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J Thorac Cardiovasc Surg 1998;115:478-479
© 1998 Mosby, Inc.

BRIEF COMMUNICATIONS

Morphologic alterations of myocardium under conditions of leftventricular assistance

Christophe Depre, MD, PhD, Xavier Havaux, BSc, Robert Dion, MD, Jean L. Vanoverschelde, MD, PhD


Brussels, Belgium

From the Divisions of Cardiology and Cardiovascular Surgery,University of Louvain Medical School, Brussels, Belgium.

Received for publication July 28, 1997 Accepted for publication August 27, 1997. Address for reprints: Christophe Depre, MD, PhD, Division ofCardiology, University of Texas Medical School, 6431 Fannin, MSB 1.608, Houston,TX 77030.

Implantation of a left ventricular assist device (LVAD) is used as abridge for patients expecting heart transplantation. By changing the loadingconditions of the failing heart, the LVAD most probably alters heart structure.We report the pathologic examination of myocardium from a patient before andafter 4 months of LVAD use. We show that unloading the heart with the LVAD leadsto a dedifferentiation process of the cardiomyocytes comparable to that found in"hibernating" myocardium.

Clinical summary. An 18-year-old malepatient was seen for idiopathic dilated cardiomyopathy that did not improve withmaximal drug therapy. Because of the unavailability of a compatible heart donor,the patient was surgically treated with partial left ventricular resection(resection of the anterolateral wall and correction of the mitralregurgitation). The lack of postoperative improvement led to the insertion of animplantable LVAD (Novacor; Baxter Healthcare Corp., Novacor Div., Oakland,Calif.). After 4 months of stabilization, the device was removed. Three monthslater, a heart donor was found and the patient underwent transplantation.Myocardial tissues retrieved during partial left ventricular resection, atexplantation of the LVAD, and at transplantation were kept for pathologicexamination. All tissue fragments were embedded in paraffin, cut in 7 µmthick sections, then stained with Masson trichrome stain and periodicacid-Schiff reaction.

Results. Morphologic characteristics ofthe fragments retrieved during partial left ventricular resection were notdifferent from normal tissue (Fig. 1, A). The cardiomyocytes covered 90% ofthe total surface, whereas extracellular matrix covered about 7%.Cardiomyocytes were globally normal in appearance on light-microscopicexamination, with cytosol filled with myofilaments and nuclei with normalchromatin content Go(Fig. 1, A). About 15% of thecardiomyocytes showed slight accumulation of glycogen in the cytosol (Fig. 2,A). After 4 months with LVAD, morphologicinspection of the myocardial tissue revealed major differences (Figs.Go1 and Go2). The cellular volumewas increased compared with the previous fragments. The rod-shaped cells foundinitially were now potato-like in appearance, dilated and sphericalGo(Fig. 2, A). Their myofilament content was dramaticallydecreased, and their nuclei were condensed and pyknotic Go(Fig.1, B). The percentage of surface covered by extracellular matrix was increasedto 13% Go(Fig. 1, B). About 95% of thecardiomyocytes showed an intracellular accumulation of glycogenGo(Fig. 2, B). In the fragments retrieved duringtransplantation, the cellular morphologic characteristics had returned to anormal pattern in most of the cells, but the percentage of intercellularfibrosis remained increased.



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  		Fig. 1. Morphologic appearanceof myocardium before and after LVAD implantation. The myofilament content isnormal before LVAD implantation (A), whereas itis reduced after 4 months of LVAD support (B).The nuclei are normal before and pyknotic 4 months after LVAD implantation(Masson's trichrome; original magnification x 20.)

 


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  		Fig. 2. Glycogen accumulationin cardiomyocytes.A, A few cardiomyocytes show an intracellularaccumulation of dark-red material compatible with glycogen. After 4 months ofLVAD support, most cardiomyocytes display an important accumulation of glycogenin their cytosol. B, Periodic acid–Schiffreaction (original magnification x20.)

 
Discussion. Our data thus show that heartstructure may create important—albeit reversible—morphologicalterations after several months of LVAD implantation. These alterations aremainly a loss of myofilaments, an intracellular accumulation of glycogen, and anincrease in extracellular matrix. The alterations that we found in this case aresimilar to those previously described in human "hibernating"myocardium.Go Go 1,2 Patients with hibernatingmyocardium in whom such morphologic alterations are found have functionalimprovement after revascularization,Go 3suggesting that these phenotypic alterations are potentially reversible. Such aphenotypic shift is still poorly understood. There is accumulating evidence thatthe structural changes observed are the consequence of a reverse differentiationprocess, because these altered cardiomyocytes are similar to fetalcardiomyocytes.Go 4 It remainsunknown, however, through what mechanisms unloading the heart with the LVADinduces such alterations and whether this adaptation is a prerequisite forsubsequent functional improvement.

References

  1. Vanoverschelde JL, Wijns W, Depre C, et al.Mechanisms of chronic regional post-ischemic dysfunction in humans: new insightsfrom the study of non-infarcted collateral-dependent myocardium. Circulation 1993;87:1513-23.[Abstract/Free Full Text]
  2. Depre C, Vanoverschelde JL, Melin JA, et al.Structural and metabolic correlates of the reversibility of chronic leftventricular ischemic dysfunction in humans. Am J Physiol 1995;268:H1265-75.[Abstract/Free Full Text]
  3. Depre C, Vanoverschelde JL, Gerber B, BorgersM, Melin JA, Dion R. Correlation of functional prognosis with myocardialmorphology and metabolism in patients undergoing coronary bypass surgery. J ThoracCardiovasc Surg 1997;113:371-8.[Abstract/Free Full Text]
  4. Ausma J, Schaart G, Thone F, et al. Chronicischemic viable myocardium in man: aspects of dedifferentiation. CardiovascPathol 1995;4:29-37.



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