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.
ABSTRACT 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).
University hospitals and AIDS centres.
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).
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%).
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.
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ABSTRACT: Two important features of dilated cardiomyopathy (DCM) are low myocardial contractility and risk of thromboembolism. Nitric oxide (NO) exerts a negative inotropic effect on the myocardium and is produced by NO-synthase, an inducible form of which (iNOS) is stimulated by tumour necrosis factor (TNF-alpha). Accordingly, we hypothesized that locally produced TNF-alpha might contribute to the pathogenesis and complications of DCM by inducing iNOS in the heart. iNOS and TNF-alpha were quantified by histochemistry and computerised image analysis in explanted heart tissues or myocardial biopsy material from patients with DCM (n = 21) or ischaemic heart disease (HD; n = 10) and from normal donor hearts (n = 9). Immunoreactivity for iNOS was strong in myocytes of DCM hearts, particularly in areas adjacent to the endocardium, and moderately intense in blood vessels of DCM and IHD hearts. The median optical density of the immunostaining for iNOS was greater in cardiac myocytes of patients with DCM (0.86, range 0.21 to 1.29) than in those from patients with IHD (0.20, range 0.095 to 0.26) (p < 0.01) or controls (0.01, range 0.001 to 0.02) (p < 0.001). Staining for TNF-alpha was observed in the vascular endothelium and smooth muscle cells of patients with DCM but not in IHD or control tissues. The localisation of iNOS and TNF-alpha within cardiac tissues in DCM suggests that TNF-alpha contributes to both the low contractility and the tendency to thromboembolism in these patients.The Lancet 04/1996; 347(9009):1151-5. · 39.06 Impact Factor
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ABSTRACT: To determine the prevalence of cardiac abnormalities in patients with human immunodeficiency virus (HIV) infection, two-dimensional Doppler echocardiography was performed on 70 consecutive patients with HIV infection, including 51 with acquired immunodeficiency syndrome (AIDS), 13 with AIDS-related complex and 6 with asymptomatic HIV infection. Of the 70 patients, 36% were hospitalized and 64% were ambulatory at the time of evaluation. The average age was 37 years; 93% were homosexual men. Echocardiographic findings included dilated cardiomyopathy in eight patients (11%), pericardial effusions in seven patients (10%) (one with impending tamponade), pleural effusion in four patients (6%) and mediastinal mass in one patient (1%). Among the 25 hospitalized patients, echocardiographic abnormalities were noted in 16 (64%), whereas among the 45 ambulatory patients, the only abnormality noted was mitral valve prolapse in 3 patients (7%) (p less than 0.0001). Dilated cardiomyopathy was the only echocardiographic lesion more common in the 25 hospitalized patients than in 20 hospitalized control patients with acute leukemia. Symptoms of congestive heart failure responded to conventional therapy. Cardiac lesions were associated with active Pneumocystis carinii pneumonia and low T helper lymphocyte counts. Dilated cardiomyopathy of unknown origin may be more common than was previously recognized in hospitalized, acutely ill patients with AIDS, but is uncommon in ambulatory patients with HIV infection. Echocardiography should be considered in the evaluation of dyspnea in hospitalized patients with HIV infection, especially those with dyspnea that is out of proportion to the degree of pulmonary disease.Journal of the American College of Cardiology 05/1989; 13(5):1030-6. · 14.09 Impact Factor
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ABSTRACT: The frequency of, course of, and factors associated with cardiovascular abnormalities in pediatric HIV are incompletely understood. A baseline echocardiogram (median age, 2.1 years) and 2 years of follow-up every 4 months were obtained as part of a prospective study on 196 vertically HIV-infected children. Age- or body surface area-adjusted z scores were calculated by use of data from normal control subjects. Although 88% had symptomatic HIV infection, only 2 had CHF at enrollment, with a 2-year cumulative incidence of 4.7% (95% CI, 1.5% to 7.9%). All mean cardiac measurements were abnormal at baseline (decreased left ventricular fractional shortening [LV FS] and contractility and increased heart rate and LV dimension, mass, and wall stresses). Most of the abnormal baseline cardiac measurements correlated with depressed CD4 cell count z scores and the presence of HIV encephalopathy. Heart rate and LV mass showed significantly progressive abnormalities, whereas FS and contractility tended to decline. No association was seen between longitudinal changes in FS and CD4 cell count z score. Children who developed encephalopathy during follow-up had depressed initial FS, and FS continued to decline during follow-up. Subclinical cardiac abnormalities in HIV-infected children are common, persistent, and often progressive. Dilated cardiomyopathy (depressed contractility and dilatation) and inappropriate LV hypertrophy (elevated LV mass in the setting of decreased height and weight) were noted. Depressed LV function correlated with immune dysfunction at baseline but not longitudinally, suggesting that the CD4 cell count may not be a useful surrogate marker of HIV-associated LV dysfunction. However, the development of encephalopathy may signal a decline in FS.Circulation 05/1998; 97(13):1246-56. · 15.20 Impact Factor