Combined mitral valve and coronary artery surgery: ischemic versus non-ischemic mitral valve disease

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1 European Journal of Cardio-thoracic Surgery 20 (2001) 270±275 Combined mitral valve and coronary artery surgery: ischemic versus non-ischemic mitral valve disease Abstract Ralf G. Seipelt*, Friedrich A. Schoendube, Jaime F. Vazquez-Jimenez, Hilmar Doerge, Meinolf Voss, Bruno J. Messmer Department of Thoracic and Cardiovascular Surgery, University Hospital RWTH Aachen, Pauwelsstrasse 30, G Aachen, Germany Received 12 February 2001; received in revised form 10 May 2001; accepted 17 May 2001 Objectives: Mitral valve combined with coronary artery surgery is associated with a higher hospital mortality than each operation in particular. Controversy exists regarding the predictive value of ischemic mitral valve disease (MVD) on outcome. Methods: Between 1984 and 1997, 262 patients underwent mitral valve operations (replacement, n ˆ 198; repair, n ˆ 64) in combination with coronary revascularization. The etiology of MVD was secondary to ischemic heart disease (group I) in 82 (31%) patients, and non-ischemic (group II) in 180 (69%) patients (rheumatic, 139 patients (53%); degenerative, 41 patients (16%)). Both groups were similar in age, cardiac risk factors and pulmonary artery pressure. Patients of group I had signi cantly more severe coronary artery disease, more often an impaired left ventricle and myocardial infarction, and were in a worse functional condition. The mean number of bypass grafts was signi cantly higher in group I. The follow-up was 98% (230/234 patients). Results: With 19.5%, the hospital mortality was signi cantly increased in group I compared with 6.7% in group II (P ˆ 0:002; overall, 10.7%). Mitral valve repair or replacement had no in uence on early outcome, although mitral valve repair was performed more often in group I (37 versus 19%). The survival (valve-related event-free survival) after discharge from hospital in the 1st, 5th and 10th year was 94 (94%), 70 (66%) and 53% (35%) in group I and 96 (95%), 79 (76%) and 54% (41%) in group II, respectively. The long-term functional capacity was equally good in both groups (New York Heart Association mean, 1.86 versus 1.72). Conclusions: Patients with ischemic MVD are in a worse cardiac condition with signi cantly higher hospital mortality than patients with non-ischemic MVD and coronary artery bypass grafting. Once discharged from hospital, both groups have comparable long-term outcomes, with the best results in patients with degenerative MVD. q 2001 Elsevier Science B.V. All rights reserved. Keywords: Mitral valve; Ischemic mitral regurgitation; Ischemic heart disease; Coronary artery bypass surgery 1. Introduction Combined mitral valve surgery and coronary artery bypass grafting is associated with a reported hospital mortality of 7± 18% [1±9], which is higher than the hospital mortality of 3% in isolated coronary artery bypass grafting [9] and 4±7% in isolated mitral valve procedures [2,4,9,10]. When both operations are performed concomitantly, the hospital mortality is substantially greater than the simple addition. The reason for such a higher mortality in the case of additional coronary artery bypass grafting is not clearly de ned, and the predictive value of the etiology of mitral valve disease (MVD) on early and late survival is still uncertain. While in some studies, the risk increases considerably in patients whose MVD represents an acute or * Corresponding author. Tel.: ; fax: address: rseipelt@post.klinikum.rwth-aachen.de (R.G. Seipelt). chronic complication of the coronary artery disease [2,4,5,8,11±14], the etiology of MVD was not related to hospital mortality in others [1,3,6,7,15,16]. Thus, the current study was undertaken to compare the early and late results of mitral valve procedure combined with coronary artery bypass grafting in patients with ischemic versus non-ischemic MVD. 2. Materials and methods 2.1. Patients Between January 1984 and December 1997, 262 patients undergoing mitral valve surgery in combination with coronary artery bypass grafting were included in the study. In the same time period, 906 patients were operated on using the isolated mitral valve procedure (MV replacement: 724 patients; MV repair: 182 patients). Patients with additional /01/$ - see front matter q 2001 Elsevier Science B.V. All rights reserved. PII: S (01)00817-X

2 R.G. Seipelt et al. / European Journal of Cardio-thoracic Surgery 20 (2001) 270± procedures were excluded. Hospital records of the study patients were reviewed to determine demographic, clinical, operative and perioperative data. All patients had cardiac catheterization within 6 months before operation (mean, 2.3 ^ 0.9 months). Preoperative left ventricular (LV) function given as the ejection fraction (EF) was determined by cineventriculography (normal, EF. 50%; mild impairment, 40±50%; moderate impairment, 30±40%; severe impairment, EF, 30%). If EF was not available, LV function was evaluated according to the left ventricular end-diastolic pressure (LVEDP: normal, LVEDP, 15 mmhg; mild impairment, 15±20 mmhg; moderate impairment, 21±25 mmhg; severe impairment, LVEDP. 25 mmhg). The degree of mitral valve regurgitation was assessed by cineventriculography and echocardiography Valve pathology According to mitral valve pathology, all patients were divided into three groups. The criteria for ischemic mitral regurgitation followed the restrictive de nition of R. Dion from Brussels [17]. Table 1 Demographic, clinical and catheterization data a,b 1. Ischemic (82 patients): diagnosis of myocardial ischemia preceding that of mitral regurgitation, no history of rheumatic heart disease, no congenital defect of the mitral valve, no evidence of degenerative valvular disease and no intraoperative or histological nding that suggested other causes of mitral regurgitation. 2. Rheumatic (139 patients): history of rheumatic heart disease, intraoperative or histological nding that suggested rheumatic MVD (mitral stenosis with or without insuf ciency or pure insuf ciency with thickened lea ets, calci ed lea ets, chordal shortening, or chordal thickening). 3. Degenerative (41 patients): Pure mitral insuf ciency with histological evidence of myxoid change. Patients with rheumatic or degenerative MVD were summarized as having `non-ischemic' MVD (n ˆ 180 patients). The distribution of important demographic, clinical and catheterization data for the two groups of ischemic and non-ischemic MVD is shown in Table 1. The two groups were similar in age, cardiac risk factors ± except history of smoking ± and pulmonary artery pressure. Patients with ischemic MVD had more extended coronary artery disease, more often an impaired LV function, a higher incidence of previous myocardial infarction overall ± and within 6 weeks before operation ± and preoperative intraaortic balloon pump (IABP). Patients with non-ischemic MVD were in a better functional condition, but more often had prior cardiac operations Operative technique All patients undergoing cardiopulmonary bypass were operated on under moderate hypothermia (288C) and cardioplegic arrest with cold hyperkalemic crystalloid cardioplegic solution. After aortic cross-clamping and induction of cardioplegic arrest, coronary revascularization was performed rst. Mostly, a reperfusion period with completion of the aortic anastomoses was then followed by a second cardioplegic arrest with cross-clamped aorta and inspection of the valvular and subvalvular mitral apparatus. Mitral valve repair was performed in 64 patients, mostly Variable Mitral valve disease P value Ischemic (n ˆ 82) Non-ischemic (n ˆ 180) Mean age ^ SD (years) 63.3 ^ ^ Female gender 21 (26) 89 (49) Prior myocardial infarction 69 (84) 31 (17) Within 6 weeks 16 (20) 3 (2) Prior cardiac operation 5 (6) 32 (18) Atrial brillation 33 (40) 105 (58) Preoperative IABP 12 (15) NYHA class II 7 (8) 5 (3) III 39 (48) 125 (69) IV 36 (44) 50 (28) Coronary artery disease One-vessel 2 (3) 69 (38) Two-vessel 17 (20) 61 (34) Three-vessel 63 (77) 50 (28) Moderately or severely impaired LV function 32 (39) 9 (5) Systolic PAP (mmhg; mean ^ SD) 44.4 ^ ^ a b Numbers in parentheses are percentages. IABP, intraaortic balloon pump; LV, left ventricular; NYHA, New York Heart Association; PAP, pulmonary artery pressure.

3 272 R.G. Seipelt et al. / European Journal of Cardio-thoracic Surgery 20 (2001) 270±275 Table 2 Operative characteristics a Variable Mitral valve disease P value Ischemic (n ˆ 82) Non-ischemic (n ˆ 180) Mitral valve repair 30 (37) 34 (19) Mean number of bypass grafts (mean ^ SD) 3.2 ^ ^ Left atrial thrombus 0 16 (9) Mean cross-clamp time (min; mean ^ SD) ^ ^ a Numbers in parentheses are percentages. carried out by annuloplasty using a Carpentier ring (n ˆ 34) or Kay±Wooler plasty of the commissures (n ˆ 23). In a few cases, more complicated reconstructions were necessary. Mitral valve replacement was accomplished in 198 patients after excision of the valvular apparatus. Forty-one patients, most in recent years of the study, had preservation of at least some portion of the native mitral valve, usually the posterior lea et. The valvular prostheses inserted included 37 (19%) bioprosthetic valves and 161 (81%) mechanical valves. The operative characteristics for the two groups of ischemic and non-ischemic MVD are recorded in Table 2. A higher rate of mitral valve repair was performed in cases of ischemic MVD (37 versus 19%). Twelve percent of cases of rheumatic MVD (17/139 patients) had mitral valve repair, whereas in patients with degenerative MVD, 42% (17/41) had mitral valve repair. The mean number of bypass grafts and aortic cross-clamping time were outstandingly higher in ischemic MVD Follow-up The follow-up clinical information about survival, valverelated events and functional status was obtained through letter or telephone contact with the patient and/or the patient's physician by the closing date of July Of 262 patients included in this study, 234 were discharged from hospital, of whom four patients were lost to followup. The follow-up was 98% with a mean of 5.7 ^ 3.5 years and comprised a total of 1304 patient-years Statistical analysis Statistical analysis was performed with the Statistical Package for Social Sciences (SPSS-Institute, Chicago, IL). Statistical differences between nominally and ordinally scaled variables were determined with the Chi-square test. Continuous variables were compared with the Wilcoxon two-sample test. P values of,0.05 were considered significant. Variables found to be signi cant or close to signi cance by univariate testing (P, 0:10) were entered into a multivariate logistic regression model to identify independent predictors of hospital mortality. The Kaplan±Meier method was used to estimate the late and event-free survival probabilities [18]; differences between groups were determined with the log-rank test at a signi cance level of 5%. For the multivariate analysis of late survival, a Cox proportional model was used [19]. 3. Results 3.1. Hospital mortality The overall hospital mortality was 10.7% (28/262 patients). The causes of death were low cardiac output in 11 patients; septic multi-organ failure in seven; intractable ventricular arrhythmia in three; myocardial infarction, stroke, hemorrhage each in two patients and endocarditis in one patient. In patients with ischemic MVD, the hospital mortality was signi cantly increased with 19.5% compared with 6.7% in patients with rheumatic or degenerative MVD and additional coronary artery bypass grafting (P ˆ 0:002; Table 3). Moderate to severe impaired LV function was the only independent predictor of hospital mortality in the ischemic MVD group (P ˆ 0:001). Advanced age and preoperative IABP were just signi cant factors by univariate analysis. The severity of mitral regurgitation had no in uence on early outcome. Independent predictors of hospital mortality in the nonischemic MVD group were re-operation (P ˆ 0:0001), moderate to severe impaired LV function (P ˆ 0:002), extended aortic cross-clamp time (P # 0:001) and male gender (P ˆ 0:009). Advanced age was a signi cant factor only with univariate analysis. The predominant mitral valve stenosis or regurgitation were not signi cant factors for early outcome. The procedure of mitral valve repair or replacement had no in uence on early outcome, either in the ischemic or non-ischemic MVD group. With isolated Table 3 Hospital mortality due to etiology of MVD a Number of patients Early deaths (n) Hospital mortality (%) Ischemic Rheumatic Degenerative a Ischemic versus rheumatic 1 degenerative: P ˆ 0:002.

4 R.G. Seipelt et al. / European Journal of Cardio-thoracic Surgery 20 (2001) 270± mitral valve surgery, the hospital mortality was 4.4% (MV replacement: 5.1%; MV repair: 1.6%) Hospital morbidity A perioperative myocardial infarction (new Q wave on electrocardiogram) was suffered by three patients in each group (ischemic 3.7% versus non-ischemic 1.7%). IABP was necessary in 34 patients (15/82 versus 19/180 patients) due to hemodynamic instability with a hospital mortality of 50%. In both groups, 16% of the patients required prolonged intubation (.24 h). Due to perioperative bleeding, 17 patients required rethoracotomy (12 versus 4%). Other serious morbidities included: permanent pacemaker in four patients; gastrointestinal bleeding in four patients; permanent stroke in eight patients; and wound complication in nine patients Late outcome The survival for ischemic versus non-ischemic MVD after discharge from hospital was nearly equal. With a 10- year survival of 65%, the subgroup of patients with degenerative MVD and coronary artery bypass grafting had the best long-term survival (Fig. 1). Advanced age was the only independent predictor of long-term survival, but only in the non-ischemic MVD group (P ˆ 0:014). Due to progression of coronary heart disease, eight patients had to be re-operated (ischemic, three patients; non-ischemic, ve patients). Twelve patients with previous mitral valve replacement underwent re-replacement of the valve (ischemic, one patient; non-ischemic, 11 patients). In ten patients, degeneration of the bioprosthesis was the reason for re-replacement; in one patient, a partial mechanical valve thrombosis, and in one patient, a paravalvular leakage as a result of endocarditis of the mechanical valve. Other complications due to mitral valve replacement included severe bleeding (n ˆ 10), thromboembolism (n ˆ 3) and endocarditis (n ˆ 5). Due to mitral valve repair failure, four patients had to be re-operated 7 months±10 Fig. 1. Kaplan±Meier survival curves after discharge from hospital for combined mitral valve operation and coronary artery bypass grafting according to etiology of MVD. There is no signi cant difference between the groups. years after the initial operation (ischemic, one patient; non-ischemic, three patients). The rate of valve-related events for all patients with mitral valve repair was with 1.8%/patient-year lower than 2.7%/patient-year for patients with mitral valve replacement. The ischemic MVD group had valve-related event-free survivals of 94, 66 and 35% at 1, 5 and 10 postoperative years, and for the non-ischemic MVD group, these values were 95, 76 and 41%, respectively (log-rank test, P ˆ 0:58). Of the late survivors, 85% (125/147 patients) are in New York Heart Association (NYHA) functional classes I and II. The long-term functional capacity is equally good in both groups (mean NYHA, 1.86 versus 1.72). 4. Discussion Patients operated on for mitral valve and additional coronary artery disease have a substantially higher hospital mortality than those having either procedure alone. For the combined operation, studies have shown a hospital mortality of 7±18% [1±9]. In isolated mitral valve operations, the hospital mortality ranges from 4 to 7% [2,4,9,10]. In the present study, we included all patients who were operated ± primarily or as re-operation ± on the mitral valve (replacement or repair) and the coronary arteries. All patients with further procedures were excluded. Therefore, we have focused the risk factors for this special group of patients. At all 262 patients ful lled the above-mentioned criteria and were included. The hospital mortality for the combined operation was 10.7%. There are recent studies, all retrospective, which investigated the risk factors for early and late survival after combined mitral valve and coronary artery surgery. In most studies, reduced LV function, advanced age and preoperative NYHA functional class IV were identi ed as predictors of hospital mortality [2,4,6,7,14]. The etiology of MVD, especially the issue of ischemic MVD on early and late outcome, is controversial. Several studies indicate a strong in uence of ischemic MVD on early results [2,4,5,8,11±14]. However, other reports show little effect on early outcome [1,3,6,7,15,16]. In the present study, we used the strict de nition of R. Dion [17] to separate the patients with true ischemic MVD. Thus, we identi ed 82 patients (31%) having an ischemic origin of MVD. All of them had moderate to severe mitral regurgitation in need of treatment, while it is our policy to leave the mitral valve untreated in cases of only mild ischemic mitral regurgitation. This is in concordance with other reports on patients with mild mitral regurgitation and better outcomes when only operated on for coronary artery disease [20,21]. In 139 patients, the MVD was rheumatic; in 41, it was degenerative. When classifying the patients with rheumatic and degenerative as `non-ischemic' MVD, the hospital mortality for this group was 6.7% (Table 3). Thus, patients with `non-ischemic' mitral valve and coronary artery

5 274 R.G. Seipelt et al. / European Journal of Cardio-thoracic Surgery 20 (2001) 270±275 surgery had an early risk comparable with patients who underwent isolated mitral valve surgery. In cases of ischemic mitral regurgitation, the combined operation carried a three times higher early risk (19.5%). The ischemic origin of MVD was an independent risk factor of hospital mortality. The reasons became evident when patients with ischemic and `non-ischemic' MVD were compared. Patients with ischemic MVD were in a signi cantly worse clinical condition. Moreover, more patients had had previous myocardial infarction, greater extension of coronary artery disease and a more impaired LV function. Also, all patients preoperatively in need of IABP had ischemic MVD. More often, the group of patients with non-ischemic MVD had undergone a previous operation, mostly mitral valve commissurotomy for rheumatic mitral stenosis. As a result of long-term MVD with an enlarged left atrium, they also suffered more often from atrial brillation. The number of coronary artery bypass grafts was higher in the ischemic MVD group. Altogether, the operation was extended and more complicated. This is re ected in the early outcome. Eighteen percent (15 patients) needed postoperative cardiac support with the IABP. The use of IABP should be taken into consideration early or even prophylactically during operation when ischemic MVD is obvious and the patient has hemodynamic instability. The long-term outcome after discharge from hospital in both groups is nearly equal with the best results in patients with degenerative MVD. Preoperative LV function is an important determinant of hospital mortality in most studies [1,2,6,7,11±14,16,21,22]. We identi ed moderate to severe impaired LV function to be an independent risk factor for early mortality in both groups. Once the patient was discharged from hospital, the preoperative LV function had no in uence, either in the ischemic or in the non-ischemic MVD group. Most patients with an impaired LV function underwent mitral valve replacement, due to our policy of preferring mitral valve replacement in cases of impaired LV function to ensure reliable postoperative valvular competence. The negative effect of mitral replacement on ventricular geometry and LV function, respectively, may be reduced by preserving parts of the subvalvular apparatus of the mitral valve as rst described by Lillehei et al. in 1964 [23]. This is in accordance with another study from 1999, which had better results with immediate mitral valve replacement with preservation of the subvalvular apparatus in patients with low EF preoperatively [21]. Moreover, it is our policy to attempt a complete myocardial revascularization in all patients in order to supply as much viable myocardium as possible and thereby improve the LV function. This could explain why early survivors with impaired LV function had almost the same long-term outcome as patients with a normal preoperative left ventricle. Mitral valve repair was performed in 37% of ischemic and 41% of degenerative MVD cases, but only in 12% of rheumatic MVD cases. The low rate of repair in cases of rheumatic MVD re ects the high incidence of advanced mitral stenosis with thickened and calci ed lea ets. The long-term outcome after repair in rheumatic MVD is associated with a higher rate of repair failure [24]. Only two of our patients with repair for rheumatic MVD had to be reoperated 5 and 10 years after the primary repair which proves the careful indication of repair procedures. In ischemic and degenerative MVD, repair procedures are common and valve-related events are low [25±27]. The presented results con rm this statement about mitral valve repair due to ischemic or degenerative disease in combined coronary artery and mitral valve operations. Forty-seven of 123 (39%) mitral valves were repaired, of whom two had to be re-operated 7 and 42 months thereafter. When comparing the repair and the replacement group, there are no signi cant differences in hospital mortality, but there is a trend towards a better early outcome in the repair group (7.7 versus 11.6%). Moreover, the rate of valve-related events in the repair group is lower (1.8 versus 2.7%/patient-year). Hence, mitral valve repair, when technically feasible, should be performed in patients with ischemic or degenerative MVD. In summary, the current study con rms the following: 1. Combined mitral valve and coronary artery surgery carries a relatively high hospital mortality (10.7%). 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