**2.6 Differential diagnosis of myocarditis in HIV**

It is difficult to assess the clinical significance of viral infection of the myocardium in HIVinfected patients. AIDS or HIV-infected patients with myocarditis most often present with signs and symptoms of congestive heart failure or asymptomatic left ventricular dysfunction. The diagnosis of dilatative cardiomyopathy in this setting is best established by echocardiography. More specific diagnosis can be established by endomyocardial biopsy, as clinically indicated. However, in the vast majority of cases endomyocardial biopsy will not identify a specific cause that will modify therapy. In a minority of patients, biopsy may establish a treatable cause of myocarditis. Therefore, the clinician should consider the specifics of each case before making a recommendation regarding whether endomyocardial biopsy is necessary [Olson 2003].

no. 2. The other 4 patients presented with dilative cardiomyopathy and ischemic areas on stress, as demonstrated in figure no. 3. All 10 patients had received HAART including

Fig. 1. Myocardic scintigraphy - ischemic areas at the antero-septal wall and myocardial

It is difficult to assess the clinical significance of viral infection of the myocardium in HIVinfected patients. AIDS or HIV-infected patients with myocarditis most often present with signs and symptoms of congestive heart failure or asymptomatic left ventricular dysfunction. The diagnosis of dilatative cardiomyopathy in this setting is best established by echocardiography. More specific diagnosis can be established by endomyocardial biopsy, as clinically indicated. However, in the vast majority of cases endomyocardial biopsy will not identify a specific cause that will modify therapy. In a minority of patients, biopsy may establish a treatable cause of myocarditis. Therefore, the clinician should consider the specifics of each case before making a recommendation regarding whether endomyocardial

**2.6 Differential diagnosis of myocarditis in HIV** 

biopsy is necessary [Olson 2003].

apex.

protease inhibitors for at least 5 years and significant changes in lipid profile.

Fig. 2. Myocardic scintigraphy - dilatative cardiomyopathy with no ischemic area.

Aside from nonspecific or infectious myocarditis, the differential diagnosis of LV dysfunction in the AIDS patient includes drug toxicity from either abuse of illicit substances or iatrogenic disease from agents used in the therapy for AIDS. AIDS patients often take a great variety of prescription and nonprescription drugs and use illicit drugs. Alcohol, cocaine, or heroin may contribute to LV dysfunction in many cases [Virmani et al., 1988; Regan et al., 1990; Soodini et al., 1991]. Pharmacotherapy is also potentially associated with LV dysfunction in AIDS patients. Therapeutic agents implicated as potential cardiac toxins include zidovudine [Herskowitz et al., 1992b; d'Amati et al., 1992], and interferon alfa-2 [Deyton et al., 1989; Zimmerman et al., 1994].

If neoplastic infiltration is suspected as a cause of LV dysfunction, cardiac computed tomography or magnetic resonance imaging may be a useful adjunct to echocardiography for characterizing cardiac involvement. Neoplastic infiltration of the heart by Kaposi sarcoma is frequently seen at autopsy and usually associated with widespread disease in the terminal phases of AIDS [Silver et al., 1984]. Non-Hodgkin lymphoma is also observed in this setting and also associated with widespread disease [Holladay et al., 1992].

In addition to HIV-related cardiac conditions, differential diagnosis also includes non-HIV disease, because the latency of HIV disease may be long and patients are at risk for development of hypertensive heart disease, coronary artery disease, or other causes of left ventricular dysfunction [Olson 2003].

Myocarditis in HIV Positive Patients 163

myocarditis, HAART regimens have reduced the prevalence of HIV-associated myocarditis to about 30% [Barbaro 2005]. One Italian study reported an almost 7-fold reduction of the prevalence of HIV-associated myocarditis from the pre-HAART era [Pugliese et al., 2000]. In that study there is no conclusive evidence that HAART reverses cardiomyopathy, but it does appear that by preventing profound immunosuppression and the development of

Cardiac dysfunction should be considered in the differential diagnosis of any HIV-infected patient with dyspnea or cardiomegaly. In the setting of AIDS or HIV infection, the diagnosis of dilated cardiomyopathy is established by echocardiography. A significant proportion, perhaps exceeding 80%, of patients with dilated cardiomyopathy may have focal, non-

Although viruses, in general, are well established as a cause of acute myocarditis, a causal role for viruses in the pathogenesis of dilated cardiomyopathy has not been demonstrated

A low CD4 count is an excellent predictor of the presence of LV dysfunction. The risk of dilated cardiomyopathy may also be increased with a history of illicit drug use [Soodini et

Myocarditis due to HIV-1 myocyte infection does not seem to be the most likely cause of LV dysfunction in patients with AIDS. It is more likely that the cause of LV dysfunction and congestive heart failure in this setting is multifactorial, related to drug toxicity, non-HIV viral infection, poor nutrition, or cytokines. Another situation in HIV positive patients that can cause myocarditis with or without ischemia is dyslipidemia as a consequence of highly active antiretroviral therapy that included protease inhibitor for a long period of time. The evaluation and management of HIV positive patients with myocarditis and specific dilated cardiomyopathies remains clinically challenging. Essential to the appropriate care of these patients is not only an understanding of the patient's cardiac morphology and

The ultimate proof that the patient has myocarditis is provided by endomyocardial biopsy,

Computed tomography or magnetic resonance imaging may help but are not widely used for diagnosis. Gadolinium-enhanced magnetic resonance imaging is used for assessment of the extent of inflammation and cellular edema, although it is still nonspecific. Delayedenhanced MRI has also been used to quantify the amount of scarring that occurred

By virtue of its safety, high degree of accuracy and reproducibility, and multiparametric nature, cardiac MRI represents the principal imaging modality that potentially addresses each of these points of care for heart failure patients. However, coronary CT angiography can aid in ruling out epicardial coronary artery stenosis as the cause of LV dysfunction in

In addition to clinical examination and biological evaluation, in the absence of cardiac MRI, a combination of ultrasound and scintigraphic investigations of the heart can provide

Because cardiac CT, CMR and cardiac scintigraphy were not widely used in patients with myocarditis and in HIV cases are only sporadic presentations, to identify particular aspects

sufficient data to establish myocardial dysfunction with or without ischemia.

but the patchy nature of the disease limits its diagnostic role [Karamitsos et al., 2009].

function but also identification of pathologic and modifiable substrate.

following acute myocarditis [Al-Mallah & Kwong 2009].

selected patients presenting with congestive heart failure.

AIDS, heart muscle remains healthier[Pugliese et al., 2000].

specific lymphocytic myocarditis [Barbaro et al., 1998a].

conclusively, including HIV infection.

**3. Conclusions** 

al., 2001].

Fig. 3. Myocardic scintigraphy - dilative cardiomyopathy and ischemic areas on stress.

#### **2.7 Treatment**

Treatment for HIV related myocarditis is generally similar to that for non-HIV related myocarditis. Symptomatic treatment is the only form of therapy for HIV positive patients with myocarditis. In the acute phase, supportive therapy including bed rest is indicated. For symptomatic patients, digoxin and diuretics provide clinical improvement. For patients with moderate to severe dysfunction, cardiac function can be supported by use of inotropes such as Milrinone in the acute phase followed by oral therapy with ACE inhibitors (Captopril, Lisinopril) when tolerated. Patients who do not respond to conventional therapy are candidates for bridge therapy with left ventricular assist devices. Heart transplantation is reserved for patients who fail to improve with conventional therapy. Patients with HIV and myocarditis have enhanced sensitivity to digoxin and anticoagulation presents risks to patients with cerebral vasculopathy and possible aneurysm formation [Howes et al., 2010].

The use of immunosuppressive regimens in these patients is controversial and no convincing benefits have been reported other than with intravenous immunoglobulin [Lipshultz et al., 1995], whose efficacy may reflect inhibition of cardiac auto antibodies by competition with Fc receptors or dampened effects of cytokines and cellular growth factors.

The introduction of highly active antiretroviral therapy (HAART) regimens has substantially modified the course of HIV disease by lengthening survival and improving quality of life of HIV-infected patients [Zareba & Lipshultz 2003]. There is also good evidence that HAART significantly reduces the incidence of cardiovascular manifestations of HIV infection. By preventing opportunistic infections and reducing the incidence of myocarditis, HAART regimens have reduced the prevalence of HIV-associated myocarditis to about 30% [Barbaro 2005]. One Italian study reported an almost 7-fold reduction of the prevalence of HIV-associated myocarditis from the pre-HAART era [Pugliese et al., 2000]. In that study there is no conclusive evidence that HAART reverses cardiomyopathy, but it does appear that by preventing profound immunosuppression and the development of AIDS, heart muscle remains healthier[Pugliese et al., 2000].
