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Reviews

Early and late outcome of left ventricular reconstruction surgery in ischemic heart disease

^a Department of Cardiothoracic Surgery, Leiden University Medical Center, Leiden, The Netherlands
^b Atlanta Cardiovascular Research Institute, Atlanta, GA, USA
^c Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands

Received 4 March 2008; received in revised form 26 June 2008; accepted 27 June 2008.

^_* Corresponding author. Address: Department of Cardiothoracic Surgery, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands. Tel.: +31 71 5264022; fax: +31 71 5266965. (Email: r.j.m.klautz{at}lumc.nl).

	Abstract

Top Abstract 1. Introduction 2. Methods 3. Results 4. Discussion 5. Limitations References

 
A systematic review of the literature was performed to determine early and late mortality associated with left ventricular (LV) reconstruction surgery and to assess the influence of different surgical techniques, concomitant surgical procedures, clinical and hemodynamic parameters on mortality. The MEDLINE database (January 1980–January 2005) was searched and from the pooled data, hospital mortality and survival were calculated. Summary estimates of relative risks (RR) were calculated for the techniques that were used and for concomitant coronary artery bypass grafting (CABG) and mitral valve surgery. The risk-adjusted relationships between mortality and clinical and hemodynamic parameters were assessed by meta-regression. A total of 62 studies (12,331 patients) were identified. Weighted average early mortality was 6.9%. Cumulative 1-year, 5-year and 10-year survival were 88.5%, 71.5% and 53.9%, respectively. Endoventricular reconstruction (EVR) showed a reduced risk for both early (RR = 0.79, p < 0.005) and late (RR = 0.67, p < 0.001) mortality compared to the linear repair (early: RR = 1.38, p < 0.001; late: RR = 1.83, p < 0.001). Early and late mortality were mainly cardiac in origin, with as predominant cause heart failure in respectively 49.7% and 34.5% of the cases. Ventricular arrhythmias caused 16.6% of early deaths and 17.2% of late deaths. Concomitant CABG significantly decreased late mortality (RR = 0.28, p < 0.001) without increasing early mortality (RR = 1.018, p = 0.858). Concomitant mitral valve surgery showed both an increased risk for early (RR = 1.57, p = 0.001) and late mortality (RR = 4.28, p < 0.001). No clinical or hemodynamic parameters were found to influence mortality. It is noteworthy that only one third of patients included in the current analysis were operated for heart failure (14 studies, 4135 patients). In this group we noted an early mortality of 11.0% with a late mortality (3-year) of 15.2%. This analysis of pooled literature data showed that LV reconstruction surgery is performed with acceptable mortality and EVR may be the preferred technique with a reduced risk for early and late mortality. Concomitant CABG improved outcome, whereas the need for mitral valve surgery appeared an index of gravity. No clinical or hemodynamic parameters were found to influence mortality; specifically LV ejection fraction and LV volumes both did not predict outcome.

Key Words: Left ventricular reconstruction surgery • Aneurysmectomy • Surgical ventricular restoration • Dor procedure • Ischemic heart disease • Heart failure

	1. Introduction

Top Abstract 1. Introduction 2. Methods 3. Results 4. Discussion 5. Limitations References

 
The formation of scar tissue after myocardial infarction leads to changes in left ventricular (LV) shape and function (remodeling) [1]. The normally elliptical LV tends to sphericity and chamber dilatation, while the transmurality of the myocardial scar determines whether or not a true LV aneurysm (dyskinetic segment) will develop [2]. Likoff and Bailey described the first aneurysmectomy in 1952 [3], subsequently followed by the first aneurysmectomy with linear repair using cardio-pulmonary bypass reported by Cooley in 1958 [4]. A number of different surgical techniques and modifications have since developed to restore LV shape and to improve LV function [4–9]. The most commonly used techniques are the endoventricular repair (EVR), with or without the use of an endoventricular patch, introduced by Dor in 1985 [4] and the aforementioned linear repair. Dor et al. demonstrated the feasibility of his procedure not only for the true LV aneurysms with a dyskinetic segment, but also for remodeled left ventricles with extensive akinesia [2]. Surgeons who advocate the different surgical techniques, all report on good short- and long-term results. Only a few reports are available that compare different surgical techniques, particularly in respect to long-term results [10–15,75]. The aims of this study were:

1. to compare early and late mortality in LV reconstruction surgery using different surgical techniques, based on pooled analysis of literature studies,

2. to evaluate the causes of early and late mortality in LV reconstruction surgery,

3. to evaluate the influence of factors including concomitant surgical procedures, clinical and hemodynamic parameters on early and late mortality.

LV reconstruction surgery is increasingly being employed as an alternative surgical therapy for patients with ischemic heart failure. In these patients the issues listed above are particular important and therefore a sub-analysis was conducted for this category of patients.

	2. Methods

Top Abstract 1. Introduction 2. Methods 3. Results 4. Discussion 5. Limitations References

 
2.1 Review of published reports
The studies were identified by means of several combined search strategies: (1) A search of the MEDLINE database (January 1980–January 2005) was conducted using the following Keywords: ‘left ventricular aneurysm’, ‘left ventricular restoration’, ‘surgical ventricular restoration’, ‘left ventricular remodeling surgery’, ‘aneurysmectomy’, and ‘Dor procedure’. (2) A manual search of six cardiothoracic surgery and cardiology journals (Annals of Thoracic Surgery, Journal of Thoracic and Cardiovascular Surgery, European Journal of Cardiothoracic Surgery, Thoracic and Cardiovascular Surgery, Circulation and Journal of the American College of Cardiology). (3) The reference lists of the reports obtained through these searches were screened for additional articles that may have been missed. Only articles in English were considered, and reviews, editorials, animal or in vitro experimental studies, abstracts and articles concerning LV reconstruction surgery for non-ischemic heart disease were disregarded. The most recent publication or the publication concerning the largest patient population was included for analysis if multiple publications were available from the same institute to avoid double counting.

2.2 Statistical analysis
The following parameters were extracted from each article and entered into the database: pooled, average and median rates of in-hospital mortality and survival, specified causes of death (whether cardiac, subdivided in heart failure, ventricular arrhythmias, acute myocardial infarction and other, non-cardiac or unknown), follow-up duration, mean age, gender, interval post myocardial infarction, patients with ischemic heart failure (defined as LV ejection fraction (EF) 35% and New York Heart Association (NYHA) class III or IV), surgical technique used, mortality and survival with concomitant CABG and mitral valve surgery, LVEF, LV end-diastolic volume index (LVEDVI), LV end-systolic volume index (LVESVI), LV end-diastolic dimension (LVEDD) and LV end-systolic dimension (LVESD). From the data, pooled, median and weighted-average early and late mortality were calculated. Cumulative survival was calculated from the pooled late mortality. Using comprehensive meta-analysis software (Borrestein M, Hedges L, Higgins J, Rothstein H. Comprehensive meta-analysis Version 2, Biotstat, Englewood, NJ (2005)), the summary estimates of relative risks (RR) were calculated for the different surgical techniques that were used and for concomitant CABG and mitral valve surgery. The relative risk (with 95% confidence intervals, CI) was calculated using a random effects model. The risk-adjusted relationship between mean age, time from infarction, LVEF, LVEDVI, LVESVI, LVEDD and LVESD and hospital mortality and survival was assessed by meta-regression. A sub-analysis on survival in patients with heart failure was conducted. A Chi-square test from homogeneity was calculated and Fisher's exact test was used for comparing events. A p value <0.05 was considered significant.

	3. Results

Top Abstract 1. Introduction 2. Methods 3. Results 4. Discussion 5. Limitations References

 
Two hundred and eight citations were returned and the articles scrutinized. After excluding non-English articles, reviews, editorials, animal or in vitro experimental studies, abstracts and articles concerning LVRS for non-ischemic heart disease, 121 articles were evaluated. After exclusion of all but the most recent publication from the same institute and those not reporting deaths, 62 articles [10–70] were entered into the pooled analysis.

3.1 Early and late mortality in LV reconstruction surgery
Pooling of all data from the 62 studies [10–70] (12,331 patients) showed a pooled early mortality (defined as in-hospital or 30-day mortality) of 6.8% and a median early mortality of 7.9%. Weighted average early mortality is 6.9%.

Forty-seven studies also reported on long-term survival [11–53,71–74], following 8571 patients for a median of 49 months. Cumulative 1-, 5- and 10-year survival was 88.5%, 71.5% and 53.9%, respectively (Fig. 1 ).

View larger version (12K): [in this window] [in a new window]   Fig. 1. Cumulative survival after LV reconstruction surgery calculated from 62 published reports (n = 12,331 patients) that reported on early mortality and 47 published reports following 8571 patients for a median of 49 months (25th, 75th percentile = 23, 62 months). Cumulative 1-, 5- and 10-year survival were 88.5%, 71.5% and 53.9%, respectively. Straight line: weighted average cumulative survival; dotted lines: 95% confidence intervals.

View larger version (11K): [in this window] [in a new window]   Fig. 2. Summary estimates of the relative risks for the different surgical techniques for early mortality. Comparing the two main techniques, EVR showed a reduced risk for early mortality (RR = 0.79, p = 0.002) compared to the linear repair (RR = 1.38, p < 0.001). LVRS: LV reconstruction surgery; Circular: direct reconstruction of LV wall using a circular patch; EVR: endoventricular reconstruction of the LV with or without a patch; linear: linear repair; linear with septoplasty: linear repair with a plasty of the interventricular septum; septo-exclusion: septo-exclusion technique.

View larger version (12K): [in this window] [in a new window]   Fig. 3. Summary estimates of the relative risks for the different surgical techniques for late mortality. Comparing the two main techniques, EVR showed a significantly reduced risk on late mortality (RR = 0.67, p < 0.001) compared to the linear repair (RR = 1.83, p < 0.001). LVRS: LV reconstruction surgery; Circular: direct reconstruction of LV wall using a circular patch; EVR: endoventricular reconstruction of the LV with or without a patch; linear: linear repair; linear with septoplasty: linear repair with a plasty of the interventricular septum; septo-exclusion: septo-exclusion technique.

View larger version (10K): [in this window] [in a new window]   Fig. 4. Comparison of left ventricular reconstruction surgery with concomitant CABG or mitral valve surgery on early (inhospital or 30-day mortality) and late (5-year) mortality. Concomitant CABG was not associated with an increased risk for early mortality (RR = 1.018, p = 0.858), but was associated with a significantly lower risk for late mortality (RR = 0.28, p < 0001). Concomitant mitral valve surgery was associated with both an increased risk for early (RR = 1.57, p = 0.001) and late mortality (RR = 4.28, p < 0.001). MVR: mitral valve surgery (repair or replacement); CABG: coronary artery bypass grafting.

3.6 Heart failure
Fourteen of the 62 (22.6%) reports included LV reconstruction surgery in patients with heart failure, with a total of 4135 patients. The pooled, median and average weighted early mortality patients with heart failure were 5.2%, 12.9% and 11.6%, respectively. Ten studies (802 patients) also reported on late mortality after LV reconstruction surgery showing a pooled, median and average weighted late mortality at 3-year follow-up of 15.7%, 14.7% and 15.7%, respectively (Fig. 5 ). Eight studies (n = 2376 patients) reported on EVR and early mortality in ischemic heart failure patients, four studies (1045 patients) reported on linear repair and early mortality in ischemic heart failure patients. Comparison of these two techniques for the relative risk of early mortality, revealed a significantly reduced risk for early mortality with EVR (RR = 0.66, p = 0.004, Fig. 6 ). There were no statistical significant relationships for any of the parameters postulated to possibly influence early and late mortality.

View larger version (14K): [in this window] [in a new window]   Fig. 5. Early (inhospital or 30-day mortality) and late (3-year) mortality in patients with heart failure. The pooled, median and average weighted early mortality (14 studies, n = 4135 patients) were 5.2%, 12.9% and 11.6%, respectively. The pooled, median and average weighted late mortality (10 studies, n = 802 patients) were 15.7%, 14.7% and 15.7%, respectively.

View larger version (5K): [in this window] [in a new window]   Fig. 6. Summary estimates of the relative risk for EVR (8 studies, n = 2376 patients) versus linear repair technique (4 studies, n = 1045 patients) in patients with heart failure. EVR shows a significantly reduced risk for early mortality (RR = 0.66, p = 0.004). EVR: endoventricular reconstruction of the LV with or without a patch; linear: linear repair.

	4. Discussion

Top Abstract 1. Introduction 2. Methods 3. Results 4. Discussion 5. Limitations References

4.1 Surgical techniques and mortality
Comparing the two most used and reported techniques, endoventricular reconstruction of the LV with or without a patch (EVR) and linear repair, EVR shows a significantly reduced risk for early mortality (RR = 0.79, p = 0.002). The linear repair technique cannot exclude the septal scar, and also carries the risk of creating a restrictive residual LV cavity, especially in large aneurysms, leading to diastolic dysfunction and LV failure [27,78,79]. Sizing of the residual LV cavity in EVR, either by an intracavitary balloon or a commercially available shaper device to a volume of 50–60 ml/m² BSA avoids creating a residual LV cavity that is restrictive [9,29,39]. Another explanation for EVR to show better results could be that EVCPP patients were operated in a more recent era with improved myocardial protection, anesthesiological techniques, and perioperative care. Because of the limited number of patients in the currently available reports, the relative risks for early mortality calculated for the linear repair with septoplasty, and the septo-exclusion techniques did not reach statistical significance. The reconstruction of the LV wall using a circular patch did however show a significantly reduced risk for early mortality (RR = 0.60, p = 0.001), but again patient numbers for this technique are limited. In the meta-analysis by Parolari et al. concerning the early outcomes following different LV reconstruction techniques, the authors also concluded that geometric reconstruction carries a reduced risk for early mortality compared to linear repair [90]. In contrast, in a sub-analysis comparing geometric and linear reconstruction techniques that were carried out in the same time lag, a difference in early mortality could not be demonstrated. Mukaddirov et al. recently published a study advocating a tailored approach (linear or patch plasty repair) in LVR depending on the specific anatomy of individual patients [99].

In the current pooled analysis, EVR also showed a significantly reduced risk for late mortality (RR = 0.67, p < 0.0001). Possibly, the complete exclusion of the septal scar and the more anatomical reconstruction leading to a more efficient myocardial fiber orientation and systolic function contributed to this reduction in late mortality [9,80]. Also the fact that grafting the left anterior descending coronary artery is more feasible in the EVR technique and may play a role [11,81,78]. The linear repair with septoplasty and direct reconstruction of the LV wall using a circular patch also both showed a significantly reduced risk for late mortality (RR = 0.72, p = 0.007 and RR = 0.63, p < 0.0001, respectively), but for both techniques available patient numbers are limited.

The factors that may have contributed to the reduced risk for mortality with the EVR technique in the pooled analysis of all patient categories may be even more important in patients with heart failure. Generally, these patients often have severely enlarged LV volumes, associated with depressed contractile function of the remote myocardium [88,89]. Indeed, we noted that in heart failure patients both early and late mortality were less with the EVCPP technique.

4.2 Fatal-failure modes of LVR
It was noted that 50% of early deaths and 30% of late deaths were caused by heart failure. With respect to the technique of reconstructing the LV cavity, three possible explanations exist for early and late LV failure: first, the aforementioned problem of creating a restrictive residual LV cavity, leading to diastolic dysfunction and LV failure; second, leaving a too large residual LV cavity only partially reverses the remodeling process and may lead to redilatation of the left ventricle. Also a residual large akinetic area has been mentioned as possible cause for redilatation. Ueno et al. demonstrated redilatation and increasing sphericity after Dor- and SAVE-procedures at intermediate follow-up, resulting in increased wall tension with reduced compliance as possible causes for late heart failure [92]. Raman et al. associated the use of a stiff and relatively big patch in EVR as cause for some adverse long-term outcomes [94]. Patch size, shape and orientation may prove to be important in preventing adverse ventricular remodeling over time, as Cirillo et al. have shown in a small group with an EVR technique using a small, obliquely oriented and oval-shaped patch [93]. Third, insufficient residual remote myocardium to survive the procedure and to translate the surgically induced morphological changes to functional improvement leads to LV failure. No data are available on preoperative assessment of the functional capacity of the remote myocardium and used as predictor of outcome after LV reconstruction surgery.

Early and late mortality due to ventricular arrhythmias in this study were 16.5% and 17.2%, respectively (of note, it is unknown whether these patients already had ventricular arrhythmias preoperatively). Early ventricular arrhythmias after LV reconstruction surgery can be ascribed to electrolyte abnormalities, tissue edema and inflammation. Late ventricular arrhythmias have been related to ventricular dilatation with high wall stress and stretch [96]. It has been postulated that LV reconstruction surgery due to volume reduction reduces arrhythmogenicity. Exclusion of the myocardial scar, concomitant complete revascularization and mechanical resynchronization further reduces the trigger for electrical instability and may render the need for an implantable cardioverter-defibrillator (ICD) unnecessary [96,97]. Some authors like Dor et al. [79] and Mickleborough et al. [5] advocate routine use of concomitant endocardiectomy of the border zone of viable and non-viable myocardium and cryotherapy to further decrease the risk of ventricular arrhythmias. These authors have reported a low late incidence of ventricular arrhythmias with this strategy. The relatively high incidence of death due to ventricular arrhythmias observed in the present pooled analysis raises the question whether LV reshaping with volume reduction, scar exclusion and revascularization is sufficient anti-arrhythmogenic to make adjunctive device therapy of little use. O’Neill et al. demonstrated a high incidence of ventricular arrhythmias after LV reconstruction surgery and advocate the use of predischarge electrophysiological studies and/or ICD implantation before hospital discharge [98]. More studies are needed to clarify the need for device therapy after LV reconstruction surgery.

4.3 Concomitant surgical procedures potentially influencing mortality
We found that concomitant myocardial revascularization with LV reconstruction surgery improved late survival without increasing the risk for early mortality. Besides symptomatic relief of angina, revascularization of viable, remote myocardium in non-scarred segments may improve compensatory contractile function [82]. Also, revascularization of the proximal left anterior descending coronary artery to improve septal perfusion may contribute favorably [11]. Another contributing factor could be that revascularization further reduced the risk for late ventricular arrhythmias. These factors probably outweigh the increase in operative and extra-corporal circulation time and thus did not result in higher early mortality. This finding underlines the importance of (complete) revascularization in these patients.

Concomitant mitral valve surgery, whether repair or replacement, shows an increased risk for early (RR = 1.57, p = 0.001) and late mortality (RR = 4.28, p < 0.001). In patients with previous anterior myocardial infarction, functional mitral regurgitation occurs mainly in the setting of LV dilatation, with tethering of the mitral valve leaflets, displacement of the subvalvular apparatus and dilatation of the mitral annulus causing secondary incompetence of the mitral valve. Functional mitral regurgitation therefore mainly reflects a more advanced stage of disease, and has been shown to be associated with an increased mortality, independent of the degree of underlying LV dysfunction [85–87]. The need for mitral valve surgery in LV reconstruction surgery is therefore an index of gravity. This is by no means an argument not to perform mitral valve surgery in these patients, since mitral regurgitation-related volume overload has been shown to promote further LV remodeling and progression of heart failure. Correcting mitral regurgitation improves clinical functional class and may prevent LV redilatation [39,72,91]. However, this analysis does not permit any conclusion on the benefits of mitral valve surgery, since no comparison between treated and non-treated patients was available in the literature.

4.4 Factors potentially influencing mortality
Besides the surgical technique and concomitant procedures, a number of parameters have been traditionally identified that influence early and late mortality. A low LVEF has been reported in earlier reports to be a predictor of higher early and late mortality [12,49,51,80]. The observation that LV dilatation is more closely related to outcome than (decreased) LVEF was first described by White at al., showing the correlation between increased LV volumes after myocardial infarction with increased mortality [83]. This work was subsequently confirmed by DiDonato et al. and Dor et al. for ventricular restoration procedures [26].

These authors have published that mortality after EVR procedures increased with larger preoperative LV volumes, irrespective of baseline LVEF [82]. Interestingly, we could neither confirm the relationship of LVEF with mortality, nor that of LV volumes in the current pooled analysis. An important explanation for this phenomenon may be the heterogeneity in the functional capacity of the residual remote myocardium. Since stroke volume is relatively constant at rest, LVEF is mainly determined by the LV end-diastolic volume. If the LV end-diastolic volume is large due to a localized (dyskinetic) scar tissue, the improvement in LVEF after a LVR procedure will parallel improvement in function. On the other hand, if the LV end-diastolic volume is large due to remodeling or cardiomyopathy, a reduction will not be accompanied by improvement in LV function. Therefore neither LVEF, nor LV volumes per se can predict improvement in LV function and outcome [84]. The failure of LVEF, LV volumes, age, gender and time interval post-myocardial infarction in predicting outcome, questions the use of these parameters in risk stratification for these patients. Newer models using advanced imaging techniques that can test for the functional capacity of the remote myocardium, like (contrast-enhanced) magnetic resonance imaging or (3D) echocardiographically derived wall motion score indexes, may prove useful for improved risk stratification.

	5. Limitations

Top Abstract 1. Introduction 2. Methods 3. Results 4. Discussion 5. Limitations References

 
A pooled analysis, when well designed and appropriately performed, is a powerful tool to combine in a single conclusion the results of different studies conducted on the same topic. Random effect models were used to control for within-study and between-study variability (random effects modeling). In addition, meta-regression analysis was used to adjust for the influence of patient demographics and prognostic indicators that covaried with the dependent variable. Despite the advantages of a pooled analysis, such as increased statistical power of a comparison and improved estimation of the effect of a treatment, several limitations of the current analysis should be addressed. Publication bias may have influenced our results, since observational studies with a poor outcome may not have been published in full-length papers. Second and most important, surgical techniques and approaches have improved over time, which affects the current results. Third, since to date no prospectively randomized controlled trials have been published concerning LV reconstruction surgery, all studies included in this analysis were observational reports.

	References

Top Abstract 1. Introduction 2. Methods 3. Results 4. Discussion 5. Limitations References

 

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