**3. Conclusions**

162 Myocarditis

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

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

**2.7 Treatment** 

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

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 conclusively, including HIV infection.

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 al., 2001].

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 function but also identification of pathologic and modifiable substrate.

The ultimate proof that the patient has myocarditis is provided by endomyocardial biopsy, but the patchy nature of the disease limits its diagnostic role [Karamitsos et al., 2009].

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

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 selected patients presenting with congestive heart failure.

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 sufficient data to establish myocardial dysfunction with or without ischemia.

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

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**8** 

**Exacerbation of Viral Myocarditis by Tobacco** 

*Steward Carney Hospital, Dorchester, Steward St. Elizabeth's Medical Center, Boston* 

More than 1 in every 10 cardiovascular deaths in the world during the year 2000 were attributable to smoking, demonstrating that it is an important preventable cause of cardiovascular mortality (Ezzati et al., 2005). It has been clearly established that exposure to environmental tobacco smoke increases the risk of cardiovascular disease among persons who have never smoked (Steenland, 1992). The cardiovascular effects of secondhand smoke are nearly as large as those confronting the principal smoker (Barnoya & Glantz, 2005). Non-smokers living with smokers have about a 25% increase in risk of death from heart disease and are more likely to suffer a stroke. Exposure to secondhand smoke may increase the risk of heart disease by non-smokers as much as 60% (Whincup et al., 2004). In 2004, Ong & Glantz estimated that only about 69% of U.S. indoor workers were covered by a smoke-free workplace policy. Making all workplaces smoke free as been accomplished for the commercial aircraft industry (Repace, 2004) would in one year prevent about 1500 myocardial infarctions and 350 strokes, and result in nearly 49 million dollars in savings in direct medical costs. These estimates are supported by reports of reduced incidence of admissions for myocardial infarction associated with smoking bans (Sargent et al., 2004). The cardiovascular effects of tobacco smoke exposure have been summarized in several excellent reviews (for example, see Barnoya and Glantz, 2005). Among the strongest pathophysiological correlates of tobacco smoking are accelerated endothelial dysfunction (Puranik & Celermajer, 2003) and acute clinical events, the latter being largely thrombotic (Ambrose & Barus, 2004). Recent studies indicate that increased oxidative stress is a potential mechanism for initiating cardiovascular dysfunction (Yang et al., 2004; Talukder et al, 2011). Tobacco smoke has also been demonstrated to increase inflammatory markers in patients exposed to secondhand smoke, including homocysteine, C-reactive protein, fibrinogen, and oxidized LDL cholesterol, (Panagiotakos et al., 2004) suggesting that an increased inflammatory response may contribute to accelerated atherosclerosis. Clearly, the incidence of ischemic coronary and peripheral vascular disease is increased in patients exposed to tobacco smoke, either as smokers or through exposure to secondhand tobacco smoke (Ambrose & Barus, 2004; Benowitz, 2003; Law & Wald, 2003; Burns, 2003; Leone et al., 2004). The cardiovascular effects of tobacco smoke exposure are summarized in Table l.

**1.1 Tobacco smoke exposure and cardiovascular disease** 

**1. Introduction** 

**Smoke: The Catecholamine Hypothesis** 

Nicolas Hanabergh and James P. Morgan

*and Tufts University School of Medicine, Boston,* 

*United States of America* 

