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Cardiovascular manifestations of HIV have been altered by the introduction of highly active antiretroviral therapy (HAART) regimens. On one hand, HAART has significantly modified the course of HIV disease, lengthened survival, and improved the quality of life of HIV-infected patients. On the other hand, the early data have raised concerns that HAART is associated with an increase in both peripheral and coronary arterial diseases.1 The HAART-associated changes are relevant only to the minority of HIV-infected individuals worldwide who have access to HAART. Thus, studies conducted before HAART became available remain globally applicable.

Most studies that have described cardiac complications in AIDS patients were postmortem, although some clinical series have been reported. It is now clear that cardiac involvement in AIDS patients is relatively common. Although most such conditions are clinically quiescent, some may have devastating and fatal outcomes. Pericardial effusion and myocarditis are among the most commonly reported abnormalities. Cardiomyopathy, endocarditis, and coronary vasculopathy have also been reported.  Symptomatic cardiac disease was described first in children but is also seen in HIV-infected adults 2,3. Patients with AIDS can have cardiac pathology related to opportunistic infections and tumors.

TYPES OF CARDIAC DISEASE

Patients with advanced HIV infection can have a variety of cardiovascular manifestations. The most common are:

  • Pericarditis
  • Myocarditis
  • Cardiomyopathy
  • Pulmonary vascular disease and pulmonary hypertension
  • An increased incidence of vascular disease including coronary artery disease

 

Pericardial Effusion

The prevalence of pericardial effusion in asymptomatic AIDS patients has been estimated at 11% before the introduction of HAART4 . HIV infection should be included in the differential diagnosis of unexplained pericardial effusion or tamponade. Pericardial effusion in HIV disease may be related to opportunistic infections or to malignancy, but most often a clear pathology is not found.1

Significant pericardial effusion has been identified in up to 40% of AIDS patients with echocardiography or autopsy 5, making this one of the most common cardiac abnormalities in AIDS patients. Most of those reported cases were, however, asymptomatic.

Dilated Cardiomyopathy

HIV disease is recognized as an important cause of dilated cardiomyopathy, with an estimated annual incidence of 15.9 in 1000 before the introduction of HAART6

Endocarditis

The prevalence of infective endocarditis in HIV-infected patients is similar to that in patients of other risk groups, such as intravenous drug users.7Estimates of endocarditis prevalence vary from 6.3% to 34% of HIV-infected patients who use intravenous drugs independently of HAART regimens.7 Right-sided valves are predominantly affected, and the most frequent agents are Staphylococcus aureus (>75% of cases), Streptococcus pneumoniae, Haemophilus influenzae, Candida albicans, Aspergillus fumigatus, and Cryptococcus neoformans.7

HIV-Associated Pulmonary Hypertension

The pathogenesis of primary pulmonary hypertension in HIV infection is multifactorial and poorly understood.1

Clinical symptoms and outcomes of patients with right ventricular dysfunction are related to the degree of pulmonary hypertension, varying from a mild asymptomatic condition to severe cardiac impairment with cor pulmonale and death.8

 

 HIV Therapy and the Heart

The principal cardiovascular actions/interactions of common HIV therapies are reported in Table 1.

 

Table 1.

Cardiovascular Actions/Interactions of Common HIV Therapies

Class

Drugs

 

Cardiac Side Effects

Antiretroviral

 

 

 

(RTI) Transcriptase Inhibitors  Nucleoside Reverse     

Abacavir (Ziagen), zidovudine (AZT, Retrovir)

 

Lactic acidosis (rare), hypotension, skeletal muscle myopathy, (mitochondrial dysfunction hypothesized, but not seen clinically)

Nonnucleoside RTI    

Delavirdine (Rescriptor), efavirenz (Sustiva), nevirapine (Viramune)

 

Delavirdine can cause serious toxic effects if given with antiarrhythmic drugs and myocardial ischemia if given with vasoconstrictors

Protease inhibitors    

Amprenavir (Agenerase), indinavir (Crixivan), nelfinavir (Viracept), ritonavir (Norvir), saquinavir (Invirase, Fortovase)

 

Implicated in premature atherosclerosis, dyslipidemia, insulin resistance, and lipodystrophy/lipoatrophy

 SUMMARY

It is clear from this article that cardiac abnormalities in AIDS patients are relatively common. The endocardium, myocardium, pericardium, and even the coronary vessels can be affected. It may be more common in more advanced HIV disease . When clinically significant cardiac complication does develop, the signs and symptoms may be misinterpreted for noncardiac causes such as pulmonary infections that can mimic heart symptoms. Therefore, it is critical that the differential diagnosis be prudently done to avoid missing treatable cardiac abnormalities.

It is hoped that HAART regimens, by improving the clinical course of HIV disease, will reduce the incidence of pericardial effusions and myocardial involvement of HIV-associated malignancies and co-infections. A careful cardiological screening, however, is warranted for patients who are being evaluated for or who are receiving HAART regimens, especially those with other known underlying cardiovascular risk factors, as the atherogenic effects of protease inhibitors may synergistically promote the acceleration of coronary heart and cerebrovascular disease and enhance the risk of death due to myocardial infarction and stroke.

References

1.Barbaro G, Fisher SD, Lipshultz SE. Pathogenesis of HIV-associated cardiovascular complications. Lancet Infect Dis. 2001; 1: 115–124.

2. Lipshultz SE, Chanock S, Sanders SP, et al. Cardiovascular manifestations of human immunodeficiency virus infection in infants and children. Am J Cardiol 1989; 63:1489.

 

3.  Luginbuhl LM, Orav EJ, McIntosh K, Lipshultz SE. Cardiac morbidity and related mortality in children with HIV infection. JAMA 1993; 269:2869.

 

4. Heidenreich PA, Eisenberg MJ, Kee LL, et al. Pericardial effusion in AIDS: incidence and survival. Circulation. 1995; 92: 3229–3234.

 

5. Fink L, Reicheck N, St. John Sutton M. Cardiac abnormalities in acquired immune deficiency syndrome. Am J Cardiol 1984;54:1161-3.

 

6.Barbaro G, Klatt EC, HIV infection and the cardiovascular system. AIOS Rev. 2002; 4: 93

 

7.Barbaro G, Di Lorenzo G, Grisorio B, et al. Cardiac involvement in the acquired immunodeficiency syndrome: a multicenter clinical-pathological study. AIDS Res Hum Retroviruses. 1998; 14: 1071–1077.

 

8.Pellicelli AM, Palmieri F, D’Ambrosio C, et al. Role of human immunodeficiency virus in primary pulmonary hypertension: case reports. Angiology. 1998; 49: 1005–1011.