Cardiomyopathies, Myocarditis and Inflammatory Disorders

Cardiomyopathies

Cardiomyopathy is defined as a structural or functional abnormality of the myocardium that is not secondary to structural heart disease, hypertension, or pulmonary vascular disease. Cardiomyopathies are usually classified as follows:

• Dilated cardiomyopathy (DCM) - in which the left ventricle is dilated and has poor systolic function.
• Hypertrophic obstructive cardiomyopathy (HOCM) - also known as idiopathic hypertrophic sub aortic stenosis. HOCM is characterized by ventricular hypertrophy (usually asymmetric) with normal systolic function but abnormal diastolic function.
• Restrictive cardiomyopathy - which is characterized by primary diastolic dysfunction, normal ventricular size and dilated atria.

Dilated cardiomyopathy

This is the most common cause of cardiomyopathy in children. It may be secondary to myocarditis, coronary artery disease, and many other conditions. In familial cases, an autosomal dominant transmission is the most frequent pattern of inheritance. Autosomal recessive, X-linked and mitochondrial inheritance have also been described.

Pathology

The heart in dilated cardiomyopathy is globular and is grossly dilated. The myocardium is pale and mottled, and the endocardium is thin. Histologically, there is myocyte hypertrophy and degeneration as well as interstitial fibrosis. This is compared to myocarditis, in which there is myocyte necrosis and lymphocytic infiltration.

Pathophysiology

Systolic dysfunction is manifested by decreased shortening and ejection fractions which leads to increased end-diastolic volume and pressure. The blood flow to kidneys is diminished with resultant salt and water retention and worsening of CHF. Myocardial fibrosis may lead to ventricular arrhythmias secondary to the development of reentry circuits in the ventricles.

Clinical Presentation

CHF signs and symptoms develop as the cardiac output decreases. These include decreased exercise tolerance and dyspnea with exertion. Infants present with poor feeding, diaphoresis during feeding, and failure to thrive. Palpitation and syncope are sometimes the earliest presentation of DCM.

Making the Diagnosis

• The condition needs to be differentiated from acute myocarditis (see below).

• The patient usually has tachycardia and tachypnea. The skin may be pale and cold. The peripheral pulses are weak and the blood pressure is in the low normal range with a narrow pulse pressure.
• Breath sounds may be diminished with rales and signs of respiratory distress. Cardiac examination reveals muffled heart sounds, gallop rhythm and possibly mitral regurgitation murmur. Hepatomegaly and other signs of venous congestion may be present.
• Chest radiograph reveals dilatation of the left ventricle and atrium. Pulmonary edema and pleural effusion may be seen.
• There may be atelectasis of the left lower lobe from compression of the left main bronchus by the dilated LA. The EKG shows nonspecific-T change as evidence of ventricular hypertrophy and atrial enlargement.
• Atrial and ventricular arrhythmias are common.
• Echocardiography shows decreased shortening fraction (the percentage of decrease in LV dimensions between diastole and systole.) The origin of the coronary arteries should be delineated to rule out coronary anomalies. Pericardial effusion may be present. Cardiac catheterization and myocardial biopsy are useful in confirming the diagnosis and evaluating the patient for potential cardiac transplantation.
• Urine examination for organic acids is important to exclude metabolic disorders. Blood studies should also be obtained for abnormalities in lactate, calcium, magnesium, carnitine, pyruvate, blood urea nitrogen (BUN) and serum electrolytes. Molecular genetic analysis for dystrophin mutations could be diagnostic in some cases.

Management

If cardiac decompensation is present, intravenous inotropic agents, such as dobutamine and dopamine (in renal doses), may be useful. Amrinone and milrinone also have positive inotropic effect and also reduce the afterload. When the patient is clinically stable, oral digoxin, ACE inhibitors and B-blockers (carvedilol) may be started. Diuretic therapy is useful for removing excess fluid. Patients with acute and severe decompensation may require ventricular assist devices or extracorporeal membrane oxygenation. Heart transplantation may be considered if all other measures fail.

Constrictive Pericarditis

Constrictive pericarditis occurs when a scarred, thickened, and calcified pericardium impairs cardiac filling.   The pathophysiological hallmark of pericardial constriction is equalization of the end-diastolic pressures in all four cardiac chambers. This occurs because the filling is determined by the limited pericardial volume, not the compliance of the chambers themselves.

Initial ventricular filling occurs rapidly in early diastole as blood moves from the atria to the ventricles without much change in the total cardiac volume. However, once the pericardial constraining volume is reached, diastolic filling stops abruptly. The stiff pericardium also isolates the cardiac chambers from respiratory changes in intrathoracic pressures, resulting in Kussmaul's sign.

Clinical Presentation

Patients with pericardial constriction typically present with manifestations of elevated systemic venous pressures and low cardiac output. Typically, there will be marked jugular venous distension, hepatic congestion, ascites, and peripheral edema. The limited cardiac output typically presents as exercise intolerance. Patients with pericardial constriction are much more likely to have left-sided or bilateral pleural effusions.

Making the Diagnosis

• The normal inspiratory drop in jugular venous distention may be replaced by a rise in venous pressure (Kussmaul's sign).
• The classic auscultatory finding of pericardial constriction is a pericardial knock. This occurs as a high-pitched sound early in diastole when there is sudden cessation of rapid ventricular diastolic filling.  
• Pericardial calcification seen on the lateral plane chest x-ray is suggestive of pericardial constriction.
• Most patients with pericardial constriction have a thickened pericardium (>2 mm) that can be imaged by echocardiography, CT, and MRI.
• Doppler echocardiography is important in the evaluation of patients with suspected pericardial constriction. The echocardiogram may demonstrate pericardial thickening and calcification. However, increased pericardial thickness can be missed on a transthoracic echocardiogram. Transesophageal echocardiography is more sensitive and accurate in determining pericardial thickness. Doppler echocardiography frequently demonstrates restricted filling of both ventricles.

Management

• In some patients with acute onset pericardial constriction, the symptoms and constrictive features may resolve with medical therapy alone. Medical management includes the use of anti-inflammatory agents, colchicine, and/or steroids.
• In more chronic pericardial constriction, definitive treatment is surgical pericardial decortication with resection of both the visceral and parietal pericardium.

Restrictive Cardiomyopathy

Restrictive cardiomyopathy (RCM) is a rare form of myocardial disease that is characterized by restrictive filling of the ventricles. In this disease the contractile function of the heart and wall thicknesses are usually normal, but the filling phase of the heart is abnormal. This occurs because the cardiac muscle is stiff and poorly compliant and does not allow ventricular filling. This inability to relax and fill with blood results in a backup of blood into the atria. RCM is the least common in children, accounting for 2.5-5% of the diagnosed cardiomyopathies. The average age of diagnosis is 5 to 6 years old and it appears to affect girls somewhat more often than boys. There is a family history of cardiomyopathy in approximately 30% of cases. In most cases the cause of the disease is unknown (idiopathic), although a genetic cause is suspected in most cases of pediatric RCM.

Clinical Presentation

Children with RCM frequently have a history of repeated lung infections. Referral to a cardiologist occurs when symptoms of heart failure are reported or cardiomegaly is seen on a chest x-ray. In approximately 10% of cases, syncope, may be the first symptom. Sudden death may also be the initial presentation in some patients. 

Making the Diagnosis

• The diagnosis of RCM is difficult to establish early in the clinical course due to the lack of symptoms.
• Therefore, in many cases, the diagnosis is made only after presentation with symptoms such as decreased exercise tolerance, new heart sound (gallop), syncope, or chest pain with exercise.
• EKG may demonstrate abnormally large electrical forces from enlargement of the atria.
• An echocardiogram may show marked enlargement of the atria, normal sized ventricles, and normal heart function. In more advanced disease states, pulmonary artery pressures may be increased.
• Cardiac catheterization is rarely needed to confirm the diagnosis. The pressure measurements often show significantly elevated pressures during diastole and varying degrees of increased pulmonary artery pressures in the absence of any other structural heart disease.
• Myocardial biopsy is rarely needed to confirm the diagnosis.
• Since childhood RCM is often genetic, once this diagnosis is established, it is important to screen other family members.

 Management

• Diuretics, beta-blockers and occasionally, afterload reducing agents.
• In children with RCM, there is a risk of clots forming inside the heart possibly leading to a stroke. Anticoagulation medications, are often used in these situations. These include aspirin, dipyridamole, warfarin, heparin, and enoxaparin.

 

Myocarditis

Myocarditis is an inflammation of cardiac myocytes associated with necrosis and degeneration.

Infection with Coxsackie B virus or adenovirus is the most common cause of myocarditis. Many other viruses, as well as bacterial infections, mycoplasma, fungi, protozoa, spirochetes and rickettsia have also been reported to cause myocarditis.

Clinical Presentation

The common presentation is a history of a recent viral infection followed by the development of signs and symptoms of CHF.

Making the Diagnosis

• The patient may have tachycardia and other signs of overt CHF.
• Chest radiography demonstrates cardiomegaly and pulmonary venous congestion. Evidence of pneumonitis may be present.
• The EKG may show sinus tachycardia, premature ventricular contractions or supraventricular tachycardia. Low voltage QRS and inverted T waves are common.
• Echocardiography and cardiac catheterization with biopsy may be necessary to differentiate myocarditis from dilated cardiomyopathy. Viral culture and viral titers may be helpful in making the diagnosis.

Management

Acutely sick patients require intravenous inotropic agents and diuretics until they can be transitioned to oral digoxin, afterload reducing agents and diuretics. The use of anti-inflammatory and immunosuppressive therapy is still controversial.  

Hypertrophic Obstructive Cardiomyopathy

Hypertrophic obstructive cardiomyopathy (HOCM) is the most common cause of sudden death in the young. The most important predictors of sudden death are a family history of sudden death and recurrent syncope. Mortality in children with HOCM is twice as high as adults. The condition is usually progressive and the symptoms depend on the age and mode of presentation.

HOCM is an inherited disorder of the cardiac muscle characterized by a hypertrophied, non-dilated left ventricle. The condition is associated with abnormal relaxation of the LV and sometimes with outflow tract obstruction. The mode of inheritance is most often autosomal dominant with variable penetrance and several genetic defects have been described.

Pathology

The hallmark of HOCM is left ventricular hypertrophy (LVH) which is characteristically asymmetric with more involvement of the ventricular septum. This asymmetric septal hypertrophy often produces sub-aortic obstruction that is exaggerated by systolic anterior movement (SAM) of the anterior mitral valve leaflet and its apposition to the bulging septum. Histologically, there is extensive myocardial fiber disarray. The myocardial cells are disorganized and are separated by loose connective tissue. The coronary arteries sometimes run within the myocardium (intramural) and show increased intimal and medial thickening causing luminal narrowing.

Clinical Presentation

Affected individuals may be asymptomatic, may have recurrent exertional dyspnea, chest pain or syncope. The condition may be recognized only after sudden death has occurred. Infants may present with CHF and the diagnosis is often missed.

Making the Diagnosis

• Beyond infancy, a heart murmur may be the mode of presentation.
• A prominent "a" wave in the jugular venous pulse may be present because of diastolic dysfunction.
• A systolic ejection murmur may be present due to LV outflow tract obstruction (LVOTO). The murmur is intensified by maneuvers that decrease the LV volume and increase the systolic anterior movement of the mitral valve leaflet such as standing or performing the Valsalva maneuver. Its intensity decreases by squatting or assuming a supine position. These maneuvers have the opposite effect of an aortic stenosis murmur.
• EKG changes are variable and may show LVH with a strain pattern (inverted T waves in the left precordial leads).   Chest radiography may be normal or have evidence of cardiomegaly. MRI and radionuclide studies are helpful in making the diagnosis and assessing systolic and diastolic functions.
• Echocardiography is the most important imaging study for the diagnosis of HOCM and allows an assessment of the pattern and degree of hypertrophy, the extent of LVOTO as well as the systolic anterior movement (SAM) of the anterior mitral leaflet.

Management

Beta-blockers are helpful in the medical management by reducing the contractility and the heart rate; thereby prolonging the diastolic time. However, these agents have no effect on the degree of LVOTO obstruction or sudden death. Digoxin, other inotropic agents, and ACE inhibitors are contraindicated in HOCM as they worsen the obstruction, though they may have a role in the end-stage dilated thin-walled HOCM hearts with impaired LV systolic function. Diuretics are also usually contraindicated as they reduce the preload and enhance the LVOTO.

Surgical myomectomy may be needed to relieve the LV obstruction. Alcohol ablation of the septal perforating coronary arteries can produce a controlled infarction and relieves the sub-aortic obstruction. There is also a role for a pacemaker or implantable defibrillator (ICD).

Patients with HOCM should avoid strenuous exercise and their families should undergo genetic counseling.