Altered myocardial phenotype after mechanical support in human beings with advanced cardiomyopathy.
BACKGROUND
Left ventricular assist devices (LVAD) provide lifesaving circulatory support to patients awaiting heart transplantation. To date, the extent to which sustained mechanical unloading alters the phenotype of pathologic myocardial hypertrophy in dilated cardiomyopathy is unknown.


METHODS
We examined left ventricular size, myocyte and myocardial immunoreactivity for atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in eight patients with advanced dilated cardiomyopathy before and after LVAD support. The mean duration of congestive heart failure was 18 +/- 5 months, and LVAD support averaged 42 +/- 4 days before heart transplantation.


RESULTS
Echocardiographically determined left ventricular mass decreased from 505 +/- 83 to 297 +/- 52 gm (p < 0.05) during LVAD support, whereas minimum myocyte diameter decreased from 28.1 +/- 0.9 to 21.7 +/- 0.6 microns (p < 0.01) in transmural myocardial tissue specimens. Overall left ventricular ANP immunopositivity decreased from 48% at LVAD placement to 12% at transplantation (p < 0.05), whereas BNP immunopositivity decreased from 28% to 4% after LVAD support. Moreover, a gradient of ANP and BNP immunostaining from subendocardium to epicardium observed before mechanical unloading diminished after LVAD support. Analysis of the relationship between left ventricular mass and ANP immunopositivity revealed a close and highly significant correlation between these variables.


CONCLUSIONS
These studies demonstrate remarkable left ventricular plasticity even in the presence of advanced cardiomyopathy. Parallel reductions in myocardial mass and myocyte size with reductions in ventricular ANP and BNP immunostaining indicate a novel regression of the phenotype of pathologic hypertrophy within the human myocardium after LVAD support.
Altemose
G T
GT
Department of Internal Medicine, Temple University School of Medicine, Philadelphia, Pa 19140, USA.
Gritsus
V
V
Jeevanandam
V
V
Goldman
B
B
Margulies
K B
KB
D000293:Adolescent; D000328:Adult; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D006332:Cardiomegaly / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D002311:Cardiomyopathy, Dilated / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy; D015150:Echocardiography, Doppler; D004699:Endocardium / Q000378:metabolism / Q000473:pathology; D005260:Female; D006321:Heart / Q000502:physiology; D006353:Heart-Assist Devices; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D020097:Natriuretic Peptide, Brain; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016277:Ventricular Function, Left / Q000502:physiology
D009419:Nerve Tissue Proteins; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor