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European Journal of Echocardiography Advance Access published online on September 26, 2008
European Journal of Echocardiography, doi:10.1093/ejechocard/jen247
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org

Right ventricular dilatation predicts survival after mitral valve repair in patients with impaired left ventricular systolic function

Anton Chrustowicz1,2,*,{dagger}, Gregor Simonis1,*,{dagger}, Klaus Matschke3, Ruth H. Strasser1 and Andrzej Gackowski2

1 Department of Internal Medicine, Cardiology and Intensive Care, University of Technology, Heart Centre Dresden, Fetscherstrasse 76, D-01307 Dresden, Germany
2 Department of Coronary Disease, Institute of Cardiology, Pradnicka 80, 31-202 Krakow, Poland
3 Department of Cardiac Surgery, University of Technology, Dresden, Germany

Received 24 May 2008; accepted after revision 31 August 2008.

* Corresponding author. Tel: +48 510599279; fax: +48 12 6336744. E-mail address: anton_chrustowicz{at}yahoo.de (A.C.); Tel: +49 351 450 1410; fax: +49 351 450 1702. E-mail address: gsimonis{at}gmx.de (G.S.)


   Abstract
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 Abstract
Introduction
 Methods
 Results
 Discussion
 Conclusion
 Funding
 Notes
 References
 
Aims: The prognostic value of the right ventricular parameters in patients with heart failure (HF) is well documented, but the data on patients undergoing mitral valve repair are lacking.

Methods and results: The association between pre-operative right ventricular dilatation and outcome was studied in 70 consecutive patients with HF who underwent elective mitral valve repair. Mean age was 67 years, 71% were men, mean pre-operative NYHA class was 2.8, mean pre-operative ejection fraction was 31%, and 47% had atrial fibrillation. The ischaemic cardiomyopathy (ICM) was the cause of HF in 32% of the patients. Perioperative mortality was 7.1% by a median logistic Euroscore of 7.5 (range 1.3–47.5). During a mean follow-up of 887 days, 35% of the patients reached the combined endpoint of overall mortality or transplantation. Reoperation was performed in four patients. One and 3 years survival rates were 88% and 72%, respectively. By multivariate Cox analysis, right ventricular dilatation, ICM, and age significantly predicted the outcome.

Conclusion: Right ventricular dilatation is an important modulator of outcome in patients with HF and mitral regurgitation.

Keywords: Heart failure; Mitral regurgitation; Right ventricle; Mitral valve repair; Survival


   Introduction
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 Abstract
 Introduction
Methods
 Results
 Discussion
 Conclusion
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Heart failure (HF) is a major cause of morbidity and mortality in the developed world. Severe mitral regurgitation (MR) occurs in ~30% of the patients with chronic HF1–3 and carries a poor prognosis, with 1 and 3 years mortality rates of 30% and 50%, respectively.1,2 Mitral valve repair was an important development in cardiac surgery, offering preservation of left ventricular function, durable results, and no need for anticoagulation.4,5 Although a variety of factors are known to predict HF outcome,6 currently there is a limited number of investigations in patients with impaired left ventricle ejection fraction (LVEF) undergoing mitral valve repair for severe MR.7–14 Age,8 previous decompensation of HF,12 ischaemic aetiology of the HF, pre-operative NYHA class,7 LVEF,5 and serum creatinine6,15 are related to postoperative prognosis. Few investigations analysed the prognostic value of the right ventricular parameters. As the surgical techniques evolve and experience in the management of the patients improves, the results of mitral valve repair change. Understanding which factors are associated with survival may identify patients who are at higher risk. The purpose of this study was to find which parameters are related to the postoperative survival of the patients with HF undergoing mitral repair with focus on the right heart.


   Methods
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 Abstract
 Introduction
 Methods
Results
 Discussion
 Conclusion
 Funding
 Notes
 References
 
All consecutive patients with depressed left ventricular systolic function and severe MR who underwent elective mitral valve repair were retrospectively included. The inclusion criteria were: (i) patients with primary left ventricular dysfunction, LVEF <40% and severe, functional MR (ii) optimized medical therapy for HF at the time of referral for surgery. Exclusion criteria were: (i) significant aortic valve stenosis or regurgitation, (ii) emergency operation, (iii) need for concomitant CABG, and (iv) significant tricuspid regurgitation. The study was approved by the institutional review board.

Echocardiography
Echocardiographic measurements were performed according to the ASE/EAE recommendation.16 Assessment of the MR severity was based on vena contracta measurement and on the proximal isoconvergence velocity method.17 Right ventricular end-diastolic diameter was measured in the parasternal long-axis view perpendicular to the interventricular septum at the level of transition to the right ventricular outflow tract and, when necessary for confirmation of findings, quantitative assessment was completed in the parasternal short-axis view and in the four-chamber view.18 Pre-operative and intraoperative transesophageal echocardiography was performed in all patients.

Endpoints and statistics
The study endpoints were cardiac mortality and a combined endpoint of overall mortality and heart transplantation. Follow-up data were recorded from the medical documentation and by phone interview with the patient's cardiologist.

Continuous variables are expressed as mean ± standard deviation or median (25th and 75th percentiles). For continuous variables, the linearity assumption was verified.

NYHA class was analysed as a qualitative parameter (II vs. III and IV), due to significant non-linearity, as were age and LVEF, the cut-off points were based on the median (70 years and 30%, respectively). The right ventricular end-diastolic diameter was analysed as a continuous variable and as a stratified qualitative variable, the cut-off points being selected according to current recommendations18 to quantify the right ventricle as normal, slightly dilated, moderate, and severely dilated.

Variables with P < 0.05 by the univariate analysis were entered in the Cox multivariate regression with stepwise selection. Both forward and backward stepwise regressions were performed to test the consistency of the final model (P for entry 0.05 and P for removal 0.1). Residual analysis and omnibus tests of model coefficients were used for the evaluation of the model fit. Life table analysis was used for the survival analysis. For illustration purposes, the prognostic data of groups were estimated using the Kaplan–Meier method; P-values of <0.05 were interpreted as statistically significant. SPSS 15 software (SPSS Inc. Chicago, IL, USA) was used.


   Results
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Discussion
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Patients
Seventy consecutive patients were included in the study. The baseline characteristics are detailed in Table 1.


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  		Table 1 Baseline characteristics

 
At the time of the referral for surgery, 91.3% of the patients were receiving ACE inhibitors, 92.7% beta-blockers, and 78.2% loop diuretics. Ischaemic cardiomyopathy (ICM) was defined as an impaired left ventricular function which could be explained by the extent of the coronary artery disease or by previous myocardial infarction. All patients with ICM underwent interventional revascularization at a previous stage. 47.7% of the patients (n = 32) had been hospitalized at least once for decompensation of the HF before referral to surgery.

Surgical techniques
The surgical access technique was the median sternotomy in all patients. All patients had undersized flexible annuloplasty rings inserted (Carpentier-Edwards Physioring); mean ring size was 28.2 ± 1.8 mm, range 24–32 mm. The median duration of the cardiopulmonary bypass was 82 min.

Short-term results
All patients survived the initial procedure. Correction of MR was feasible in all patients with no patient having more than mild MR by intraoperative transesophageal echocardiography. Thirty-day mortality was 7.1% (five patients). Median logistic Euroscore was 6.9 in perioperative survivors and 12.6 in non-survivors. The cause of death was refractory HF in four patients and sepsis in one patient.

Late results
Mean follow-up time was 887 days (2.4 years). Re-intervention was necessary in four patients (5.7%): re-repair in two patients and valve replacement in two patients. Endocarditis occurred in two patients.

Twenty-five patients (35%) reached the combined endpoint of overall mortality or transplantation. End-stage HF was the primary cause of late death in 16 patients (22.8%), heart transplantation was performed in one patient. In the operative survivors, 1 and 3 years freedom of death or transplantation was 88% and 72%, respectively. For the entire cohort, 1 and 3 years freedom of death or transplantation was 81% and 66%, respectively. Predictors for cardiac death by univariate analysis were ICM (P = 0.02), right ventricular end-diastolic diameter (RVEDD) (P = 0.01), and age over 70 years (P = 0.02). For the combined endpoint of overall mortality and heart transplantation variables which achieved statistical significance by univariate analysis were ICM (P < 0.001), RVEDD (P = 0.01), and age over 70 years (P = 0.02). Candidate variables entered in the stepwise multivariate Cox regression were ICM, RVEDD, and age. For the multivariate analysis, two models were build: first included RVEDD analysed as a continuous variable and the second included the qualitative stratified RVEDD variable. Multivariate Cox analysis revealed that RVEDD was an independent predictor of outcome for both endpoints of late cardiac mortality (Table 2) and overall mortality and heart transplantation (Table 3 and Figure 1B).


Figure 1
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  		Figure 1 Overall survival of the patients according to ischaemic cardiomyopathy and RVEDD. ICM, ischaemic cardiomyopathy; RVEDD, right ventricular end-diastolic diameter.

 


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  		Table 2 Multivariate Cox regression: predictors for late cardiac death

 


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  		Table 3 Multivariate Cox regression: predictors for the combined endpoint

 

   Discussion
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The cause of right heart dilatation in patients with HF and MR is the increased right ventricular afterload. Feasibility for the assessment of right ventricular dimensions is high, with low inter- and intraobserver variability in normal subjects,19,20 as also in patients with COPD21 or arrhythmogenic right ventricular cardiomyopathy.22 RVEDD showed a satisfactory correlation with right ventricular ejection fraction in both normal subjects19 and patients with enlargement of the right ventricle.22 In patients with HF, RVEDD >31 mm had important prognostic implications.23 The discordance in degree of right and left ventricular dilation was a powerful predictor of survival in patients with dilated cardiomyopathy.15 Recent studies have focused on the role of the right heart parameters. In patients with HF, tricuspid annular plane systolic excursion had significant prognostic value; RVEDD was significantly higher in patients with lower tricuspid annular plane systolic excursion.24 Di Mauro et al.25 found that in patients with MR and impaired left ventricular contractility, tricuspid annular plane systolic excursion and tricuspid annular plane systolic velocity significantly predicted survival after mitral valve repair, the study did not included the analysis of the right ventricular size. Despite the fact that RVEDD is a standard component of the echocardiographic report,16,18 data on the prognostic role of right ventricular dilatation in patients with MR are lacking. The curved shape of the right ventricular free wall requires care when measuring the right ventricular dimensions by echocardiography and in cases with only mild right ventricular dilatation, confirmation of echocardiographic findings using multiple views may be required. The demonstrated importance of RVEDD in this study supports the need for inclusion of the right ventricle assessment in the prognostic evaluation of patients with severe MR and impaired LVEF.

The ICM was also a major predictor of outcome in the current study (Figure 1A). Because concomitant surgical revascularization influences survival,26 in this study we included patients with ischaemic heart disease who had revascularization at an earlier stage. Most previous studies found worse survival in patients with ICM,27–29 but there are few data comparing survival in patients with ischaemic or idiopathic cardiomyopathy after mitral valve repair. In the largest published trial in patients with mitral valve repair, Gillinov et al.30 compared two matched patient groups with ischaemic and degenerative MR. The study group involved ~50% patients with moderate or severe left ventricular dysfunction. The aetiology of MR had no influence on outcome but extents of coronary artery disease and left ventricular dysfunction. Five years survival was equal in the matched groups irrespective of the ischaemic or degenerative mechanism of MR.

Study limitations
The limitations of this study include the single centre experience, the lack of data on the right ventricular contractility, and the small number of patients.


   Conclusion
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conclusion
Funding
 Notes
 References
 
The present study found that in patients with HF undergoing mitral repair, right ventricular dilatation carries important prognostic information. Further multicentre detailed studies on the assessment of the right ventricle are needed.


   Funding
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 Funding
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A.C. was supported by a research grant from the European Society of Cardiology.

Conflict of interest: none declared.


   Notes
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{dagger} A.C. and G.S. contributed equally to this work. Back


   References
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 Discussion
 Conclusion
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