Methods

A total of 122 patients with HF and moderate to severe MR were included. The patients were scheduled for restrictive mitral annuloplasty, accompanied by coronary artery bypass grafting if indicated. In patients with HF with idiopathic cardiomyopathy, restrictive mitral annuloplasty was performed with concomitant placement of a CorCap (Acorn Cardiovascular, St. Paul, Minnesota) cardiac support device if significant LV dilation (LV diameter >65 mm) was measured on the preoperative echocardiographic examination. All patients underwent surgery using a midline sternotomy with normothermic cardiopulmonary bypass and intermittent anterograde warm blood cardioplegia. The mitral valve was exposed through a transseptal approach. The ring size (Carpentier Edwards Physioring, Edwards Lifesciences, Irving, California) was determined after careful measurement of the height of the anterior leaflet. Then, downsizing by 2 sizes was performed (ie, when ring measured 30, the size of the annuloplasty ring was 26). The rings were inserted using 14 to 16 deep U -shaped simple horizontal sutures with Ethibond 2-0 (Ethicon, Somerville, New Jersey) or Ti-Cron 2-0 (Syneture, Norwalk, Connecticut). Tricuspid annuloplasty was performed with a Carpentier Edwards Classic or MC3 ring (Edwards Lifesciences) in patients with tricuspid regurgitation exceeding grade 2 or in the presence of a dilated tricuspid annulus >40 mm (or 21 mm/m ² indexed to the body surface area) on the echocardiogram. In all patients, the results of mitral annuloplasty were assessed by intraoperative transoesophagal echocardiography. No residual MR and the coaptation of mitral leaflets of ≥8 mm at the A2-P2 level (A2: middle scallop of the anterior mitral leaflet, P2: middle scallop of the posterior mitral leaflet) were the criteria for successful mitral valve repair. If these criteria were not fulfilled, additional downsizing was performed.

In patients undergoing surgical revascularization, the coronary artery bypass grafts were implanted before mitral valve annuloplasty. If a cardiac support device (CorCap, Acorn Cardiovascular) was used, it was applied on the beating heart, and then it was fixed by sutures to the dorsal base of the heart, along the atrioventricular groove. After completion of the mitral valve repair, the extracorporeal circulation was weaned out and the final fitting of CorCap was ensured on a full and beating heart with appropriate filling. The aim was to obtain a snug fit, without reduction of LV diameter of >10% (as measured by transesophageal echocardiography) compared to preoperative dimensions, as described earlier.

Before surgical intervention, transthoracic echocardiography (System Five or Vivid 7, GE Norway, Horten, Norway) was performed and repeated at hospital discharge and mid-term follow-up (2.6 ± 1.6 years). Transthoracic echocardiography at discharge was used to confirm the absence of MR, and the preoperative and mid-term follow-up echocardiographic examinations were used to perform measurements of LV and left atrial (LA) volumes and dimensions, geometric analysis of the left ventricle and mitral valve, and quantification of MR.

The severity of MR was quantitatively determined by proximal isovelocity surface area and by vena contracta method according to the current guidelines. The effective regurgitant orifice and regurgitant volume were calculated according to the formula. The vena contracta was defined as the narrowest part of the regurgitant jet recorded in the parasternal long-axis view.

The LV and LA volumes and LV geometry were measured according to the recommendations of the American Society of Echocardiography and European Association of Echocardiography for chamber quantification. In the parasternal long-axis view, the LV end-diastolic diameter, LV end-systolic diameter, and LA diameter were measured. The LV end-diastolic volume, LV end-systolic volume, and LV ejection fraction were estimated using Simpson’s disk method from the apical 4- and 2-chamber views. The LA volume was assessed using the area-length method. The systolic and diastolic LV sphericity indexes were calculated as the ratio between the LV short-axis diameter and the LV long-axis diameter at end-systole and end-diastole, respectively.

To evaluate the apical displacement of the mitral leaflets, the leaflet tethering lengths were measured in the apical 4- and 2-chamber views in mid-systole ( Figure 1 ). The end-diastolic and end-systolic frames were determined from the mitral leaflet closure and opening, respectively, and the middle frame was used for measurements in mid-systole. In the apical 4-chamber view, the distance between the posterior papillary muscle and median portion of the mitral annulus was measured (posterior papillary muscle tethering length in the apical 4-chamber view; Figure 1 ). In the apical 2-chamber view, the distance between the anterior and posterior papillary muscles and the contralateral part of the mitral annulus were measured (anterior papillary muscle tethering length and posterior papillary muscle tethering length in the 2-chamber view, respectively; Figure 1 ).

Measurements of PM tethering lengths, mitral tenting area, and mitral tenting height. (A) White line represents posterior PM tethering length measured in apical 4-chamber view. (B) Measurements of papillary muscle tethering lengths, as measured in 2-chamber view. White lines represent anterior and posterior PM tethering lengths measured from head of anterior and posterior PM to contralateral part of mitral annulus, respectively. (C) White line represents measurement of coaptation-to-septum distance, defined as distance between septum at hinge point of aortic valve cups and coaptation point of mitral valve leaflets. (D) Measurements of mitral tenting area and tenting height in long-axis view. Tenting area depicted by continuous white line , and tenting height corresponds to dotted line drawn between coaptation point and mitral annulus in long-axis view.

In the long-axis view, the coaptation-to-septum distance was measured in mid-systole, as the distance between the septum at the hinge point of the aortic valve cups and coaptation point of the mitral valve leaflets ( Figure 1 ). Evaluation of the geometry of the mitral valve was performed in mid-systole, as previously described. In the parasternal long-axis view, tenting area, tenting height, and coaptation length were measured. The tenting area was measured as the area enclosed between the annular line and the mitral leaflets, and the tenting height was defined as the distance between the coaptation point and the annular line ( Figure 1 ). The coaptation length was measured as the length of apposition of the anterior and posterior mitral leaflets.

The tethering of mitral leaflets was estimated by calculation of the basal mitral anterior leaflet angle (ALA _base ), the distal mitral anterior leaflet angle (ALA _tip ), and the posterior mitral leaflet angle (PLA). The ALA _base was defined as the angle between the annular plane and the basal portion of the anterior leaflet, and the PLA was defined as the angle between the annular plane and the posterior leaflet ( Figure 2 ). The ALA _tip was defined as the angle between the annular plane and the anterior leaflet tip distance (which corresponded to the distance between the median part of mitral annulus and the coaptation point; Figure 2 ). The angles were calculated according to previously reported formulas. The mitral annular area was obtained from its dimensions in the 4- and 2-chamber views, using an ellipsoid assumption.

Method of quantification of ALA _base , ALA _tip , and PLA. Measurements depicted on echocardiographic image of mitral valve in apical 4-chamber view in mid-systole. Formulas used for calculations of angles were as follows: ALA _base = (bending distance/anterior leaflet bending distance)/sinus; ALA _tip = (coaptation distance/anterior tip leaflet distance)/sinus; PLA = (coaptation distance/posterior leaflet length)/sinus.

Operative risk was calculated according to EuroSCORE. Continuous data are presented as the mean ± SD and dichotomous data as the number of patients (percentage), as appropriate. Patients were divided into 2 groups according to the presence of MR at mid-term follow-up: patients without recurrent MR if no or mild MR was observed (effective orifice regurgitant area <0.20 cm ² , regurgitant volume <30 ml/beat, and vena contracta <0.3 cm), and patients with recurrent MR if moderate or severe MR was observed (effective orifice regurgitant area ≥0.20 cm ² , regurgitant volume ≥30 ml/beat, and vena contracta ≥0.3 cm). The preoperative and mid-term follow-up echocardiographic measurements of the patients without recurrent MR were compared to those of the patients with recurrent MR. The differences in clinical and echocardiographic baseline (preoperative) characteristics between the patients with and without recurrent MR were evaluated using Student’s t tests or the chi-square tests, as appropriate. Changes (from baseline to follow-up) in the echocardiographic data were analyzed by repeated measurements analysis of variance, and the interaction between the evaluation point (preoperatively vs during follow-up) and group (patients with recurrent MR vs patients without recurrent MR) was tested.

Univariate and multivariate Cox proportional hazard regression analyses were applied to further study the relation between the baseline characteristics and recurrent MR. On multivariate analysis, the stepwise backward method was used to identify the predictors of MR, with significant univariate predictors entered as covariates. The variables were checked for colinearity, and, if the correlation coefficient between 2 variables was >0.7, only 1 variable was retained in the model. A p value <0.05 was regarded as statistically significant. Statistical analysis was performed using the Statistical Package for Social Sciences for Windows, version 16.0 (SPSS, Chicago, Illinois).

Results

The demographic, clinical, and surgical characteristics of the patients are listed in Table 1 . The mean age was 62 ± 11 years, and 61% of patients were men. Most patients (85%) had New York Heart Association functional class III or IV. Patients were receiving optimal medical treatment for HF. No clinically relevant difference was found in the demographic or clinical characteristics between the patients with recurrent MR and those without recurrent MR at mid-term follow-up.

In 37% of patients, the CorCap cardiac support device was implanted concomitantly with restrictive mitral annuloplasty ( Table 1 ). The average mitral ring size used for annuloplasty was 26; in 53% of patients, tricuspid annuloplasty was also performed. Twelve patients had chronic atrial fibrillation and underwent a perioperative atrial fibrillation ablation procedure. No clinically relevant differences were found in the surgical characteristics between the patients with and without recurrent MR.

Preoperative echocardiographic quantitative analysis of MR revealed moderate to severe MR with a mean effective regurgitant orifice area of 0.33 cm ² , regurgitant volume of 47 ml, and vena contracta of 5.5 mm ( Table 2 ).

Of 122 patients, 10 died during the perioperative period, 112 were discharged from the hospital (with MR grade 0 to 1) and 3 patients died before the mid-term echocardiographic follow-up examination. In the final analysis, 109 patients with HF were included (56 with dilated cardiomyopathy and 53 with ischemic cardiomyopathy). All 109 patients underwent echocardiographic and clinical follow-up. At the mid-term follow-up, 88 patients (81%) continued to have MR grade 0 or 1, and MR greater than grade 2 was observed in 21 patients (19%). Of the patients with recurrent MR, grade 2, 3, and 4 MR was present in 14 (13%), 6 (5%) and 1 (1%), respectively.

The LV end-diastolic and end-systolic volume decreased from 217 ± 72 ml to 167 ± 61 ml and from 162 ± 65 ml to 119 ± 55 ml, respectively (p <0.001). The LV end-diastolic diameter decreased from 66 ± 8 mm to 60 ± 10 mm (p <0.001), and the LV end-systolic diameter decreased from 59 ± 9 mm to 52 ± 12 mm (p <0.001). A slight increase in the LV ejection fraction was observed (from 27 ± 9% to 31 ± 12%, p <0.001).

The preoperative MR severity was similar in patients with and without recurrent MR ( Table 2 ). In addition, no difference was noted in the preoperative LV and LA diameters or volumes ( Table 3 ). Concerning mitral valve geometry, patients with recurrent MR presented with greater preoperative ALA _base , ALA _tip , and PLA than the patients without recurrent MR (p <0.05; Table 4 ). In addition, patients with recurrent MR had a significantly increased tenting area and tenting height before surgery, and the coaptation length was lower than that in to the patients without recurrent MR (p <0.05; Table 4 ). Furthermore, the systolic and diastolic LV sphericity indexes were greater in patients with recurrent MR than those without recurrent MR (p <0.05; Table 4 ). The posterior and anterior papillary muscle tethering length and the coaptation-to-septum distance were similar in the patients with and without recurrent MR. Finally, the mitral annulus area was similar in both groups of patients.

Table 4

Evolution of echocardiographic geometric measurements of left ventricle and mitral valve in patients without and with recurrent mitral regurgitation (MR) at mid-term follow-up

Variable	MR at Follow-Up				p Value (Time vs Group Comparison)
	No (n = 88)		Yes (n = 21)
	Preoperative	Follow-Up	Preoperative	Follow-Up
Mitral valve geometry
Basal mitral anterior leaflet angle (°)	31 ± 6	24 ± 6 ⁎	38 ± 5 ⁎	38 ± 5	<0.001
Distal mitral anterior leaflet angle (°)	12 ± 3	11 ± 3 ⁎	19 ± 3 ⁎	19 ± 4	<0.05
Posterior mitral leaflet angle (°)	40 ± 10	60 ± 11 ⁎	54 ± 9 ⁎	66 ± 9 †	0.01
Tenting area (cm 2 )	2.1 ± 0.3	1.4 ± 0.4 ⁎	2.9 ± 0.7 ⁎	2.1 ± 0.5 †	NS
Tenting height (mm)	10.2 ± 1.2	9.1 ± 1.4 ⁎	12.6 ± 2.4 ⁎	12.0 ± 1.9	NS
Coaptation length (mm)	5.5 ± 1.2	8.7 ± 1.2 ⁎	4.9 ± 1.1 ⁎	6.7 ± 1.5 †	0.001
Mitral annulus (cm 2 )	10.1 ± 2.8	5.3 ± 1.5 ⁎	10.8 ± 2.9	7.0 ± 2.5 †	<0.001
Left ventricular geometry
Sphericity index diastole	68 ± 9	60 ± 8*	75 ± 8*	71 ± 7 †	NS
Sphericity index systole	65 ± 9	57 ± 9*	72 ± 9*	69 ± 8	NS
Posterior papillary muscle length 4-chamber view (mm)	41 ± 5	36 ± 5*	43 ± 5	40 ± 4 †	NS
Posterior papillary muscle length 2-chamber view (mm)	40 ± 6	33 ± 5*	42 ± 5	37 ± 6 †	NS
Anterior papillary muscle length 2-chamber view (mm)	40 ± 5	34 ± 5*	42 ± 5	38 ± 5 †	<0.05
Coaptation-to-septum distance (mm)	40 ± 5	35 ± 5*	42 ± 6	40 ± 5 †	<0.001

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