Clinical course of cardiomyopathy in HIV-infected patients with or without encephalopathy related to the myocardial expression of tumour necrosis factor-alpha and nitric oxide synthase.
OBJECTIVE
To define whether the development of encephalopathy influences the clinical course of HIV-associated cardiomyopathy (HIV-DCM) in relation to the myocardial expression of tumour necrosis factor-alpha (TNF-alpha) and inducible nitric oxide synthase (iNOS).


METHODS
Prospective study.


METHODS
University hospitals and AIDS centres.


METHODS
115 HIV-infected patients with echocardiographic diagnosis of HIV-associated cardiomyopathy (34 with encephalopathy and 81 without encephalopathy) were followed for a mean of 24 +/- 3.2 months. All patients underwent endomyocardial biopsy for determination of myocardial immunostaining intensity of TNF-alpha and iNOS. Cerebrospinal fluid (CSF) from patients with encephalopathy was examined for the presence of viruses. Patients underwent clinical examination every 3 months and echocardiographic examination every 6 months. The intensity of TNF-alpha and iNOS immunostaining was also evaluated on postmortem cerebral tissue of patients who died of congestive heart failure (CHF).


RESULTS
A greater impairment of echocardiographic parameters was observed in patients with HIV-associated cardiomyopathy after development of encephalopathy. These parameters tended to worsen progressively during the follow-up period and were inversely correlated with HIV-1 viral load, CD4 cell count, mini mental status score and the intensity of myocardial and cerebral TNF-alpha and iNOS staining. CSF specimens were available in 29 patients with encephalopathy. HIV-1 sequences were detected in CSF of all these patients with cytomegalovirus sequences in two. The mortality rate for CHF was greater among patients with encephalopathy (73% versus 12%).


CONCLUSIONS
The development of encephalopathy has an adverse effect on the clinical course of HIV-associated cardiomyopathy. In the relationship between cardiomyopathy and encephalopathy, the activation of iNOS by TNF-alpha may have a significant pathogenetic role in HIV disease.
Barbaro
G
G
Department of Emergency Medicine, University La Sapienza, Rome, Italy.
Di Lorenzo
G
G
Soldini
M
M
Giancaspro
G
G
Grisorio
B
B
Pellicelli
A M
AM
D'Amati
G
G
Barbarini
G
G
D015526:AIDS Dementia Complex / Q000150:complications* / Q000378:metabolism / Q000821:virology; D000328:Adult; D002311:Cardiomyopathy, Dilated / Q000150:complications* / Q000378:metabolism / Q000401:mortality / Q000821:virology; D002540:Cerebral Cortex / Q000378:metabolism / Q000821:virology; D002555:Cerebrospinal Fluid / Q000821:virology; D004452:Echocardiography; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000378:metabolism / Q000821:virology; D015497:HIV-1 / Q000502:physiology; D006321:Heart / Q000821:virology; D006801:Humans; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D012367:RNA, Viral / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D019562:Viral Load
D012367:RNA, Viral; D014409:Tumor Necrosis Factor-alpha; D019001:Nitric Oxide Synthase