Original Contribution

Mid-Term Clinical Outcomes Following Percutaneous Mitral Valve Edge-to-Edge Repair

Ozan M. Demir, MBBS1*; Martina Maria Ruffo, MD1*; Cosmo Godino, MD2; Marco Ancona, MD1; Francesco Ancona, MD3; Stefano Stella, MD3; Andrea R. Munafó, MD2; Antonio Sisinni, MD2; Eustachio Agricola, MD3; Antonio Colombo, MD1; Alaide Chieffo, MD1; Matteo Montorfano, MD1

*Joint first authors

Ozan M. Demir, MBBS1*; Martina Maria Ruffo, MD1*; Cosmo Godino, MD2; Marco Ancona, MD1; Francesco Ancona, MD3; Stefano Stella, MD3; Andrea R. Munafó, MD2; Antonio Sisinni, MD2; Eustachio Agricola, MD3; Antonio Colombo, MD1; Alaide Chieffo, MD1; Matteo Montorfano, MD1

*Joint first authors

Abstract: Background. Approximately 50% of patients with severe mitral regurgitation (MR) referred for surgery have prohibitive surgical risk. MitraClip (Abbott Vascular) is an alternative therapy option in these patients. The aim of this study is to evaluate mid-term outcome in patients who underwent MitraClip implantation. Methods. All consecutive patients with ≥2+ MR and high risk for conventional surgical therapy who underwent MitraClip implantation at our unit were included in the analysis. The primary endpoint was all-cause mortality and secondary endpoint was heart failure rehospitalization. Results. From October 2008 to December 2016, a total of 162 patients underwent MitraClip procedure at our unit. The mean follow-up duration was 819.8 ± 671.1 days. Acute procedural success was achieved in 141 of 162 patients (87.0%) and was not significantly different between primary and secondary MR patients (P=.09). Mortality rates were 14.4%, 28.7%, 38.7%, and 49.3% at 1 year, 2 years, 3 years, and 5 years, respectively. Rehospitalization rates for heart failure were 21.7%, 34.3%, 44.2%, and 56.6% at 1 year, 2 years, 3 years, and 5 years, respectively. At follow-up, patients exhibited significant improvement in New York Heart Association functional classification (P<.001). On multivariate analysis, baseline left ventricular ejection fraction (LVEF) <30% (odds ratio, 6.62) and baseline MR severity (odds ratio, 3.40) were the strongest predictors of mortality. Primary MR (odds ratio, 0.20) was associated with lower risk of mortality compared with secondary MR. Conclusions. Treatment of MR with MitraClip results in significant symptomatic improvement with excellent short-term results. However, 5-year mortality was 49.3%; baseline LVEF <30% and MR severity are the strongest predictors of mortality, while primary MR was a predictor for lower risk of mortality when compared with secondary MR.

J INVASIVE CARDIOL 2020;32(12):E313-E320. Epub 2020 October 10.

Key words: heart failure, MitraClip, mitral regurgitation, mitral valve disease 


Mitral regurgitation (MR) is the most prevalent valvular disease in the United States and the second most common valvular heart disease requiring surgery in Europe.1 More than 10% of individuals ≥75 years old have varying degrees of MR.2,3 Although surgical intervention has been considered the “gold standard” therapy for patients with severe symptomatic MR, the Heart Survey4 revealed that only about 50% of these patients are referred to surgery due to advanced age, comorbidities, and impaired left ventricular function. The MitraClip percutaneous mitral valve edge-to-edge repair device (Abbott Vascular) is an alternative treatment option in this patient population. The MitraClip percutaneous procedure mirrors the Alfieri edge-to-edge technique, resulting in mitral-leaflet approximation. Numerous studies have demonstrated the feasibility and safety of the MitraClip device. The EVEREST I (Endovascular Valve Edge-to-Edge Repair Study) demonstrated the feasibility, safety, and efficacy of the MitraClip device.5 Subsequently, the EVEREST II (Endovascular Valve Edge-to-Edge Repair) trial compared percutaneous repair with surgical intervention, demonstrating that percutaneous repair was less effective at reducing MR but safer than surgical treatment, and showed similar improvements in clinical outcomes.6 Recently, two large, randomized studies demonstrated conflicting outcomes. In the MITRA-FR (Percutaneous Repair With the MitraClip Device for Severe Functional/Secondary Mitral Regurgitation) study, there was no difference in rate of death or unplanned hospitalization for heart failure at 1-year follow-up in the device arm compared with the control arm.7 In the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) study, there was significant reduction in all-cause death and annualized rate of all hospitalizations at 2-year follow-up for heart failure in the deice arm as compared with the control group.8 However, the vast majority of data for the MitraClip device are principally based on treatment in patients with secondary MR, and patient outcomes beyond 1 or 2 years remain poorly defined. The aim of this study is to report mid-term clinical outcomes after percutaneous mitral valve edge-to-edge repair for severe primary and secondary MR.

Methods

Study design. This registry included consecutive patients with MR grade ≥2+ (including primary and secondary MR) who were at high risk for conventional surgical therapy and underwent mitral valve percutaneous edge-to-edge repair using MitraClip from October 2008 to December 2016 at the Interventional Cardiology Unit of San Raffaele Hospital in Milan, Italy. All patients were discussed by an interdisciplinary heart team, which included an interventional cardiologist, a cardiac surgeon, an imaging cardiologist, and an anesthesiologist. The heart team agreed that the MitraClip procedure should be performed for all patients included in this study. 

Baseline clinical data and hospital outcomes were collected via review of medical records by an independent researcher. Follow-up data were obtained via review of medical records and telephone interviews with the patient and/or family. The severity of MR was graded by transthoracic or transesophageal echocardiogram in accordance with international guidelines9 by an imaging cardiology consultant, including the following parameters: radius of proximal isovelocity surface area (PISA radius); effective regurgitant orifice area (EROA); vena contracta width; and regurgitant volume. The severity of MR was graded as 1 (mild), 2 (moderate), 3 (moderate to severe), and 4 (severe). In addition, the etiology of the MR was classified as either primary (degenerative) or secondary (functional); secondary MRs were also subclassified into ischemic and non-ischemic etiologies. 

Procedure. The MitraClip system is a 4 mm-wide, polyester-covered, cobalt-chromium, v-shaped device with 2 movable arms. The procedure is performed under general anesthesia with fluoroscopic and transesophageal echocardiographic guidance via femoral venous access. Following transseptal puncture, a steerable, 24 Fr sheath is positioned in the left atrium.10 The MitraClip catheter is then advanced across the mitral valve into the left ventricle with the clip arms opened in a perpendicular orientation to the coaptation line. When the opened arms are drawn back, the leaflets fall into the clip and are secured between the arms and the grippers, which creates a double-orifice valve. At this point, if there was acceptable reduction in the severity of MR without significant increase in mitral transvalvular gradients, the MitraClip was released. In patients with suboptimal results, a second MitraClip was implanted and the patient was re-evaluated; a third MitraClip was implanted if necessary.11 

Endpoint and definitions. Procedural success was defined as a reduction in the severity of MR to ≤ moderate (≤2+) without complications.6 Clinical and echocardiographic follow-up exams were performed at discharge and subsequently at outpatient visit and/or telephone consultation. The primary endpoint was all-cause mortality at numerous time intervals from the procedure (1, 2, 3, and 5 years). The secondary endpoint was heart failure rehospitalization at numerous time intervals from the procedure (1, 2, 3, and 5 years). Other endpoints included clinical symptoms and echocardiographic parameters following the procedure, principally New York Heart Association (NYHA) functional class, severity of MR, and left ventricular ejection fraction (LVEF). Follow-up echocardiograms were performed at the time of last clinical follow-up.

Statistical analysis. Results for continuous variables are expressed as mean ± standard deviation and compared using Student’s 2-tailed t-tests. Results for categorical variables are expressed as frequency (percentage) and compared using the Chi-square or Fisher’s exact test. Freedom from death and freedom from rehospitalization for heart failure were presented as Kaplan-Meier curves and log-rank test to evaluate differences between groups. MR severity and NYHA functional class were compared between different time points using Bowker’s test. Multivariate logistic regression analysis with backward stepwise selection of variables was performed to identify independent predictors of mortality; P-value for entry was set at .05 and P-value for exit was set at .10. The model included the following prespecified patient predictors: age, sex, primary MR, ischemic secondary MR, logistic EuroScore, hypertension, hypercholesterolemia, diabetes mellitus, previous myocardial infarction (MI), coronary artery disease (CAD), previous percutaneous coronary intervention (PCI), previous coronary artery bypass graft (CABG), chronic kidney disease (CKD), chronic obstructive pulmonary disease (COPD), NYHA functional class, baseline LVEF, baseline LVEF <60%, baseline LVEF <30%, baseline MR severity, postprocedural MR >2, length of hospitalization (days), and procedural failure. Results of these analyses are presented as odds ratio (OR) with 95% confidence interval (CI). For all tests, a value of P<.05 was considered significant. All analyses were performed using SPSS 24.0 (IBM) and Prism GraphPad 7.0 (GraphPad Software).

Results

Baseline clinical characteristics and echocardiographic parameters. From October 2008 to December 2016, a total of 162 patients (mean age, 74.8 ± 8.3 years) were treated with percutaneous mitral valve edge-to-edge repair at our unit. Secondary MR was the most common etiology (80%); of these, 57% were due to underling ischemic cardiomyopathy. Baseline clinical characteristics and echocardiographic parameters are outlined in Table 1. There was higher prevalence of men (77% vs 59%; P<.001), diabetes mellitus (35% vs 19%; P<.001), hypertension (72% vs 66%; P<.001), hypercholesterolemia (59% vs 38%; P<.001), COPD (26% vs 22%; P<.001), CAD (72% vs 31%; P<001), prior MI (58% vs 9%; P<.001), prior PCI (55% vs 25%; P<.001), and prior CABG (25% vs 9%; P<.001) in patients with secondary MR compared with primary MR, respectively. There was a trend toward higher NYHA functional class in secondary MR patients compared with primary MR patients (2.7 ± 0.7 vs 2.5 ± 0.8, respectively; P=.09) However, in secondary MR patients, there was higher prevalence of NYHA functional class ≥3+ dyspnea and previous hospitalization for heart failure (89% vs 41% in primary MR patients; P<.001). Patients with secondary MR had higher logistic EuroScores (23.3 ± 18.2 vs 14.7 ± 10.5 in primary MR patients; P<.01). Patients with secondary MR had lower LVEF (31.3 ± 11.7% vs 61.8 ± 7.0%; P<.001), larger left ventricular end diastolic volume (LVEDV) (209.7 ± 73.2 mL vs 114.1 ± 28.6 mL; P<.001), and larger left ventricular end systolic volume (LVESV) (145.0 ± 66.6 mL vs 45.8 ± 18.7 mL; P<.001) compared with patients with primary MR. Indexed LVEDV was 108.3 ± 41.4 mL/m2 in the whole population and remained higher in patients with secondary MR compared with primary MR (116.0 ± 40.0 mL/m2 vs 67.3 ± 18.5 mL/m2, respectively; P<.001). At baseline, 95% of secondary MR patients and 100% of primary MR patients had MR graded ≥3+ on echocardiogram (P=.20).

Procedural and in-hospital outcomes. Acute procedural success was achieved in 141 of 162 patients (87.0%) and was not significantly different between primary and secondary MR patients (P=.09). From these, 1 clip was implanted in 62 patients (38%), 2 clips were implanted in 76 patients (47%), and 3 or more clips were implanted in 3 patients (2%), with no difference between primary and secondary MR patients.  Overall, in-hospital mortality occurred in 9 of 162 patients (5.5%). Four of these patients were due to cardiac etiology. No MI or stroke was observed. Four patients (2.4%) had postprocedural acute kidney injury. Two patients (1.2%) had major systemic infection. At discharge, echocardiographic assessment revealed that 11.7% of patients had MR grade >2+ and 88.3% had MR grade ≤2; there was no difference between primary and secondary MR patients (P=.17). The mean length of hospital stay was 6.7 ± 4.6 days.

Follow-up and clinical outcomes. Clinical follow-up data were available in 150 patients (93%). The mean follow-up duration was 819.8 ± 671.1 days. Rates of mortality were 14.4%, 28.7%, 38.7%, and 49.3% at 1 year, 2 years, 3 years, and 5 years, respectively, without significant differences between primary and secondary MR patients at 1 year (P=.69) and 5 years (P=.22). The overall Kaplan-Meier probability of survival at 5 years was 50.7% (Figure 1A). Of the deaths, 23.3% were deemed cardiac in origin, 4% were classified as sudden unexpected death, and 76.7% were deemed non-cardiovascular in nature. Rates of re-hospitalization for heart failure were 21.7%, 34.3%, 44.2%, and 56.6% at 1 year, 2 years, 3 years, and 5 years, respectively, without significant differences between primary and secondary MR patients at 1 year (P=.43) and 5 years (P=.13). Conversely, the probability of being free from readmission was 43.4% (Figure 1B). Reintervention following the initial MitraClip procedure was necessary in the following patients: 1 (0.7%) underwent mitral surgery; 1 (0.7%) had repeat MitraClip procedure; and 5 (3.3%) underwent placement of a left ventricular assist device. No significant differences were observed between groups in terms of reintervention. 

Patients are stratified by NYHA functional class during follow-up in Figure 2A. At the last follow-up, patients exhibited a significant improvement (P<.001) in NYHA classification, with most patients (60.7%) in NYHA functional class II or lower. Reduction in MR immediately post procedure (baseline), at hospital discharge, and at last follow-up exam is shown in Figure 2B. There was a significant improvement in MR at discharge (P<.001), with only 11.7% of patients classified as MR >2+. This effect persisted (P<.001) at the last follow-up visit, with 39.8% of the patients with MR>2+ and the vast majority (60.2%) with MR ≤2+.

Echocardiographic follow-up. Table 2 illustrates echocardiographic parameters before and after MitraClip procedure. There were no significant changes in LVEF, LVEDV, LVESV, or left atrial volumes at follow-up compared with baseline in both secondary MR and primary MR groups. However, there was a reduction in systolic pulmonary artery pressure in secondary MR patients at follow-up compared with baseline (49.6 ± 15.2 mm Hg at baseline vs 45.4 ± 14 mm Hg at follow-up; P=.04). Indexed LVEDV was 108.3 ± 41.4 mL/m2 for the whole population and 116.0 ± 40.0 mL/m2 in patients with secondary MR.

Predictors of all-cause death. Table 3 presents analyses for the prediction of all-cause mortality. On multivariate analysis, age (OR, 1.10; P<.001), logistic EuroScore (OR, 1.04; P=.01), baseline LVEF <30% (OR, 6.62; P<.001), and baseline MR severity (OR, 3.40; P=.03) were predictors of mortality. Primary MR (OR, 0.20; P=.05) was associated with lower risk of mortality compared with secondary MR. There was a trend toward postprocedural MR >2 being a predictor for mortality (OR, 3.57; P=.09). Ischemic functional MR, length of hospitalization, and procedural failure were not predictors of mortality. 

Discussion

The main findings of our study are as follows: (1) 5-year mortality rate of patients undergoing MitraClip procedure was 49%; (2) 5-year rate of rehospitalization for heart failure was 57%; (3) there was an improvement of NYHA functional class (P<.001) during mid-term follow-up for both secondary MR and primary MR, with most patients (60.7%) in NYHA functional class II or lower; (4) a recurrence of MR >2+ occurred in 39.8% of patients during follow-up; (5) baseline LVEF <30% and baseline MR severity were the strongest predictors of mortality; and (6) primary MR was a predictor for lower mortality risk compared with secondary MR.

Our study population has clinical characteristics similar to other registries and trials, such as the ACCESS-EU (Percutaneous Mitral Valve Interventions in the Real World European Population) registry,12 the TRAMI (Transcatheter Mitral Valve Interventions) registry,13 and the TCVT (Transcatheter Valve Treatment) registry.14 On the other hand, patients treated are very different from the initial EVEREST5 cohort. In our study, MitraClip patients were older than in the EVEREST II study, had lower LVEF (37.4 ± 16.3% vs 60.0 ± 10.1%), and had the opposite distribution of MR etiology, with prevalence of secondary MR in 80% of our patients vs 27% of EVEREST II patients.6 However, the prevalence of secondary MR in our study was comparable with the patient populations in the TRAMI registry (71%),13 the TCVT registry (72%),14 and the ACCESS-EU registry (77%).12 It is important to note that previous studies, akin to our study, demonstrate that primary and secondary MR are two conditions that differ from each other in several ways. Principally, baseline patient characteristics of patients affected by secondary MR resulted in significantly higher cardiovascular risk profiles compared with patients with primary MR. Moreover,  patients with secondary MR are characterized by significantly lower LVEF and higher LVEDD and LVEDV, in keeping with the underlying pathophysiological mechanisms of the 2 etiologies.15

Procedural success was achieved in 141 of 162 patients (87.0%), which is higher than in the EVEREST II study6 (77%), but lower than in the ACCESS-EU registry12 (91%), TRAMI registry13 (97%), and TCVT registry14 (95.4%). This may be explained by the fact that our study enrolled patients from 2008 to 2016; if we take into consideration only patients who underwent MitraClip from 2012 to 2016, the procedural success achieved was 90.1%, reflecting the growing experience with this complex technique over time. The mean length of hospital stay in our study was 6.7 ± 4.6 days, 9 days in the TRAMI registry,13 6 days in the ACCESS-EU registry,12 and 5 days in the TCVT registry.14 

Echocardiography at time of discharge revealed the presence of MR >2+ in 19 of 162 patients (11.7%), whereas 143 of 162 patients (88.3%) had no MR or mild MR. There was a great improvement in MR (P<.001) at discharge, and this effect persisted (P<.001) at the last follow-up, with 39.8% of patients with MR >2+. Furthermore, NYHA functional class showed improvement (P<.001) during follow-up for both secondary MR and primary MR patients, with most patients (60.7%) in NYHA functional class II or lower. Hence, the present study confirms that transmitral valve repair confers sustained clinical benefits, as already observed in other registries.

The 1-year mortality rate was 14.4%, which is comparable to the mortality reported in the most recent registries (19.8% in the TRAMI registry,13 17.3% in the ACCESS-EU registry,12 and 15.3% in the TCVT registry14), with no significant difference in the rates of mortality between secondary MR and primary MR patients (P=.68). Our study has longer follow-up in comparison with previous studies; this allowed us to use Kaplan-Meier curve analysis to determine the mortality rate up to 5 years as 49.3%; conversely, the probability of survival at 5 years was 50.7%. The rate of heart failure rehospitalization was similar to other studies (21.7% at 1 year in our study and 22.8% in the TCVT registry).14 At 2 years, 3 years, and 5 years, the rates of rehospitalization increased to 34.3%, 44.2%, and 56.6%, respectively.

Recently, Ozturk et al16 evaluated the impact of MitraClip implantation on 256 patients who were high surgical risk with severe MR. Despite high procedural success rates of 91.3%, at 5-year follow-up the authors reported no significant changes in LV volumes or LVEF following MitraClip procedure. Importantly, the authors reported sustained reduction of MR (MR ≤2) at 5 years in 74% of patients and that the majority of patients (65.4%) had improved NYHA functional class ≤II. Of note, the baseline characteristics of this population were lower risk than our population, including better LVEF and lower LV volumes. At 5 years, all-cause mortality was 16% and was significantly higher in patients with secondary MR. This is remarkably better than our study, which may be secondary to the baseline patient characteristics outlined. Furthermore, Buzzatti et al17 showed higher 5-year mortality (about 50%) with good mid-term results, including reduction of MR and improved symptoms in 339 patients with relevant MR. In line with the current results, they found markedly worse outcomes and higher mortality in patients with secondary MR associated with worse LV remodeling and function. EVEREST II 5-year outcomes18 demonstrated that the rate of postprocedural adverse events declined from 30-day to 1-year follow-up and remained stable thereafter up through 5 years. At 5 years, reduction in MR severity to ≤2 was observed in 75% of patients, and there was reduction in LVEDV and LVESV compared with baseline.

Two large, randomized studies have been published on the utility of MitraClip in patients with severe MR: the MITRA-FR7 and COAPT8 studies. The MITRA-FR study included 304 patients with severe secondary MR, defined according to European guidelines9 as EROA >20 mm2 or right ventricular (RV) volume >30 mL/beat. At baseline, the mean EROA was 31 ± 10 mm2 and the mean indexed LVEDV was 135 ± 35 mL/m2. At 1-year follow-up, there was no difference in rate of death or unplanned hospitalization for heart failure in the device arm compared with the control arm (24.3% vs 22.4% and 48.7% vs 47.4%, respectively).7 The COAPT study included 614 patients with severe secondary MR, defined according to United States guidelines19 as EROA >30 mm2 or RV volume >45 mL/beat. At baseline, the mean EROA was 41 ± 15 mm2 and the mean indexed LVEDV was 101 ± 34 mL/m2. At 2-year follow-up, there was a significant reduction in any-cause death rate in the device arm (29.1% vs 46.1% in the control group; P<.001). Furthermore, the annualized rate of all hospitalizations for heart failure was 35.8% per patient-year in the device group vs 67.9% per patient-year in the control group (P<.001).8 In comparison, in our study, the indexed LVEDV was 108.3 ± 41.4 mL/m2 for the whole population and 116.0 ± 40.0 mL/m2 in patients with secondary MR, and mortality rates at 1 year and 2 years were 14.4% and 28.7%, respectively. Hence, our baseline population and mortality outcomes were in keeping with the COAPT trial population.

Study limitations. Our study presents some limitations. First, its observational nature makes it susceptible to the usual types of bias ascribed to this design. Second, there is no control or surgical group for comparison of outcomes. Third, the number of patients in the primary MR group is relatively low. However, this is a real-world population, where the principal use of MitraClip has been focused on secondary MR. Fourth, the follow-up period varies between patients; again, this is a reflection of our real-world study population undergoing MitraClip procedure and we report follow-up that is significantly longer than previous studies. Finally, the variance in patient follow-up also affected the time point at which echocardiograms were performed between patients. Hence, this heterogenicity in time points may have contributed to the similarities in the vast majority of echocardiographic parameters between baseline and follow-up. 

Conclusion

Treatment of MR with MitraClip results in significant symptomatic improvement, with excellent short-term results. However, we observed a 5-year mortality rate of 49%, as well as a 5-year rehospitalization for HF rate of 57%. Baseline LVEF <30% and baseline MR severity are the strongest predictors of mortality, while primary MR compared with secondary MR was a predictor for lower risk of mortality. 

*Joint first authors.


From the 1Interventional Cardiology Unit; 2Cardiology Unit; and 3Echocardiography Unit, Cardio-Thoracic-Vascular Department, San Raffaele Scientific Institute IRCCS, Milan, Italy.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.

Manuscript accepted March 23, 2020.

Address for correspondence: Alaide Chieffo, MD, Department of Interventional Cardiology, San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan, Italy. Email: chieffo.alaide@hsr.it

References
  1. Enriquez-Sarano M, Akins CW, Vahanian A. Mitral regurgitation. Lancet. 2009;373:1382-1394. 
  2. Savage DD, Garrison RJ, Devereux RB, et al. Mitral valve prolapse in the general population. I. Epidemiologic features: the Framingham study. Am Heart J. 2018;106:571-576. 
  3. Savage DD, Devereux RB, Garrison RJ, et al. Mitral valve prolapse in the general population. 2. Clinical features: the Framingham study. Am Heart J. 2018;106:577-581. 
  4. Iung B, Baron G, Butchart EG, et al. A prospective survey of patients with valvular heart disease in Europe: the Euro heart survey on valvular heart disease. Eur Heart J. 2003;24:1231-1243. 
  5. Feldman T, Kar S, Rinaldi M, et al. Percutaneous mitral repair with the MitraClip system. Safety and midterm durability in the Initial EVEREST (endovascular valve edge-to-edge repair study) cohort. J Am Coll Cardiol. 2009;54:686-694. 
  6. Feldman T, Foster E, Glower DD, et al. Percutaneous repair or surgery for mitral regurgitation. N Engl J Med. 2011;364:1395-1406. 
  7. Obadia J-F, Messika-Zeitoun D, Leurent G, et al. Percutaneous repair or medical treatment for secondary mitral regurgitation. N Engl J Med. 2018;379:2297-2306. 
  8. Stone GW, Lindenfeld J, Abraham WT, et al. Transcatheter mitral-valve repair in patients with heart failure. N Engl J Med. 2018;379:2307-2318.
  9. Baumgartner H, Falk V, Bax JJ, et al. 2017 ESC/EACTS guidelines for the management of valvular heart disease. Eur Heart J. 2017;38:2739-2791.
  10. Silvestry FE, Rodriguez LL, Herrmann HC, et al. Echocardiographic guidance and assessment of percutaneous repair for mitral regurgitation with the Evalve MitraClip: lessons learned from EVEREST I. J Am Soc Echocardiogr. 2007;20:1131-1140. 
  11. Alegria-Barrero E, Chan PH, Foin N, et al. Concept of the central clip: when to use one or two MitraClips®. EuroIntervention. 2014;9:1217-1224.
  12. Maisano F, Franzen O, Baldus S, et al. Percutaneous mitral valve interventions in the real world: early and 1-year results from the ACCESS-EU, A prospective, multicenter, nonrandomized post-approval study of the MitraClip therapy in Europe. J Am Coll Cardiol. 2013;62:1052-1061. 
  13. Puls M, Lubos E, Boekstegers P, et al. One-year outcomes and predictors of mortality after MitraClip therapy in contemporary clinical practice: results from the German transcatheter mitral valve interventions registry. Eur Heart J. 2016;37:703-712. 
  14. Nickenig G, Estevez-Loureiro R, Franzen O, et al. Percutaneous mitral valve edge-to-edge repair: in-hospital results and 1-year follow-up of 628 patients of the 2011-2012 pilot European Sentinel registry. J Am Coll Cardiol. 2014;64:875-884. 
  15. Chiarito M, Pagnesi M, Martino EA, et al. Outcome after percutaneous edge-to-edge mitral repair for functional and degenerative mitral regurgitation: a systematic review and meta-analysis. Heart. 2018;104:306-312. 
  16. Öztürk C, Friederich M, Werner N, Nickenig G, Hammerstingl C, Schueler R. Single-center five-year outcomes after interventional edge-to-edge repair of the mitral valve. Cardiol J. 2019 July 17 (Epub ahead of print). 
  17. Buzzatti N, Denti P, Scarfò IS, et al. Mid-term outcomes (up to 5 years) of percutaneous edge-to-edge mitral repair in the real-world according to regurgitation mechanism: a single-center experience. Catheter Cardiovasc Interv. 2019;94:427-435. 
  18. Kar S, Feldman T, Qasim A, et al. Five-year outcomes of transcatheter reduction of significant mitral regurgitation in high-surgical-risk patients. Heart. 2019;105:1622-1628. 
  19. Nishimura RA, Otto CM, Bonow RO, et al. 2017 AHA/ACC focused update of the 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2017;70:252-289. 
/sites/invasivecardiology.com/files/articles/images/E313-E320%20Demir%20JIC%202020%20Dec%20wm%20copy.pdf