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Ann Thorac Surg 2000;69:1836-1841
© 2000 The Society of Thoracic Surgeons

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Original articles: Cardiovascular

Partial left ventriculectomy: which patients can be expected to benefit?

^a Cardiovascular Research Laboratories, Department of Surgery, Texas Heart Institute at St. Luke’s Episcopal Hospital, Houston, Texas, USA
^b Cardiovascular Research Laboratories, Department of Pathology, Texas Heart Institute at St. Luke’s Episcopal Hospital, Houston, Texas, USA
^c Department of Surgery, Dedinje Cardiovascular Institute, Belgrade, Yugoslavia
^d Department of Pathology, Dedinje Cardiovascular Institute, Belgrade, Yugoslavia
^e Department of Cardiology, Dedinje Cardiovascular Institute, Belgrade, Yugoslavia

Address reprint requests to Dr Frazier, Texas Heart Institute, PO Box 20345, MC 3–147, Houston, TX 77225–0345
e-mail: mmallia{at}heart.thi.tmc.edu

	Abstract

Top Abstract Introduction Patients and methods Results Comment References

 
Background. Although some patients with end-stage heart disease will benefit from a partial left ventriculectomy, no criteria have been found for identifying this group preoperatively. Our experience with partial left ventriculectomy at two institutions—the Texas Heart Institute in Houston, TX, USA, and Dedinje Cardiovascular Institute in Belgrade, Yugoslavia—showed a higher survival rate and better postoperative myocardial function in the Yugoslavian patients.

Methods. We reviewed data from 42 patients (21 at each center) who had idiopathic cardiomyopathy, a left ventricular end-diastolic dimension of more than 70 mm, wall thickness of 1 cm or greater, and New York Heart Association class III or IV symptoms. The only significant difference in preoperative status between the two groups was duration of symptoms. Histologic specimens, blinded as to origin, were graded with regard to myocyte hypertrophy, cytoplasmic vacuolation, and fibrosis. Computer-assisted myocyte and nuclear morphometry was also performed.

Results. Immediately postoperatively, there were no significant intergroup differences in the reduction in cardiac dimension or in corrections of mitral regurgitation. During 6-month follow-up, however, the Texas Heart Institute patients had a lower cardiac index (1.8 versus 3.0 L·min^-1·m^-2; p = 0.001) and left ventricular ejection fraction (24% versus 34%; p = 0.006) than the Dedinje Cardiovascular Institute patients. The Texas Heart Institute patients differed from the Dedinje Cardiovascular Institute patients in the degree of severe or moderate changes in myocyte hypertrophy (90% versus 29%; p = 0.0003) and fibrosis (71% versus 29%; p = 0.006), as well as in the measurements of median myocyte diameter (35 ± 7 µm versus 27 ± 4 µm; p = 0.0002) and median nuclear size (15 ± 4 µm versus 12 ± 2 µm; p = 0.0029).

Conclusions. In the Texas Heart Institute patients, the significant intergroup difference in clinical outcome may have been related to increased myocyte hypertrophy and fibrosis. Further studies should be performed to determine the usefulness of these criteria in selecting patients for partial left ventriculectomy.

	Introduction

Top Abstract Introduction Patients and methods Results Comment References

 
The primary options for treating end-stage heart disease refractory to conventional therapy are heart transplantation, which is hampered by a shortage of donor organs, and mechanical circulatory support, which is expensive and not well defined as a long-term treatment option. Recently, partial left ventriculectomy (PLV), as introduced by Batista and colleagues [1], has been used for treating end-stage heart disease. The rationale of PLV is simple: reduced (ie, more normal) heart size will enhance ventricular function. Unfortunately, this procedure has had only limited success in the United States, although better outcomes have been achieved in developing countries [2, 3]. This difference in outcomes may have resulted from variation in patient populations being treated. Criteria for preoperatively identifying the patients most likely to benefit from PLV are poorly defined.

In 1996, several months after being introduced at the Texas Heart Institute (THI), PLV was undertaken at the Dedinje Cardiovascular Institute (DCI) in Belgrade as part of an ongoing professional exchange between these two centers. After more than a year, it became apparent that although the two series were similar with respect to preoperative characteristics, surgical techniques, and postoperative therapies, the DCI patients had better survival rates and myocardial function after PLV when compared with patients in Houston. In an effort to understand these results, we looked at our THI experience with left ventricular assist device use in patients with advanced heart failure. This experience has shown that severe cellular aberrations invariably accompanied dilated cardiomyopathy, and recovery of myocardial function correlated with the improved histologic appearance of the myocytes [4]. To determine whether cellular aberrations might be associated with the difference in outcome among patients in our two centers, we retrospectively compared histologic specimens from the two patient groups who underwent PLV and correlated the results with the clinical outcomes.

	Patients and methods

Top Abstract Introduction Patients and methods Results Comment References

 
Complete data, including 6-month follow-up results, were available for 42 patients who underwent PLV (21 patients at each center). In all cases, the primary diagnosis was idiopathic dilated cardiomyopathy. Patient selection was based on standard criteria for heart transplantation [5], including a left ventricular end-diastolic diameter of 7 cm or greater, as documented by recent echocardiography. Patients were selected who had longstanding congestive heart failure and no other effective treatment option. All patients had been approved for cardiac transplant.

Mitral regurgitation did not differ significantly between the two groups of patients (THI, 18 of 21 patients; DCI, 17 of 21 patients) nor did the procedures used to treat mitral disease. Procedures used for both groups included annuloplasty, Alfieri midvalvular repair, and mitral valve replacement.

Baseline medical therapy for both groups included digitalis, angiotensin-converting enzyme inhibitors, and diuretics. Because the majority of patients in both groups were New York Heart Association class IV, use of ß-blockers was limited by patient tolerance. Postoperative medical therapy was standardized for both institutions and included angiotensin-converting enzyme inhibitors, ß-blockers, and amiodarone.

Each patient underwent two-dimensional transthoracic echocardiography at baseline (1 to 10 days before operation), at hospital discharge (10 days to 1 month after operation), and at follow-up examination (6 months after operation). Right-sided heart catheterization with a Swan-Ganz thermodilution catheter was performed at these same intervals. Baseline values were provided by intraoperative data obtained after the induction of anesthesia. In addition, coronary angiograms were performed in all patients to rule out the possibility of ischemic cardiomyopathy.

Surgical procedure
At both centers, cardiopulmonary bypass was established according to standard techniques [6], and PLV was performed according to the modified method of Batista and colleagues [1, 7].

Histopathologic analysis
All 42 histologic specimens were studied in the Pathology Department of St. Luke’s Episcopal Hospital at THI. The specimens were fixed with buffered 10% formalin, embedded in paraffin, cut into 5-µm-thick sections, and stained with hematoxylin-eosin and Masson trichrome. Specimens were randomly sampled, and two to five sections were cut from each specimen. From the sections, two to five tissue blocks were processed for light microscopy. All fields were observed, and 10 randomly selected high-power fields were reviewed per block. Each specimen was assessed blindly and independently by the same three pathologists. To ensure that the investigators were not selecting fields with the most severely diseased tissue, we included all locations—subendocardial and transmural—in a random fashion. Sampling was not uniform among the samples, and areas of fibrosis (white discoloration) were apparent in the gross specimens, as would be the case in any patient of this type. Myocyte hypertrophy, cytoplasmic vacuolation, and fibrosis were analyzed subjectively, and myocyte and nuclear hypertrophy was analyzed morphometrically. After all results were recorded, they were averaged for each variable.

Semiquantitative analysis
Myocyte hypertrophic changes
Hypertrophy was defined as an increase in the width of the myocyte, accompanied by nuclear hyperchromasia, angulation, and pointing. Hypertrophy was considered mild (grade 1) if it involved focal changes, moderate (grade 2) if it entailed multifocal changes, and severe (grade 3) if it involved marked, diffuse changes affecting most of the specimen.

Cytoplasmic vacuolation
Vacuolation of myocytes (myocytolysis) was characterized by perinuclear halos. It was considered mild (grade 1) if it involved occasional focal halos in the perinuclear area alone, moderate (grade 2) if it entailed multifocal halos, and severe (grade 3) if it involved diffuse halos throughout most of the cytoplasm.

Fibrosis
The specimens were evaluated for the extent of myocyte replacement by collagen fibers. For each specimen, at least 10 microscopic fields were evaluated at low power, the grade being determined by the number of fields that showed fibrosis. Fibrosis was considered mild (grade 1) if it affected less than two fields, moderate (grade 2) if it involved two to five fields, and severe if it affected more than five fields. Findings were confirmed with Masson trichrome staining.

Morphometric analysis
All specimens were evaluated with a computer-assisted automated micrometry program on an image-analysis system (Cell Analysis System 200 Image Analyzer; Becton Dickinson Cellular Image Systems, Franklin Lakes, NJ). For each specimen, five microscopic fields (three longitudinal and two transverse fields) were examined at high power. The widths of three myocyte fibers and their corresponding nuclei on each slide were measured at the longest diameter, based on oblong shape.

Statistical analysis
Data were expressed as mean ± standard deviation. We used ² testing to compare the two groups with respect to categoric variables; if the expected number for any given cell was less than five, Fisher’s exact test was used. Continuous variables were assessed with Student’s unpaired t test for intergroup comparisons and Student’s paired t test for intragroup comparison of repeated measurements. A p value of less than 0.05 was considered significant.

	Results

Top Abstract Introduction Patients and methods Results Comment References

 
Group characteristics
There were no significant intergroup differences between THI and DCI patients in age (54 ± 12 years versus 52 ± 12 years), sex (male to female ratio, 15:6 versus 18:3), New York Heart Association class (class III, 33% versus 24%; class IV, 67% versus 76%), or preoperative cardiac function variables (cardiac index, left ventricular ejection fraction, and left ventricular end-diastolic diameter). The only difference noted was duration of symptoms before surgery (THI median, 60 months [range, 24 to 120 months] versus DCI median, 26 months [range, 12 to 121 months]; p = 0.05). Both groups had a similar immediate postoperative decrease in left ventricular end-diastolic diameter (from 7.3 cm preoperatively to 5.7 cm for THI patients; from 7.4 cm to 5.4 cm for DCI patients; p=0.443). However, with respect to cardiac index and left ventricular ejection fraction, there were significant intergroup differences between the immediate and 6-month postoperative results (Table 1), the DCI patients having better functional improvement. Immediately postoperatively, the mean cardiac index was 1.9 L·min^-1·m^-2 for THI patients and 2.6 L·min^-1·m^-2 for DCI patients (p = 0.0008). A significant difference was maintained at 6 months postoperatively, with a cardiac index of 1.8 L·min^-1·m^-2 for THI patients and 3.0 L·min^-1·m^-2 for DCI patients (p = 0.0014). In the THI group, the left ventricular ejection fraction increased from 19% preoperatively to 23% immediately after operation, and to 24% at 6 months; in the DCI group, the left ventricular ejection fraction increased from 21% preoperatively to 34% immediately after operation, and this value was retained at 6 months (immediately postoperatively, p = 0.0035; 6 months postoperatively, p = 0.0043).

View larger version (130K): [in this window] [in a new window]   Fig 1. Transverse sections of the myocardium in THI (A) and DCI (B) specimens, confirming the difference in hypertrophy and showing the similarity in vacuolation (magnification x20). (DCI = Dedinje Cardiovascular Institute, Belgrade; THI = Texas Heart Institute, Houston.)

View larger version (144K): [in this window] [in a new window]   Fig 2. Low-power photomicrograph showing the dramatic difference in the amount of fibrosis between THI (A) and DCI (B) specimens (magnification x4). (DCI = Dedinje Cardiovascular Institute, Belgrade; THI = Texas Heart Institute, Houston.)

View larger version (126K): [in this window] [in a new window]   Fig 3. Photomicrograph showing extensive fibrosis in the THI specimen (A) and a minimal amount or absence of fibrosis in the DCI specimen (B) (magnification x10). (DCI = Dedinje Cardiovascular Institute, Belgrade; THI = Texas Heart Institute, Houston.)

View larger version (127K): [in this window] [in a new window]   Fig 4. Photomicrograph confirming the extensive fibrosis in the THI specimen (top left) and a minimal amount or absence of fibrosis in the DCI specimen (bottom left). (Masson trichrome, magnification x4.) Longitudinal section of myocardium in THI (top right) and DCI (bottom right) specimens, showing an obvious difference in hypertrophy as confirmed by morphometric analysis (magnification x20). (DCI = Dedinje Cardiovascular Institute, Belgrade; THI = Texas Heart Institute, Houston.)

	Comment

Top Abstract Introduction Patients and methods Results Comment References

 
The results of this study suggest that myocardial reserve, as reflected by the degree of histologic derangement of the myocytes themselves, may correlate with the clinical benefit of PLV. Clearly, patient selection is a key factor in the success of this procedure. From a standpoint of physics, the anatomic advantages of a reduction in heart size in patients with cardiomegaly and congestive heart failure to a more normal mass to diameter relationship seems like a real solution. However, in patients with congestive heart failure, the myocardial dysfunction is generally believed to be initiated by abnormalities at the cellular level. These cellular abnormalities can receive no acute benefit from gross anatomic changes such as those achieved by ventricular reduction alone.

Eighteen months after PLV was introduced at DCI, we noted a significant difference between the clinical outcomes of patients at THI and patients at DCI. Although the clinical presentations were similar between the two groups (as confirmed by functional status and echocardiography), clinical outcomes have been better among the DCI patients [7]. The single clinical variable that differed significantly between the two groups was duration of symptoms before operation. The THI group had an average duration of symptoms 34 months longer than the DCI group.

This may have occurred because more options (transplantation, cardiac assist devices, aggressive medical therapy) were available in the United States. Aggressive medical management in the United States has improved the symptoms of congestive heart failure for many severely ill patients [8]. When cardiac transplantation is not a viable option (as in Brazil or Yugoslavia), patients may be referred for surgical therapy earlier in their illness. A shorter duration of illness may result in less cellular degeneration and more myocardial reserve. Patients selected before cellular function becomes seriously deranged may be better candidates for PLV. In our experience, beneficial long-term results have mainly been confined to patients who underwent ventricular unloading by an assist device before PLV, resulting in overall improvement in myocardial cellular function, as well as anatomic and histologic normalization of the diseased heart [9].

We found that fibrosis and severe myocardial hypertrophy indicate a less favorable prognosis after PLV. To further study this wide variability in similar patient cohorts, we analyzed the histology of the resected specimens. The results reflected a higher degree of both fibrosis and hypertrophy in the specimens from THI. By using morphometric data, we were able to assess this difference more objectively. The median diameter of cardiac myocytes in the specimens from THI patients were significantly larger than those of the specimens from DCI patients. The correlation to clinical outcomes was representative. Stolf and coworkers [10] have also noted that greater myocyte diameter is significantly associated with an unfavorable outcome.

In treating patients with congestive heart failure, our challenge is to be able to define accurately the stage of disease and to apply the appropriate treatment. Unfortunately, a precise classification system—one based on histologic and other variables and similar to that available in oncology—does not exist. For operations to be beneficial, interventions such as anatomic remodeling (PLV), valve replacement, or coronary artery bypass grafting should be considered before loss of end-organ function and while adequate myocardial reserve exists. Physiologic data such as that obtained from dobutamine stress echocardiography, which may be a reflection of myocardial reserve, should also be considered, as well as the anatomic measurements (end-diastolic dimension) that now form the primary indication for PLV procedures.

Currently, we are investigating the use of cardiac magnetic resonance imaging to assist in assessing myocardial fibrosis. Duration of symptoms also may be used as a guideline for selecting patients for PLV. If intervention with PLV is to be of value, it should be performed before histologic deterioration occurs. Unfortunately, the hemodynamic status of the patients in this study did not seem to correlate with the histologic findings from the myocardial tissue taken at PLV. In the Houston group, the myocardium had more extensive myocyte hypertrophy and myocardial fibrosis. Although patients at THI and DCI were clinically comparable (similar preoperative cardiac function), the Houston group had significantly poorer results.

In summary, these results suggest that improved ventricular function after ventricular reduction operation is dependent on cellular function as well as on macroanatomic considerations at the time of the procedure. This study correlates histologic markers with clinical outcomes in a small sampling of patients who underwent PLV. Patients with better clinical outcomes had less myocyte hypertrophy and fibrosis, as well as smaller myocyte and nuclear diameters. We believe that PLV has a role in the treatment of heart failure, especially when the potential for benefit can be more precisely defined preoperatively. Just as patients with similar cancerous lesions in the lung may benefit from the same operation only if metastases have not occurred, patients will benefit from PLV only if there is satisfactory preservation of myocyte function.

	References

Top Abstract Introduction Patients and methods Results Comment References

 

1. Batista R.J.V., Santos J.L.V., Takeshita N., Bocchino L., Lima P.N., Cunha M.A. Partial left ventriculectomy to improve left ventricular function in end-stage heart disease. J Card Surg 1996;11:96-97.[Medline]
2. Batista R.J.V., Verde J., Nery P., et al. Partial left ventriculectomy to treat end-stage heart disease. Ann Thorac Surg 1997;64:634-638.[Abstract/Free Full Text]
3. McCarthy P.M., Starling R.C., Wong J., et al. Surgery for acquired heart disease. J Thorac Cardiovasc Surg 1997;114:755-765.[Abstract/Free Full Text]
4. Frazier O.H., Benedict C.R., Radovancevic B., et al. Improved left ventricular function after chronic left ventricular unloading. Ann Thorac Surg 1996;62:675-682.[Abstract/Free Full Text]
5. Miller L.W., Kubo S.H., Young J.B., Stevenson L.W., Loh E., Costanzo M.R. Report of the Consensus Conference on Candidate Selection for Heart Transplantation 1993. J Heart Lung Transplant 1995;14:562-571.[Medline]
6. Frazier O.H., Sweeney M.S., Radovancevic B., Cooley D.A. Surgical treatment of heart disease. In: Willerson J.T., ed. . Treatment of heart disease. New York: Gower Medical Publishing, 1992:3-12.
7. Gradinac S., Miric M., Popovic Z., et al. Partial left ventriculectomy for idiopathic dilated cardiomyopathy. Ann Thorac Surg 1998;66:1963-1968.[Abstract/Free Full Text]
8. Stevenson L.W. Tailored therapy before transplantation for treatment of advanced heart failure. J Heart Lung Transplant 1991;10:468-476.[Medline]
9. Frazier O.H., Radovancevic B., Odegaard P., et al. Reduction in patients with idiopathic cardiomyopathy awaiting heart transplantation. J Heart Lung Transplant 1997;16:80.
10. Stolf N.A., Moreira L.F., Bocchi E.A., et al. Determinants of midterm outcome of partial left ventriculectomy in dilated cardiomyopathy. Ann Thorac Surg 1998;66:1585-1591.[Abstract/Free Full Text]

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