ORIGINAL R ESEARCH AR TICLE
Percutaneous Mitral Repair with the MitraClip System in Patients with Mild-to-Moderate and Severe Heart Failure: A Single-Centre Experience € kmen Turan,1 Stephan Kische,2 Ibrahim Ilkay Bozdag-Turan,1* Liliya Paranskaya,1* Ralf Birkemeyer,1 R. Go 1 2 1 1 Akin, Jasmin Ortak, Yannik Stoeckicht, Jochen Schubert, Bernd Westphal,1 Christoph A. Nienaber1 & € seyin Ince2 Hu 1 Heart Center Rostock, University Hospital Rostock, Rostock, Germany 2 Department of Cardiology, Vivantes Klinikum Friedrichshain, Berlin, Germany
Keywords Clinical outcomes; Left ventricular remodeling; MitraClip; Severe heart failure. Correspondence H. Ince, M.D., Ph.D., Heart Center Rostock, University Hospital Rostock, ErnstHeydemann-Str. 6, 18057 Rostock, Germany. Tel.: +49 (0)381 494 7797; Fax: +49 (0)381 494 7798; E-mail: [email protected]
doi: 10.1111/1755-5922.12058 *These authors contributed equally to the manuscript.
SUMMARY Aims: Edge-to-edge repair of mitral regurgitation (MR) with the MitraClip (MC) system is increasingly applied in advanced heart failure. Our objective was to compare outcomes in patients with mild-to-moderate and severe systolic heart failure. Methods and results: Between February 2010 and July 2012, 121 patients with MR of at least grade 3+ and a mean EuroSCORE II of 10.6% underwent MC implantation. Thirty-nine had a left ventricular ejection fraction (LVEF) of ≤30% (group A) and 82 of >30% (group B).Procedural success was comparable in both groups (100% vs. 95.2%) with multiple (>2) clip implantation in 34% and 25% of patients, respectively. At 12 months, absolute reduction in MR grade (2.3 vs. 2.2) and relative reduction in mitral valve orifice area (48% vs. 42%) were also comparable. New York Heart Association class had improved independent from baseline LVEF (P < 0.001). In-hospital mortality was low in both groups (2.6% vs. 2.4%), but there was a strong trend for higher 12-month mortality in group A (34% vs. 18%, P = 0.05) with no significant difference in the overall rate of major adverse cerebrovascular and cardiac events (36.8% vs. 28.9%, P = 0.38). On multivariate analysis, MR grade after repair was the strongest predictor of mortality (OR 2.121, 95% CI 1.095–4.109), whereas systolic impairment was no independent predictor. Conclusions: Percutaneous mitral valve repair led to comparable symptomatic improvement in patients with mild-to-moderately or severely reduced LV function. LV-EF < 30% was not an independent predictor of short-term mortality, which was mainly governed by residual MR after repair.
Introduction The presence of moderate to severe mitral valve regurgitation (MR) due to primary valve disease or left ventricular (LV) dysfunction is associated with increased morbidity and mortality [1–4]. Although optimal medical treatment improves symptoms and reduces severity of MR in selected candidates [5,6], surgical repair is the standard of care [7]. However, its effectiveness is not well established for severe secondary mitral regurgitation (MR) in refractory end-stage heart failure [8]. Therefore, in clinical practice, a large percentage of symptomatic patients with severe MR do not undergo conventional surgery due to severely impaired LV function [9–11]. Percutaneous edge-to-edge mitral valve (MV) repair using the MitraClip (MC) device (Abbott Laboratories, Abbott Park, IL, USA) has been developed as an alternative interventional treatment for MR. MC is the only nonsurgical system for MV repair, which has been evaluated in surgical low- and high-risk patients
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[11–17]. Several trials demonstrated the feasibility and safety of MC implantation as well as the effective MR reduction and symptomatic benefits after MC in different groups of patients including patients with severe LV dysfunction [18–24]. The symptomatic improvement even in patients with end-stage heart failure raises the question of the importance of impaired LV function for patient selection for the MC procedure. We therefore thought to compare the outcome of patients with mild-to-moderate and severe systolic heart failure in a single-center cohort of 121 MC patients.
Materials and Methods Study Population From February 2010 to December 2012, 121 patients with severe MR underwent MC implantation at the University Heart Center in Rostock, Germany. This population represents the entire cohort
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treated with MC at our institution and includes patients during our learning curve. All data were prospectively collected and analyzed in a computerized database. Treatment for MR was indicated according to current guidelines [25] and therapeutic approach discussed with the interdisciplinary heart-team. Surgical risk was assessed with the logistic EuroSCORE [26] and the Society of Thoracic Surgeons (STS) mortality risk calculation [27]. Exclusion criteria for MC implantation included significant mitral stenosis and acute endocarditis. The investigation conforms to the principles outlined in the Declaration of Helsinki. The local ethical committee approved the study protocol. All patients gave written informed consent for the MC procedure and follow-up.
Preoperative/Perioperative Evaluation and Treatment As a part of preinterventional screening, patients underwent echocardiography and invasive cardiac evaluation with coronary angiography, left ventriculography, and right-heart catheterization. All procedures were performed as previously described [20–23] in a hybrid operation theater under general anesthesia using fluoroscopic and transesophageal 2- and 3-dimensional echocardiographic guidance. The number of clips to be implanted was at the discretion of the primary operator.
Postintervention aspirin 100 mg and clopidogrel 75 mg were administered for 6 months. Patients with an indication to take vitamin K antagonists underwent individualized anticoagulation management.
Echocardiographic Evaluation Echocardiographic measurements were taken prior to the MC procedure, during the procedure, and immediately after and at 12-month follow-up. Severity of MR was graded according to current guidelines [28]. Grading criteria for postprocedural MR were adapted to the quantitative assessment of severity in percutaneous MV repair as reported by Foster et al. [29]. Measurements of LV volumes and left ventricular ejection fraction (LVEF) were taken using the biplane Simpson’s method. The mitral valve orifice area (MVOA) was assessed using planimetry (2D and 3D/ QULAB-Philips) intraoperatively, before and after clip implantation; in addition, the pressure half-time method was used at discharge.
Follow-Up Clinical and complete echocardiographic follow-up was performed baseline, at discharge, and 12 months after the procedure. Data concerning re-interventions and cardiac re-hospitalizations were collected together with information about major cardiac and
Table 1 Baseline clinical characteristics of both groups
Age, years SD Male gender, n (%) BMI (kg/m2) SD, n (%) EuroSCORE II SD STS score SD Ischemic cardiomyopathy, n (%) Dilated cardiomyopathy, n (%) Device therapy (ICD), n (%) MR type, n (%) Functional Organic/combined Previous cardiac surgery, n (%) Prior acute decompensate heart failure, n (%) Previous stroke, n (%) COPD, n (%) Diabetes mellitus, n (%) Prior neoplasia, n (%) Hypertension, n (%) Atrial fibrillation, n (%) NYHA class III or IV, n (%) Chronic renal failure GFR (mL/min/1.73 m2) SD GFR < 30 mL/min/1.73 m2 GFR 30–50 mL/min/1.73 m2
All patients (n = 121)
Patients with EF ≤ 30 (n = 38)
Patients with EF > 30 (n = 83)
77 7 69 (57.0) 26 5 10.6 5.6 10.9 6.4 51 (42.1) 21 (17.4) 15 (12.4)
74 8 26 (68.4) 25 4 12.7 6.1 13.0 6.7 23 (60.5) 15 (39.5) 10 (26.3)
79 6 43 (51.8) 27 5 9.7 5.2 10.0 6.0 28 (33.7) 6 (7.2) 5 (6.0)
60 mmHg, n (%) LVEDD, mm SD LVESD, mm SD LVEDV, mL SD LVESV, mL SD MR grade acute, mean SD 12-month follow-up (n = 117) LVEF, % SD Annulus diameter, mm SD MVOA, cm2 SD mTPG, mmHg SD SPP, mmHg SD SPP > 60 mmHg, n (%) LVEDD, mm SD LVESD, mm SD LVEDV, mL SD LVESV, mL SD MR grade acute, mean SD
Patients with EF ≤ 30 (n = 38)
42 3.9 5.2 2.3 50 28 59 46 161 102 3.4
16 0.3 0.9 0.8 13 (23.1) 9 11 71 65 0.5
23 4.0 5.8 2.3 53 11 66 55 220 165 3.4
44 3.8 3.0 3.3 42 6 58 45 146 90 1.1
16 0.3 0.6 1.3 12 (5.0) 9 11 67 52 0.6
46 3.7 3.0 3.3 40 4 57 43 142 88 1.4
15 0.3 0.6 1.2 10 (3.7) 9 11 63 49 0.8
5 0.2 0.8 0.8 12 (28.9) 10 10 78 67 0.5
Patients with EF > 30 (n = 83)
P
11 0.3 0.8 0.9 13 (20.5) 8 10 48 36 0.5
30
Follow up
Figure 3 Influence of MitraClip treatment on New York Heart Association (NYHA) class at 12-month follow-up in patients with mildto-moderate and severe heart failure. MitraClip treatment lead to improvement in NYHA class at discharge and 12-month follow-up in both groups. No significant differences in NYHA at discharge and 12-month follow-up between both groups.
70
81.9%
0.8
NYHA
20 10
1.0
P = 0.17
P = 0.24
40 30
61
Cumulative survival
NYHA (%)
50
62
61
60
EF30 1000
Figure 4 One-year cumulative survival for group A (EF < 30%) and group B (EF > 30%). No significant difference of 1-year cumulative survival was performed between both groups.
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Table 4 Clinical outcome at 12-month follow-up
NYHA class III/IV, (%) MACCE, n (%) MACCE (excluding MV surgery), n (%) Death, n (%) Procedural, n (%) In-hospital, n (%) Thirty days, n (%) Myocardial infarction, n (%) CVA, n (%) Major bleeding, n (%) MV surgery total, n (%) Acute Elective CHF requiring hospitalization, n (%) New MR grade 3, n (%)
Cumulative incidence
Patients with EF ≤ 30 (n = 38)
Patients with EF > 30 (n = 83)
P-value
11 38 30 28 0 3 4 3 0 7 9 1 8 27 10
6 14 14 13 0 1 1 2 0 4 0 0 0 10 4
5 24 16 15 0 2 3 1 0 3 9 1 8 17 6
0.17 0.38 0.059 0.051 – 0.94 0.78 0.18 – 0.13 0.035 0.50 0.048 0.47 0.64
(9.1)/1 (0.8) (31.4) (24.8) (23.1) (0) (2.5) (3.3) (3.4) (0) (5.8) (7.4) (0.8) (6.6) (22.3) (9.3)
(15.8)/0 (0) (36.8) (36.8) (34.2) (0) (2.6) (2.6) (5.3) (0) (10.5) (0.0) (0.0) (0.0) (26.3) (11.1)
(6.0)/1 (1.2) (28.9) (19.3) (18.1) (0) (2.4) (3.6) (1.2) (0) (3.6) (10.8) (1.2) (9.6) (20.5) (8.3)
CHF, congestive heart failure; CVA, cerebro-vascular accident; MACCE indicates major adverse cardiovascular and cerebrovascular events (defined as the composite of death, myocardial infarction, stroke, mitral surgery, and major bleeding); MR, mitral regurgitation; MV, mitral valve; NYHA, New York Heart Association.
in patient with EF < 30% (34% vs. 18%, P = 0.05). Moreover, 1-year cumulative survival curve showed no significant difference between both groups (65.8% vs. 81.9%; Figure 4). The cause of death in high-risk group (EF < 30%) was 38% cardiac (heart failure/myocardial infarction) and 62% noncardiac (pneumonia/ sepsis/gastrointestinal bleeding/chronic obstructive pulmonary disease [COPD]). In spite of that MACCE with and without MV surgery at 12 months did not differ significantly (36.8% vs. 28.9%, P = 0.38 and 36.8% vs. 19.3%, P = 0.059; Table 4) because patients with EF > 30% had significantly more often MV surgery during follow-up (0% vs. 9.6%, P = 0.048). Indication for open MV surgery in nine patients was new MR grade 3 (n = 6), partial leaflet detachments (n = 2), and significant mitral stenosis (n = 1).
Predictors of Mortality Multivariate analysis identified residual MR grade after MC procedure as strongest predictor of 12-month mortality (OR 2.121, 95% CI 1.095–4.109). Baseline mTPG (OR 1.487, 95% CI 1.004–2.204) was also an independent predictor. EF < 30% however was not an independent predictor of mortality (Table 5).
Discussion We compared the effect of MC treatment on MR, LV remodeling, clinical symptoms, and outcomes in patients with mild-tomoderate and severe heart failure in a prospective single-center registry. The feasibility and safety of MC treatment was initially demonstrated in patient cohorts also suitable for surgical therapy [11–16]. Our finding that percutaneous edge-to-edge repair could be safely performed with good clinical and echocardiographic results in surgical high-risk patients with or without
ª 2014 John Wiley & Sons Ltd
Table 5 Multivariate analysis for determinants for mortality
EuroSCORE II STS score COPD mTPG, baseline MVOA, after MitraClip LVEF ≤ 30 MR grade after MitraClip, mean
Significance
OR
95% CI
0.307 0.641 0.056 0.048 0.331 0.370 0.026
1.040 1.016 2.303 1.487 1.470 1.441 2.121
0.965–1.121 0.952–1.084 0.978–5.423 1.004–2.204 0.676–3.200 0.649–3.198 1.095–4.109
CI, confidence interval; COPD, chronic obstructive pulmonary disease; LVEF, left ventricular ejection fraction; MR, mitral regurgitation; MVOA, mitral valve orifice area; OR, odds ratio; STS, Society of Thoracic Surgeons; mTPG, mean transmitral pressure gradient. Omnibus test P = 0.002 (all variables that differed with a P-value < 0.1 at univariate analyses were included in the multivariate model).
severely impaired systolic LV function fits well with the finding of a recent study also observing sustained clinical and echocardiographic benefit after MC implantation in a patient cohort with high surgical risk [30]. None of our patients died during the procedure which is encouraging, taking into account the expected perioperative mortality of approximately 11% according to EuroSCORE II, respectively, STS score and the observed 8% mortality in a surgical cohort following restrictive mitral annuloplasty in ischemic MR [31]. Furthermore, the postoperative benefit of surgical therapy in patients with severe secondary MR in refractory end-stage heart failure is equivocal [32–34]. Therefore, no clear guideline recommendation concerning this treatment has been given [8]. Franzen et al. [35] as well as Neuss et al. [36] have recently shown a significant and over 6 months sustained improvement in NYHA class, 6-min walk test, and LV remodeling after MC implantation
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in patients with end-stage heart failure. We found a comparable clinical improvement in our patient cohort with severely impaired LV function. Interestingly, their clinical improvement during the first year after the MC procedure was very similar to that of the patients with mild-to-moderately impaired LV function. Thus, the symptomatic benefit of the percutaneous edge-to-edge repair does not seem to depend on the baseline LV function. At 12-month follow-up, the patient cohort with severely impaired LV function (EF < 30%) showed a strong trend for a higher mortality, whereas the cohort with the mild-to-moderately impaired LV function (EF > 30%) received significantly more often further surgical MV interventions. The latter might be related to the fact that patients with an ejection fraction > 30% and organic or combined MR type are considered more appropriate surgical candidates after failure of an MC repair than patients with an ejection fraction < 30% and functional MR type even if they are considerably older. On multivariate analysis, however
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Conclusion Edge-to-edge repair of severe secondary MR in patients with severely impaired LV function is similarly clinically effective and safe as repair for mixed morphologies in patients with mild-tomoderately impaired LV function. Short-term survival depends rather on the quality of repair than on the baseline LV function.
Conflict of Interest The authors declare no conflict of interest.
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73
Percutaneous Mitral Repair with the MitraClip System in Patients with Mild-to-Moderate and Severe Heart Failure: A Single-Centre Experience € kmen Turan,1 Stephan Kische,2 Ibrahim Ilkay Bozdag-Turan,1* Liliya Paranskaya,1* Ralf Birkemeyer,1 R. Go 1 2 1 1 Akin, Jasmin Ortak, Yannik Stoeckicht, Jochen Schubert, Bernd Westphal,1 Christoph A. Nienaber1 & € seyin Ince2 Hu 1 Heart Center Rostock, University Hospital Rostock, Rostock, Germany 2 Department of Cardiology, Vivantes Klinikum Friedrichshain, Berlin, Germany
Keywords Clinical outcomes; Left ventricular remodeling; MitraClip; Severe heart failure. Correspondence H. Ince, M.D., Ph.D., Heart Center Rostock, University Hospital Rostock, ErnstHeydemann-Str. 6, 18057 Rostock, Germany. Tel.: +49 (0)381 494 7797; Fax: +49 (0)381 494 7798; E-mail: [email protected]
doi: 10.1111/1755-5922.12058 *These authors contributed equally to the manuscript.
SUMMARY Aims: Edge-to-edge repair of mitral regurgitation (MR) with the MitraClip (MC) system is increasingly applied in advanced heart failure. Our objective was to compare outcomes in patients with mild-to-moderate and severe systolic heart failure. Methods and results: Between February 2010 and July 2012, 121 patients with MR of at least grade 3+ and a mean EuroSCORE II of 10.6% underwent MC implantation. Thirty-nine had a left ventricular ejection fraction (LVEF) of ≤30% (group A) and 82 of >30% (group B).Procedural success was comparable in both groups (100% vs. 95.2%) with multiple (>2) clip implantation in 34% and 25% of patients, respectively. At 12 months, absolute reduction in MR grade (2.3 vs. 2.2) and relative reduction in mitral valve orifice area (48% vs. 42%) were also comparable. New York Heart Association class had improved independent from baseline LVEF (P < 0.001). In-hospital mortality was low in both groups (2.6% vs. 2.4%), but there was a strong trend for higher 12-month mortality in group A (34% vs. 18%, P = 0.05) with no significant difference in the overall rate of major adverse cerebrovascular and cardiac events (36.8% vs. 28.9%, P = 0.38). On multivariate analysis, MR grade after repair was the strongest predictor of mortality (OR 2.121, 95% CI 1.095–4.109), whereas systolic impairment was no independent predictor. Conclusions: Percutaneous mitral valve repair led to comparable symptomatic improvement in patients with mild-to-moderately or severely reduced LV function. LV-EF < 30% was not an independent predictor of short-term mortality, which was mainly governed by residual MR after repair.
Introduction The presence of moderate to severe mitral valve regurgitation (MR) due to primary valve disease or left ventricular (LV) dysfunction is associated with increased morbidity and mortality [1–4]. Although optimal medical treatment improves symptoms and reduces severity of MR in selected candidates [5,6], surgical repair is the standard of care [7]. However, its effectiveness is not well established for severe secondary mitral regurgitation (MR) in refractory end-stage heart failure [8]. Therefore, in clinical practice, a large percentage of symptomatic patients with severe MR do not undergo conventional surgery due to severely impaired LV function [9–11]. Percutaneous edge-to-edge mitral valve (MV) repair using the MitraClip (MC) device (Abbott Laboratories, Abbott Park, IL, USA) has been developed as an alternative interventional treatment for MR. MC is the only nonsurgical system for MV repair, which has been evaluated in surgical low- and high-risk patients
66
Cardiovascular Therapeutics 32 (2014) 66–73
[11–17]. Several trials demonstrated the feasibility and safety of MC implantation as well as the effective MR reduction and symptomatic benefits after MC in different groups of patients including patients with severe LV dysfunction [18–24]. The symptomatic improvement even in patients with end-stage heart failure raises the question of the importance of impaired LV function for patient selection for the MC procedure. We therefore thought to compare the outcome of patients with mild-to-moderate and severe systolic heart failure in a single-center cohort of 121 MC patients.
Materials and Methods Study Population From February 2010 to December 2012, 121 patients with severe MR underwent MC implantation at the University Heart Center in Rostock, Germany. This population represents the entire cohort
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treated with MC at our institution and includes patients during our learning curve. All data were prospectively collected and analyzed in a computerized database. Treatment for MR was indicated according to current guidelines [25] and therapeutic approach discussed with the interdisciplinary heart-team. Surgical risk was assessed with the logistic EuroSCORE [26] and the Society of Thoracic Surgeons (STS) mortality risk calculation [27]. Exclusion criteria for MC implantation included significant mitral stenosis and acute endocarditis. The investigation conforms to the principles outlined in the Declaration of Helsinki. The local ethical committee approved the study protocol. All patients gave written informed consent for the MC procedure and follow-up.
Preoperative/Perioperative Evaluation and Treatment As a part of preinterventional screening, patients underwent echocardiography and invasive cardiac evaluation with coronary angiography, left ventriculography, and right-heart catheterization. All procedures were performed as previously described [20–23] in a hybrid operation theater under general anesthesia using fluoroscopic and transesophageal 2- and 3-dimensional echocardiographic guidance. The number of clips to be implanted was at the discretion of the primary operator.
Postintervention aspirin 100 mg and clopidogrel 75 mg were administered for 6 months. Patients with an indication to take vitamin K antagonists underwent individualized anticoagulation management.
Echocardiographic Evaluation Echocardiographic measurements were taken prior to the MC procedure, during the procedure, and immediately after and at 12-month follow-up. Severity of MR was graded according to current guidelines [28]. Grading criteria for postprocedural MR were adapted to the quantitative assessment of severity in percutaneous MV repair as reported by Foster et al. [29]. Measurements of LV volumes and left ventricular ejection fraction (LVEF) were taken using the biplane Simpson’s method. The mitral valve orifice area (MVOA) was assessed using planimetry (2D and 3D/ QULAB-Philips) intraoperatively, before and after clip implantation; in addition, the pressure half-time method was used at discharge.
Follow-Up Clinical and complete echocardiographic follow-up was performed baseline, at discharge, and 12 months after the procedure. Data concerning re-interventions and cardiac re-hospitalizations were collected together with information about major cardiac and
Table 1 Baseline clinical characteristics of both groups
Age, years SD Male gender, n (%) BMI (kg/m2) SD, n (%) EuroSCORE II SD STS score SD Ischemic cardiomyopathy, n (%) Dilated cardiomyopathy, n (%) Device therapy (ICD), n (%) MR type, n (%) Functional Organic/combined Previous cardiac surgery, n (%) Prior acute decompensate heart failure, n (%) Previous stroke, n (%) COPD, n (%) Diabetes mellitus, n (%) Prior neoplasia, n (%) Hypertension, n (%) Atrial fibrillation, n (%) NYHA class III or IV, n (%) Chronic renal failure GFR (mL/min/1.73 m2) SD GFR < 30 mL/min/1.73 m2 GFR 30–50 mL/min/1.73 m2
All patients (n = 121)
Patients with EF ≤ 30 (n = 38)
Patients with EF > 30 (n = 83)
77 7 69 (57.0) 26 5 10.6 5.6 10.9 6.4 51 (42.1) 21 (17.4) 15 (12.4)
74 8 26 (68.4) 25 4 12.7 6.1 13.0 6.7 23 (60.5) 15 (39.5) 10 (26.3)
79 6 43 (51.8) 27 5 9.7 5.2 10.0 6.0 28 (33.7) 6 (7.2) 5 (6.0)
60 mmHg, n (%) LVEDD, mm SD LVESD, mm SD LVEDV, mL SD LVESV, mL SD MR grade acute, mean SD 12-month follow-up (n = 117) LVEF, % SD Annulus diameter, mm SD MVOA, cm2 SD mTPG, mmHg SD SPP, mmHg SD SPP > 60 mmHg, n (%) LVEDD, mm SD LVESD, mm SD LVEDV, mL SD LVESV, mL SD MR grade acute, mean SD
Patients with EF ≤ 30 (n = 38)
42 3.9 5.2 2.3 50 28 59 46 161 102 3.4
16 0.3 0.9 0.8 13 (23.1) 9 11 71 65 0.5
23 4.0 5.8 2.3 53 11 66 55 220 165 3.4
44 3.8 3.0 3.3 42 6 58 45 146 90 1.1
16 0.3 0.6 1.3 12 (5.0) 9 11 67 52 0.6
46 3.7 3.0 3.3 40 4 57 43 142 88 1.4
15 0.3 0.6 1.2 10 (3.7) 9 11 63 49 0.8
5 0.2 0.8 0.8 12 (28.9) 10 10 78 67 0.5
Patients with EF > 30 (n = 83)
P
11 0.3 0.8 0.9 13 (20.5) 8 10 48 36 0.5
30
Follow up
Figure 3 Influence of MitraClip treatment on New York Heart Association (NYHA) class at 12-month follow-up in patients with mildto-moderate and severe heart failure. MitraClip treatment lead to improvement in NYHA class at discharge and 12-month follow-up in both groups. No significant differences in NYHA at discharge and 12-month follow-up between both groups.
70
81.9%
0.8
NYHA
20 10
1.0
P = 0.17
P = 0.24
40 30
61
Cumulative survival
NYHA (%)
50
62
61
60
EF30 1000
Figure 4 One-year cumulative survival for group A (EF < 30%) and group B (EF > 30%). No significant difference of 1-year cumulative survival was performed between both groups.
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Table 4 Clinical outcome at 12-month follow-up
NYHA class III/IV, (%) MACCE, n (%) MACCE (excluding MV surgery), n (%) Death, n (%) Procedural, n (%) In-hospital, n (%) Thirty days, n (%) Myocardial infarction, n (%) CVA, n (%) Major bleeding, n (%) MV surgery total, n (%) Acute Elective CHF requiring hospitalization, n (%) New MR grade 3, n (%)
Cumulative incidence
Patients with EF ≤ 30 (n = 38)
Patients with EF > 30 (n = 83)
P-value
11 38 30 28 0 3 4 3 0 7 9 1 8 27 10
6 14 14 13 0 1 1 2 0 4 0 0 0 10 4
5 24 16 15 0 2 3 1 0 3 9 1 8 17 6
0.17 0.38 0.059 0.051 – 0.94 0.78 0.18 – 0.13 0.035 0.50 0.048 0.47 0.64
(9.1)/1 (0.8) (31.4) (24.8) (23.1) (0) (2.5) (3.3) (3.4) (0) (5.8) (7.4) (0.8) (6.6) (22.3) (9.3)
(15.8)/0 (0) (36.8) (36.8) (34.2) (0) (2.6) (2.6) (5.3) (0) (10.5) (0.0) (0.0) (0.0) (26.3) (11.1)
(6.0)/1 (1.2) (28.9) (19.3) (18.1) (0) (2.4) (3.6) (1.2) (0) (3.6) (10.8) (1.2) (9.6) (20.5) (8.3)
CHF, congestive heart failure; CVA, cerebro-vascular accident; MACCE indicates major adverse cardiovascular and cerebrovascular events (defined as the composite of death, myocardial infarction, stroke, mitral surgery, and major bleeding); MR, mitral regurgitation; MV, mitral valve; NYHA, New York Heart Association.
in patient with EF < 30% (34% vs. 18%, P = 0.05). Moreover, 1-year cumulative survival curve showed no significant difference between both groups (65.8% vs. 81.9%; Figure 4). The cause of death in high-risk group (EF < 30%) was 38% cardiac (heart failure/myocardial infarction) and 62% noncardiac (pneumonia/ sepsis/gastrointestinal bleeding/chronic obstructive pulmonary disease [COPD]). In spite of that MACCE with and without MV surgery at 12 months did not differ significantly (36.8% vs. 28.9%, P = 0.38 and 36.8% vs. 19.3%, P = 0.059; Table 4) because patients with EF > 30% had significantly more often MV surgery during follow-up (0% vs. 9.6%, P = 0.048). Indication for open MV surgery in nine patients was new MR grade 3 (n = 6), partial leaflet detachments (n = 2), and significant mitral stenosis (n = 1).
Predictors of Mortality Multivariate analysis identified residual MR grade after MC procedure as strongest predictor of 12-month mortality (OR 2.121, 95% CI 1.095–4.109). Baseline mTPG (OR 1.487, 95% CI 1.004–2.204) was also an independent predictor. EF < 30% however was not an independent predictor of mortality (Table 5).
Discussion We compared the effect of MC treatment on MR, LV remodeling, clinical symptoms, and outcomes in patients with mild-tomoderate and severe heart failure in a prospective single-center registry. The feasibility and safety of MC treatment was initially demonstrated in patient cohorts also suitable for surgical therapy [11–16]. Our finding that percutaneous edge-to-edge repair could be safely performed with good clinical and echocardiographic results in surgical high-risk patients with or without
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Table 5 Multivariate analysis for determinants for mortality
EuroSCORE II STS score COPD mTPG, baseline MVOA, after MitraClip LVEF ≤ 30 MR grade after MitraClip, mean
Significance
OR
95% CI
0.307 0.641 0.056 0.048 0.331 0.370 0.026
1.040 1.016 2.303 1.487 1.470 1.441 2.121
0.965–1.121 0.952–1.084 0.978–5.423 1.004–2.204 0.676–3.200 0.649–3.198 1.095–4.109
CI, confidence interval; COPD, chronic obstructive pulmonary disease; LVEF, left ventricular ejection fraction; MR, mitral regurgitation; MVOA, mitral valve orifice area; OR, odds ratio; STS, Society of Thoracic Surgeons; mTPG, mean transmitral pressure gradient. Omnibus test P = 0.002 (all variables that differed with a P-value < 0.1 at univariate analyses were included in the multivariate model).
severely impaired systolic LV function fits well with the finding of a recent study also observing sustained clinical and echocardiographic benefit after MC implantation in a patient cohort with high surgical risk [30]. None of our patients died during the procedure which is encouraging, taking into account the expected perioperative mortality of approximately 11% according to EuroSCORE II, respectively, STS score and the observed 8% mortality in a surgical cohort following restrictive mitral annuloplasty in ischemic MR [31]. Furthermore, the postoperative benefit of surgical therapy in patients with severe secondary MR in refractory end-stage heart failure is equivocal [32–34]. Therefore, no clear guideline recommendation concerning this treatment has been given [8]. Franzen et al. [35] as well as Neuss et al. [36] have recently shown a significant and over 6 months sustained improvement in NYHA class, 6-min walk test, and LV remodeling after MC implantation
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in patients with end-stage heart failure. We found a comparable clinical improvement in our patient cohort with severely impaired LV function. Interestingly, their clinical improvement during the first year after the MC procedure was very similar to that of the patients with mild-to-moderately impaired LV function. Thus, the symptomatic benefit of the percutaneous edge-to-edge repair does not seem to depend on the baseline LV function. At 12-month follow-up, the patient cohort with severely impaired LV function (EF < 30%) showed a strong trend for a higher mortality, whereas the cohort with the mild-to-moderately impaired LV function (EF > 30%) received significantly more often further surgical MV interventions. The latter might be related to the fact that patients with an ejection fraction > 30% and organic or combined MR type are considered more appropriate surgical candidates after failure of an MC repair than patients with an ejection fraction < 30% and functional MR type even if they are considerably older. On multivariate analysis, however
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Conclusion Edge-to-edge repair of severe secondary MR in patients with severely impaired LV function is similarly clinically effective and safe as repair for mixed morphologies in patients with mild-tomoderately impaired LV function. Short-term survival depends rather on the quality of repair than on the baseline LV function.
Conflict of Interest The authors declare no conflict of interest.
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