**7.1 Viral myocarditis**

Amongst the multiple infectious etiologies which have been implicated as the cause of clinically significant acute myocarditis, viral myocarditis being the most common and the enterovirus coxsackie B being the most significant. Numerous seroepidemiologic and molecular studies were linked coxsackievirus B to outbreaks of myocarditis occurred before the 1990s. The spectrum of viruses that were detected in endomyocardial biopsy samples shifted from coxsackievirus B to adenovirus in the late 1990s. In the last decade a number of reports implicate new viruses in the etiology of myocarditis and dilated cardiomyopathy. The parvovirus B19 was identified in patients with myocarditis in Germany (Kühl et al., 2005; Mahrholdt et al., 2006) and hepatitis C virus was reported in Japan (Matsumori 2005, 2006) as well.

Early studies suggested that cardiac involvement occurred in 3.5 to 5 percent of patients during outbreaks of coxsackievirus infection (Gerzen et al., 1972; Grist & Bell, 1969). Most cases of enteroviral myocarditis or pericarditis occur in children and young adults in whom more than two-thirds are male. In the majority of patients, active myocarditis remains unsuspected because the subclinical and self-limited pattern of presentation or the presence of myocarditis may infer only by the finding of transient electrocardiographic ST-T-wave abnormalities. In addition, subtle cardiac symptoms and signs may be overshadowed by the systemic manifestations of the underlying infection or disease process. Clinically, the patients give a history of a preceding upper respiratory febrile illness or a flu-like syndrome, and viral nasopharyngitis or tonsillitis may be evident. In the United States Myocarditis Treatment Trial, 89 percent of subjects reported a syndrome consistent with a viral prodrome (Mason et al., 1995). The patient may also have fever, myalgias, and muscle tenderness that is followed by chest pain, dyspnea or arrhythmias, and occasionally heart

Clinical Presentation 15

In addition to the coxsackievirus B, other members of the genus Enterovirus (coxsackievirus A, echovirus, and poliovirus) and many other viruses have also been associated less frequently with myocarditis; these viruses include influenza virus, Epstein–Barr virus, cytomegalovirus, human herpesvirus (Kindermann et al., 2008) and varicella-zoster virus. Myocarditis and pericarditis were reported in association with influenza virus infection during the 1918–1919 pandemic. Unusually, myocarditis has also been described as a complication of mumps in a severe but usually self-limited form. Molecular diagnostic assays have implicated mumps virus in some cases of endocardial fibroelastosis following myocarditis as well. In more recent study of 172 patients with a biopsy sample showing myocarditis, the most common viruses were parvovirus B19, 36.6 percent; enterovirus, 32.6 percent; co-infection with HHV-6 and parvovirus B19, 12.6 percent human herpesvirus 6

The novel influenza virus A (H1N1) pandemic began in Mexico in 2009 and rapidly spread worldwide. The cardiac complications of H1N1 infection were uncommonly reported. Sudden death as a result of myocarditis was a rare recognized complication in otherwise immunocompetent individuals, despite the absence of significant respiratory tract infection. A report from Japan described 10 patients presented with fulminant myocarditis which was confirmed by endomyocardial biopsy in 6 patients, 8 of the cases were rescued (Ukimura et al., 2009). Also, a documented influenza myocarditis was reported due to 2009 pandemic H1N1 virus occurred in a previously healthy adult (Haessler et al., 2010). Another reported fatal case of acute myocarditis in an immunocompetent young woman, the autopsy revealed a predominantly lymphocytic myocarditis (Gdynia et al., 2011). On the other hand, cases diagnosed with fulminant myocarditis were described in pediatric population with fatal

Though viral myocarditis is most often self-limited and without sequelae, fulminant condition with arrhythmias, heart failure occurs. Arrhythmias are common and are occasionally difficult to manage. Patients with fulminant myocarditis may require mechanical cardiopulmonary support or cardiac transplantation, but the majority survived and many demonstrate substantial recovery of ventricular function. Patients with myocarditis and pulmonary hypertension are at a particularly high risk of death. Deaths attributed to heart failure, tachyarrhythmias, and heart block has been reported and it seems prudent to monitor the electrocardiogram of patients with arrhythmias, especially during the acute illness. In some patients, myocarditis simulates acute myocardial infarction, with chest pain, electrocardiographic changes, and elevated serum levels of myocardial enzymes. Additionally, viral myocarditis are assumed to be the major causes of chronic dilated cardiomyopathy, some cases of myocarditis may recur as well, however the number of cases with acute myocarditis that progresses to chronic dilated cardiomyopathy remains

The human immunodeficiency virus type I (HIV-1) infection that causes the acquired immunodeficiency syndrome (AIDS) has became a worldwide pandemic. It has been identified for more than 3 decades, during which time a number of factors may altered the nature of cardiac manifestation. Notably, the survival in adult with HIV infection and AIDS is prolonged as a result of earlier detection and the use of highly active antiretroviral therapy (HAART), (Hoover et al., 1993; Palella et al., 1998). On the other hand, disorders

(HHV-6), 10.5 percent; adenovirus, 8.1 percent (Kuhl et al., 2005).

outcomes within a 30-day of presentation (Bratincsák et al., 2010).

**7.2 Human immunodeficiency virus (HIV) myocarditis** 

anonymous.

failure. A pericardial friction rub is documented in half of cases, and the electrocardiogram shows ST segment elevations or ST- and T-wave abnormalities. Most adults recover completely and only a minority of cases progress to chronic dilated cardiomyopathy.


Table 2. Some key clinical hints among specific forms of myocarditis that help with the clinical diagnosis.

failure. A pericardial friction rub is documented in half of cases, and the electrocardiogram shows ST segment elevations or ST- and T-wave abnormalities. Most adults recover

Clinical clues Clinical diagnosis Comments

Sarcoid myocarditis

Hypersensitive/ eosinophilic myocarditis

Anthracyclinesinduced myocarditis

Chagas disease

Lyme disease

Acute rheumatic

Peripartum cardiomyopathy

Giant-cell myocarditis

Table 2. Some key clinical hints among specific forms of myocarditis that help with the

fever

Viral myocarditis Often self-limited

Enlarged lymph nodes suggest systemic sarcoidosis

The apical aneurysm

Varying degrees of atrioventricular conduction block is

Higher incidence of thromboembolism (hypercoagulable state of pregnancy). More often when left ventricular ejection fraction <35 %

Syncope or sudden death develop due to ventricular arrhythmias or heart

block

is typical in advanced disease

common

completely and only a minority of cases progress to chronic dilated cardiomyopathy.

Preceding upper respiratory febrile or flu-

Patients present with chronic heart failure,

arrhythmias or heart block with no response

Cutaneous rash (pruritic, maculopapular), fever, peripheral eosinophilia or a temporal relation with recently initiated medications

like illness (viral nasopharyngitis

dilated cardiomyopathy and new

or the use of multiple medications

History of travel to Central or South America, Systemic or pulmonary

History of residence or travel through the endemic area; previous tick bites; prior or current erythema migrans lesions and coexistence of neurologic dysfunction

Previous history of rheumatic heart disease or symptoms defined by Jones criteria e.g. erythema marginatum, polyarthralgia, chorea, subcutaneous nodules fever or

Heart failure developing in the last month of pregnancy or within 5 months following

Sustained ventricular tachycardia in rapidly progressive heart failure associated with thymoma, autoimmune disorders, or high-

Patients treated anti-neoplastic chemotherapeutic agents

or tonsillitis)

to standard care

thromboembolism

arthralgia

delivery

grade heart block

clinical diagnosis.

In addition to the coxsackievirus B, other members of the genus Enterovirus (coxsackievirus A, echovirus, and poliovirus) and many other viruses have also been associated less frequently with myocarditis; these viruses include influenza virus, Epstein–Barr virus, cytomegalovirus, human herpesvirus (Kindermann et al., 2008) and varicella-zoster virus. Myocarditis and pericarditis were reported in association with influenza virus infection during the 1918–1919 pandemic. Unusually, myocarditis has also been described as a complication of mumps in a severe but usually self-limited form. Molecular diagnostic assays have implicated mumps virus in some cases of endocardial fibroelastosis following myocarditis as well. In more recent study of 172 patients with a biopsy sample showing myocarditis, the most common viruses were parvovirus B19, 36.6 percent; enterovirus, 32.6 percent; co-infection with HHV-6 and parvovirus B19, 12.6 percent human herpesvirus 6 (HHV-6), 10.5 percent; adenovirus, 8.1 percent (Kuhl et al., 2005).

The novel influenza virus A (H1N1) pandemic began in Mexico in 2009 and rapidly spread worldwide. The cardiac complications of H1N1 infection were uncommonly reported. Sudden death as a result of myocarditis was a rare recognized complication in otherwise immunocompetent individuals, despite the absence of significant respiratory tract infection. A report from Japan described 10 patients presented with fulminant myocarditis which was confirmed by endomyocardial biopsy in 6 patients, 8 of the cases were rescued (Ukimura et al., 2009). Also, a documented influenza myocarditis was reported due to 2009 pandemic H1N1 virus occurred in a previously healthy adult (Haessler et al., 2010). Another reported fatal case of acute myocarditis in an immunocompetent young woman, the autopsy revealed a predominantly lymphocytic myocarditis (Gdynia et al., 2011). On the other hand, cases diagnosed with fulminant myocarditis were described in pediatric population with fatal outcomes within a 30-day of presentation (Bratincsák et al., 2010).

Though viral myocarditis is most often self-limited and without sequelae, fulminant condition with arrhythmias, heart failure occurs. Arrhythmias are common and are occasionally difficult to manage. Patients with fulminant myocarditis may require mechanical cardiopulmonary support or cardiac transplantation, but the majority survived and many demonstrate substantial recovery of ventricular function. Patients with myocarditis and pulmonary hypertension are at a particularly high risk of death. Deaths attributed to heart failure, tachyarrhythmias, and heart block has been reported and it seems prudent to monitor the electrocardiogram of patients with arrhythmias, especially during the acute illness. In some patients, myocarditis simulates acute myocardial infarction, with chest pain, electrocardiographic changes, and elevated serum levels of myocardial enzymes. Additionally, viral myocarditis are assumed to be the major causes of chronic dilated cardiomyopathy, some cases of myocarditis may recur as well, however the number of cases with acute myocarditis that progresses to chronic dilated cardiomyopathy remains anonymous.

#### **7.2 Human immunodeficiency virus (HIV) myocarditis**

The human immunodeficiency virus type I (HIV-1) infection that causes the acquired immunodeficiency syndrome (AIDS) has became a worldwide pandemic. It has been identified for more than 3 decades, during which time a number of factors may altered the nature of cardiac manifestation. Notably, the survival in adult with HIV infection and AIDS is prolonged as a result of earlier detection and the use of highly active antiretroviral therapy (HAART), (Hoover et al., 1993; Palella et al., 1998). On the other hand, disorders

Clinical Presentation 17

toxoplasmosis described in 1 to 16 percent autopsy series of patients dying of AIDS (Anderson et al., 1988; Baroldi et al., 1988; Matturri et al., 1990). Cytomegalovirus is another common opportunistic infection in patients with late stage AIDS that can cause myocarditis in selected patients (Barbaro et al., 1998; Niedt & Schinella, 1985). Other virus identified within the myocardium of HIV-infected or AIDS patients, either at antemortem endomyocardial biopsy or from autopsy material, have included Epstein-Barr and coxsackie B virus in adults (Barbaro et al., 1998; Dittrich et al., 1988) These viruses may be present as either primary infection or as coinfection and can occur with or without associated myocarditis and with or without associated LV dysfunction. Other infections like, myocardial tuberculosis appears to be rare (Miller-Catchpole et al., 1989). Fungal myocarditis is another unusual complication of disseminated infection that is identified most often at autopsy. Various fungal organisms identified in the myocardium at autopsy with associated myocarditis. Cardiac cryptococcus has been diagnosed in association with congestive heart failure and resolved after therapy (Kinney et al., 1989; Lafont et al., 1987;

Other possible etiologies of LV dysfunction are drug toxicity from either abuse of illicit substances or iatrogenic disease from agents used in the therapy for AIDS. Alcohol, cocaine, or heroin may contribute to LV dysfunction in many cases (Brown et al., 1991; Peng et al., 1989; Soodini & Morgan, 2001). Therapeutic agents implicated as potential cardiac toxins include zidovudine (d'Amati et al., 1992; Herskowitz et al., 1992), interleukin-2 (Samlowski et al., 1989) and interferon alfa-2 (Deyton et al., 1989; Zimmerman et al., 1994). 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

Nowadays, myocarditis of infectious etiology caused by non-viral agents is less frequent worldwide. Bacterial involvement of the heart is uncommon, but when it does occur, it is usually as a complication of endocarditis. Various bacteria include (*Corynebacterium diphtheriae, Streptococcus pyogenes, Staphylococcus aureus, Haemophilus pneumoniae, Salmonella* spp., *Neisseria gonorrhoeae, Leptospira, Borrelia burgdorferi, Treponema pallidum, Brucella, Mycobacterium tuberculosis,* Actinomyces*, Chlamydia* spp., *Coxiella brunetti, Mycoplasma pneumoniae* and *Rickettsia* spp). Bacteria like streptococcal and staphylococcal species and *Bartonella, Brucella, Leptospira,* and *Salmonella* species can spread to the myocardium as a consequence of severe cases of endocarditis. Some forms of bacterial myocarditis will be

Worldwide, the most common bacterial cause of myocarditis is diphtheria. As early as 1806, a relationship between infection (diphtheria) and chronic heart disease was postulated, but it was not until the 1970s, with the advent of endomyocardial biopsy, that the diagnosis of

The risk of developing cardiac toxicity is proportional to the severity of local infection. *Corynebacterium diphtheriae* produce toxins that inhibit protein synthesis that can cause myocarditis and leads to a dilated, flabby, hypocontractile heart. The manifestations of

Lewis et al., 1985).

disease (Holladay et al., 1992).

**7.3 Bacterial myocarditis** 

discussed below.

**7.3.1 Diphtheritic myocarditis** 

myocarditis could be established during life.

such as hypertension, hyperglycemia, hyperlipidemia, lipodystrophy and coronary artery disease appeared to add further comorbidity to HIV infection (Fisher & Lipshultz, 2001; Friis-Møller et al., 2007; Tershakovec et al., 2004).

Human immunodeficiency virus is the most common cardiac pathologic finding at autopsy in HIV infected patients with prevalence as high as 70 percent (Anderson et al., 1988; Baroldi et al., 1988, Lewis, 1989). Myocarditis identified at autopsy or on endomyocardial biopsy in HIV-infected patients is most often nonspecific and manifested as focal, inflammatory lymphocytic infiltrates without myocyte necrosis. However, it is uncertain whether the myocarditis so frequently observed at autopsy is clinically relevant.

Myocarditis should be considered in any HIV-infected patient with dyspnea or cardiomegaly. It is most often present with signs and symptoms of congestive heart failure or asymptomatic left ventricular (LV) dysfunction established by echocardiography. Of note, the clinical features of concomitant noncardiac disorders may mask cardiac involvement and steer to inaccurate approach, since myocardial manifestations due of HIV infection may respond at least transiently to standard therapy. A prospective long-term clinical and echocardiographic follow-up study of asymptomatic HIV-positive patients showed a mean annual incidence of progression to dilated cardiomyopathy of 15.9 cases per 1,000 patients. The exact pathogenesis of myocarditis in the AIDS is unclear. Possible direct action of HIV on the myocardial tissue or an autoimmune process induced by HIV, possibly in association with other cardiotropic viruses. It is difficult to assess the clinical significance of viral infection of the myocardium in HIV infected patients. A histologic diagnosis of myocarditis was reported in 83 percent of patients with dilated cardiomyopathy. This significant proportion had focal, nonspecific lymphocytic myocarditis (Barbaro et al., 1998).

Dilated cardiomyopathy can be subclinical or may present with overt clinical findings. Cardiac involvement is often subclinical as echocardiographic studies have demonstrated LV dysfunction in 41 percent of asymptomatic HIV-positive individuals (Corallo et al., 1988). However, in the primary care setting, AIDS cardiac complications are unusual. One autopsy series demonstrated no cardiac disease in 115 consecutive autopsies of patients who died of AIDS-related complications (Lewis, 1989). In one series of 416 HIV-positive patients from Rwanda without a previous history of cardiovascular disease and not receiving HAART reported an echocardiographically evident dilated cardiomyopathy in 17.7 percent (Twagirumukiza et al., 2007). The overt clinical involvement is seen in 10 percent of HIV patients, and the most common clinically significant finding is a dilated cardiomyopathy associated with typical findings of congestive heart failure, namely edema and shortness of breath.

Apart from the clinical manifestation which may be seen as a direct consequence of HIV infection, a more likely, as a consequence of possible etiologies related to non-HIV cardiotrophic viral infection, postviral autoimmune mechanism, drug toxicity or neoplastic infiltration by Kaposi sarcoma or lymphoma.

Since the introduction of HAART regimens there has been a marked reduction in the incidence of myocarditis and opportunistic infections, which has led to a nearly 30 percent reduction in HIV-associated cardiomyopathy (Barbaro, 2005). Opportunistic infections include bacteria, fungi, protozoa, and viruses are the most frequent cause of morbidity and mortality in AIDS which is identified in 10 to 15 percent of cases (Hofman et al., 1993). However, symptomatic disease appears to be rare. Toxoplasma gondii is the most frequently documented infectious cause of myocarditis associated with AIDS. Myocardial

such as hypertension, hyperglycemia, hyperlipidemia, lipodystrophy and coronary artery disease appeared to add further comorbidity to HIV infection (Fisher & Lipshultz, 2001;

Human immunodeficiency virus is the most common cardiac pathologic finding at autopsy in HIV infected patients with prevalence as high as 70 percent (Anderson et al., 1988; Baroldi et al., 1988, Lewis, 1989). Myocarditis identified at autopsy or on endomyocardial biopsy in HIV-infected patients is most often nonspecific and manifested as focal, inflammatory lymphocytic infiltrates without myocyte necrosis. However, it is uncertain whether the

Myocarditis should be considered in any HIV-infected patient with dyspnea or cardiomegaly. It is most often present with signs and symptoms of congestive heart failure or asymptomatic left ventricular (LV) dysfunction established by echocardiography. Of note, the clinical features of concomitant noncardiac disorders may mask cardiac involvement and steer to inaccurate approach, since myocardial manifestations due of HIV infection may respond at least transiently to standard therapy. A prospective long-term clinical and echocardiographic follow-up study of asymptomatic HIV-positive patients showed a mean annual incidence of progression to dilated cardiomyopathy of 15.9 cases per 1,000 patients. The exact pathogenesis of myocarditis in the AIDS is unclear. Possible direct action of HIV on the myocardial tissue or an autoimmune process induced by HIV, possibly in association with other cardiotropic viruses. It is difficult to assess the clinical significance of viral infection of the myocardium in HIV infected patients. A histologic diagnosis of myocarditis was reported in 83 percent of patients with dilated cardiomyopathy. This significant proportion had

Dilated cardiomyopathy can be subclinical or may present with overt clinical findings. Cardiac involvement is often subclinical as echocardiographic studies have demonstrated LV dysfunction in 41 percent of asymptomatic HIV-positive individuals (Corallo et al., 1988). However, in the primary care setting, AIDS cardiac complications are unusual. One autopsy series demonstrated no cardiac disease in 115 consecutive autopsies of patients who died of AIDS-related complications (Lewis, 1989). In one series of 416 HIV-positive patients from Rwanda without a previous history of cardiovascular disease and not receiving HAART reported an echocardiographically evident dilated cardiomyopathy in 17.7 percent (Twagirumukiza et al., 2007). The overt clinical involvement is seen in 10 percent of HIV patients, and the most common clinically significant finding is a dilated cardiomyopathy associated with typical findings of congestive heart failure, namely edema and shortness of

Apart from the clinical manifestation which may be seen as a direct consequence of HIV infection, a more likely, as a consequence of possible etiologies related to non-HIV cardiotrophic viral infection, postviral autoimmune mechanism, drug toxicity or neoplastic

Since the introduction of HAART regimens there has been a marked reduction in the incidence of myocarditis and opportunistic infections, which has led to a nearly 30 percent reduction in HIV-associated cardiomyopathy (Barbaro, 2005). Opportunistic infections include bacteria, fungi, protozoa, and viruses are the most frequent cause of morbidity and mortality in AIDS which is identified in 10 to 15 percent of cases (Hofman et al., 1993). However, symptomatic disease appears to be rare. Toxoplasma gondii is the most frequently documented infectious cause of myocarditis associated with AIDS. Myocardial

Friis-Møller et al., 2007; Tershakovec et al., 2004).

myocarditis so frequently observed at autopsy is clinically relevant.

focal, nonspecific lymphocytic myocarditis (Barbaro et al., 1998).

infiltration by Kaposi sarcoma or lymphoma.

breath.

toxoplasmosis described in 1 to 16 percent autopsy series of patients dying of AIDS (Anderson et al., 1988; Baroldi et al., 1988; Matturri et al., 1990). Cytomegalovirus is another common opportunistic infection in patients with late stage AIDS that can cause myocarditis in selected patients (Barbaro et al., 1998; Niedt & Schinella, 1985). Other virus identified within the myocardium of HIV-infected or AIDS patients, either at antemortem endomyocardial biopsy or from autopsy material, have included Epstein-Barr and coxsackie B virus in adults (Barbaro et al., 1998; Dittrich et al., 1988) These viruses may be present as either primary infection or as coinfection and can occur with or without associated myocarditis and with or without associated LV dysfunction. Other infections like, myocardial tuberculosis appears to be rare (Miller-Catchpole et al., 1989). Fungal myocarditis is another unusual complication of disseminated infection that is identified most often at autopsy. Various fungal organisms identified in the myocardium at autopsy with associated myocarditis. Cardiac cryptococcus has been diagnosed in association with congestive heart failure and resolved after therapy (Kinney et al., 1989; Lafont et al., 1987; Lewis et al., 1985).

Other possible etiologies of LV dysfunction are drug toxicity from either abuse of illicit substances or iatrogenic disease from agents used in the therapy for AIDS. Alcohol, cocaine, or heroin may contribute to LV dysfunction in many cases (Brown et al., 1991; Peng et al., 1989; Soodini & Morgan, 2001). Therapeutic agents implicated as potential cardiac toxins include zidovudine (d'Amati et al., 1992; Herskowitz et al., 1992), interleukin-2 (Samlowski et al., 1989) and interferon alfa-2 (Deyton et al., 1989; Zimmerman et al., 1994). 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).

### **7.3 Bacterial myocarditis**

Nowadays, myocarditis of infectious etiology caused by non-viral agents is less frequent worldwide. Bacterial involvement of the heart is uncommon, but when it does occur, it is usually as a complication of endocarditis. Various bacteria include (*Corynebacterium diphtheriae, Streptococcus pyogenes, Staphylococcus aureus, Haemophilus pneumoniae, Salmonella* spp., *Neisseria gonorrhoeae, Leptospira, Borrelia burgdorferi, Treponema pallidum, Brucella, Mycobacterium tuberculosis,* Actinomyces*, Chlamydia* spp., *Coxiella brunetti, Mycoplasma pneumoniae* and *Rickettsia* spp). Bacteria like streptococcal and staphylococcal species and *Bartonella, Brucella, Leptospira,* and *Salmonella* species can spread to the myocardium as a consequence of severe cases of endocarditis. Some forms of bacterial myocarditis will be discussed below.

### **7.3.1 Diphtheritic myocarditis**

Worldwide, the most common bacterial cause of myocarditis is diphtheria. As early as 1806, a relationship between infection (diphtheria) and chronic heart disease was postulated, but it was not until the 1970s, with the advent of endomyocardial biopsy, that the diagnosis of myocarditis could be established during life.

The risk of developing cardiac toxicity is proportional to the severity of local infection. *Corynebacterium diphtheriae* produce toxins that inhibit protein synthesis that can cause myocarditis and leads to a dilated, flabby, hypocontractile heart. The manifestations of

Clinical Presentation 19

atrioventricular block, which was usually symptomatic (McAlister et al., 1989). Wenckebach periodicity occurred in 40 percent and complete atrioventricular block in 50 percent; other findings include bundle branch and fascicular blocks, which are rare. In another report, 38 percent of patients with Lyme carditis required a temporary pacemaker (Goldings & Jericho, 1986). Patients with a PR interval greater than 300 milliseconds carry a highest risk for progression to complete heart block, which may develop rapidly (Steere et al., 1980). Complete heart block caused by Lyme disease typically resolves within one week, and more minor conduction disturbances within six weeks (Fish, 2008; McAlister et al., 1989). More reports showed heart block usually persists for 3 to 42 days and often resolves spontaneously (Costello et al., 2009; Cox et al., 1991; Steere et al., 1980; van der Linde et al., 1989). In Europe, scattered case reports have suggested that *B. burgdorferi* may, in isolated cases, be a cause of chronic cardiomyopathy (Bartůnek et al., 2006; Palecek et al., 2010). This has not been shown in the United States. A small Dutch series evaluated 42 patients with dilated cardiomyopathy (Vlay et al., 1991). Nine were seropositive for anti-B. burgdorferi;

six recovered fully, two had a partial response, and one showed no improvement.

Typhoid fever is a life-threatening illness rarely complicated by myocarditis. Salmonella myocarditis may produce variable clinical manifestations from latent to severe clinical forms, such as acute congestive heart failure or sudden cardiac death (Al-Aqeedi et al., 2009; Burt et al., 1990). Postmortem studies suggest that myocarditis is a major cause of sudden unexpected death in young adults and may account for 20 percent of cases (Feldman &

Myocarditis sometimes occurs as a complication of Yersinia. Clinical evidence of Campylobacter-associated myocarditis described in association with *Campylobacter* spp. enteritis (Kotilainen et al., 2006). Mild, self-limited myocarditis accompanies 10 percent of cases of Yersinia induced arthritis and can occur independently. Typical manifestations include cardiac murmurs and transient electrocardiographic abnormalities, such as prolongation of the PR interval and nonspecific ST-segment and T wave changes. The syndrome of Yersinia-induced arthritis and carditis can be confused with acute rheumatic

Myocardial involvement is a rare manifestation of Legionella infection, though, the most common extrapulmonary site of Legionnaires' disease is the heart. Numerous reports have described myocarditis, pericarditis, postcardiotomy syndrome, and prosthetic valve endocarditis (Antonarakis et al., 2006; Lowry & Tompkins, 1993; Tompkins et al., 1988). Most cases have been hospital acquired. Legionella carditis in the adult population is invariably seen in association of pneumonia, however, isolated Legionella myocardial

Cardiac abnormalities rarely reported in conjunction with *Mycoplasma pneumoniae* infection including myocarditis and pericarditis (Martin & Bates, 1991; Paz & Potasman, 2002).

involvement without associated pneumonia have been reported (Burke et al., 2009).

**7.3.3 Salmonella myocarditis** 

McNamara, 2000).

fever.

**7.3.4 Yersinia myocarditis** 

**7.3.5 Legionella myocarditis** 

**7.3.6 Mycoplasma myocarditis** 

diphtheritic myocarditis include various dysrhythmias, conduction disturbances, and dilated cardiomyopathy. Cardiomegaly and severe congestive heart failure typically appear after the first week of illness. However, clinically evident cardiac manifestation like dyspnea, decreased heart sounds, gallop rhythm or cardiac dilatation is much less common, occurring in 10 to 25 percent of all patients with diphtheria (Morgan et al., 1963).

Myocarditis occurred in 22 percent of 656 hospitalized patients with diphtheria in the Kyrgyz Republic in 1995; 7 percent of patients with myocarditis and 2 percent of patients without myocarditis died (Kadirova et al., 2000). Myocarditis as evidenced by electrocardiographic changes such as ST-T wave changes, QTc prolongation, and/or firstdegree heart block can be detected in as many as two-thirds of cases, often occurring when local respiratory symptoms are improving (Boyer & Weinstein, 1963; Lumio et al., 1948). The conduction system is frequently involved. The complete heart block result from diphtheritic myocarditis was almost always fatal before temporary cardiac pacemakers were developed. Diphtheritic myocarditis considered the most serious complication and remains the major cause of mortality (Kneen et al., 2004). The death rate is highest during the first week of illness particularly among patients with bull-neck diphtheria and among patients with myocarditis who develop ventricular tachycardia, atrial fibrillation, or complete heart block.

#### **7.3.2 Lyme myocarditis**

Lyme disease is an inflammatory disease caused by infection with the spirochete *Borrelia burgdorferi*. In United States, carditis occurs in approximately 5 percent, while, it is less frequent in Europe, affecting approximately 0.3 to 4.0 percent of untreated adults (Cox et al., 1991). This difference may be related to infection by different organisms.

A careful history should address risk factors or possible evidence of *B. burgdorferi* infection particularly in the presence of atrioventricular conduction abnormalities (McAlister et al., 1989). These include history of residence or travel through an endemic area; previous tick bites; prior or current erythema migrans lesions and coexistence of objective or subjective neurologic dysfunction compatible with neurologic Lyme disease. Cardiac Lyme disease occurs during the early disseminated phase of the disease, usually within weeks to a few months after infection (Fish, 2008). In a patient with suspected Lyme disease after a tick bite, the possibility of coinfection with Ehrlichia (ehrilichiosis) and Babesia (babesiosis) should be considered as both can also cause myocarditis.

There is a male predominance of approximately 3:1 in cardiac Lyme disease (Vlay, 1993). Patients with cardiac involvement may be asymptomatic and clinically inapparent. However, some patients develop symptomatic myocarditis with cardiac muscle dysfunction and/or associated pericarditis (Vlay et al., 1991) (Lorcerie et al., 1987). Symptoms mainly include palpitations, shortness of breath, chest pain, presyncope or syncope. In a review of 84 patients with Lyme carditis, the United States Centers for Disease Control and Prevention reported palpitations in 69 percent, conduction abnormalities in 19 percent, myocarditis in 10 percent and left ventricular failure 5 percent (Ciesielski et al., 1989). Endomyocardial biopsy samples resemble idiopathic lymphocytic myocarditis, and rarely the spirochetal organisms are identified (Cox et al., 1991; McAlister et al., 1989; Stanek et al., 1990).

Atrioventricular conduction block of varying degrees are the most common manifestation of Lyme carditis. In some patients, heart block is the first and only manifestation of Lyme disease (Kimball et al., 1989). Patients may present with first degree heart block but can progress to second degree or complete heart block over a short period of time (Peeters et al., 1990). One review of 52 patients with Lyme carditis found that 87 percent had

diphtheritic myocarditis include various dysrhythmias, conduction disturbances, and dilated cardiomyopathy. Cardiomegaly and severe congestive heart failure typically appear after the first week of illness. However, clinically evident cardiac manifestation like dyspnea, decreased heart sounds, gallop rhythm or cardiac dilatation is much less common,

Myocarditis occurred in 22 percent of 656 hospitalized patients with diphtheria in the Kyrgyz Republic in 1995; 7 percent of patients with myocarditis and 2 percent of patients without myocarditis died (Kadirova et al., 2000). Myocarditis as evidenced by electrocardiographic changes such as ST-T wave changes, QTc prolongation, and/or firstdegree heart block can be detected in as many as two-thirds of cases, often occurring when local respiratory symptoms are improving (Boyer & Weinstein, 1963; Lumio et al., 1948). The conduction system is frequently involved. The complete heart block result from diphtheritic myocarditis was almost always fatal before temporary cardiac pacemakers were developed. Diphtheritic myocarditis considered the most serious complication and remains the major cause of mortality (Kneen et al., 2004). The death rate is highest during the first week of illness particularly among patients with bull-neck diphtheria and among patients with myocarditis who develop ventricular tachycardia, atrial fibrillation, or complete heart block.

Lyme disease is an inflammatory disease caused by infection with the spirochete *Borrelia burgdorferi*. In United States, carditis occurs in approximately 5 percent, while, it is less frequent in Europe, affecting approximately 0.3 to 4.0 percent of untreated adults (Cox et al.,

A careful history should address risk factors or possible evidence of *B. burgdorferi* infection particularly in the presence of atrioventricular conduction abnormalities (McAlister et al., 1989). These include history of residence or travel through an endemic area; previous tick bites; prior or current erythema migrans lesions and coexistence of objective or subjective neurologic dysfunction compatible with neurologic Lyme disease. Cardiac Lyme disease occurs during the early disseminated phase of the disease, usually within weeks to a few months after infection (Fish, 2008). In a patient with suspected Lyme disease after a tick bite, the possibility of coinfection with Ehrlichia (ehrilichiosis) and Babesia (babesiosis) should be

There is a male predominance of approximately 3:1 in cardiac Lyme disease (Vlay, 1993). Patients with cardiac involvement may be asymptomatic and clinically inapparent. However, some patients develop symptomatic myocarditis with cardiac muscle dysfunction and/or associated pericarditis (Vlay et al., 1991) (Lorcerie et al., 1987). Symptoms mainly include palpitations, shortness of breath, chest pain, presyncope or syncope. In a review of 84 patients with Lyme carditis, the United States Centers for Disease Control and Prevention reported palpitations in 69 percent, conduction abnormalities in 19 percent, myocarditis in 10 percent and left ventricular failure 5 percent (Ciesielski et al., 1989). Endomyocardial biopsy samples resemble idiopathic lymphocytic myocarditis, and rarely the spirochetal

organisms are identified (Cox et al., 1991; McAlister et al., 1989; Stanek et al., 1990).

Atrioventricular conduction block of varying degrees are the most common manifestation of Lyme carditis. In some patients, heart block is the first and only manifestation of Lyme disease (Kimball et al., 1989). Patients may present with first degree heart block but can progress to second degree or complete heart block over a short period of time (Peeters et al., 1990). One review of 52 patients with Lyme carditis found that 87 percent had

1991). This difference may be related to infection by different organisms.

considered as both can also cause myocarditis.

occurring in 10 to 25 percent of all patients with diphtheria (Morgan et al., 1963).

**7.3.2 Lyme myocarditis** 

atrioventricular block, which was usually symptomatic (McAlister et al., 1989). Wenckebach periodicity occurred in 40 percent and complete atrioventricular block in 50 percent; other findings include bundle branch and fascicular blocks, which are rare. In another report, 38 percent of patients with Lyme carditis required a temporary pacemaker (Goldings & Jericho, 1986). Patients with a PR interval greater than 300 milliseconds carry a highest risk for progression to complete heart block, which may develop rapidly (Steere et al., 1980). Complete heart block caused by Lyme disease typically resolves within one week, and more minor conduction disturbances within six weeks (Fish, 2008; McAlister et al., 1989). More reports showed heart block usually persists for 3 to 42 days and often resolves spontaneously (Costello et al., 2009; Cox et al., 1991; Steere et al., 1980; van der Linde et al., 1989). In Europe, scattered case reports have suggested that *B. burgdorferi* may, in isolated cases, be a cause of chronic cardiomyopathy (Bartůnek et al., 2006; Palecek et al., 2010). This has not been shown in the United States. A small Dutch series evaluated 42 patients with dilated cardiomyopathy (Vlay et al., 1991). Nine were seropositive for anti-B. burgdorferi; six recovered fully, two had a partial response, and one showed no improvement.
