Molecular normalization of dystrophin in the failing left and right ventricle of patients treated with either pulsatile or continuous flow-type ventricular assist devices.
OBJECTIVE
We investigated the integrity of dystrophin in left ventricle (LV) and right ventricle (RV) of patients with end-stage heart failure due to ischemic cardiomyopathy (IHD) or dilated cardiomyopathy (DCM), and compared the efficacy of pulsatile or continuous flow assist devices on dystrophin reverse remodeling.


BACKGROUND
Recently we demonstrated that the amino (N)-terminus of dystrophin is preferentially disrupted in failing LV myocardium irrespective the underlying etiology, and that this defect is reversed by mechanical unloading using left ventricular assist device (LVAD) therapy.


METHODS
Myocardial samples were obtained from seven normal controls, seven failing hearts (either DCM or IHD), and 14 failing-heart patients who underwent placement of either pulsatile (7 patients) or continuous flow (7 patients) LVADs for progressive refractory HF. The expression and integrity of dystrophin in these samples were determined by immunohistochemistry using antibodies against the N-terminal and carboxyl (C)-terminal domains.


RESULTS
Immunohistochemical staining identified disruption of the N-terminal dystrophin in both LVs and RVs of all seven failing-heart patients, whereas the C-terminus was normal. Furthermore, this disruption was reversed in 12 of the 14 patients after LVAD therapy using either pulsatile or continuous devices; the degree of the reverse remodeling was similar in both ventricles, although greater recovery was noted in patients treated with pulsatile flow devices.


CONCLUSIONS
Integrity of the N-terminus of dystrophin is a useful indicator of both LV and RV function. In addition to improving LV hemodynamics, LVAD therapy results in amelioration of the myocardial structure of the right cardiac chamber.
Department of Pediatrics (Cardiology), Baylor College of Medicine, Houston, Texas 77030, USA.
Matteo
M
Vatta
Sonny J
SJ
Stetson
Shinawe
S
Jimenez
Mark L
ML
Entman
George P
GP
Noon
Neil E
NE
Bowles
Jeffrey A
JA
Towbin
Guillermo
G
Torre-Amione
D000328:Adult; D002311:Cardiomyopathy, Dilated / Q000150:complications; D016189:Dystrophin / Q000032:analysis* / Q000235:genetics; D005260:Female; D006333:Heart Failure / Q000209:etiology / Q000473:pathology / Q000601:surgery*; D006352:Heart Ventricles / Q000737:chemistry; D006353:Heart-Assist Devices; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000150:complications; D011474:Prosthesis Design; D020257:Ventricular Remodeling
D016189:Dystrophin