Catheterization and Cardiovascular Interventions 85:899–903 (2015)

Influence of Percutaneous Mitral Valve Repair Using R System on Renal Function in Patients the MitraClipV With Severe Mitral Regurgitation Tienush Rassaf,* MD, Jan Balzer, MD, Christos Rammos, MD, Tobias Zeus, MD, Katharina Hellhammer, MD, Silke v. Hall, MD, Rabea Wagstaff, MSc, and Malte Kelm, MD Background: In patients with mitral regurgitation (MR), changes in cardiac stroke volume, and thus renal preload and afterload may affect kidney function. Percutaneous R system can be a therapeutic alternative mitral valve repair (PMVR) with the MitraClipV R therapy on renal function and clinito surgical valve repair. The influence of MitraClipV cal outcome parameters is unknown. Methods and Results: Sixty patients with severe R system in an open-label observational MR underwent PMVR using the MitraClipV study. Patients were stratified according to their renal function. All clips have been implanted successfully. Effective reduction of MR by 2–3 grades acutely improved KDOQI class. Lesser MR reduction (MR reduction of 0–1 grades) led to worsening of renal function in patients with pre-existing normal or mild (KDOQI 1–2) compared to severe (KDOQI 3–4) renal dysfunction. Reduction of MR was associated with improvement in Minnesota Living with Heart Failure Questionnaire (MLHFQ), NYHA-stadium, and 6-minute walk test. Conclusion: Successful PMVR was associated with an improvement in renal function. The improvement in renal function was associated with the extent of MR reduction and pre-existing kidney dysfunction. Our data emphasize the relevance of PVMR to stabilize the cardiorenal axis in patients with severe MR. VC 2014 Wiley Periodicals, Inc. Key words: mitral valve disease; mitral valve disease; percutaneous intervention; renal disease; chronic

INTRODUCTION

Functional mitral regurgitation (MR) is a frequent complication of ischemic or non-ischemic dilated cardiomyopathy as a consequence of left ventricular remodeling [1]. Medically, refractory MR has a strong negative impact on survival [2]. In patients with MR, changes in cardiac stroke volume, renal preload, and afterload may affect kidney function. This further deteriorates outcome in patients with chronic heart failure. Surgical mitral valve repair for medically refractory functional MR in patients with advanced heart failure has been demonstrated to improve left ventricular function and hemodynamics [3]. The impact of the surgical intervention on renal function, however, is not known. Percutaneous mitral valve repair (PMVR) with the R system can be a therapeutic alternative to MitraClipV surgical valve repair in high-risk patients [4–6]. R therapy influences renal funcWhether the MitraClipV tion and clinical outcome parameters in patients with severe MR was not known. We therefore sought to investigate how the R therapy influences pre-existing renal dysMitraClipV C 2014 Wiley Periodicals, Inc. V

function and how this affects the functional status in patients with severe MR.

Additional Supporting Information may be found in the online version of this article. Division of Cardiology, Pulmonology and Vascular Medicine, €sseldorf, MediDepartment of Medicine, University Hospital Du €sseldorf, Germany cal Faculty, Moorenstrasse 5, 40225, Du Grant sponsor: German Research Foundation; Grant number: DFG RA969/7-2. Conflict of interest: Nothing to report. *Correspondence to: Tienush Rassaf, MD, Division of Cardiology, Pulmonology and Vascular Medicine, University Hospital D€usseldorf, Moorenstrasse 5, D-40225 D€usseldorf, Germany. E-mail: [email protected] Received 2 June 2014; Revision accepted 10 October 2014 DOI: 10.1002/ccd.25705 Published online 17 October 2014 in Wiley Online Library (wileyonlinelibrary.com)

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METHODS Study Population

Sixty patients with severe MR characterized by trans-thoracic and trans-esophageal echocardiography R system were undergoing PMVR using the MitraClipV included in the study. Patients were stratified following the Kidney Disease Outcomes Quality Initiative (KDOQI) classification in a group with mild (KDOQI 1–2) and moderate to severe (KDOQI 3–4) renal dysfunction. Patients undergoing hemodialysis were excluded. Patients’ characteristics are listed in Table I. Study Design The objective of this open-label observational study R therwas to evaluate the influence of the MitraClipV apy on renal function and clinical outcome parameters in patients with severe MR. Study procedures were in accordance with the Declaration of Helsinki, the institutional Ethics Committee of the HeinrichHeine University approved the study protocol and the study is registered at clinical trials (NCT02033811). Patients were stratified in a non-blinded fashion either to the group with mild (KDOQI 1–2) or moderate to severe (KDOQI 3–4) renal dysfunction. Renal function was determined three days after clip implantation by measurement of creatinine and glomerular filtration rate. Three months after the procedure, follow-up examinations were performed with assessment of left ventricular end-diastolic diameter (LVEDD) and functional status according to New York Heart Association (NYHA) criteria, MLHF Q (Minnesota Living with Heart Failure Questionnaire), and the 6-minute walk test (6-MWT). R System MitraClipV R device and procedure have been The MitraClipV described before in detail [5,6]. In brief, with the guidance of fluoroscopy and transesophageal echocardiography transseptal puncture was performed. Then the transseptal sheath was exchanged for the steerable guide catheter and dilator. The Clip Delivery System (CDS) was introduced into the guide catheter and the R device advanced into the left atrium. The MitraClipV CDS was brought to the mitral valve, where leaflets were grasped and the clip deployed.

Statistical Methods

Results are expressed as mean 6 standard error (SE) unless stated otherwise. Differences between groups were compared using unpaired Student’s two-tailed

TABLE I. Patient Characteristics KDOQI 1–2 n ¼ 30

KDOQI 3–4 n ¼ 30

P-value

67.8 6 2.4 19 26.0 6 0.96 12.4 6 2.3 26 25

73.9 6 1.4 20 27.2 6 0.83 23.6 6 3.6 28 24

0.04 0.65 0.37 0.01 0.34 0.941

Cardiomyopathy Ischaemic (n) Dilated (n)

14 16

19 11

0.07 0.28

MR type Functional MR (n) Organic MR (n)

27 3

28 2

0.35 0.35

27 29.1 6 2.3 6,468 6 919

27 30.1 6 1.8 8,749 6 2181

1 0.73 0.32

126.4 6 8.1

138.6 6 8.9

0.86

Age (y) Male gender (n) BMI (kg/m2) Logistic EuroSCORE (%) NYHA Class III/IV (n) MR III (n)

Procedural characteristics 1-Clips implanted Fluoroscopy time (min) Radiation exposure (cGy cm2) Total duration (min) Cardiac function EF (%) Cardiac Output (l/min) Systolic PAP (mm Hg) TAPSE (mm) Biochemical characteristics Hemoglobin (g/dl) Creatinine (mg/dl) BNP (mg/dl) GFR (ml/min) Comorbidities Chronic obstructive pulmonary disease (n) Hypertension (n) Coronary artery disease (n) Coronary artery bypass graft (n) Diabetes mellitus (n) Atrial fibrillation (n) Pacemaker or ICD implant (n) Medication ACE-I/ARB (n) MRA Diuretics Beta blocker

39.2 6 3.0 4.0 6 0.21 40.3 6 3.7 18.3 6 0.9

41.0 6 3.2 3.9 6 0.22 40.4 6 3.4 17.0 6 1.1

0.68 0.89 0.98 0.37

12.9 6 0.3 0.9 6 0.1 2,732 6 560 82.4 6 4.3

12.4 6 0.4 2.3 6 0.5 2,884 6 422 44.3 6 2.1

0.20 0.01 0.83 0.01

5

8

0.20

27 14 6

29 19 9

0.30 0.07 0.49

8 17 14

10 17 10

0.52 1 0.44

19 12 23 22

13 14 26 24

0.18 0.55 0.39 0.11

t-test. Comparisons between groups were made using Chi-square test and P values of less than 0.05 were regarded statistically significant. All statistical tests were conducted using Prism 5.0 (GraphPad) for Mac OS.

Catheterization and Cardiovascular Interventions DOI 10.1002/ccd. Published on behalf of The Society for Cardiovascular Angiography and Interventions (SCAI).

MitraClip and Renal Function

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Fig. 1. Distribution of renal function according to KDOQI (Kidney Disease Outcomes Quality Initiative) stages in patients undergoing the MitraClip procedure (A). B: Beneficial effect of MR reduction on renal function was pronounced in patients with preexisting moderate to severe (KDOQI 3–4) compared to normal renal function or mild (KDOQI 1–2) renal dysfunction

(P < 0.0001). C: Greater MR reduction (MR reduction of 2–3 MR grades) acutely improved KDOQI class irrespective of preexisting renal function. D: Lesser MR reduction (MR reduction of 0–1 grades) led to worsening of renal function in patients with pre-existing normal or mild (KDOQI 1–2) compared to severe (KDOQI 3–4) renal dysfunction (*denotes P 5 0.01).

RESULTS

Secondary Endpoints—Effects of MitraClip on Functional Status The secondary endpoints were related to alterations in LVEDD, NYHA-class, MLHFQ, and 6-MWT. The influence of the MitraClip procedure on LVEDD after three months was dependent on the pre-existing renal function (Fig. 2). PMVR improved MLHF Q (44 6 3 to 36 6 2; P < 0.0001), NYHA classifications (3.3 6 0.1 to 2.3 6 0.1; P < 0.0001), and 6-MWT (306 6 21 to 328 6 20; P < 0.05) in patients with KDOQI 1–2 and in patients with KDOQI 3–4 (MLHF Q 43 6 3 to 36 6 3; P < 0.001, NYHA 3.0 6 0.1 to 2.2 6 0.1; P < 0.0001) without affecting the 6-MWT in the latter group (273 6 18 to 266 6 17; P > 0.05) three months after the MitraClip-procedure (Fig. 3). Further analyses, comparing the effects of pre-existing renal function and an effective (2–3 grades) vs. a slight (0–1 grades) reduction of MR on the functional status, did

Successful clip implantation was performed in all patients. No more than one Mitraclip was necessary. Patients with mild renal dysfunction were slightly younger (67.8 6 2.4 vs. 73.9 6 1.4, P ¼ 0.04) and had a lower logistic EuroSCORE (12.4 6 2.3 vs. 23.6 6 3.6, P ¼ 0.01) than patients with moderate to severe renal dysfunction. Detailed patients’ characteristics are listed in Table I. Primary Endpoint—Acute Effect of MitraClip on Renal Function

The primary endpoint of this study was the acute effect of the MitraClip procedure on renal function, classified following KDOQI. Effective reduction of MR by 2–3 grades acutely improved KDOQI class, whereas lesser MR reduction (0–1 grade) led to deterioration in renal function in patients with normal to mild (KDOQI 1–2) renal dysfunction (Fig. 1).

Catheterization and Cardiovascular Interventions DOI 10.1002/ccd. Published on behalf of The Society for Cardiovascular Angiography and Interventions (SCAI).

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not reveal any differences in our study (Supporting Information Figs. 1 and 2). DISCUSSION

The key findings of the present study are: (i) PMVR R procedure can be performed using the MitraClipV safely and efficaciously in patients with impaired renal function; (ii) effective reduction of MR by 2–3 grades acutely improved renal function; (iii) lesser reduction of MR was associated with a deterioration in renal function in patients with normal to mild (KDOQI 1–2) compared to moderate to severe (KDOQI 3–4) renal dysfunction. Patients with heart failure and MR have a bad prognosis. This becomes even worse when renal function is

Fig. 2. Changes on LVEDD after 3 months are affected by pre-existing renal dysfunction (P < 0.0002).

impaired, mostly due to changes in stroke volume, preload, and afterload, mechanisms that all affect renal R system has function. PMVR using the MitraClipV emerged as a therapeutic alternative to surgical valve repair in patients who are at high risk and who are unsuitable for conventional surgery. The implantation of a MitraClip exerts acute hemodynamic effects. Whereas immediately after MR reduction, reduction in the amplitude of the v wave can be seen [7,8], the mean left atrial pressure, pulmonary capillary wedge pressure, pulmonary arterial pressure, and the left ventricular end-diastolic pressure can decrease or remain unchanged [7–9]. In the majority of patients, a reduction in MR is associated with an increase in stroke volume and concomitant decrease in systemic vascular resistance [7]. This results in an improvement in cardiac output and cardiac index. An increase in the systolic arterial pressure can also be observed, but the diastolic or mean arterial pressures remain unchanged [8]. Those hemodynamic effects may be responsible for the improvement of renal function in our study population and explain why improvement in renal function was only seen, when MR was reduced by 2–3 grades. However, the long-term hemodynamic effects of the MitraClip procedure are still unknown and it is unclear whether the acute hemodynamic effects seen immediately after clip implantation are still measurable in a long-term follow-up. We did not perform post-clip cardiac catheterization and therefore cannot provide data on hemodynamic parameters after clip-implantation. The more pronounced reversal of kidney dysfunction associated with marked reduction of MR by >2 grades may be indicative of a dual beneficial effect of the MitraClip procedure: (i) the increase in cardiac stroke volume improves kidney

Fig. 3. PMVR led to a significantly improvement of (A) MLHF Q (Minnesota Living with Heart Failure Questionnaire), (B) NYHA classifications, and (C) 6-min walk test in patients with KDOQI 1–2 and in patients with KDOQI 3–4 three months after the MitraClip-procedure; *** denotes P < 0.0001, ** denotes P < 0.001, * denotes P

Influence of percutaneous mitral valve repair using the MitraClip® system on renal function in patients with severe mitral regurgitation.

In patients with mitral regurgitation (MR), changes in cardiac stroke volume, and thus renal preload and afterload may affect kidney function. Percuta...
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