Transcatheter Mitral Valve Repair Using MitraClip in Patients With Renal Transplantation

Objectives. To evaluate the renal function in patients with renal transplantation 1 month after treatment of their severe symptomatic mitral regurgitation using transcatheter mitral valve repair (TMVRep) using MitraClip (Abbott Cardiovascular). Methods. We enrolled 22 patients with previous history of end-stage renal disease and kidney transplant with severe symptomatic mitral regurgitation (MR) in this study. Each patient was evaluated by the structural heart team and underwent transesophageal echocardiographic evaluation for MR etiology, severity, and location of the MR jet, as well as to rule out left atrial appendage clot formation. Serum creatinine and estimated glomerular filtration rate using the Modification of Diet in Renal Disease formula were measured at baseline and at 1-month follow-up. Results. Fourteen patients (64%) were male and mean age of the study group was 50.4 ± 11.0 years. Mean ejection fraction was 29.0 ± 5.6%. The majority (86%) of the MRs treated were classified as functional MR. Follow-up creatinine values were significantly lower after treatment of their symptomatic MR with TMVRep compared with baseline creatinine values (baseline, 3.2 ± 0.49 mg/dL; follow-up, 1.99 ± 0.31 mg/dL; P<.05). Conclusions. TMVRep in patients with renal transplantation was associated with lower serum creatinine values at 1-month follow-up and represents an alternative to surgery in this high-risk group of patients. Further studies are needed to confirm our findings and to find the best treatment option for these patients. 

J INVASIVE CARDIOL 2021;33(8):E628-E631. Epub 2021 June 28.

Key words: renal function, renal transplantation, transcatheter mitral valve repair

Mitral regurgitation (MR) is a highly prevalent valvular heart disease. It is also the most common valvular disease in patients with renal disease, with a 1.3- to 1.8-fold greater incidence of MR compared with patients without chronic kidney disease.^1,2 On the other hand, because renal and cardiac functions are closely interconnected, the hemodynamic changes that occur with MR can influence the renal function as well. Therefore, increased forward cardiac output after surgical or transcatheter treatment of MR may influence renal function. In fact, recent data suggest that renal function can improve after transcatheter mitral valve repair (TMVRep), both acutely and in the long term.^3,4

Renal transplantation (RTx) is the optimal treatment for most patients with end-stage kidney disease (ESRD).⁵ With the increased numbers and improved survival of RTx recipients over the recent years, the prevalence of cardiovascular diseases in these patients, including valvular heart disease, is increasing. However, due to the high mortality rates in RTx patients requiring valve replacement or repair,⁶ the number of eligible RTx patients undergoing transcatheter treatment of valvular disease is expected to grow rapidly in the near future.

Although a number of studies have shown the effect of TMVRep on renal function,^3,4,7,8 there is a paucity of data in patients with RTx. Accordingly, the aim of the present study was to evaluate the changes in renal function in RTx patients who developed severe MR and underwent TMVRep after the transplantation.

A total of 22 patients with previous history of ESRD and kidney transplant with severe symptomatic MR were enrolled in this study. Each patient was evaluated by our structural heart team, and the most appropriate treatment for their MR was discussed and determined by the team. All patients had both transthoracic as well as three-dimensional transesophageal evaluation of their MR etiology, severity, and location of the MR jet, as well as to rule out left atrial appendage clot formation. All patients were referred by our renal transplant team and followed by them before and after the procedure. All patients had labs including renal function and calculated glomerular filtration rate (GFR) using the Modification of Diet in Renal Disease formula both at baseline and at 1-month follow-up.

Statistical analysis. All parameters were expressed as mean ± standard deviation or percentages. Data was analyzed using SPSS, version 21 (SPSS). Normality was assessed by Shapiro-Wilk test. A paired sample t-test was used to analyze the change in serum creatinine over time. A P-value of <.05 was considered to be statistically significant. 

A total of 22 patients were included in the study. Fourteen patients (64%) were men and mean age of the study group was 50.4 ± 11.0 years. Eighteen patients (82%) had diabetes mellitus, 16 (73%) had hypertension, and 17 (77%) had hyperlipidemia. Mean ejection fraction was 29.0 ± 5.6%. The majority (86%) of the MR treated was functional MR. Baseline characteristics of the patients can be found in Table 1. Follow-up creatinine values were significantly lower after treatment of their symptomatic MR with TMVRep compared with baseline creatinine values (baseline, 3.2 ± 0.49 mg/dL; follow-up, 1.99 ± 0.31 mg/dL; P<.05) (Figure 1). 

The main finding of the current study was that creatinine values at 1-month follow-up were significantly lower compared with baseline in patients with RTx who underwent TMVRep. To the best of our knowledge, this is the first study on the effects of TMVRep in patients with RTx. 

Renal transplantation is the optimal form of renal replacement therapy in the majority of patients with ESRD.⁵ However, RTx is still a state of chronic renal insufficiency and patients with renal failure have increased risk for MR.^2,9 The presence as well as severity of MR, on the other hand, have been shown to be independently associated with renal dysfunction.^10,11 Although surgery is the treatment of choice for severe MR, it carries the risk of postoperative renal dysfunction.^12,13 Moreover, Sharma et al reported that RTx patients requiring valve replacement have very high in-hospital and 2-year mortality rates after the cardiac surgery.⁶ Therefore, transcatheter valvular therapies represent a promising alternative in these patients.¹⁴ 

A number of studies investigated the effect of TMVRep on renal function. Rassaf et al studied the acute effects and found that the effective reduction of MR by MitraClip (Abbott Cardiovascular) by 2-3 grades acutely improved Kidney Disease Outcomes Quality Initiative class.³ However, in this study, lesser MR reduction led to worsening of renal function in patients with normal to mild renal dysfunction. Another study in patients from the EVEREST-II trial, EVEREST-II high-risk registry, and multicenter REALISM registry showed an acute and modest improvement in estimated glomerular filtration rate (eGFR) even before discharge. Furthermore, while patients with baseline CKD stage 1 or 2 had a slight reduction in eGFR, reduction in MR severity to moderate or less by MitraClip procedure was associated with a small improvement in eGFR at 1 year in patients with moderate or severe CKD at baseline.⁴ In their study, Kaneko et al observed 28% of the patients had improved renal function 6 months after TMVRep.⁷ In contrast to previous studies, they observed that baseline renal function or grade of MR reduction was not different in patients with and without improved renal function. Finally, in a recent large study, Sawalha et al showed that renal function improved in 25% of patients with CKD stage 3 and in 50% with CKD stage 4-5 at 30-day and 90-day readmission, suggesting that TMVRep could potentially improve CKD stage, although these patients had worse outcomes after TMVRep.⁸ Our study differs from these studies in terms of the patient population. We included only RTx patients with deterioration in their renal function and demonstrated significant improvement in renal function. 

MR can facilitate worsening of renal function via the reduction in the left ventricular forward stroke volume, increased pulmonary pressure, and renal venous pooling.^15,16 Reduction of MR increases forward stroke volume both in the acute phase and in the long term,^17,18 which can increase renal perfusion and improve renal function. Accordingly, in a previous study, eGFR was significantly improved at 12 months among patients with eGFR <60 mL/min per 1.73 m² who underwent MitraClip  procedure, which was only observed in the patients with >9% increase in forward stroke volume.¹⁹ However, there can be other contributors to the improvement in renal function after reduction of MR.¹⁵ Hemodynamic changes in valvular disease can trigger neurohormonal responses, including activation of the sympathetic nervous system.²⁰ Increased cardiac efficiency and increased forward stroke volume¹⁸ may decrease neurohormonal activation, which in turn improves renal function. In a study in patients with heart failure, Ozturk et al showed that secondary MR was associated with increased sympathetic nerve activity. Investigators also showed that reduction of MR with the MitraClip  procedure reduced sympathetic nerve activity and improved baroreflex gain.²¹ Finally, endothelial dysfunction is another recognized contributor to the cross-talk between cardiac and renal functions.^15,22 In fact, Rammos et al studied 27 patients treated with MitraClip and found that endothelial function measured by flow-mediated dilation improved at 3-month follow-up.²³ These results may indicate that there is a complex interaction between the renal function and MR, comprising indirect effects in addition to direct hemodynamic effects. 

Study limitations. There are a number of limitations of the current study. First, there is a lack of invasive or non-invasive measurements of hemodynamic parameters at baseline or at follow-up. Second, we did not measure biomarkers, such as brain natriuretic peptide, which can be related to outcomes.⁷ Finally, the patient numbers were relatively low due to limiting our study to a specific patient group.

Transcatheter repair of MR in patients with RTx is associated with lower serum creatinine values at follow-up, and represents an alternative to surgery in this group of patients in addition to guideline-guided medical therapy and cardiac resynchronization therapy. Further studies are needed to confirm our findings and to find the best treatment option for these patients.