Reversible right ventricular dysfunction in HIV-infected patients.

The introduction of highly active antiretroviral therapy (HAART) has significantly improved the clinical outcome of HIV disease with increased survival rates. However, the introduction of HAART has generated a contrast in the cardiac manifestations of AIDS. In developed countries, we observed an approximate 30% reduction in the prevalence of HIV-associated cardiomyopathy, possibly related to a reduction of opportunistic infections and myocarditis. (1) In developing countries, however, where the availablity of HAART is limited and the pathogenic impact of nutritional factors is significant, we observed an approximate 32% increase in the prevalence of HIV-associated cardiomyopathy and a related high mortality rate from congestive heart failure. Also, some HAART regimens in developed countries, especially those including protease inhibitors, may cause iatrogenic metabolie syndrome (HIV-lipodystrophy syndrome) that is associated with an increased risk of cardiovascular disease with an estimated incidence of 1.4 cardiac events per 1,000 years of therapy according to the Framingham score. (1)

In this issue of the Southern Medical Journal, Rangasetty et al report two cases of reversible right ventricular dysfunction responsive to HAART. (2) The clinical course of these cases and the response to HAART precludes hemodynamically significant coronary artery disease as a cause of this phenomenon. However, impairment of the coronary microcirculation may be responsible for reversible ventricular dysfunction, possibly in association with an altered autonomic function. (3) Transient ventricular asynergy may develop due to regional differences in the distribution of cardiac sympathetic nerve endings.

HIV-associated myocarditis also cannot be excluded. Dendritic myocardial cells are infected by HIV-1 in patchy distributions and play a pathogenic role in the interaction between HIV-1 and the myocytes and in the activation of multifunctional cytokines (eg, tumor necrosis factor-[alpha]) that contribute to progressive and late tissue damage. (4) It is possible that a transient right ventricular dysfunction occurred secondary to the altered catecholamine dynamics (or autonomic function) in the acute phase of a focal HIV-associated myocarditis and that the prompt administration of HAART affected the cytotoxic effects of cytokines released by infected myocardial cells.

After the introduction of HAART, we observed an increased incidence of HIV-associated pulmonary hypertension. (1) Moreover, HIV infection is often incidentally discovered in patients with pulmonary hypertension. A key pathogenic role in this specific form of primary pulmonary hypertension is played by pulmonary interstitial cells. These cells, infected by HIV-1, may release specific cytokines (eg, endothelin-1) that by vasoconstriction of the endothelial cells and proliferation of the smooth muscle cells cause the classic plexogenic vascular lesions. HAART has a therapeutic role in the early stages of HIV-associated pulmonary hypertension (right ventricular systolic pressure assessed by echocardiography >35 and < 50 mm Hg). (5) Both patients described by Rangasetty et al had a right ventricular systolic pressure <50 mm Hg and in both patients, HAART may have affected the action of cytokines released early by infected pulmonary interstitial cells. It is my opinion that the transient right ventricular dysfunction may have been due to either a focal myocarditis with associated autonomic dysfunction or to an early stage of HIV-associated pulmonary hypertension.

The strength of this article is the focus on a topic of critical importance: HIV infection is an independent cardiovascular risk factor. HIV-infected patients are at risk to develop cardiovascular events, even in the early stage of the disease. A careful cardiac screening is therefore warranted for all HIV-infected patients to detect subclinical abnormalities that independently predict adverse outcomes and identify risk groups for early intervention and therapy. Moreover, close collaboration between cardiologists and infectious disease specialists may be useful for careful risk stratification of cardiovascular issues, in accordance with the most recent clinical guidelines. (6)

References

1. Barbaro G. Reviewing the cardiovascular complications of HIV infection after the introduction of highly active antiretroviral therapy. Curr Drug Targets Cardiovasc Haematol Disord 2005;5:337-343.

2. Rangasetty UC, Rahman AM, Hussain N. Reversible right ventricular dysfunction in patients with HIV infection. South Med J 2006;99: 274-278.

3. Shahmanesh M, Bradbeer CS, Edwards A, et al. Autonomic dysfunction in patients with human immunodeficiency virus infection. Int J STD AIDS 1991;2:419-423.

4. Barbaro G. HIV-associated cardiomyopathy: etiopathogenesis and clinical aspects. Herz 2005;30:486-492.

5. Barbaro G, Lucchini A, Barbarini G. Highly active antiretroviral therapy in naive patients with HIV-associated pulmonary hypertension. HIV AIDS Rev 2004;3:5-7.

6. Volberding PA, Murphy RL, Barbaro G. et al. The Pavia Consensus Statement. AIDS 2003;17 S170-S179.

Giuseppe Barbaro, MD

From the Cardiology Unity, Department of Medical Pathophysiology, University La Sapienza, Rome, Italy.

Reprint requests to Dr. Giuseppe Barbaro, Chief, Cardiology Unit, Department of Medical Pathophysiology, University La Sapienza, Viale Anicio Gallo 63, 00174 Rome, Italy. Email: [e-mail]

Accepted December 2, 2005.