**2. Clinicopathological classification**

Over the past two decades, a great deal of confusion may be traced to the changing diagnostic criteria, multifaceted classifications, and varying patterns of infectious disease. The details of classifications will be discussed in other chapter in this book.

The morphologic criteria for the diagnosis of myocarditis by means of endomyocardial biopsy interpretation was proposed by the Dallas criteria authors in 1986 who defined myocarditis as a process characterized by the presence of an inflammatory cell infiltration of the myocardium with necrosis and/or degeneration of myocytes that is not typical of the myocardial damage of ischemic heart disease. The inflammatory cells are typically lymphocytic but may also include eosinophilic, neutrophilic, giant cells, granulomatous, or mixed cellularity infiltration. The amount of inflammation and its distribution may be mild, moderate, or severe and focal, confluent, or diffuse, respectively. A retrospective study of 112 consecutive patients with biopsy-confirmed myocarditis demonstrated, 55 percent lymphocytic; 22 percent borderline (inflammatory cellular infiltrate with no evidence of myocyte necrosis); 10 percent granulomatous; 6 percent giant cell and 6 percent eosinophilic form of myocarditis (Magnani et al., 2006). The viral etiology of myocarditis is thought to be the primary causative agents in most cases. However, a direct causative relationship still less well established in many clinical occasions. The majority of these cases are classified as lymphocytic myocarditis.

The Dallas criteria considered to be the first attempt to develop standardized histopathological description of biopsy samples from patients presented with myocarditis (Aretz et al., 1987). However, the histopathology alone can be inadequate to identify the presence of active myocarditis. Some clinicians feel that the definition is too narrow owing to the limitation by variable interpretation, lack of clinical prognostic values, and low sensitivity (Baughman, 2006). A combination of histopathologic characteristics and clinical criteria has been proposed in 1991 (Lieberman et al., 1991) as an alternative scheme to be utilized in the diagnosis of myocarditis. Histologic evidence of myocarditis was demonstrated in 35 of 348 patients submitted to endomyocardial biopsy over 5 years. Analysis of the histologic findings and clinical course of these patients resulted in a clinicopathologic classification of myocarditis in which four clinical subgroups are identified.

## **2.1 Fulminant myocarditis**

The fulminant myocarditis is less frequent form of presentation. Patients presents with acute heart failure and cardiogenic shock up to two weeks after a distinct viral prodrome. They have severe cardiovascular compromise and may require mechanical circulatory support. Multiple foci of active myocarditis are typical. The histopathologic finding does not match the clinical phenotypic severity. The ventricular dysfunction often normalizes if patients survive the acute illness or results in death (McCarthy et al., 2000). In one series, 14 of 147 patients (10.2 percent) with clinical myocarditis presented in a fulminant fashion, with the triad of hemodynamic compromise, rapid onset of symptoms (usually within 2 weeks), and fever (McCarthy et al., 2000). On follow up, 93 percent of the original cohorts were alive and

presumptive diagnosis if imaging studies and a compatible clinical scenario suggest new onset cardiomyopathy. The clinical manifestations of suspected patients with myocarditis

Over the past two decades, a great deal of confusion may be traced to the changing diagnostic criteria, multifaceted classifications, and varying patterns of infectious disease.

The morphologic criteria for the diagnosis of myocarditis by means of endomyocardial biopsy interpretation was proposed by the Dallas criteria authors in 1986 who defined myocarditis as a process characterized by the presence of an inflammatory cell infiltration of the myocardium with necrosis and/or degeneration of myocytes that is not typical of the myocardial damage of ischemic heart disease. The inflammatory cells are typically lymphocytic but may also include eosinophilic, neutrophilic, giant cells, granulomatous, or mixed cellularity infiltration. The amount of inflammation and its distribution may be mild, moderate, or severe and focal, confluent, or diffuse, respectively. A retrospective study of 112 consecutive patients with biopsy-confirmed myocarditis demonstrated, 55 percent lymphocytic; 22 percent borderline (inflammatory cellular infiltrate with no evidence of myocyte necrosis); 10 percent granulomatous; 6 percent giant cell and 6 percent eosinophilic form of myocarditis (Magnani et al., 2006). The viral etiology of myocarditis is thought to be the primary causative agents in most cases. However, a direct causative relationship still less well established in many clinical occasions. The majority of these cases are classified as

The Dallas criteria considered to be the first attempt to develop standardized histopathological description of biopsy samples from patients presented with myocarditis (Aretz et al., 1987). However, the histopathology alone can be inadequate to identify the presence of active myocarditis. Some clinicians feel that the definition is too narrow owing to the limitation by variable interpretation, lack of clinical prognostic values, and low sensitivity (Baughman, 2006). A combination of histopathologic characteristics and clinical criteria has been proposed in 1991 (Lieberman et al., 1991) as an alternative scheme to be utilized in the diagnosis of myocarditis. Histologic evidence of myocarditis was demonstrated in 35 of 348 patients submitted to endomyocardial biopsy over 5 years. Analysis of the histologic findings and clinical course of these patients resulted in a clinicopathologic classification of myocarditis in which four clinical subgroups are

The fulminant myocarditis is less frequent form of presentation. Patients presents with acute heart failure and cardiogenic shock up to two weeks after a distinct viral prodrome. They have severe cardiovascular compromise and may require mechanical circulatory support. Multiple foci of active myocarditis are typical. The histopathologic finding does not match the clinical phenotypic severity. The ventricular dysfunction often normalizes if patients survive the acute illness or results in death (McCarthy et al., 2000). In one series, 14 of 147 patients (10.2 percent) with clinical myocarditis presented in a fulminant fashion, with the triad of hemodynamic compromise, rapid onset of symptoms (usually within 2 weeks), and fever (McCarthy et al., 2000). On follow up, 93 percent of the original cohorts were alive and

The details of classifications will be discussed in other chapter in this book.

will be discussed in details.

lymphocytic myocarditis.

**2.1 Fulminant myocarditis** 

identified.

**2. Clinicopathological classification** 

transplant free 11 years following initial biopsy, compared with only 45 percent in those with more classic forms of acute myocarditis.

#### **2.2 Acute myocarditis**

Classically, patients with acute myocarditis presents with a less distinct onset of illness with nonspecific symptoms related to the heart. Viral prodrome occurs between 20 and 80 percent of the cases, can be readily missed by the patient, and thus cannot be relied upon for diagnosis. They present with an established ventricular dysfunction and may respond to immunosuppressive therapy or their condition may progress to dilated cardiomyopathy. In a series of 245 patients with clinically suspected myocarditis, the most common symptoms include fatigue (82 percent); dyspnea on exertion (81 percent); arrhythmias (55 percent, both supraventricular and ventricular); palpitations (49 percent); and chest pain at rest (26 percent), (Kuhl et al., 2005). The presentation can mimic acute coronary syndromes in view of troponin release, ST segment elevation on electrocardiogram, and segmental wall motion abnormalities on echocardiogram.

#### **2.3 Chronic active myocarditis**

This group of patients with chronic active myocarditis represents the majority of older adult with myocarditis. They are also presents with a less distinct onset of illness and often insidious with symptoms compatible with moderate ventricular dysfunction such as fatigue and dyspnea. Affected patients may initially respond to immunosuppressive therapy but often have clinical and histologic relapses and develop ventricular dysfunction associated with chronic inflammatory changes, and mild to moderate fibrosis on histological study including giant cells.

#### **2.4 Chronic persistent myocarditis**

This group of patients with chronic persistent myocarditis, whom also presents with a less distinct onset of illness, is characterized by a persistent histological infiltrate, often with foci of myocyte necrosis but without ventricular dysfunction, despite other cardiovascular symptoms such as chest pain or palpitation.

The previously depicted four forms are still used to describe the clinical presentation and progression of myocarditis, particularly in the absence of ongoing histological evaluation. These categories may also provide some prognostic information and may suggest which patients can or cannot benefit from immunosuppressive therapy.

A new diagnostic criteria derived from limited data was proposed in 2009. The Lake Louise Consensus Criteria utilizes the cardiac magnetic resonance imaging (CMR) for the diagnosis of myocarditis (Friedrich et al., 2009). The CMR enhances the ability to detect myocardial inflammation through noninvasive means, as well as to improve diagnostic accuracy. In these criteria, four major domains are considered when making the diagnosis including, clinical presentation compatible with myocarditis, evidence of new or recent onset myocardial damage, increased T2 signal or delayed enhancement on CMR (compatible with myocardial edema and inflammation), and endomyocardial biopsy evidence of myocardial inflammation. The use of CMR appears suitable to identify patients with significant ongoing inflammation, which may be especially important for patients with recurrent or persisting symptoms and in patients with new onset heart failure. The awareness came out that the

Clinical Presentation 7

1. Subclinical presentation (most cases of viral myocarditis) 2. Nonspecific symptoms (e.g fatigue, arthralgias and myalgias)

Chest pain (concomitant pericarditis)

Elevated jugular venous pressure

Signs of cardiovascular collapse and shock

Diminished intensity of first heart sound

Pericardial friction rub and effusion (concomitant myopericarditis)

Diffuse apex beat and laterally displaced (cardiomegaly)

Third and fourth heart sound summation gallops Murmurs of mitral or tricuspid valves regurgitation

Presyncope or syncope (atrioventricular block) Sudden cardiac death (dysrhythmic death)

Flu-like syndrome (e.g pharyngitis or tonsillitis) Thromboembolic symptoms (systemic or pulmonary)

Palpitation (arrhythmias)

1. Normal or unremarkable findings 2. Relevant physical signs, including :

> Tachypnea Cyanosis

Tachycardia

Bibasilar crackles Hepatomegaly

Peripheral edema

Ascites

Shortness of breath, orthopnea or paroxysmal nocturnal

3. Clinical presentation, including :

dyspnea Pedal edema

Fever

 **Clinical manifestations** 

 **Physical findings** 

Table 1. The most significant clinical manifestations and physical findings in patient with

The medical history may embrace a number of hints that merits an emphasis. Previous history of rheumatic heart disease or symptoms defined by Jones criteria e.g. fever or arthralgia can be a clue for the clinical diagnosis acute rheumatic fever. History of tick bite may correlate with suspected Lyme disease. Patients treated for neoplastic disorders with chemotherapeutic agents like doxorubicin may draw attention to anthracyclines-induced myocarditis. History of travel to Central or South America can be a clue for the diagnosis of Chagas disease. Additionally, giant-cell myocarditis should be considered in patients with acute dilated cardiomyopathy associated with thymoma, autoimmune disorders, ventricular tachycardia, or high-grade heart block. Furthermore, an unusual cause of myocarditis, such as cardiac sarcoidosis, should be suspected in patients who present with chronic heart

myocarditis

recommendations proposed by these criteria are based on limited data and that not all centers will be able to apply all components of the suggested protocol.
