DISCUSSION

This is the most important cardiovascular manifestation of HIV infection and is likely to become even more prevalent as HIV infected patients live longer with the advent of ART.

This may present as myocarditis, dilated cardiomyopathy or isolated left or right ventricular dysfunction.⁷⁸

The prevalence of heart muscle disease as high as 15% has been reported.¹⁵ Heart muscle disease is associated with a poor prognosis, and results in symptomatic heart failure in up to 5% of HIV patients,^15,78 a reflection that majority is usually asymptomatic.

MYOCARDITIS IN HIV INFECTION

Histologically, myocarditis has been defined by the Dallas criteria, which require the presence of an inflammatory infiltration of the myocardium with adjacent myocyte necrosis or degeneration that is not typical of the ischaemic damage associated with coronary artery disease.⁷⁹ Application of this strict definition may be inappropriate in the context of

HIV/AIDS where adequate immune response is impaired in the phase of profound immunosuppression. The prevalence of myocarditis in HIV infected patients has been

difficult to establish with estimates ranging from 6% to 52%.^{16, 80} Myocardial involvement in HIV infection is multifactorial, the virus itself may cause myocarditis in HIV infection, either directly or indirectly via autoimmune processes, or via one of many opportunistic organisms, drug-related cardiac toxicity, nutritional deficiencies or prolonged immunosuppression. No specific aetiologic factor was found in more than 80% of cases of myocarditis in one series.

Bacterial, viral, fungal and protozoal organisms have all been implicated in the development

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of myocarditis in HIV infected patients.⁷⁸ The severity of myocardial disease ranges from incidental microscopic inflammatory findings at autopsy to clinically significant cardiac disease with chronic cardiac dysfunction. It is associated with a poor prognosis, and results in symptomatic heart failure in up to 5% of HIV patients.¹⁵ HAART has also significantly reduced the incidence of myocarditis thus reducing the prevalence of HIV-associated cardiomyopathy by almost 7-fold from the pre-HAART era.¹⁵

DILATED CARDIOMYOPATHY (DCM) AND HIV

Cardiac failure due to DCM was first described in 1986 in three patients with AIDS.⁸¹ Clinical left ventricular dysfunction is rapidly fatal in the later stages of AIDS. Both LV systolic and diastolic function deteriorate as the CD4 lymphocyte count decreases in HIV infection.¹⁵

Omotoso et al⁸² in Ilorin, North central part of Nigeria, reported a 32.1% prevalence of HIV infection in patients with heart failure from dilated cardiomyopathy indicating a possible association between HIV infection and dilated cardiomyopathy. The authors⁸² concluded that dilated cardiomyopathy is a major cause of heart failure in this environment and that HIV can play a significant role in its pathogenesis. The high prevalence of HIV infection (32.1%) among patients with DCM when compared to 7.3% of HIV-infected patients without DCM suggests possible association but does not establish causality.⁸² Causality in the study was not established because other possible aetiological factors of DCM were not objectively excluded due to the study design and possible lack of facilities to demonstrate other cardiotropic viruses, and to do endomyocardial biopsy as stated by the investigators. Although DCM is associated with a significantly reduced CD4 cell count,⁸³ no association has been found between progression of left ventricular dysfunction and the rate of cell count decline.⁸⁴ Lilshultz et al⁸⁴ study however, was on paediatric population. The aetiology of HIV cardiomyopathy is complex and multifactorial. The most likely causative factors include

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preceding myocarditis attributable either to HIV infection or secondary infectious agents, nutritional deficiencies (e.g. selenium, carnitine, vitamin B1 and B12), metabolic and endocrine abnormalities and autonomic insufficiency. Cytokine imbalances have also been implicated in the pathogenesis of HIV-related cardiomyopathy. Pro-inflammatory cytokines (e.g. tumour necrosis factor α, interleukin1, interleukin 6 and glycoprotein 130) are elevated in patients with congestive cardiac failure.⁸⁵ HIV-infected endothelial cells are believed to produce the excessive IL-1 and IL-6, with elevated cytokine levels directly depressing myocardial function. ⁸⁵ Autoimmunity may have a role in the pathogenesis of HIV associated cardiomyopathy because autoantibody levels to anti-α myosin were reported to be increased in HIV infected patients compared with controls, and those with evidence of poor left ventricular function were especially likely to have them.⁸⁶ Drugs commonly used in the treatment of HIV disease and its complications (e.g. Zidovudine) are also associated with dilated cardiomyopathy.⁸⁷Another factor associated with the occurrence of DCM in HIV/AIDS patients is the clinical disease severity and the degree of immunosuppression measured by the CD4 count. This was reported by Nzuobontane et al⁸⁸ in a study comparing three groups of HIV positive with AIDS and HIV positive non-AIDS patients with healthy HIV negative controls. DCM was observed to occur more frequently (23.3%) in the AIDS group compared to 4.2% in the HIV positive non-AIDS group and none among the controls.

In that study too, patients with profound immunosuppression, CD4 <100 cells/mm³ had significantly higher prevalence of DCM (31.6%) than patients with CD4 >100 cells/mm³ (6.1%). The outlook of HIV/AIDS patients with DCM is poor. Occurrence of dilated cardiomyopathy is an independent risk factor for death,⁸⁸ and reports of studies of the course of myocardial disease in HIV/AIDS found that survival was significantly reduced in the subjects with DCM compared to those with normal hearts¹⁵

Left ventricular diastolic and systolic dysfunctions are common findings in HIV/AIDS disease. It can be symptomatic or asymptomatic and has been shown to occur in the early stages of the disease. Barbaro et al⁸⁹ in studying 1,236 asymptomatic patients demonstrated that significant impairment of systolic and diastolic function may be detected by echo confirming an early involvement of the heart in asymptomatic HIV/AIDS disease compared

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to controls. They also reported a 19.7% reduction in the ejection fraction, 55.7% increase in wall motion score, and a 34.6% reduction in mitral E/A ratio. The reported prevalence of left ventricular dysfunction in HIV infection in post-mortem studies in the pre-HAART era varied from 2%¹⁵ to over 40%.⁷⁹ Symptomatic heart failure developed in approximately 5% of patients, most of whom had end stage AIDS.¹⁵ Left ventricular dysfunction, dilated cardiomyopathy, and myocarditis all occur with increased frequency in AIDS patients.⁹⁰ In a pre-HAART study, global left venticular hypokinesis was found in 14.5% of patients and was associated with lower CD4 counts, and congestive heart failure was diagnosed in about 2% of patients.⁹⁰ Causes may include a direct effect of HIV, other cardiotropic viruses, ART toxicity, cytokines, opportunistic infections (OIs), illicit drug use, or nutritional deficiencies from chronic illness.⁹⁰ Hypertension and other associated cardiovascular conditions can also predispose to ventricular dysfunction,⁹⁰ which may progress to overt heart failure.

Hypertension is regarded as the commonest cause of heart failure in Nigeria and other African countries.⁹¹Hypertension has also been reported that it may contribute to the aetiology of dilated cardiomyopathy.⁹²

Okeahialam et al⁹³ in Jos, North central part of Nigeria reported more left ventricular systolic dysfunction in AIDS patients. Most of these patients had normal ventricular size but significantly reduced fractional shortening when compared with the HIV negative controls⁹³ Diastolic indices were, however, not reported.⁹³

Danbauchi et al⁹⁴ in Zaria, Kaduna state, Northern part of Nigeria reported diastolic dysfunction in 30% of patients with stage III/IV HIV infection. Most of these patients were asymptomatic, further confirming that most cardiac abnormalities in HIV/AIDS patients are clinically silent.⁹⁴