with CKD than in the general population. Here we review the use of MitraClip and its application in patients with kidney disease.

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MitraClip and CKD

Given the interrelationships between the heart and kidneys, it is plausible that repair of the mitral valve, including repair performed by the transcatheter approach, might have a favorable impact on kidney function in some patients in whom a component of the kidney disease is a consequence of decreased effective arterial volume.

In one such study (1), 854 patients with moderate to severe or severe MR (3+ or 4+, respectively) who underwent TMVR with the MitraClip device in multicenter investigational trials (2, 3) and the REALISM (Real World Expanded Multicenter Study of the MitraClip® System) continued access registry were evaluated. The distribution of the estimated GFRs (eGFRs) of the patients at the baseline of the study was as follows: CKD stage 1 or 2 (eGFR ≥60 mL/min per 1.73 m2), n = 438; CKD stage 3 (eGFR 30–59 mL/min per 1.73 m2), n = 364; and CKD stage 4 (eGFR <30 mL/min per 1.73 m2), n = 52. Follow-up evaluation after 1 year revealed improvements in eGFR in patients with more advanced CKD. In the overall cohort with paired baseline and 1-year data (n = 579), the mean change in eGFR was −1.0 ± 15.2 mL/min per 1.73 m2 (p = 0.10). For patients with CKD stage 1 or 2 at baseline (n = 319), the eGFR was decreased 1 year after the procedure (−4.1 ± 16.6 mL/min per 1.73 m2). However, among patients with CKD stage 3 at baseline (n = 227), the mean eGFR increased (+2.6 ± 12.4 mL/min per 1.73 m2), and among patients with CKD stage 4 or 5 at baseline (n = 33), this increase in eGFR was even greater (+4.8 ± 9.5 mL/min per 1.73 m2). When examined by CKD stage, 36.4% of patients with CKD stage 4 or 5 at baseline were found to have improved to CKD stage 3 1 year after the MitraClip procedure. When the clinical characteristics of patients who experienced improvement in kidney function (defined as increase in eGFR ≥5 mL/min per 1.73 m2 at 1 year) were compared with those who did not, only New York Heart Association class 3 or class 4 at baseline were independently associated with this degree of improvement in eGFR (odds ratio 2.2, 95% confidence interval 1.41–3.57, p = 0.007). These findings suggest that TMVR with the MitraClip has the potential to improve the eGFR in some patients with more advanced CKD, especially when the latter is related to heart failure.

As with transcatheter aortic valve replacement (TAVR), an important question about TMVR with the MitraClip is whether CKD has an impact on mortality. An unadjusted analysis done in the same study (1) indeed showed that the 1-year survival rate was associated with baseline kidney function. The mortality rate at 1 year was 15.0% for the overall cohort. When stratified by stage of CKD, mortality rates were found to be 9.0%, 20.6%, and 26.0% among patients with CKD stage 1 or 2, stage 3, and stage 4 or 5, respectively (p < 0.001).

Another multicenter study demonstrated an association between CKD and worse outcomes. That study used a multicenter registry of 173 patients treated with MitraClip between 2009 and 2012 at three centers (4). The patients were divided into three groups: advanced CKD (creatinine clearance [CrCl] <30 mL/min, group 1, n = 20), moderate CKD (CrCl 30–60 mL/min, group 2, n = 78) and normal kidney function (CrCl >60 mL/min, group 3, n = 75). Only 1 patient in group 1 was using dialysis. Patients with advanced CKD were significantly older and had higher values on the logistic EuroSCORE. There was no significant difference in the procedural success rate among the three groups. Data for all-cause mortality (16.2%) and readmissions due to heart failure (10%) with a mean follow-up time of 16.2 ± 11.1 months were available in 130 patients (17 patients in group 1, 61 patients in group 2, and 52 patients in group 3). Mortality rates differed significantly between the groups (52.9% for group 1, 8.2% in group 2, and 13.5% in group 3, p < 0.001). With regard to a combined endpoint of death or readmission due to heart failure, a significant difference between the groups was noted, with advanced CKD (group 1) being identified as an independent predictor of the combined event (hazard ratio 4.8, 95% confidence interval 1.1–21.3, p = 0.04).

Another study assessed the impact of CKD on the clinical outcomes of MitraClip with up to 12 months of follow-up. In that study, 214 patients undergoing TMVR with MitraClip were included (5). The patients were divided into two groups: baseline CKD (n = 113) or no CKD (n = 101). Patients with baseline CKD had either moderate CKD (stage 3, n = 91 [80.5%]) or severe CKD (stage 4, n = 22 [19.5%]). EuroSCORE II and the Society of Thoracic Surgery score were higher in the CKD group. Patients were followed up for 1 year after the procedure. The primary safety endpoint was the incidence of major adverse events and was higher in the CKD group than in the group without CKD (12.4% vs. 2.0%, p = 0.003). The primary efficacy endpoint (freedom from death, surgery for mitral valve dysfunction, or grade ≥3+ MR at 12 months) was significantly lower in the CKD group than in the no-CKD group (65.8% vs. 84.2%, log-rank p = 0.005). Baseline CKD was found to be an independent predictor of the primary efficacy endpoint (adjusted hazard ratio 2.48, 95% confidence interval 1.29–4.79, p = 0.006).

An additional study showed that CKD is associated with worse outcomes in patients undergoing TMVR with MitraClip (6). In that study, 212 consecutive patients who underwent TMVR with MitraClip were enrolled and were divided into three groups. The groups had normal eGFR (60 mL/min per m2 ≤eGFR in 70 patients (34%), mild CKD (30 mL/min per m2 ≤eGFR <60 mL per min/m2 in 106 patients (51%), and severe CKD (eGFR <30 mL/min per m2 in 30 patients (15%). The median follow-up period was 475 ± 425 days. Patients in the CKD groups were older, had higher logistic EuroSCOREs, and higher N-terminal pro B-type natriuretic peptide levels than did those in the normal eGFR group. Univariate Cox regression analysis showed that severe CKD was associated with an increased risk for all-cause death (p = 0.002, hazard ratio 3.423), and multivariable Cox regression analysis also revealed an association between severe CKD and all-cause death (p = 0.001, hazard ratio 4.322).

The authors also evaluated the impact of MitraClip on kidney function among the study patients (6). Kidney function data after 6 months were available for 81 patients. Three of the patients were using hemodialysis and were excluded, and 78 patients were studied. Improvement of kidney function was noted in 22 patients (28%). In addition, among the patients whose kidney function improved after MitraClip placement, the long-term survival rate was significantly higher than in the patients whose kidney function did not improve (p = 0.028).

A recent study of MitraClip and kidney function used the National Cardiovascular Data Registry Transcatheter Valve Therapy Registry (7). In that study, 5213 patients who underwent the MitraClip procedure were evaluated. CrCl was <60 mL/min in 77% of patients (n = 4010) and <30 mL/min in 23% (n = 1183) of patients. The primary outcome was a composite of all-cause mortality, stroke, and new requirement for dialysis. The rates of the primary outcome were higher in patients with lower CrCl, occurring in 1.4% of those with CrCl >60 mL/min, 2.7% of those with CrCl 30 to <60 mL/min, 5.2% of those with CrCl <30 mL/min, and 7.8% of dialysis patients (p < 0.001). Following a similar pattern, patients with lower CrCl had higher 1-year mortality rates, with a rate of 13.2% of those with CrCl >60 mL/min, in 18.8% of those with CrCl 30 to <60 mL/min, in 29.9% of those with CrCl <30 mL/min, and in 32.3% of dialysis patients (p < 0.001). Hence, this study also demonstrates that CKD is associated with worse outcomes after MitraClip.

Whereas the outcomes after MitraClip are worsened by the presence of CKD, an important question is how such patients would fare without the procedure being performed. Although direct comparisons are not available for patients with CKD who receive MitraClip compared with no procedural intervention, several inferences can perhaps be drawn. In the general population, the annual mortality rate for medically treated patients with primary severe MR is up to 6%, and intervention by mitral valve replacement or repair is well known to be associated with an improved survival rate and reduced symptoms (8). Patients with MR and CKD appear to have far worse survival rates than do those without CKD, as evidenced in one study in which the 5‐year survival rate of patients with severe MR and CKD was 37%, compared with 65% for severe MR without CKD (9). Hence, although outcomes with MitraClip in patients with CKD are less favorable than in those without CKD, it seems likely that this is outweighed by a reduction in the mortality rate that would be found in the absence of such intervention.

Conclusions

In a manner similar to what has been observed with TAVR, CKD is associated with worse outcomes in patients undergoing MitraClip placement, including higher mortality rates compared with non-CKD patients. Among the benefits of MitraClip, some patients with CKD experience an improvement in their kidney function after MitraClip placement, likely as a result of improved effective arterial volume. Our growing understanding of these relationships can help us best select the patients who can benefit significantly from this procedure.

Acknowledgements

Given the interrelationships between the heart and kidneys, it is plausible that repair of the mitral valve, including repair performed by the transcatheter approach, might have a favorable impact on kidney function in some patients in whom a component of the kidney disease is a consequence of decreased effective arterial volume.

June 2020 (Vol. 12, Number 6)

References

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3. Whitlow PL, et al Acute and 12-month results with catheter-based mitral valve leaflet repair: The EVEREST II (Endovascular Valve Edge-to-Edge Repair) High Risk Study. J Am Coll Cardiol 2012; 59:130–139.

4. Estévez-Loureiro R, et al Effect of advanced chronic kidney disease in clinical and echocardiographic outcomes of patients treated with MitraClip system. Int J Cardiol 2015; 198:75–80.

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8. Enriquez-Sarano M, et al Mitral regurgitation. Lancet 2009; 373:1382–1394.

9. Samad Z, et al Prevalence and outcomes of left‐sided valvular heart disease associated with chronic kidney disease. J Am Heart Assoc 2017; 6:e006044.