Impact of Pulmonary Hypertension on Outcomes in Patients With Functional Mitral Regurgitation Undergoing Percutaneous Edge-to-Edge Repair




Preexisting pulmonary hypertension (PH) is associated with poor outcomes after surgical mitral valve repair for functional mitral regurgitation (FMR). However its clinical impact on MitraClip therapy remains unknown. The aim of this study was therefore to evaluate the impact of preexisting PH on MitraClip therapy for patients with FMR. Ninety-one consecutive patients who had FMR and who underwent the MitraClip procedure were studied. They were divided into 2 groups on the basis of pulmonary artery systolic pressure: the PH group (n = 48) and the non-PH group (n = 43). PH was defined as pulmonary artery systolic pressure >50 mm Hg using Doppler echocardiography. Procedural success (defined as magnetic resonance reduction to grade 2+ or less) and 30-day mortality were similar in the 2 groups. At 12 months, New York Heart Association functional class had improved to class I or II in most patients in the PH (from 2.9% to 94.3%) and non-PH (from 9.4% to 96.9%) groups. The mean pulmonary artery systolic pressure of the PH group significantly decreased from baseline but remained higher than that of the non-PH group (50.8 ± 15.3 vs 36.7 ± 11.6 mm Hg, p <0.001). After a mean of 25.0 ± 16.9 months of follow-up, Kaplan-Meier analysis demonstrated significantly higher all-cause mortality in the PH group. In Cox regression analysis, preexisting PH was the most powerful predictor of all-cause mortality (hazard ratio 3.731, 95% confidence interval 1.653 to 8.475, p = 0.002). In conclusion, MitraClip therapy reduced FMR and alleviated symptoms with an excellent early safety profile in the PH and non-PH groups. However, preexisting PH was associated with worse all-cause mortality.


Highlights





  • The presence of PH did not affect procedural success.



  • The presence of PH did not decrease the safety profile of the MitraClip.



  • The MitraClip improved pulmonary artery pressure in patients with PH.



  • Improvement of 12-month clinical outcomes was observed even with the presence of PH.



  • PH was associated with worse long-term mortality.



Functional mitral regurgitation (FMR) is commonly seen in patients with left ventricular (LV) dysfunction and even if mild is associated with limited quality of life and worse mortality. Surgical repair of the mitral valve (MV) is effective to reduce FMR and improve the quality of life. However, this has been underused because of a lack of evidence of survival benefit and high-risk features in the target patient population. Percutaneous edge-to-edge repair with the MitraClip system (Abbott Vascular, Menlo Park, California) is a catheter-based therapy to treat patients with moderate to severe or severe mitral regurgitation (MR). This novel device demonstrated comparable improvement of clinical outcomes compared with conventional MV surgery and had a better safety profile than surgery. Recent studies support the excellent safety profile and potential clinical benefit of the MitraClip procedure for patients with severe FMR. Previous studies reported that preexisting pulmonary hypertension (PH) was strongly related to adverse cardiac events after MV surgery for FMR. However the impact of preexisting PH on procedural and clinical outcomes has not been reported in patients who undergo the MitraClip procedure. Therefore, the aim of this study was to evaluate the effect of preexisting PH on the clinical outcomes of patients who underwent the MitraClip procedure for FMR.


Methods


From January 2006 to June 2012, 91 consecutive patients underwent the MitraClip procedure for treatment of clinically significant FMR. FMR was defined as MR caused by incomplete leaflet coaptation in the presence of normal MV anatomy and regional or global LV remodeling. Ischemic MR was defined as MR as a consequence of chronic myocardial ischemia or myocardial infarction. All patients underwent the MitraClip procedure under the EVEREST II clinical trial (n = 15), the REALISM registry (a continued-access registry of EVEREST II; n = 68), or the compassionate-use program (n = 8). Inclusion and exclusion criteria of the EVEREST II trial were reported previously. Briefly, all patients were candidates for MV surgery with cardiopulmonary bypass, had moderate to severe (3+) or severe (4+) chronic MR with LV ejection fractions >25%, and had LV end-systolic dimensions ≤55 mm. Asymptomatic patients despite significant chronic MR were required to have new-onset atrial fibrillation, PH, or evidence of LV dysfunction (LV ejection fraction 25% to 60% or LV end-systolic dimension 40 to 55 mm). Patients who underwent the MitraClip procedure under the compassionate-use program (n = 8) met ≥1 exclusion criterion of the EVEREST II trial: LV ejection fraction <25% in 2 patients, MV area <4.0 cm 2 in 1 patient, and extreme high risk or inoperative candidate for MV surgery in 5 patients.


Percutaneous edge-to-edge repair with the MitraClip system was performed as previously described. Briefly, the 24Fr steerable guide catheter is introduced into the left atrium using femoral venous access and the transseptal approach. The clip delivery system is inserted into the left atrium through the guide catheter and positioned above the origin of the MR jet. The clip delivery system is then advanced to the LV just below the MV, and both leaflets are grasped. After adequate leaflet insertion and MR reduction, the clip is released. If necessary, a second MitraClip device is deployed for further reduction of MR. The procedure was performed under general anesthesia using transesophageal echocardiography (2- and 3-dimensional) and fluoroscopic guidance. MR reduction to grade 2+ or less was defined as procedural success in the present study.


All echocardiographic examinations were performed at our institution. The severity of MR was graded according to American Society of Echocardiography guidelines. Pulmonary artery systolic pressure (PASP) was measured using peak tricuspid regurgitation jet velocity, combined with an estimate of right atrial pressure. On the basis of the guidelines for the management of patients with valvular heart disease, PH was defined as PASP > 50 mm Hg at rest as measured by transthoracic echocardiography.


After the MitraClip procedure, patients underwent follow-up evaluations at scheduled intervals (1, 6, and 12 months and then annually) with transthoracic echocardiography per protocol at our institution. For patients who were unable to be present at follow-up, telephone interviews were conducted to establish their survival status. Death certificates or in-hospital records were collated to confirm death and its cause. All procedural and clinical data were entered into an established interventional cardiology laboratory database approved by the Cedars-Sinai Medical Center Institutional Review Board.


Continuous variables are presented as mean ± SD and categorical variables as numbers and proportions. Continuous variables were tested for a normal distribution with the Shapiro-Wilk test. Continuous variables following a normal distribution were compared using Student’s unpaired t tests for comparisons between groups and Student’s paired t tests for within-group comparisons. Continuous variables not following a normal distribution were compared using Mann-Whitney tests for comparisons between groups and Wilcoxon’s signed-rank test for within-group comparisons. Categorical variables were compared using chi-square or Fisher’s exact tests. A nonparametric repeated-measures analysis of variance (Friedman test) was used to assess differences among serial measurements of PASP in each group. Wilcoxon’s signed-rank test was applied as the post hoc test. Survival was estimated using the Kaplan-Meier method. The log-rank test was used to assess mortality between the groups. To determine predictors of all-cause death after percutaneous edge-to-edge repair, multivariate analyses of time to events was performed using a Cox proportional-hazards model. Clinical factors that were considered to have potential prognostic impact included in the analysis were as follows: age, gender, presence of symptoms classified according to New York Heart Association (NYHA) functional class, chronic atrial fibrillation, LV end-systolic dimension, the LV ejection fraction, and the severity of MR at baseline. Results are reported as adjusted hazard ratios with 95% confidence intervals. All 2-sided p values <0.05 were considered statistically significant. All statistical analyses were performed using SPSS version 20 (SPSS, Inc, Chicago, Illinois).




Results


The baseline clinical and echocardiographic characteristics are presented in Table 1 . Most patients presented in NYHA functional class III or IV in the PH and non-PH groups. Patients in the PH group were more likely to have chronic atrial fibrillation and systemic hypertension. The prevalence of chronic obstructive pulmonary disease was similar between the PH and non-PH groups. Effective regurgitant orifice area, regurgitant volume, and regurgitant fraction trended higher, and grade 4+ MR was seen more frequently in the PH group than in the non-PH group.



Table 1

Baseline characteristics






































































































































































Variable Pulmonary Hypertension p Value
No(n = 43) Yes(n = 48)
Age (years) 73.7 ± 11.5 76.5 ± 10.8 0.277
Men 58.1% (25) 64.6% (31) 0.528
Heart failure 34.9% (15) 25.0% (12) 0.303
Coronary artery disease 62.8% (27) 62.5% (30) 0.977
Myocardial infarction 32.6% (14) 31.2% (15) 0.894
Chronic atrial fibrillation 39.5% (17) 60.4% (29) 0.047
Hypertension 69.8% (30) 89.6% (43) 0.018
Diabetes mellitus 30.2% (13) 35.4% (17) 0.599
Dialysis 7.0% (3) 8.3% (4) 0.562
Chronic obstructive pulmonary disease 20.9% (9) 16.7% (8) 0.602
Percutaneous coronary intervention 25.6% (11) 35.4% (17) 0.310
Coronary artery bypass grafting 41.9% (18) 45.8% (22) 0.703
Implantable cardioverter defibrillator 14.0% (6) 6.2% (3) 0.191
NYHA functional class III/IV 93.0% (40) 97.9% (47) 0.268
STS risk score (%) 10.4 ± 7.7 11.8 ± 7.7 0.219
Echocardiography
LV ejection fraction (%) 41.9 ± 15.2 42.2 ± 17.0 0.949
LV end-diastolic diameter (mm) 56.4 ± 7.6 57.0 ± 8.1 0.717
LV end-systolic diameter (mm) 43.4 ± 10.4 43.9 ± 9.3 0.811
LA diameter (mm) 47.9 ± 6.1 50.6 ± 9.4 0.196
MR grade 0.014
MR grade 3+ 27.9% (12) 8.3% (4)
MR grade 4+ 72.1% (31) 91.7% (44)
Effective regurgitant orifice area (cm 2 ) 0.45 ± 0.1 0.52 ± 0.2 0.062
Regurgitant volume (ml) 71.0 ± 18.8 80.3 ± 35.3 (n = 47) 0.120
Regurgitant fraction (%) 61.0 ± 10.0 62.6 ± 11.5 (n = 47) 0.487
Tricuspid regurgitation pressure gradient (mmHg) 30.7 ± 9.0 48.5 ± 9.4 <0.001
Systolic PAP (mm Hg) 38.1 ± 9.8 63.5 ± 9.0 <0.001
MR etiology 0.842
Ischemic 60.5% (26) 62.5% (30)
Non-ischemic 39.5% (17) 37.5% (18)

Values are mean ± SD or % (n).

Defined as presence of significant blockage (>70%) in any of the native coronary arteries, or history of mechanical revascularization, or objective evidence of an old myocardial infarction.



As presented in Table 2 , procedural success was achieved in most patients in the 2 groups, with similar fluoroscopic times, procedural times, device times, and numbers of clips implanted. In 5 of 7 unsuccessful procedures (3 in the PH group and 2 in the non-PH group), clip implantation could not achieve MR reduction to grade 2+ or less. No clip was placed in 2 patients in the PH group. One patient did not receive a clip, because of inadequate reduction of MR. The second patient developed significant mitral stenosis (mean transmitral pressure gradient 8 mm Hg) with the first clip. In these 2 cases, the clips were removed outside the body without complications. No emergent cardiac surgery and death were observed during the procedure or subsequent hospital stay. At discharge, echocardiographic mean transmitral pressure gradient was similar between the PH and non-PH groups (3.4 ± 1.6 vs 3.4 ± 1.8 mm Hg, respectively, p = 0.964). At 30-day follow-up, although 2 patients died from noncardiac causes in the PH group, 30-day mortality was not significantly different in the PH and non-PH groups (4.2% vs 0%, p = 0.275). Two patients in the PH group developed strokes <30 days after MitraClip implantation, and both had chronic atrial fibrillation. No other major adverse events, such as myocardial infarction, renal failure, septicemia, or gastrointestinal complications requiring surgery, were observed in either group.



Table 2

Procedural and safety outcomes



















































Variable Pulmonary Hypertension p Value
No(n = 43) Yes(n = 48)
Procedural success 95.3% (41) 89.6% (43) 0.303
Fluoroscopic time (minutes) 38.6 ± 20.7 42.0 ± 22.0 0.340
Procedure time (minutes) 128.9 ± 56.7 (n = 40) 138.7 ± 76.6 (n = 43) 0.743
Device time (minutes) 99.1 ± 55.0 (n = 40) 110.3 ± 76.6 (n = 43) 0.753
No. of MitraClips implanted 0.396
1 55.8% (24) 52.1% (25)
2 44.2% (19) 43.8% (21)
Hospital stay (days) 1.3 ± 1.0 1.5 ± 1.3 0.546

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Dec 1, 2016 | Posted by in CARDIOLOGY | Comments Off on Impact of Pulmonary Hypertension on Outcomes in Patients With Functional Mitral Regurgitation Undergoing Percutaneous Edge-to-Edge Repair
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