Pericardial Disease and Myocarditis

Pericarditis

Common pericardial diseases include pericarditis, cardiac tamponade, and constrictive pericarditis.

Causes

Tuberculosis is a common cause of pericarditis in underdeveloped countries.

Causes in developed countries include:

• idiopathic (most common) — etiology is assumed to be viral

• postcardiac-injury syndromes (including post-myocardial infarction pericarditis)

• connective tissue diseases

• cancer

• uremia

Diagnosis

Pericarditis often manifests with pleuritic pain that is typically worse when lying down and relieved by sitting forward. These symptoms may be preceded by a viral prodrome. Diagnosis of pericarditis is usually made based on the presence of two of the following features:

• typical chest pain

• typical electrocardiogram (ECG) changes (PR-segment depression, diffuse ST changes; diffuse concave-upward ST-segment elevation is a classic finding)

• auscultation of a pericardial friction rub

• presence of pericardial effusion on echocardiography

Elevated inflammatory markers, cardiac MRI findings of inflammation, or both can be useful in equivocal settings. Additional testing for the underlying cause may be necessary based on clinical suspicion.

(Source: Acute Pericarditis. N Engl J Med 2014.)

Abbreviations: CT, computed tomography; ECG, electrocardiogram; MRI, magnetic resonance imaging; NSAID, nonsteroidal anti-inflammatory drug (Source: Acute Pericarditis. N Engl J Med 2014.)

Treatment

Patients with idiopathic pericarditis are usually treated with aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs), as well as with colchicine. Glucocorticoids are avoided because of an association with higher rate of recurrence and are reserved for patients with symptoms that do not respond to NSAIDs or who have recurrent pericarditis. More-advanced therapies for refractory recurrent pericarditis include azathioprine, immunoglobulins, anakinra (interleukin-1-receptor antagonist), and rilonacept (interleukin-1-alpha and interleukin-1-beta cytokine trap).

Complications

Pericardial effusion is a common complication of pericarditis usually caused by accumulation of serous fluid, pus, or blood within the pericardial space. As an effusion grows, the pericardium initially stretches to accommodate the fluid. Once the limit of the pericardium’s compliance is reached (see figure below), intrapericardial pressure rises more acutely and can lead to cardiac tamponade.

• Diagnosis: Echocardiography is the primary diagnostic tool for pericardial effusion. Other findings include QRS alternans on ECG or an enlarged cardiac silhouette on chest x-ray. Chest CT can also detect an effusion, but it is not primarily used for this purpose because of the ease and availability of echocardiography. Pericardiocentesis may be necessary for establishing a diagnosis, such as cytology of the fluid to detect malignant cells from metastatic cancer, which will impact the patient’s overall treatment.

• Treatment: Stable pericardial effusions without tamponade can be monitored with serial echocardiograms and treatment of the underlying cause.

Cardiac tamponade is a form of cardiogenic shock caused by impaired ventricular filling and thus reduced cardiac output. Because the pericardium can expand to accommodate a higher volume if the fluid accumulates slowly, the size of a pericardial effusion is typically indicative of the effusion’s chronicity and not whether tamponade is present.

(Source: Acute Cardiac Tamponade. N Engl J Med 2003.)

• Diagnosis: Diagnosis of cardiac tamponade is made based on hemodynamic and echocardiographic evidence of impaired ventricular filling. Findings include:

  • physical examination: hypotension, elevated jugular venous pressure, pulsus paradoxus: fall in arterial systolic blood pressure (SBP) of 10 mm Hg or more during normal inspiration

    • In normal physiology, inspiration decreases intrathoracic pressure and increases venous return to the right ventricle, which subsequently causes the interventricular septum to bulge toward the left ventricle. However, because the left ventricular free wall can shift to compensate for the septal bulge, left ventricular filling is either unaffected or modestly decreased. The net effect is either no effect on SBP or a slight drop in SBP. In cardiac tamponade, this ventricular interdependence is exaggerated by the increased pericardial pressure and the fixed pericardial volume, thus leading to abnormal drop in SBP with respiration, as demonstrated by pulsus paradoxus and some of the echocardiographic signs.

  • echocardiography: dilated inferior vena cava, collapse of right atrium during systole, collapse of right ventricle during diastole, increased flow across the tricuspid valve and decreased flow across the mitral valve with inspiration and vice versa with expiration, reciprocal change in right- and left-ventricle chamber size with respiration (i.e., interventricular septum moves to the left with inspiration and to the right with expiration)

  • catheterization: equalization of diastolic pressures in all four cardiac chambers, inspiratory rise in right ventricular pressure and fall in left ventricular pressure

• Treatment: The treatment of cardiac tamponade is immediate pericardiocentesis. Sometimes, if the fluid is loculated or localized to parts of the heart inaccessible by percutaneous means, a surgical pericardial window may be necessary.

Constrictive Pericarditis

Recurrent pericarditis or injury (e.g., radiation or cardiac surgery) to the pericardium can lead to constrictive pericarditis, a condition in which the pericardium becomes thick, fibrotic, and adherent to the epicardium. Constrictive physiology is similar to that of cardiac tamponade in that there is a fixed pericardial volume and exaggerated ventricular interdependence.

Diagnosis: Patients with constrictive pericarditis usually present with symptoms of heart failure. Notable physical examination findings include ascites, cachexia, Kussmaul sign (increase in jugular venous pulse with inspiration due to fixed filling of the right ventricle), pulsus paradoxus, and a pericardial knock. The key to the diagnosis of constrictive pericarditis is to distinguish it from other causes of heart failure. Some of the features include:

• echocardiography: increased pericardial thickness, dilated inferior vena cava, exaggerated respiratory variation in tricuspid and mitral-valve inflow, abnormal septal motion

• cardiac CT: increased pericardial thickness and calcification

• cardiac MRI: late gadolinium enhancement of the pericardium

Treatment: Initial treatment of constrictive pericarditis includes similar medical therapy as for heart failure and recurrent pericarditis. Patients with refractory and chronic disease may require definitive treatment with pericardiectomy, which is a procedure associated with high morbidity and mortality. Because of the high risks, pericardiectomy is usually a treatment of last resort.

Myocarditis

Causes

Causes of myocarditis include:

• viral infection: most common; a wide range of pathogens including coxsackie B virus, echovirus, other enteroviruses, adenovirus, influenza virus, human parvovirus B19, coronavirus (e.g., Covid-19)

• other pathogens (e.g., group A streptococcus [rheumatic myocarditis], Borrelia burgdorferi [Lyme myocarditis], Trypanosoma cruzi [Chagas disease])

• giant-cell myocarditis: an idiopathic disease with distinct histology and typically severe illness

• drug reactions: various drugs including methyldopa, clozapine, hydrochlorothiazide, benzodiazepines, tricyclic antidepressants

• autoimmune myocarditis: as an isolated phenomenon or associated with systemic autoimmune disease

• immune checkpoint inhibitors: used in the treatment of some cancers can cause severe and sometimes fatal myocarditis

Diagnosis

Clinical manifestations of myocarditis range from mild dyspnea or chest pain to fulminant cardiogenic shock or death. Diagnosis is based on the following findings:

• nonspecific electrocardiographic changes (often) or diffuse ST elevation with or without PR depression if there is concomitant pericarditis

• elevated biomarkers of cardiac injury (a minority of cases)

• ECG to rule out other sources of heart failure

• cardiac MRI to detect myocardial injury and edema

• endomyocardial biopsy to provide definitive diagnosis (usually performed in patients with an acute coronary syndrome [ACS]-like presentation but normal coronary arteries or in patients with unexplained new-onset heart failure)

Treatment

Patients with viral myocarditis are generally treated with supportive therapy for left ventricular dysfunction and standard heart-failure treatment and arrhythmia management as needed. Patients with giant-cell myocarditis are treated with immunosuppression (often combinations of agents).