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Interact CardioVasc Thorac Surg 2007;6:340-344. doi:10.1510/icvts.2006.146274
© 2007 European Association of Cardio-Thoracic Surgery
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Institutional report - Valves

Recurrence of functional mitral regurgitation in patients with dilated cardiomyopathy undergoing mitral valve repair: how to predict it{star}

Gabriele DiGiammarco*, Roberta Liberi, Mirko Giancane, Carlo Canosa, Sabina Gallina, Alessandro Di Francesco, Giuseppe Spira and Michele Di Mauro

Department of Cardiology and Cardiac Surgery, University ‘G D'Annunzio’, S Camillo de Lellis Hospital, via Forlanini 50, 66100 Chieti, Italy

Received 10 October 2006; received in revised form 28 February 2007; accepted 2 March 2007

{star} Presented at the joint 20th Annual Meeting of the European Association for Cardio-thoracic Surgery and the 14th Annual Meeting of the European Society of Thoracic Surgeons, Stockholm, Sweden, September 10–13, 2006.

*Corresponding author. Tel.: +39-0871358628; fax: +39-0871357552.

E-mail address: gabriele.digiammarco1{at}tin.it (G. Di Giammarco).


   Abstract
Top
 Abstract
1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
 Conference discussion
 References
 
This study was aimed at identifying predictive variables for recurrence of mitral regurgitation (MR) in patients with dilated cardiomyopathy (DCM) undergoing mitral valve (MV) repair. From January 1997 to December 2005, 142 patients with DCM, 105 (73.9%) ischemic and 37 (26.1%) non-ischemic, underwent MV repair. Mean age was 66±10 years and mean MR grade was 3.2±0.7 (scale 1+ to 4+). Ninety-seven (71% ischemic, 29% non-ischemic), out of 98 still alive at follow-up, were included in this retrospective analysis. In all cases MV posterior annuloplasty was performed; all patients were followed-up by echocardiography (mean time interval of 44±28 months) to evaluate MR recurrence (≥2+/4+). Thirty-day mortality was 9.2% (13 patients). Mean MR grade at follow-up was 0.9±0.9. Four-year freedom from MR recurrence was 65.5%±8.3. Cox analysis showed left ventricular end-diastolic volume index (LVEDVi, OR=1.03, P=0.016, AUC=0.72), left ventricular end-systolic volume index (LVESVi, OR=1.03, P=0.033, AUC=0.71), left ventricular ejection fraction (LVEF, OR=0.82, P=0.001, AUC=0.72), mitral valve coaptation depth (MVCD, OR=1.6, P=0.017, AUC=0.72) to be predictive variables for MR recurrence. Preoperative left ventricular dilatation and function along with degree of papillary muscle displacement can be helpful in identifying patients with higher probability to undergo a durable MV repair.

Key Words: Functional mitral incompetence; Dilated cardiomyopathy; Valve surgery; Mitral annuloplasty


   1. Introduction
Top
 Abstract
 1. Introduction
2. Materials and methods
 3. Results
 4. Discussion
 Conference discussion
 References
 
Mitral valve regurgitation is a frequent complication of dilated cardiomyopathy (DCM) affecting survival [1]. It is secondarily due to mitral annulus dilation and/or papillary muscle dysfunction linked in the evolution towards refractory heart failure [2, 3]. Even if heart transplantation, provided good indication, is the gold standard in the treatment of congestive heart failure, the limited availability of donor organs makes this option not frequently available. Mitral reconstruction may therefore represent a valuable choice either as definitive treatment or as bridge to transplant.

Perioperative mortality of mitral valve repair in patients with severe ventricular dysfunction has been reported to range between 2.1 and 11% [4], one of the determinants of adverse outcome being the recurrence of regurgitation.

The present study analyses the 4-year results of 142 patients with DCM either ischemic or without a severe impairement of left ventricular function submitted to mitral annuloplasty.


   2. Materials and methods
Top
 Abstract
 1. Introduction
 2. Materials and methods
3. Results
 4. Discussion
 Conference discussion
 References
 
Between January 1997 and December 2005, 142 patients with DCM and mitral regurgitation (MR) ≥2+/4+ were referred for surgery. There were 108 males (76%) and 34 females (24%); the mean age was 66±10 years (mean±S.D.; range 41–83). All patients showed left ventricular systolic dysfunction with LVEF from 20–35%, LVEDV from 118 ml/m2 to 141 ml/m2 (122±27 ml/m2), LVESV from 77 ml/m2 to 88 ml/m2 (81±22 ml/m2), MVCD ranging between 8.7–11.2 mm (9.4 mm±2.2 mm S.D.). Out of 142 patients, 105 (74%) had a history of myocardial ischemia with or without previous necrosis; in the remaining patients (37 patients; 26%) DCM was classified as idiopathic. The mean preoperative NYHA functional class was 3.07±0.7. Eighty-six patients (61%) showed congestive heart failure symptoms on admission.

Patient population and preoperative data are reported in Table 1.


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  		Table 1 Preoperative echographic and clinical data

 
All the patients were operated on through a median sternotomy. Cardiopulmonary bypass (CPB) was in all cases instituted from both venae cavae and ascending aorta.

Myocardial protection was achieved by means of an intermittent antegrade warm blood cardioplegia in 131 patients (92.3%) [5]; in 11 patients (7.7%) HTK solution was used under mild systemic hypothermia [6].

The trans-septal approach to the MV was used in the majority of cases (86 patients; 61%).

Echocardiography, either transthoracic or transesophageal, was systematically used to obtain measurements related to MV anatomy and function.

A posterior, intertrigonal mitral valve annuloplasty aimed to annular over-reduction was performed in all cases using three different techniques in time according to surgeon preference. A DeVega-like annuloplasty [7] was the first option used (30 patients; 21%). A 45-mm strip of gluteraldehyde-treated autologous pericardium [8] was subsequently used as the technique of choice in 64 patients (45%), as we found this distance almost applicable in all patients in the aim to over-reduce the posterior mitral annulus. In the last 48 patients (34%) we used a commercially available flexible ring (Miniband, SORIN Group S.p.A-Milano, Italy; MRS, KOHLER Chemie-Alsbach-Hahnlein, Germany).

Coronary bypass grafting was performed in 99/105 (94.3%) patients with ischemic DCM with a mean number of distal anastomosis of 2.24±1.2.

The mean duration of CPB and aortic cross-clamping were 99.4±44.8 min and 78.9±35.7 min, respectively (108± 43.6 min/86.2±34 min in ischemic DCM; 75±39.3 min/58.6±33 min in non-ischemic DCM; P<0.0001).

Ninety-eight patients still alive at a mean follow-up of 32.7±22.4 months (range 1–108 months) were enrolled for echocardiographic control; their characteristics are reported in Table 2. One of them was interviewed by phone but refused to be controlled by echo (99% completeness).


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  		Table 2 Characteristics of patients included in the study compared to the whole group

 
Preoperative, intraoperative and postoperative parameters were inserted in a database. The distribution of continuous variables is expressed as mean±S.D. and comparison was tested by a two-tailed t-test (Mann-Whitney). Categorical variables were compared by {chi}2-test and Fisher's exact test as appropriate. Preoperative and intraoperative variables were analyzed for their relationship with postoperative mortality and morbidity and comparison was made between the subgroups. Survival rate was calculated according to Kaplan–Meier method. Cox-analysis was used to identify predictive variables. The power prediction and cut-off values were identified by means of ROC analysis. P≤0.05 was considered significant.


   3. Results
Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
4. Discussion
 Conference discussion
 References
 
Thirty-day mortality was 9.2% (13/142) (10 patients in ischemic group; three patients in non-ischemic group; P=ns). Late mortality was 24% (31/129), 27.4% (26/95) in the ischemic DCM, and 14.7% (5/34) in non-ischemic DCM. The primary causes were myocardial necrosis (10 patients), acute cardiac failure (seven patients) and stroke (three patients). The cumulative survival and the event-free survival are reported in Figs. 1–2Go.


Figure 1
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  		Fig. 1. Five-year cumulative survival.

 

Figure 2
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  		Fig. 2. Event-free survival.

 
Echographic control (mean follow-up was 44±28 months) was performed in all cases to evaluate MR recurrence. Mean MR grade was 0.9±0.9, with 14 patients (14.4%) showing a 2+/4+ MR, four patients (4.2%) showing a 3+/4+ MR and one patient (1%) 4+ MR. Four-year freedom from MR recurrence was 65.5±8.3% (Fig. 3).


Figure 3
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  		Fig. 3. Four-year freedom from MR recurrence.

 
Preoperative LVEDV (OR=1.03, P=0.016, AUC=0.70), LVESV (OR=1.03, P=0.033, AUC=0.73), LVEF (OR=0.82, P=0.001, AUC=0.64), MVCD (OR=1.6, P=0.017, AUC=0.72) were found as predictive variables for recurrence of mitral regurgitation in the whole group. Preoperative LVESV (P=0.046, AUC=0.69), LVEF (P=0.0016, AUC=0.80) in ischemic DCM were found as predictive variables. Cut-off values according to ROC-analysis are reported in Table 3.


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  		Table 3 Cut-off values at echocardiography

 
No significant impact on late MR recurrence was found according to the three techniques used to perform the annuloplasty.

The presence of a 2+/4+ MR at hospital discharge (6/142 patients) was strongly related to rapid worsening of valve function (OR=4.1).


   4. Discussion
Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
Conference discussion
 References
 
The treatment of mitral regurgitation in patients with DCM and severe left ventricular dysfunction remains one of the most challenging issues in cardiac surgery. The appearance of valvular dysfunction produces a further decrease of ventricular performance leading to a life expectancy shortening through a self maintaining mechanism [1].

Many surgical options have been proposed in time to achieve a durable result or at least clinical stabilization [8].

Mitral valve annuloplasty is by far the most diffuse one. The technique is highly reproducible, relatively easy, with expected low impact on so compromised patients. Its limitation is due to DCM pathophysiological background: left ventricular remodelling is the cause of changing morphology that leads to papillary muscle displacements with leaflet tethering leading to MR recurrence.

A prosthesis implantation undoubtedly guarantees durable competence at mitral level. This option is indeed related to many technical problems: the need of pronounced annular diameter undersizing and mitral valve sparing techniques [9], a higher in-hospital mortality and morbidity [10].

Looking at the literature, early results of mitral annuloplasty are equally good in all experiences reported, the only difference being in hospital mortality clearly related to the severity of systemic involvement of a long-lasting heart failure.

Late results are compromised by the recurrence of MR that is either the cause or effect of the disease. In a severely impaired left ventricle, a mild MR could be ominous in determining a progressive volume increase due to diastolic overload.

Particular attention should therefore be paid to properly select patients who could highly benefit from this surgical technique with the aim to achieve a low rate of MR recurrence in the follow-up.

Our technical choice was to over-reduce the annular size, just acting on the posterior circumference of the mitral annulus, using the two trigons as fixed point of the annular structure. During the course of our experience we adopted three different techniques that showed no influence on late results.

Other Authors used to perform the annuloplasty with complete rings claiming at possible annular re-dilation along the anterior circumference of the valve; this mechanism was first described by Szalay et al. [11] but its influence needs to be proven. The strategy proposed by De Bonis and Coll [12], to add the edge-to-edge technique to annuloplasty with a complete ring (rigid or semirigid) in case of important tethering, could be helpful to stabilize the mitral repair with a solid coaptation between the leaflets. According to their experience, a complete ring, rigid or semirigid on the valve is needed to reduce the possible increase of the pulling forces on the anterior mitral contour in the aim to avoid too early recurrences of mitral regurgitation [13].

Our experience using a posterior annuloplasty in DCM started in 1996. The event-free survival on 97 patients postoperatively submitted to serial echography revealed only five patients (5.2%) with a 3+ (four patients) or 4+ (one patient) mitral regurgitation. Fourteen additional patients (14.4%) showed a 2+ MR. The overall freedom from MR recurrence was 65.5% at a mean follow-up of 44 months. This result appeared to be independent from the technical option chosen to accomplish the procedure.

Patients were recruited on the basis of symptoms of heart failure (NYHA 3 or 4 81%); dyspnoea was the prevalent symptom across the total population and no regional wall motion abnormalities were found. The change in ventricular morphology was evident with a sphericity index of 0.71.

Beyond all technical disputes the main issue of this study is to try to define in this subset of patients some additional selection criteria based on geometrical and volumetric considerations. The cut-off value found for LVEDV could be important in deciding to perform prosthesis implantation with valve sparing in those patients showing very large ventricular volumes.

Actuarial survival in our series is comparable to others: Gillinov and Coll [10] in a quite large cohort of patients affected by ischemic MR report a 77% survival at 1 year and 55% at 5 years. We found a difference in 5-year survival of the two subgroups studied in favor of non-ischemic patients, even if this difference was not significant. This demonstrates that, beyond the common feasture of DCM, the underlying cause of this morphological situation is definitely important in drawing some conclusions.

As all retrospective studies on this topic, some limitations concerning the patients selection could be advocated. Indeed, we analzsed a group of consecutive patients admitted to the hospital with the clinical and echographic feature of DCM with no evidence of regional wall motion abnormality. Functional MR at different degrees was the shared sign along with symptoms of congestive heart failure, even if this pathological condition ‘is not a valvular disease but a ventricular one’. In spite of being apparently homogeneous, patients suffering from this disease show different levels of systemic involvement and various degrees of myocardial function impairment. Different surgical options have been used reaching almost equal goals. Being aware of this background our hope is to contribute to find some more tool to properly select good surgical candidates and good surgical strategies for patients who too often come to our observation too late. Concerning the length of echographic follow-up, a mean duration <4 years could be considered an additional limitation of this study. On the basis of these results we finally believe that a prospective randomised trial, if realistic, even considering the technical choice (annuloplasty vs. valve implantation), is needed to confirm patient selection criteria or postoperative results.


   Conference discussion
Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
 Conference discussion
References
 
Dr. A. Galloway (New York, New York, USA): This is a very nice demonstration on what happens with this type of annuloplasty in dilated cardiomyopathy.

I have one comment and one question. The comment is that I think it is increasingly accepted, based on both experimental studies and clinical data from Bolling's group and others, that flexible devices are worse than rigid or semi-rigid devices for repair of mitral regurgitation in patients with ischemic or dilated cardiomyopathy. The difference in recurrence rates is roughly 10% at 3–5 years vs. 30%. We have data from NYU, where we observed a 7% recurrence of significant regurgitation after repair of patients with ischemic or dilated cardiomyopathy, using overcorrection with either a rigid ring or a semi-rigid band, whereas with suture annuloplasty or posterior plication techniques we have seen recurrence of MR occurs in 30–40%. Therefore, I think it's very hard to draw meaningful conclusions if the technique employed uses suture valvuloplasty or flexible devices, as overcorrection with a rigid device has become the standard.

The real question relating to this paper and the prior paper, is how do you predict which ventricle is going to re-dilate? We believe there may be good ways to do this, such as by assessing the amount of recruitable myocardium preoperatively, or by assessing ischemic load and reversibility in ischemic patients. What is the switch for progressive cardiac dilation? Did you do any preoperative studies to look at the ability to recruit contractility in the myocardium, such as dobutamine echocardiography? Clearly the ventricles that are going to shrink postoperatively are going to do better in terms of recurrence of MR as well, as we saw earlier, and the ventricles that are going to progressively dilate are more likely to continue to have MR. Did you do any studies to assess recruitability in your preoperative evaluation?

Dr. Di Giammarco: For the first part of the comment, and actually I forgot to tell you, we did not find any correlation with the technical surgical choice, either the flexible posterior, semi-rigid, or the annuloplasty with the DeVega or pericardium, so we did not find any correlation with that.

Regarding the preoperative study, we did not have the data of dobutamine tests for all the patients, all of the ischemic patients. So I agree with you that it probably needs to be added to a prospective study in order to discern which patient is going to likely dilate or not.


   References
Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
 Conference discussion
 References
 

  1. Blondheim DS, Jacobs LE, Kotler MN, Costacurta GA, Parry WR. Dilated cardiomyopathy with mitral regurgitation: decreased survival despite a low frequency of left ventricular thrombus. Am Heart J 1991; 122:763–771.[CrossRef][Medline]
  2. Bolling SF, Deeb GM, Brunsting LA, Bach DS. Early outcome of mitral valve reconstruction in patients with end-stage cardiomyopathy. J Thorac Cardiovasc Surg 1995; 109:676–683.[Abstract/Free Full Text]
  3. Bach DS, Bolling SF. Early improvement in congestive heart failure after correction of secondary mitral regurgitation in end-stage cardiomyopathy. Am Heart J 1995; 129:1165–1170.[CrossRef][Medline]
  4. Bolling SF, Pagani FD, Deeb GM, Bach DS. Intermediate-term outcome of mitral reconstruction in cardiomyopathy. J Thorac Cardiovasc Surg 1998; 115:381–386.[Abstract/Free Full Text]
  5. Calafiore AM, Teodori G, Mezzetti A, Bosco G, Verna AM, Di Giammarco G, Lapenna D. Intermittent antegrade warm blood cardioplegia. Ann Thorac Surg 1995; 59:398–402.[Abstract/Free Full Text]
  6. Krohn E, Stinner B, Fleckenstein M, Gebhard MM, Bretschneider HJ. The cardioplegic solution HTK. Eur J Physiology 1989; 415:269–275.[CrossRef]
  7. Rabago G, De Vega NG, Castillon R, Moreno T, Fraile J, Azpitarte J, Batanero J. The new De Vega technique in tricuspid annuloplasty (results in 150 patients). J Cardiovasc Surg 1980; 21:231–238.[Medline]
  8. Kron IL, Green GR, Cope JT. Surgical relocation of the posterior papillary muscle in chronic ischemic mitral regurgitation. Ann Thorac Surg 2002; 74:600–601.[Abstract/Free Full Text]
  9. Calafiore AM, Di Mauro M, Gallina S, Di Giammarco G, Iacò AL, Teodori G, Tavarozzi I. Mitral valve surgery for chronic ischemic mitral regurgitation. Ann Thorac Surg 2004; 77:1989–1997.[Abstract/Free Full Text]
  10. Gillinov AM, Wierup PN, Blackstone EH, Bishay ES, Cosgrove DM, White J, Lytle BW, McCarthy P. Is repair preferable to replacement for ischemic mitral regurgitation? J Thorac Cardiovasc Surg 2001; 122:1125–1141.[Abstract/Free Full Text]
  11. Szalay ZA, Civelek A, Hohe S, Brunner-La Rocca HP, Klovekorn WP, Knez I, Vogt PR, Bauer EP. Mitral annuloplasty in patients with ischemic vs. dilated cardiomyopathy. Eur J Cardiothorac Surg 2003; 23:567–572.[Abstract/Free Full Text]
  12. De Bonis M, Lapenna E, La Canna G, Ficarra E, Pagliaro M, Torracca L, Maisano F, Alfieri O. Mitral valve repair for functional mitral regurgitation in end-stage dilated cardiomyopathy: role of the ‘edge-to-edge’ technique. Circulation 2005; 112:402–408.
  13. Calafiore AM, Gallina S, Di Mauro M, Gaeta F, Iacò AL, D'Alessandro S, Mazzei V, Di Giammarco G. Mitral valve procedure in dilated cardiomyopathy: repair or replacement? Ann Thorac Surg 2001; 71:1146–1152.[Abstract/Free Full Text]




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