Regression of cellular hypertrophy after left ventricular assist device support.

BACKGROUND Although multiple studies have shown that the left ventricular assist device (LVAD) improves distorted cardiac geometry, the pathological mechanisms of the "reverse remodeling" of the heart are unknown. Our goal was to determine the effects of LVAD support on cardiac myocyte size and shape. METHODS AND RESULTS Isolated myocytes were obtained at cardiac transplantation from 30 failing hearts (12 ischemic, 18 nonischemic) without LVAD support, 10 failing hearts that received LVAD support for 75+/-15 days, and 6 nonfailing hearts. Cardiac myocyte volume, length, width, and thickness were determined by use of previously validated techniques. Isolated myocytes from myopathic hearts exhibited increased volume, length, width, and length-to-thickness ratio compared with normal myocytes (P<0.05). However, there were no differences in any parameter between myocytes from ischemic and nonischemic cardiomyopathic hearts. Long-term LVAD support resulted in a 28% reduction in myocyte volume, 20% reduction in cell length, 20% reduction in cell width, and 32% reduction in cell length-to-thickness ratio (P<0.05). In contrast, LVAD support was associated with no change in cell thickness. These cellular changes were associated with reductions in left ventricular dilation and left ventricular mass measured echocardiographically in 6 of 10 LVAD-supported patients. CONCLUSIONS These studies suggest that the regression of cellular hypertrophy is a major contributor to the "reverse remodeling" of the heart after LVAD implantation. The favorable alterations in geometry that occur in parallel fashion at both the organ and cellular levels may contribute to reduced wall stress and improved mechanical performance after LVAD support.

[1]  K E Muffly,et al.  Structural Remodeling of Cardiac Myocytes in Patients With Ischemic Cardiomyopathy , 1992, Circulation.

[2]  W. Roberts,et al.  Pathologic Anatomy of the Cardiomyopathies , 1975 .

[3]  M C Oz,et al.  Potential of left ventricular assist devices as outpatient therapy while awaiting transplantation. , 1994, The Annals of thoracic surgery.

[4]  G. Cooper,et al.  Atrophy Reversal and Cardiocyte Redifferentiation in Reloaded Cat Myocardium , 1984, Circulation research.

[5]  Reversibility of the structural effects of pressure overload hypertrophy of cat right ventricular myocardium , 1986, The Anatomical record.

[6]  A. DeMaria,et al.  Recommendations Regarding Quantitation in M-Mode Echocardiography: Results of a Survey of Echocardiographic Measurements , 1978, Circulation.

[7]  P. Anversa,et al.  Myocardial Infarction in Rats: Infarct Size, Myocyte Hypertrophy, and Capillary Growth , 1986, Circulation research.

[8]  G. Cooper,et al.  Load Regulation of the Structure, Composition, and Function of Mammalian Myocardium , 1982, Circulation research.

[9]  G. Cooper,et al.  Complete Reversibility of Cat Right Ventricular Chronic Progressive Pressure Overload , 1984, Circulation research.

[10]  H Harasaki,et al.  Left ventricular echocardiographic and histologic changes: impact of chronic unloading by an implantable ventricular assist device. , 1996, Journal of the American College of Cardiology.

[11]  C A Beltrami,et al.  Structural basis of end-stage failure in ischemic cardiomyopathy in humans. , 1994, Circulation.

[12]  B. Radovancević,et al.  The effect of prolonged left ventricular support on myocardial histopathology in patients with end-stage cardiomyopathy. , 1992, ASAIO journal.

[13]  N. Reichek.  Echocardiographic assessment of left ventricular hypertrophy. , 1982, European heart journal.

[14]  E. Sonnenblick,et al.  Cellular basis of chronic ventricular remodeling after myocardial infarction in rats. , 1991, Circulation research.

[15]  V. Jeevanandam,et al.  Altered myocardial phenotype after mechanical support in human beings with advanced cardiomyopathy. , 1997, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[16]  P. Anversa,et al.  The cellular basis of pacing-induced dilated cardiomyopathy. Myocyte cell loss and myocyte cellular reactive hypertrophy. , 1995, Circulation.

[17]  K. Rakušan,et al.  Remodeling of myocyte dimensions in hypertrophic and atrophic rat hearts. , 1991, Circulation research.

[18]  J Hurley,et al.  Sizing particles with a Coulter counter. , 1970, Biophysical journal.

[19]  E. Lakatta,et al.  Morphological and contractile characteristics of rat cardiac myocytes from maturation to senescence. , 1989, The American journal of physiology.

[20]  J. Thomas,et al.  Effect of the implantable left ventricular assist device on neuroendocrine activation in heart failure. , 1995, Circulation.

[21]  J. Schaper,et al.  Altered nucleus/cytoplasm relationship and degenerative structural changes in human dilated cardiomyopathy. , 1994, Cardioscience.

[22]  O H Frazier,et al.  Multicenter clinical evaluation of the HeartMate 1000 IP left ventricular assist device. , 1992, The Annals of thoracic surgery.

[23]  A. Gerdes,et al.  Transverse shape characteristics of cardiac myocytes from rats and humans. , 1994, Cardioscience.

[24]  A. Gerdes,et al.  Regional differences in myocyte size in normal rat heart , 1986, The Anatomical record.

[25]  O. Frazier,et al.  Improved left ventricular function after chronic left ventricular unloading. , 1996, The Annals of thoracic surgery.

[26]  P. Tatham,et al.  Size measurements on isolated rat heart cells using Coulter analysis and light scatter flow cytometry. , 1979, Biochimica et biophysica acta.

[27]  M C Oz,et al.  Reversal of chronic ventricular dilation in patients with end-stage cardiomyopathy by prolonged mechanical unloading. , 1995, Circulation.