Mid-term results of mitral valve repair using flexible bands versus complete rings in patients with degenerative mitral valve disease: a prospective, randomized study

In this prospective, randomized study, 171 patients with degenerative MV disease who were scheduled for isolated MV repair in our Institute from September 2011 through September 2014 were enrolled (CONSORT flow diagram, Figure 1). Participants were randomly assigned following a simple randomization procedure to complete semirigid ring (SR group) or flexible posterior annuloplasty band (FB group), according to computerized random numbers on the day before surgery. Eligible participants were adults aged 18 years or more with degenerative MV disease [7] who met the indications for MV operation according to the American College of Cardiology/American Heart Association guidelines [8]. Exclusion criteria were previous open cardiac surgery, indication for concomitant aortic valve replacement, or left ventricle (LV) impairment (ejection fraction <40%). The Local Ethics Committee approved the study design, and all the patients provided informed consent. The present study was conducted in compliance with the Declaration of Helsinki.

Mean age of the participants in each group was 57 (23–75) and 54 (19–74) years, respectively. There were no differences in sex, age, preoperative New York Heart Association (NYHA) functional class, and comorbidities (Table 1).

The primary endpoint was freedom from moderate or severe mitral regurgitation (MR) recurrence. Secondary endpoints included survival, freedom from reoperations, and freedom from severe MR recurrence. The severity of MR was evaluated and defined in accordance with the recommendations [9]. Valve-related complications were evaluated and defined in accordance with the guidelines [10].

Real-time two-dimensional/three-dimensional transesophageal echocardiography (TEE, Phillips iE33, Philips Ultrasound Inc., PA, USA) was performed after the induction of anesthesia for MV lesion estimation. Cold crystalloid cardioplegic solution (Custodiol® HTK Solution, Dr. Franz Köhler Chemie, Alsbach-Hahnlein, Germany) was used for myocardial protection with antegrade root flow.

The two most experienced surgeons in MV repair in our Institute performed the operations in the study. Surgeons were evenly split between the treatment groups. The surgical technique for MV repair was chosen according to the MV lesion (Table 2). The most common techniques were quadrangular (“sliding maneuver”) or triangular resection for posterior MV prolapse, and artificial chordal replacement (separate or loop technique) for anterior leaflet pathology. The minimally invasive approach through the right fourth intercostal space with femoral–femoral cannulation for arterial and venous lines was used in 29.4% (n = 25) and 31.4% (n = 27) of patients in the SR and FB groups, respectively.

All mitral valve repairs were performed with flexible bands (“C Flex”, CardiaMed, Penza, Russia) or complete rings (“D Ring”, CardiaMed, Penza, Russia), which routinely use since 2005. The ring size was selected according to the size of the anterior leaflet and the intertrigonal distance. In Barlow’s cases, 36–40 mm rings were used. Flexible bands were implanted along the posterior mitral semicircle with an extension to both commissures for 3–5 mm. Valve competence was assessed intraoperatively by saline test and “ink-test” (symmetrical closure line, coaptation depth ≥ 5 mm, absence of leaflet prolapse and regurgitation jet).

After bypass weaning, patients were followed-up with TEE. In cases with residual MR ≥ grade 2, cardiopulmonary bypass was re-established, and the valve was re-repaired or replaced; residual MR grade 1 (mild) was left alone. Intraoperative data and concomitant procedures are shown in Table 2.

All patients underwent TTE evaluation before discharge. In total, 170 patients were discharged and followed-up periodically by cardiologists and surgeons. After discharge, examinations were scheduled annually. When annual clinic visits were unavailable, follow-up was performed by contact with the referring cardiologist, the patient or their family. Anticoagulation therapy with an international normalized ratio (INR) target in the range of 2.5–3.0 was prescribed for all patients after surgery. The decision to stop anticoagulation therapy with Coumadin was based on echocardiography (normal left ventricle function, presence of atrial contractility) and Holter data (absence of atrial fibrillation, flutter, tachycardia) after 3 months. Echocardiograms obtained from outside physicians were re-analyzed at our Institute by the most experienced echocardiographers. Clinical follow-up was completed in 165 patients (97.1%), and five patients were lost to follow-up. Follow-up echocardiography was performed 6–12 months after the operation and every year thereafter. Seventy-nine (94.0%) of the 84 discharged patients in the SR group and 78 (90.7%) of the 86 patients in the FB group underwent follow-up TTE. The mean duration from the operation to echocardiographic follow-up was 20.2 (95% confidence interval [CI], 18.6–21.8) months. The mean clinical follow-up period was 24.7 (95% CI, 23.5–27.0) months.

Assuming 5% significance (two sided), 80% power, event rates of 20 and 5% in the complete ring and flexible band groups, respectively, and a hazard ratio for significant MR recurrence of 0.23 and expected 5% withdrawal rate, the sample size (total n = 170 in both groups) was calculated using log-rank test (Freedman method) of freedom from MR recurrences in two groups. Data are presented as mean ± SD or median with range. The variables of the two groups were compared using the unpaired t test for continuous variables with normal distribution or the Mann-Whitney U test for other distributions. To analyze the risk factors of early postoperative complications, we reviewed preoperative and intraoperative variables (Tables 1, 2, 3); a multivariate logistic regression model was used to calculate odds ratios (ORs). Estimates of survival and event-free survival for reoperation and the recurrence of significant MR were calculated using the Kaplan-Meier method and are reported with 95% CIs. Patients were censored at the time of reoperation or at the time of death. Estimates are reported with their standard errors. Comparison of the curves was established by using the log-rank test for mid-term results. To analyze risk factors of late mortality, reoperation, and MR recurrence, we reviewed preoperative and intraoperative variables (Tables 1, 2, 3); multivariable Cox proportional hazard regression models were used to calculate HRs. HRs and 95% CIs were calculated. The inclusion criterion for the multivariable model was P value ≤0.2) in the univariable analysis. The significance level in the final “multivariable” model assessed as the 0.05. Stata/MP for Windows v. 13.0 (StataCorp. 2013. Stata Statistical Software: Release 13. College Station, TX: StataCorp LP.) was used for the statistical analysis.

The data that support the findings of this study are available from Meshalkin National Medical Research Center but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publically available. Data are however available from the authors upon reasonable request and with permission of Meshalkin National Medical Research Center.

All echocardiographic parameters significantly changed from the preoperative to immediate postoperative period at discharge, except transmitral pressure gradients and LV end-systolic diameter (LVESD) (Table 3). There were no significant between-group differences in changes in LV function and left and right atria remodeling; however, transmitral peak and mean pressure gradients were significantly lower in the FB group. The mitral orifice area did not differ between the groups. The TTE before discharge revealed that 5 (5.9%) and 4 (4.7%) patients in the SR and FB groups, respectively, had grade 2 residual MR (p = 0.719). Follow-up echocardiography data at 24 months are shown in Table 3. The repeated-measures analysis of variance in the FB group revealed significant changes in LV end-diastolic diameter (LVEDD), LV end-diastolic volume (LVEDV), and LV end-systolic volume (LVESV) at discharge; moreover, these parameters and LVESD were also decreased at 24 months of follow up. Meanwhile, the LVEF significantly decreased at discharge; however, it significantly increased during the follow-up. In the SR group, there were no significant differences in LV function changes at serial examinations. We also revealed higher transmitral pressure gradients in the SR group, including significant differences in systolic pulmonary artery pressure among patients with sinus rhythm, with favorable results in the FB group.

At the latest follow-up, 158 patients were alive. There were 3 late deaths among the 84 patients in the SR group (mortality 3.6%), and 4 late deaths among the 81 patients in the FB group (mortality 4.9%). The causes of death in the SR group were endocarditis (1 case), malignancy (1 case), and unknown cause (1 case); two of them were regarded as cardiac-related deaths. The causes of death in the FB group were ischemic stroke (2 cases), acute myocardial infarction (1 case), and pulmonary edema (1 case), all of which were cardiac-related. The Kaplan-Meier survival rates at 2 years were 96.0 ± 2.3% (95% CI, 88.6–98.7%) and 94.3 ± 2.8% (95% CI, 85.5–97.9%) in the SR and FB groups, respectively (Figure 2) (log-rank, p = 0.899).

The Kaplan-Meier freedom from cardiac-related death at 2 years was 97.7 ± 2.0% (95% CI, 89.1–99.3%) and 94.3 ± 2.8% (95% CI, 85.5–97.9%) in the SR and FB groups, respectively (Additional file 1: Figure S1) (log-rank, p = 0.411). The multivariable Cox regression hazard model did not identify independent risk factors of late death.

Moderate or severe MR was observed in 12 (15.2%) of 79 patients and 7 (9.0%) of 78 patients in the SR and FB groups, respectively (p = 0.343). Among them, 3 patients in the SR group underwent redo MV surgery. The Kaplan-Meier estimate for freedom from recurrence of moderate or severe MR at 2 years was 85.3 ± 5.0% (95% CI, 71.9–92.6%) and 95.3 ± 2.7% (95% CI, 85.9–98.5%) in the SR and FB groups, respectively, (log-rank test, p = 0.011) (Figure 3A). The multivariable Cox proportional hazard model identified residual MR before discharge as an independent risk factor of late recurrence of significant MR (HR, 4.1; 95% CI, 1.5–11.5) (Additional file 2: Table S1).

Among them, severe MR was observed in 7 (9.7%) and 1 (1.3%) patient(s) in the SR and FB groups, respectively. The Kaplan-Meier estimate for freedom from severe MR at 2 years was 84.8 ± 6.8% (95% CI, 65.1–93.8%) and 98.7 ± 1.3% (95% CI, 90.8–99.8%) in the SR and FB groups, respectively (log-rank test, p = 0.006) (Figure 3B). The multivariable Cox proportional hazard model identified residual MR before discharge as an independent risk factor of late recurrence of severe MR (HR, 8.4; 95% CI, 1.6–43.3).

Reoperations were required in 3 patients in the SR group for partial ring dehiscence in all cases. The MV was re-repaired in 2 patients and replaced in 1 case. The Kaplan-Meier estimate for freedom from reoperation at 2 years of follow-up was 97.0 ± 2.1% (95% CI, 88.4–99.3%) and 100% in the SR and FB groups, respectively (Figure 4) (log-rank, p = 0.044). The Cox regression hazard model did not identify any preoperative or intraoperative risk factor of late reoperations.