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Ann Thorac Surg 2007;84:451-458
© 2007 The Society of Thoracic Surgeons

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Original Articles: Cardiovascular

Mitral Valve Replacement Versus Repair: Propensity-Adjusted Survival and Quality-of-Life Analysis

^a Department of Cardiothoracic Surgery, Helsinki University Hospital, Helsinki, Finland
^b Department of Surgery, Kuopio University Hospital, Kuopio, Finland
^c Department of Anesthesiology, Kuopio University Hospital, Kuopio, Finland
^d Department of Cardiology, Kuopio University Hospital, Kuopio, Finland

Accepted for publication March 20, 2007.

^_* Address correspondence to Dr Hippeläinen, Department of Surgery, Kuopio University Hospital, PO Box 1777, Kuopio, FIN-70211, Finland (Email: mikko.hippelainen{at}kuh.fi).

This article has been selected for the open discussion forum on the CTSNet Web Site: http://www.ctsnet.org/sections/newsandviews/discussions/index.html

 

	Abstract

Top Abstract Introduction Patients and Methods Results Comment References

 
Background: We investigated whether mitral valve repair (MVP) is superior to mitral valve replacement (MVR) in terms of survival and quality of life during the long-term follow-up.

Methods: One hundred eighty-four consecutive patients underwent MVP or MVR for mitral regurgitation with or without concomitant coronary artery bypass grafting. Clinical data were recorded prospectively, and the data for the Nottingham Health Profile quality-of-life analysis was collected cross-sectionally. Propensity score analysis was used for the study group matching.

Results: The mean follow-up time was 7.3 ± 1.4 years. After adjustment for baseline characteristics by the propensity score method, there was a statistically significant survival benefit for the patients who underwent MVP (p = 0.02). Risk factors for death were preoperative unstable angina pectoris (relative risk ratio, 4.4; 95% confidence interval, 2.2 to 8.8), age older than 60 years (relative risk ratio, 1.1; 95% confidence interval, 1.0 to 1.1), use of mitral prosthesis (relative risk ratio, 2.7; 95% confidence interval, 1.4 to 5.3), preoperative renal insufficiency (relative risk ratio, 1.0; 95% confidence interval, 1.0 to 1.007), and preoperative cerebrovascular disorder (relative risk ratio, 2.7; 95% confidence interval, 1.0 to 5.3). The quality of life of the MVP and MVR groups did not differ from each other, but the MVP and the MVR patients had lower energy and mobility scores than an age- and sex-matched reference population.

Conclusions: Survival is longer after MVP than after MVR. The quality of life of MVP and MVR patients does not differ from each other. In terms of most quality-of-life variables, patients who undergo mitral valve operations cope similarly to an age- and sex-matched reference population. Only the scores reflecting energy and mobility were lower in the patients who were operated on than in the reference population.

During the past two decades, mitral valve repair (MVP) has become an established procedure for the treatment of patients with mitral regurgitation as a result of ischemic or structural origin. The performance of MVP has increased from 24.6% to 39.8% between the years 1990 and 2000 [1]. There is a number of nonrandomized and largely retrospective reports on the results of MVP compared with mitral valve replacement (MVR), and these reports appear to favor MVP over MVR in terms of operative mortality and morbidity, survival, need for reoperations, and thromboembolic complications [2–7].

Traditionally, the results of surgical interventions are measured in terms of survival, mortality, morbidity, complications, symptom recurrence, and need for reoperations. On the other hand, most valve operations are performed on elderly patients who tend to prefer quality of life (QoL) over life expectancy. Under these circumstances, the survival variable does not reflect the primary intention of treatment, although the outcome of surgical operations must also be evaluated in terms of their impact on health-related QoL [8]. This argument leads to a somewhat frustrating need to balance between the impaired current health status and the expected benefits of surgery, keeping well in mind the risks and disadvantages of cardiac surgery. The question is, how to choose cardiac therapies to optimize the patient-related outcomes?

Some authors have reported significant favorable effects of mitral valve surgery on the overall health status of patients irrespective of age [9–11]. On the other hand, others have reported only slight improvement of QoL after cardiac valve surgery [12]. Thus, further studies are needed to address the relations between operative treatment and QoL of patients with mitral valve regurgitation to support decision-making whether to operate or not.

This study analyzed the outcome after mitral valve surgery by comparing MVP and MVR in terms of survival, QoL, and risk factor assessment during long-term follow-up. The technique of propensity score analysis was used to reduce selection bias and heterogeneity in the study population.

	Patients and Methods

Top Abstract Introduction Patients and Methods Results Comment References

 
Study Population
The study population consisted of 184 consecutive patients who underwent a primary mitral valve procedure at the Kuopio University Hospital between January 1992 and December 1996. Of these, 113 (61%) also underwent concomitant coronary artery bypass grafting (CABG; 53% in the MVR group, 72% in the MVP group). Exclusion criteria were mitral stenosis, aortic or tricuspid valve replacement, previous valve repair or replacement, and congenital heart disease. The baseline and perioperative patient characteristics are given in Tables 1 and 2. The study protocol was approved by the ethics committee of the Kuopio University Hospital. Patients gave informed consent.

Statistical Analysis
Definitions, data analyses, and reporting were based on the guidelines and recommendations of the Joint Society of Thoracic Surgeons and the American Association for Thoracic Surgery Ad Hoc Liaison Committee for Standardizing Definitions of Prosthetic Heart Valve Morbidity [13]. Differences between groups were compared with the ² test or Fisher’s exact test, as appropriate. Means and standard deviations were computed for continuous variables, and proportions were compared with the nonparametric Mann-Whitney U test or Student’s t test, as appropriate. Late survival and time-dependent events were assessed by Kaplan–Meier survival analysis, and the log-rank test was used for univariate analysis of mortality and morbidity followed by Cox’s multivariate analysis for statistically significant univariate factors.

The theoretical basis of propensity score analysis has been published elsewhere [14]. Briefly, propensity scores are used to create matched pairs or matched sets that are balanced with respect to many observed covariates. The resulting matched sets are heterogeneous within the covariates, but the covariates aim to have uniform distributions in treated and control groups, which makes the groups as a whole comparable [15].

Propensity score analysis was carried out in our study to estimate the probability that a patient might undergo MVP versus MVR and to eliminate the effect of nonrandomization and selection bias. First, logistic regression analysis of several preoperative variables was performed to generate a single propensity score for each patient. Practically, we included all possible covariates that we were able to trace and that were expected to be a potential contributing factor for determining whether or not a patient would receive an MVP or MVR (Table 3). The model had an area under the receiver operating characteristic curve of 0.841 and a Hosmer-Lemeshow goodness of fit p value of 0.73. Second, we used a subset analysis, in which patients were grouped according to the magnitude of their propensity score into five quintiles, after which their characteristics and outcomes were compared within these quintiles. Groups with similar propensity scores appeared to be reasonably well matched with respect to all characteristics. Differences with a p value less than 0.05 were considered statistically significant.

The questionnaire was mailed to the patients during the closing interval (n = 134), and nonresponders (n = 3) were contacted and interviewed by phone. Nine patients could not be reached (n = 8) or refused (n = 1) to participate, which yielded a follow-up ratio of 93% (125 of 134 patients). The average interval between surgery and administration of the QoL analysis was 7.5 ± 1.4 years (6.9 years in the MVP and 8.2 years in the MVR groups).

	Results

Top Abstract Introduction Patients and Methods Results Comment References

 
Late Survival
The actual and 5-year survival rates were 74.2% and 81.2% in MVP group and 59.6% and 73.5% in MVR group, respectively. After adjustment for baseline characteristics by the propensity score method, there was a statistically significant survival benefit for the patients who had undergone MVP (p = 0.02; Fig 1).

View larger version (17K): [in this window] [in a new window]   Fig 1. Propensity-matched Kaplan–Meier survival curves. (MVP = mitral valve repair; MVR = mitral valve replacement.)

Cardiac Death (Fatal Myocardial Infarction)
Thirty-three patients (17.9%) died during follow-up (later than 30 days after the mitral procedure) because of acute myocardial infarction. Mortality attributable to acute myocardial infarction was 18.8% in the MVP group and 17.2% in the MVR group (Table 4). Coronary artery bypass grafting was simultaneously performed in all patients in the MVP group (100%) and in most of the patients in the MVR group (88.2%).

Noncardiac Death
There were 24 noncardiac deaths (13.0%). Noncardiac mortality was 5.9% in the MVP group and 19.2% in the MVR group (p = 0.06; Table 4) and was attributable to malignancy in 9 patients (4.9%), pneumonia in 2 patients (1.1%), acute pancreatitis in 2 patients (1.1%), cerebral infarction in 1 patient (0.5%), cerebral hemorrhage in 1 patient (0.5%) and other causes in 9 patients (4.9%). Both cerebral deaths occurred in the MVR group, and both patients were receiving anticoagulation treatment with warfarin.

Risk Factors for Death
Table 5 shows the relationship between various perioperative predictors and late survival. Among the 16 variables that were evaluated, five turned out to be statistically significantly associated with mortality. These were preoperative unstable angina pectoris, advanced age older than 60 years, mitral prosthesis, preoperative renal insufficiency (creatinine > 105 µmol/L), and preoperative cerebrovascular disorder.

Quality of Life
Figure 2 shows the NHP scores in the MVP and MVR groups together with the scores standardized to the Finnish adult population. The scores were similar in the MVP and MVR groups. However, statistical differences emerged between the study groups (MVP and MVR), on the one hand, and the reference population, on the other, in the QoL dimensions describing energy (p = 0.002 and p = 0.004, respectively) and mobility (p = 0.01 and p = 0.03, respectively). Thirty-seven variables were tested for impairment of QoL, and 14 of these turned out to be statistically significant (p < 0.05). These contributors were statistically significantly worse in the MVP and MVR groups than in the reference population and were mainly related to physical activity and physical capacity (ie, energy and mobility), but the dimensions describing pain and social isolation were also affected by varying risk ratios (Table 6).

View larger version (31K): [in this window] [in a new window]   Fig 2. Nottingham Health Profile quality-of-life (QoL) analysis. Statistical differences between the mitral valve repair (MVP) and mitral valve replacement (MVR) groups versus an age- and sex-matched reference population are shown as follows: *p = 0.002; **p = 0.004; #p = 0.01; ##p = 0.03.

	Comment

Top Abstract Introduction Patients and Methods Results Comment References

During the years, the reconstructive techniques developed by Carpentier and colleagues [2, 3, 7] have shown that mitral repair seems to be superior to mitral replacement. In our study, we found that survival in the MVP group was, indeed, significantly better than in the MVR group (p = 0.02). Moss and colleagues [18] have published similar results in a population of 322 patients and concluded that MVP is related to improved survival but that there is a trend to increased reoperations; their follow-up had a median of 3.4 years. In our study of 184 patients with a mean follow-up of 7.3 ± 1.4 years, there was no significant difference in the rate of reoperations or reexaminations within the MVP and MVR groups. Several authors have recently confirmed the results concerning lower mortality and morbidity after mitral repair, especially in terms of a low rate of late valve-related complications, such as thromboembolism and bleeding events, which are attributable to the need for anticoagulation [4, 5]. In this study, there was no difference in rate of late complications between the two groups. Because long-term prognosis, ie, life expectancy, is affected by coronary artery disease and underlying ventricular function, patients with severe coronary artery disease have impaired survival. One might argue that our results are preferentially coronary artery disease–related rather than valve-related because patients with CABG were included. In our series, concomitant CABG was performed in 72% of the patients in the MVP group and 53% in the MVR group (p = 0.008). The corresponding mean ejection fractions were 0.54 and 0.63, respectively (p < 0.0001). Obviously, the patients in the MVP group presented with more severe coronary artery disease and worse left ventricular function than patients in the MVR group. One would thus expect that survival in the MVP group would be worse than in the MVR group, but this was not the case in our study.

The combination of mitral valve and coronary artery disease is a growing challenge, in which two separate but interdependent pathophysiologic mechanisms potentiate each other. An increasing number of patients with these coexisting diseases have been offered the option to have cardiac surgery. Recently published data demonstrate that mitral insufficiency is independently associated with reduced survival in combination with CABG [19, 20]. Herlitz and coworkers [21] found in a small study population (n = 35) who underwent both mitral valve surgery and CABG that the combination was independently associated with death and rehospitalization. The early mortality rate was 11.4%, and the 5-year survival was 45.2%. The only independent predictor of an adverse outcome was a low (<0.40) preoperative ejection fraction [21]. Mortality and survival figures appeared better in our series; early mortality and 5-year survival were 4.3% and 81.2%, respectively. In addition, in our study CABG caused by preoperative unstable angina pectoris turned out to be an independent predictor of late mortality, whereas CABG without preoperative unstable angina was not associated with mortality. Flameng and colleagues [22] concluded in a large series of 741 patients who underwent the combination procedure (32 MVP and 180 MVR) that patient-related variables (age, female sex), concomitant renal failure, cardiac function (New York Heart Association class III or IV), left ventricular dysfunction, mitral regurgitation, coronary artery disease, nonsinus rhythm, and the aortic cross-clamp time are the most important predictors of an adverse outcome of patients who have undergone a mitral valve operation and CABG simultaneously. Our results agree very well with these findings, as we found that the following variables were associated with reduced survival: preoperative unstable angina pectoris, age older than 60 years, mitral prosthesis instead of valvular repair, preoperative renal insufficiency, and preoperative cerebrovascular disorder.

We also studied the patients’ QoL to identify the risk factors for impaired postoperative QoL after mitral surgery. The average interval between surgery and administration of the QoL analysis was approximately 7.5 years in both groups. It is obvious that the long interval eliminates the potential confounding effects of early postoperative adversities on the QoL scores. The QoL of patients who had undergone MVP and MVR was similar. There was a statistical difference in dimensions of energy and mobility between the MVP and MVR groups, on the one hand, and the standardized reference population, on the other hand. With respect to other QoL variables, patients who had undergone mitral operations and an age- and sex-matched reference population did not differ from each other. Two recent articles report that MVP might be better than MVR from the QoL perspective [23, 24], but our study and that by Immer and coworkers [25] do not support these findings.

We assessed the determinants of the inferior QoL of the patients who had undergone MVP or MVR. Among 37 tested variables, 14 were associated with an inferior QoL. The risk factors that affected several dimensions of QoL (>3) affected mainly physical conditions (ie, energy, mobility, and pain) rather than mental dimensions (sleep, social isolation, and emotion). The most significant variables associated with a poor QoL were New York Heart Association class, age older than 60 years, and need for nitroglycerin and diuretics. This is not unexpected, because these variables portray symptomatic ischemic heart condition and heart failure, which are known to impair QoL. The relation between age and New York Heart Association class with regard to impaired QoL has also been reported by Chocron and colleagues [26].

Our study has obvious limitations. First, it was not randomized. Blackstone [27, 28] has clearly expressed that it is very difficult to design prospective randomized clinical trials that compare only, for example, the effect of the type of valve surgery in terms of outcome. The obvious reasons are that such studies carry great heterogeneity of patients, and operative techniques cannot always be selected randomly. Thus, treatment is confounded by selection bias, and any observed survival differences could relate to a number of concealed underlying causes. This leads to the inescapable conclusion that, in most cases, clinical studies are primarily clinical observations rather than randomized trials in the classic sense. In our study, we attempted to adjust for selection factors by multivariate analysis, investigating outcome by logistic regression. We used propensity score matching by grouping the patients into five quintiles according to the magnitude of their propensity score. Finally, survival analysis was carried out within the groups. Another limitation is the single-center nature of our study. Mitral valve repair is a demanding procedure often performed only in high volume centers. Thus, one has to be careful when applying our result to smaller centers.

Despite these limitations, we conclude that the survival is longer after MVP than MVR, and patients who underwent mitral valve operations cope similarly to an age- and sex-matched reference population. An increasing number of elderly patients with coexisting coronary artery and mitral valve disease have been offered the option for cardiac surgery, and, in addition to survival benefit, the impact of cardiac surgery on patients’ health-related QoL must have particularly been considered.

	References

Top Abstract Introduction Patients and Methods Results Comment References

 

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This Article Abstract Full Text (PDF) Online Discussion Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Mikko J. Hippeläinen Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jokinen, J. J. Articles by Hartikainen, J. E.K. Search for Related Content PubMed PubMed Citation Articles by Jokinen, J. J. Articles by Hartikainen, J. E.K. Related Collections Valve disease