Cardiomyopathies

Introduction and Classification

• Cardiomyopathy is an intrinsic disease of the myocardium which is not associated with a structural deformity of the heart.
• It is considered a primary cardiomyopathy when the etiology is unknown.
• It is considered a secondary cardiomyopathy if the myocardial disease is attributed to a systemic disease.
• Classification often utilizes the MOGE(s) approach, integrating Morphofunctional phenotype, Organ involvement, Genetic or familial inheritance pattern, and Etiology.
• The major morphofunctional categories include dilated, hypertrophic, and restrictive cardiomyopathy.

Dilated Cardiomyopathy (DCM)

Definition and Epidemiology

• DCM is defined by myocardial systolic insufficiency and dilatation of the left ventricular lumen.
• It is the most common cause of pediatric cardiomyopathy.
• DCM accounts for over 50% of pediatric cardiomyopathy cases.
• The estimated incidence is 0.57 cases per 100,000 children.

Etiology and Genetics

• Between 50% and 66% of pediatric cases are categorized as idiopathic.
• Approximately 25-30% of cases have an identifiable familial component.
• Genetic mutations most commonly involve force generation (sarcomeric genes like MYH7, TNNT2, TNNI3) and force transmission.
• Myocarditis is the most common secondary or potentially treatable form of DCM, accounting for 14-22% of cases.
• Other correctable or secondary causes must be excluded before diagnosing idiopathic DCM.

Pathophysiology

• Reduced contractility is the primary defect.
• The left ventricle progressively dilates to maintain cardiac output.
• Annular dilation of the mitral valve leads to non-coaptation of the leaflets and secondary mitral regurgitation.

Clinical Presentation

• Age of presentation follows a bimodal distribution with peaks in infancy and adolescence.
• The onset of cardiac failure may be acute or insidious.
• Common symptoms include shortness of breath (50%), gastrointestinal upset, poor feeding, and fatigue.
• Physical examination reveals cardiomegaly, tachycardia, an S3 gallop, and occasionally a murmur of mitral regurgitation.

Diagnostic Evaluation

• Chest X-ray: Reveals cardiomegaly with pulmonary venous congestion.
• Electrocardiogram (ECG): Shows non-specific ST and T changes, low voltages, or left ventricular hypertrophy.
• Echocardiogram: Confirms a dilated ventricular cavity without hypertrophy of the free wall or septum, along with reduced left ventricular contractility.

Management and Prognosis

• Medical management centers on decongestive therapy.
• Angiotensin-converting enzyme (ACE) inhibitors serve as useful vasodilators.
• Beta-blockers, such as carvedilol, reduce vasoconstriction, decrease myocardial oxygen demand, and improve outcomes.
• Advanced heart failure may require admission to an intensive care unit, inotropic support, or mechanical circulatory support.
• The highest risk period is the first year after diagnosis.
• Overall, normalization of cardiac size and function occurs in 20-40% of childhood DCM cases.

Hypertrophic Cardiomyopathy (HCM)

Definition and Epidemiology

• HCM is defined as intrinsic myocardial hypertrophy not consequent to a hemodynamic stimulus.
• Diagnosis requires excluding physiological hypertrophy and pathological hypertrophy caused by hypertension or aortic stenosis.
• The incidence is estimated at 0.47 cases per 100,000 children.
• HCM accounts for approximately 40% to 42% of pediatric cardiomyopathies.

Etiology and Genetics

• HCM is generally transmitted as an autosomal dominant trait.
• Primary HCM is mainly caused by mutations in genes encoding cardiac sarcomere proteins, such as the beta-myosin heavy chain.
• The genetic profile of children with HCM is highly heterogeneous compared to adults.

Pathophysiology

• The condition features myocardial disarray, subendocardial fibrosis, and interstitial fibrosis.
• The interventricular septum frequently bulges into the left ventricle, causing disproportionate hypertrophy.
• Left Ventricular Outflow Tract (LVOT) obstruction occurs in about 25% of patients.
• Systolic anterior motion (SAM) of the anterior mitral valve leaflet contributes to the dynamic outflow obstruction during systole.
• Cellular disarray and fibrosis lead to impaired relaxation and significant diastolic dysfunction.

Clinical Presentation

• Patients frequently present with exertional dyspnea, anginal chest pain, palpitation, and syncope.
• Sudden cardiac death can occur and may be the initial manifestation of the disease.
• The pulse typically features a sharp upstroke with a bisferiens character.
• Auscultation reveals a forcible apex beat and an ejection systolic murmur at the left sternal edge.
• The murmur's intensity increases with standing (which decreases ventricular volume) and decreases with squatting (which increases ventricular volume).

Diagnostic Evaluation

• Echocardiogram: Confirms a hypertrophied, non-dilated left ventricle. Diagnosis in children uses a maximal wall thickness Z-score > 5 to 7 standard deviations.
• Electrocardiogram (ECG): Shows prominent initial R waves in right precordial leads and deep Q waves in the left chest leads. A Wolff-Parkinson-White (WPW) pattern may be present.

Management and Prognosis

• Medical therapy includes the use of non-vasodilating beta-blockers to decrease myocardial contractility and minimize LVOT obstruction.
• Selected patients at high risk of sudden cardiac death require an implantable cardioverter defibrillator (ICD).
• Surgical intervention (septal myectomy) is indicated for patients with symptomatic severe outflow obstruction refractory to medical therapy.

Restrictive Cardiomyopathy (RCM)

Definition and Epidemiology

• RCM is characterized by restrictive filling and reduced diastolic volume of either or both ventricles.
• Systolic function and wall thickness remain normal or near normal.
• It is a rare form of pediatric cardiomyopathy with an incidence of 0.03-0.04 cases per 100,000 children.
• It accounts for only 2.5-5% of pediatric cardiomyopathies.
• The mean age at diagnosis is typically older, ranging from 6 to 10 years.

Etiology and Genetics

• Outside of tropical regions, the majority of childhood RCM cases are classified as idiopathic.
• Secondary infiltrative causes, such as amyloidosis, sarcoidosis, and hemochromatosis, are exceedingly rare in children.
• Causative genetic mutations are increasingly identified.
• Troponin mutations (TNNI3, TNNT2) and desmin (DES) mutations are prominent genetic causes.

Pathophysiology

• RCM is caused by increased myocardial rigidity without concurrent hypertrophy.
• Impaired ventricular filling leads to severe diastolic dysfunction.
• Elevated filling pressures subsequently cause massive biatrial enlargement, pulmonary edema, and reactive pulmonary hypertension.

Clinical Presentation

• Children frequently present with respiratory complaints, exercise intolerance, and dyspnea.
• The respiratory symptoms are often incorrectly diagnosed as asthma or reactive airway disease.
• Syncope may occur due to ischemia, conduction disturbances, or thromboembolism.
• Right-sided heart failure signs, such as hepatomegaly, are frequently observed.

Diagnostic Evaluation

• Echocardiogram: The findings are typically pathognomonic. Shows massive biatrial enlargement with normal-sized ventricles and normal systolic function. Abnormal mitral inflow with a short deceleration time is also present.
• Electrocardiogram (ECG): Usually abnormal, demonstrating biatrial enlargement and non-specific ST-T wave abnormalities.
• Cardiac Catheterization: Hemodynamic studies differentiate RCM from constrictive pericarditis. Left ventricular end-diastolic pressure (LVEDP) typically exceeds right ventricular end-diastolic pressure (RVEDP) by more than 4 mmHg in RCM.

Management and Prognosis

• The prognosis of children with RCM is significantly worse than that of other cardiomyopathies, with very high historical mortality rates.
• No medical therapies currently improve the underlying diastolic dysfunction.
• Management is primarily symptom-based, relying on the judicious use of diuretics to relieve pulmonary and systemic venous congestion.
• Heart transplantation remains the only definitive and ultimate treatment option. Due to the high rate of sudden death, patients are frequently listed for transplantation soon after diagnosis.