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J Thorac Cardiovasc Surg 2008;136:1514-1521
© 2008 The American Association for Thoracic Surgery

Acquired Cardiovascular Disease

Use of quantitative analysis of remote myocardial fibrosis with delayed-enhancement magnetic resonance imaging to predict outcomes after surgical ventricular restoration for ischemic cardiomyopathy

^a Division of Cardiovascular Surgery, Department of Surgery, Osaka University Graduate School of Medicine, Suita, Japan
^b Department of Radiology, Osaka University Graduate School of Medicine, Suita, Japan

Received for publication December 23, 2007; revisions received February 12, 2008; accepted for publication March 23, 2008.

^_* Address for reprints: Goro Matsumiya, MD, Division of Cardiovascular Surgery, Department of Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, Japan. (Email: matsumg{at}surg1.med.osaka-u.ac.jp).

	Abstract

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Objective: Preserved myocardial function remote from surgical site is crucial for good outcome after surgical ventricular restoration in ischemic cardiomyopathy. We hypothesized that left ventricular scarring untouched by operation would negatively affect postoperative outcome.

Methods: In 15 consecutive patients (mean age 61 ± 12 years, mean left ventricular ejection fraction 20% ± 7.5%), left ventricular assessments by magnetic resonance imaging and right heart catheterization were performed before and after operation. Left ventricular basal scarring remote from surgical exclusion site was quantified from hyperenhancement area on preoperative delayed-enhancement magnetic resonance imaging as percentage of fibrosis (total infarct size relative to ventricular mass).

Results: Calculated percentage of fibrosis varied from 0% to 29.9% (mean 12% ± 9.6%). Percentage of fibrosis linearly correlated with significantly worse postoperative hemodynamic variables and left ventricular function recovery: left ventricular ejection fraction (P = .0005, R = –0.79), left ventricular end-systolic volume index (P = .05, R = 0.51), mean pulmonary arterial pressure (P = .004, R = 0.70), pulmonary capillary wedge pressure (P = .009, R = 0.65), and cardiac index (P = .005, R = –0.69). At mean 30-month follow-up, 4 patients with recurrent heart failure had significantly greater percentage of fibrosis than did those without recurrence (19% ± 8.2% vs 8.8% ± 8.6%, P = .04).

Conclusion: Amount of myocardial scarring at left ventricular base affected postoperative left ventricular function and hemodynamic improvements. Preoperative quantitative assessment of remote myocardial status with delayed-enhancement magnetic resonance imaging may predict outcomes for patients undergoing surgical ventricular restoration.

	Introduction

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Surgical ventricular restoration (SVR) is increasingly being used as a treatment for ischemic cardiomyopathy. Several reports, including the RESTORE (the international Reconstructive Endoventricular Surgery returning Torsion Original Radius Elliptical shape to the left ventricle) group experience, have shown good midterm to long-term survivals with acceptable operative mortality.^1-5 Current relative contraindications for SVR are severe pulmonary hypertension, right ventricular dysfunction, and diastolic dysfunction with severe mitral regurgitation.^3,4,6 Several recent studies, however, have suggested that SVR is not necessarily contraindicated for patients with those presumed high surgical risks.^7-9 Although the ongoing Surgical Treatment for Ischemic Heart Failure trial may address open and controversial issues about SVR in patients with ischemic heart failure,¹⁰ there is currently no consensus regarding indications for SVR.

Preoperative assessment of myocardial status can provide a meaningful perspective on the application of SVR. To predict whether myocardium remains stunned or hibernating or has been irreversibly infarcted, magnetic resonance imaging (MRI) is now gaining widespread use.^2,4,9,11 Especially, delayed-enhancement MRI (DE-MRI) is an important diagnostic tool to determine the nonfunctional infarcted area that should be excluded with SVR.^11,12 Moreover, it provides additional information regarding the myocardial status remote from the region of planned exclusion.¹¹ Because remote myocardial asynergy directly affects the surgical outcome,^3,13 assessment of remote myocardial status with DE-MRI may be critical in patient selection. No study to date, however, has quantitatively investigated how much viable remote myocardium is crucial for a good outcome.

In this study, we focused on the amount of remote myocardial fibrosis, especially left ventricular (LV) basal fibrosis, quantitatively assessed by DE-MRI, and evaluated the correlation with surgical outcomes to elucidate appropriate risk stratification.

	Materials and Methods

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Patients
Ethical committee approval was obtained for this retrospective study, and informed consent was obtained from all patients. We included 15 consecutive patients who underwent DE-MRI study for the assessment of myocardial status before SVR between 2001 and 2007. The patients underwent MRI study 4.1 ± 1.1 weeks before the operation. Table 1 shows preoperative clinical profiles of all the patients. There were 12 men and 3 women, with a mean age of 61 ± 11 years (42–77 years). Thirteen patients (86.7%) were in New York Heart Association (NYHA) functional class III or IV. SVR was performed for large anteroseptal scars (4 dyskinetic and 11 akinetic). Seven patients had a history of another myocardial infarction in the territory of the circumflex or right coronary artery. Mean delay from first anterior myocardial infarction to the operation was 961 ± 950 days, and all patients had a chronic process of LV remodeling. No one had a preoperative history of spontaneous ventricular arrhythmia.

View larger version (87K): [in this window] [in a new window]   Figure 1. Preoperative and postoperative long-axis delayed-enhancement magnetic resonance images in patient with anteroapical dyskinetic aneurysm. Preoperative image shows transmural hyperenhancement area at anteroapical wall (A, arrowheads). After operation, hyperenhancement area was completely excluded with endoventricular patch (B, arrows).

Quantitative Assessment of Myocardial Scar Tissue
We specifically evaluated the LV basal scar tissue remote from the site of surgery. Quantification of the scarred myocardium was performed with the two most basal DE-MRI images just beneath the aortic valve, which represented the most basal part of the LV ( Figure 2). In this study population, there were no patients in whom anteroseptal myocardium at the most basal part had been entirely infarcted with the transmural extent of hyperenhancement tissue. The most LV basal images were carefully defined in consensus by two observers (K.T. and G.M.). To quantify the myocardial mass of the LV, the endocardial and epicardial borders were traced for each slice. Hyperenhancement area was defined as any region with a signal intensity at least 2 SD above a reference normal myocardial region.¹⁷ The hyperenhancement regions were automatically contoured, and the area of hyperenhancing tissue was calculated. DE-MRI analysis was verified by an experienced observer (S.H.) blinded to the surgical procedure. Measurement of hyperenhancement area was repeated three times in each case to minimize the potential errors, and the mean was used as the final value. Then the volumes of the LV wall and scarred myocardium were calculated by adding the areas and multiplying the resulting value with slice thickness. We expressed hyperenhancement mass as a percentage of the LV mass (percentage of fibrosis).

View larger version (125K): [in this window] [in a new window]   Figure 2. Representative short-axis delayed-enhancement magnetic resonance images of left ventricular base in patients with anteroseptal infarction (A), anteroseptal with posterolateral infarction (B), and anteroseptal with inferoposterior infarction (C). Myocardial scarring was clearly identified as hyperenhancement region (arrow).

Neurohormonal Assessment
Serum brain natriuretic peptide was measured at the time of preoperative and postoperative MRI studies.

Postoperative Medical Regimens
Most patients had postoperative heart failure regimens, including β-blockers, angiotensin-converting enzyme inhibitors, or angiotension II receptor blockers, and spironolactone. Three patients who had postoperative ventricular arrhythmia develop were treated with amiodarone.

Statistical Analysis
SPSS software (version 11.0; SPSS Inc, Chicago, Ill) was used for statistical analyses. The quantitative data are presented as mean ± SD. Values obtained from preoperative and postoperative data were compared with the paired t test. The unpaired t test was used to compare the groups. The continuous variables were compared with linear regression analysis.

	Results

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Early Outcomes
All patients tolerated the operation, and 30-day mortality was nil. Three patients required intra-aortic balloon pumping but could be weaned in the early perioperative period. One patient who had refractory ventricular tachycardia develop required an implantable defibrillator in the early postoperative period. Postoperative hemodynamic and functional parameters were improved significantly. NYHA functional class improved significantly, from 3.2 ± 0.6 preoperatively to 1.9 ± 0.8 postoperatively (P < .0001). Degree of mitral regurgitation was less than grade 2 in all patients postoperatively and decreased significantly, from 2.0 ± 1.5 to 0.2 ± 0.4 (P = .002). Serum brain natriuretic peptide level decreased significantly, from 640 ± 731 pg/mL to 358 ± 454 pg/mL (P = .02). In all cases, SVR improved LVEF and LV volumes. LV end-diastolic volume index decreased from 169 ± 51 mL/m² to 105 ± 37 mL/m² (P < .0001), and LVESVI decreased from 134 ± 50 mL/m² to 74 ± 34 mL/m² (P < .0001). LVEF improved from 20% ± 7.5% to 31% ± 10% (P = .0001). Mean change in ejection fraction (EF) was 10% ± 6.9%. Mean PAP decreased from 26 ± 10 mm Hg to 22 ± 7.1 mm Hg, but this change did not reach statistical significance (P = .06). There were no significant differences between preoperative and postoperative values of PCWP (18 ± 7.6 mm Hg vs 15 ± 6.8 mm Hg, P = .28) and cardiac index (2.4 ± 0.4 L/[min · m²] vs 2.6 ± 0.6 L/[min · m²], P = .28).

Distribution of Hyperenhancement Area on DE-MRI
There was no hyperenhancement area on the LV base in 2 patients with dyskinetic anteroapical aneurysm. Among the remaining 13 patients, hyperenhancement area was identified at the anteroseptal wall in 6 cases and at the anteroseptal with the lateral or inferior wall or both in 7 cases ( Figure 3). Percentage of fibrosis ranged from 0% to 29.9%, with a mean value of 12% ± 9.6%. In particular, patients with a history of left main trunk occlusion (Figure 2, B) or large inferoposterior myocardial infarction (Figure 2, C) had a larger percentage of fibrosis. At the basal area analyzed by MRI in this study, the former group of patients had diffuse subendocardial anteroseptal to lateral scarring, whereas the latter group had near-transmural inferoposterior scarring.

View larger version (9K): [in this window] [in a new window]   Figure 3. Location of myocardial scarring on LV base and percentage of fibrosis in individual patient. AS, Anteroseptal wall; AS+I/L, anteroseptal with inferior or lateral wall.

View larger version (17K): [in this window] [in a new window]   Figure 4. Scatter graphs showing linear regressions between percentage of fibrosis and postoperative (Post) left ventricular ejection fraction (LVEF), left ventricular end-systolic volume index (LVESVI), mean pulmonary arterial pressure (PAP), pulmonary capillary wedge pressure (PCWP), and cardiac index (CI).

View larger version (163K): [in this window] [in a new window]   Figure 5. Heart specimen showing basal ventricular section 3.7 months after operation. Note broad inferoposterior transmural infarction (black arrows) consistent with findings on preoperative short-axis delayed-enhancement magnetic resonance imaging (upper left inset, white arrows). A, Anterior wall; LV, left ventricle; S, septum, RV, right ventricle; I, inferior wall.

View larger version (10K): [in this window] [in a new window]   Figure 6. Relationship between latest New York Functional Heart Association (NYHA) functional class and percentage of fibrosis. Filled circles indicate patients with recurrent congestive heart failure (CHF). Two of these patients died, and 2 recovered from New York Heart Association class III to II after medical treatments.

	Discussion

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We found a significant correlation between percentage of fibrosis and lesser improvement of postoperative LV systolic function and symptoms (Figure 4). Our data indicate the extent of LV basal fibrosis is associated with postoperative global cardiac function. Theoretically, resection of the akinetic or dyskinetic scar tissue and reshaping of the spherical LV to a more elliptical shape by SVR reduces wall stress and produces a more helical fiber orientation, which improves regional myocardial performance in remote viable muscle.¹⁸ Various previous studies have confirmed this theoretic benefit of SVR. Taniguchi and coworkers¹⁹ reported that reduction of regional afterload by LV aneurysmectomy improved velocity of circumferential shortening in noninfarcted myocardial segments. With regard to remote myocardial performance, Dor and colleagues² and Dor and Di Donato¹³ showed its importance with the centerline method on ventriculography. Some studies wtih MRI tagging methods have also shown improvements in regional myocardial function after SVR to be most marked at the base LV and in the inferior wall, remote from the surgical site.^20,21 Consequently, these studies, including our own, demonstrate that residual remote myocardial function, especially LV basal function, generates the improvement in global LV systolic function after SVR.

Our patients underwent various surgical interventions, including revascularization and reduction of mitral regurgitation, that also improve global pump function. There are still no conclusive data regarding the role of SVR in itself for ischemic cardiomyopathy because of the lack of randomized studies. The Surgical Treatment for Ischemic Heart Failure trial may address these controversial issues in a randomized, controlled setting.¹⁰

Interestingly, percentage of fibrosis had significant positive correlations with postoperative mean PAP and PCWP, which were sustained even after the aggressive correction of mitral regurgitation by restrictive annuloplasty. This finding indicates the role of the elevation of LV filling pressure as a result of reduced compliance of the LV after SVR related to the extent of remote myocardial fibrosis. Previous reports have demonstrated that SVR contributed to the rise in mean PAP by reducing compliance of the LV in some patients.²² Most recently, Menicanti and colleagues³ clearly showed that patients with severe diastolic dysfunction had an increased operative risk during SVR.³ In addition to the systolic impairment, extent of infarct scarring contributed to abnormal ventricular chamber stiffness with diastolic dysfunction in an experimental animal model of myocardial infarction.²³ Our data therefore suggest that patients with broad LV basal scarring seen on DE-MRI may have substantial risks with SVR in terms of diminished compliance of the LV.

In this small series, we achieved acceptable early results with respect to improvements in LV function and functional status and decrease in brain natriuretic peptide level. The average increase in LVEF of 10% ± 6.9% is similar to values reported in other series^1,3-6; however, there are still no obvious data on which patients will have meaningful recovery after SVR. In our series, 6 patients had less benefit in terms of systolic improvement (EF <10%). They had significantly larger percentages of fibrosis, although their degree of preoperative LV remodeling was similar to that of patients with good improvement (EF >10%; Table 3). This result was consistent with the previous recommendation of Menicanti and Di Donato⁶ that poor basal function may be a relative contraindication for SVR. Because of poor postoperative recovery of systolic function, patients with poor basal function are likely to be a high-risk group, as previous studies have demonstrated.^1,3,4,6 Actually, in our population, patients with postoperative heart failure symptoms had significantly higher percentage of fibrosis (Table 4). Although our study did not have statistically sufficient power to clarify a risk factor for adverse outcome because of the small number of patients, our results do imply that remote myocardial fibrosis visible on DE-MRI could be a key determinant in patient selection for SVR. A further study including a larger population is needed to elucidate an optimal cutoff value of percentage of fibrosis to predict late adverse outcomes.

	Limitations

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There are several limitations of this study. The number of patients was small, and selection bias is possible. Another limitation is the lack of later imaging studies. For instance, myocardium may take as long as 1 year to respond to coronary revascularization.²⁴ In our study, 10 of 15 patients underwent CABG concurrently with SVR. Time course of myocardial recovery may have influenced postoperative global LV function and degree of reverse LV remodeling.

Regarding the technical aspects, a variety of surgical procedures could influence outcomes. SVR is still not a standard technique, however, and the optimal choice remains to be investigated. We agree with Suma and associates⁵ that the extent of visible endocardial scarring is not a reliable indicator of the borders between functioning and nonfunctioning wall, especially in broad akinetic aneurysms.⁵ In this study period, with the aid of both preoperative DE-MRI evaluation of the extent of nonviable scar tissue and intraoperative myocardial inspection under the beating heart, we used the SAVE procedure for broad anteroseptal akinesia to exclude as much scar tissue as possible and to create the elliptical LV shape.¹⁴

Finally, quantification of myocardial hyperenhancement on DE-MRI was measured only at the LV base, because preoperative precise determination of the hyperenhancement area that is not excluded by the operation is often difficult at the mid to apical LV, especially in patients with broad anteroseptal scarring. Moreover, inferior and posterior myocardial infarctions usually extend from the basal to the apical area. Basal myocardial status thus represents extension of infarction at circumflex and right coronary artery system. That may be one explanation why the percentage of fibrosis at the basal area correlates with postoperative LV function. We therefore believe that assessment of the basal portion is the most simple and helpful method of prediction.

	Conclusion

Top Abstract Introduction Materials and Methods Results Discussion Limitations Conclusion References

 
In conclusion, the amount of LV basal scar tissue affected LV function and functional recovery after SVR. Patients with a large amount of LV basal scarring are a high-risk group. Preoperative assessment of remote myocardial status with DE-MRI may predict surgical outcomes of patients undergoing SVR.

	References

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This Article Abstract Full Text (PDF) 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 Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Goro Matsumiya Hajime Matsue Masayuki Sakaki Taichi Sakaguchi Tomoyuki Fujita Yoshiki Sawa Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Takeda, K. Articles by Sawa, Y. Search for Related Content PubMed Articles by Takeda, K. Articles by Sawa, Y. Related Collections Coronary disease Myocardial infarction