Primary Myocardial Diseases (Cardiomyopathy)

A. Pathology and Pathophysiology

• 1.

  A massive ventricular hypertrophy is present. Although asymmetric septal hypertrophy (ASH), formerly known as IHSS, is the most common type, a concentric hypertrophy with symmetric thickening of the LV sometimes occurs. Occasionally an intracavitary obstruction may develop during systole, partly because of systolic anterior motion (SAM) of the mitral valve against the hypertrophied septum, called hypertrophic obstructive cardiomyopathy (HOCM). In some patients, midcavity obstruction is caused by anomalous insertion of anterolateral papillary muscle into the anterior mitral leaflet, rather than SAM.

• 2.

  So-called apical hypertrophic cardiomyopathy is a variant of HCM in which hypertrophy is confined to the left ventricular apex, without intracavitary obstruction (and with giant negative T waves on the electrocardiogram [ECG]). This subtype is present in about 25% of patients with HCM in Japan and less than 10% in other parts of the world.

• 3.

  The myocardium itself has an enhanced contractile state, but diastolic ventricular filling is impaired because of abnormal stiffness of the LV. This may lead to LA enlargement and pulmonary venous congestion, producing congestive symptoms (exertional dyspnea, orthopnea, paroxysmal nocturnal dyspnea).

• 4.

  About 80% of LV stroke volume occurs in the early part of systole when little or no obstruction exists, resulting in a sharp upstroke of arterial pulse.

• 5.

  A unique aspect of HOCM is the variability of the degree of obstruction from moment to moment.

  • a.

    The obstruction to LV output worsens when LV volume is reduced (as seen with positive inotropic agents, reduced blood volume, lowering of SVR).

  • b.

    The obstruction lessens when the LV systolic volume increases (negative inotropic agents, leg raising, blood transfusion, increasing SVR).

• 6.

  Ten percent to 20% of infants of diabetic mothers develop a transient form of HCM with or without LVOT obstruction. Children with Noonan syndrome commonly have HOCM (see Table 1.1 ).

B. Clinical Manifestations

• 1.

  Easy fatigability, dyspnea, palpitation, anginal chest pain, or syncope may be the presenting complaint. Some 30% to 60% of cases are seen in adolescents and young adults with positive family history.

• 2.

  A sharp upstroke of the arterial pulse is characteristic. A late systolic ejection murmur may be audible at the MLSB and LLSB or at the apex. A holosystolic murmur (of MR) is occasionally present. The intensity and even the presence of the heart murmur vary from examination to examination in patients with HOCM.

• 3.

  The ECG may show LVH, ST-T changes, abnormally deep Q waves with diminished or absent R waves in the left precordial leads (LPLs), and arrhythmias. Occasionally “giant” negative T waves are seen in the LPLs in patients with apical hypertrophic cardiomyopathy. Occasionally, cardiac arrhythmia or first-degree AV block is seen.

• 4.

  Chest radiographs may show mild LV enlargement with globular heart.

• 5.

  Echo studies may demonstrate the following.

  • a.

    LV hypertrophy can be seen as concentric hypertrophy, localized segmental hypertrophy, ASH, or localized to the apex. ASH is present when the septal thickness is 1.4 times or greater than the posterior LV wall thickness.

  • b.

    In obstructive type, SAM of the mitral valve may be demonstrated. Doppler peak gradient in the LVOT of ≥30 mm Hg indicates an obstructive type.

  • c.

    In adults, LV diastolic wall thickness ≥15 mm (or on occasion, 13 or 14 mm), usually with LV dimension <45 mm, is accepted as HCM. For children, z score of ≥2 relative to body surface area (BSA) is compatible with the diagnosis.

  • d.

    Highly trained athletes may show LV hypertrophy, but the LV wall thickness ≥13 mm is very uncommon. In addition, it is always associated with an enlarged LV cavity (with LV diastolic dimension >54 mm, with ranges of 55 to 63 mm). Therefore trained adult athletes with LV wall thickness >16 mm and a nondilated LV cavity are likely to have HCM.

  • e.

    The Doppler examination of the mitral inflow demonstrates signs of diastolic dysfunction with a decreased E velocity, an increased A velocity, and a decreased E:A ratio (usually <0.8) ( Fig. 11.2 ). These abnormalities are, however, nonspecific for HCM; they are also seen with dilated cardiomyopathy.

    

• 6.

  Natural history.

  • a.

    Obstruction may be absent, stable, or progressive (especially in genetically predisposed individuals).

  • b.

    Sudden and unexpected death may occur during sports or vigorous exercise, due to ventricular fibrillation.

  • c.

    Atrial fibrillation may cause stroke or heart failure.

C. Management

• 1.

  The goals of management are to (a) reduce LVOT obstruction (by reducing LV contractility and by increasing LV volume), (b) increase ventricular compliance, and (c) prevent sudden death (by preventing or treating ventricular arrhythmias). However, most therapeutic modalities used do not significantly reduce mortality rate.

• 2.

  General care.

  • a.

    Patients with HCM should avoid strenuous exercise or competitive sports, regardless of age, gender, symptoms, LVOT obstruction, or treatment.

  • b.

    Genetic testing for HCM sequencing and deletion/duplication panels are available from blood, oral rinse, or buccal (cheek) swabs.

  • c.

    First-degree relatives and other family members should be screened.

• 3.

  A β-adrenergic blocker (such as propranolol, atenolol, or metoprolol) or a calcium channel blocker (principally verapamil) is the drug of choice in the obstructive subgroup. These drugs reduce the degree of obstruction, decrease the incidence of anginal pain, and have antiarrhythmic actions.

  • a.

    A combination therapy with atenolol and verapamil may be considered in those patients with excessive LV hypertrophy and severe LVOT obstruction.

  • b.

    In small children, propranolol is the drug of choice due to liquid formulation and a low side effect profile. The dosage is 2 to 4 mg/kg/day given in three divided doses, with the heart rate goal of 80 to 100 beats/min.

  • c.

    In older children, metoprolol is typically used.

  • d.

    In infants of diabetic mothers, β-adrenergic blockers are used when the LVOT obstruction is present. In most of these infants, LV hypertrophy spontaneously resolves within the first 6 to 12 months of life.

• 4.

  Prophylactic therapy with either β-adrenergic blockers or verapamil is controversial in patients without LVOT obstruction. Some favor prophylactic use of these drugs even in the absence of LVOT obstruction; others limit prophylactic drug therapy to young patients with a family history of premature sudden death and those with particularly marked LVH.

• 5.

  The following drugs are contraindicated: digitalis, other inotropic agents, and vasodilators tend to increase LVOT obstruction; diuretics may reduce LV volume and increase LVOT obstruction (but may be used in small doses to improve respiratory symptoms).

• 6.

  For drug-refractory patients with obstruction, Morrow’s myotomy-myectomy or percutaneous alcohol ablation may be considered.

  • a.

    In Morrow’s procedure, hypertrophied LV septum is resected through a transaortic approach to reduce the obstruction.

  • b.

    In alcohol ablation, absolute alcohol is injected into a target septal perforator branch of the left anterior descending coronary artery to produce “controlled” myocardial infarction.

• 7.

  Implantable cardioverter defibrillator (ICD) has been proved to be effective in preventing sudden death. The following are risk factors for sudden death in HCM and may be indications for an ICD.

  • a.

    Prior cardiac arrest (ventricular fibrillation)

  • b.

    Spontaneous sustained ventricular tachycardia (defined as three or more beats at ≥120 beats/min on Holter ECG)

  • c.

    Family history of premature sudden death

  • d.

    Unexplained syncope, particularly in young patients

  • e.

    LV thickness ≥30 mm, particularly in adolescents and young adults

  • f.

    Nonsustained VT

  • g.

    Abnormal exercise blood pressure (BP) (attenuated response or hypotension)

• 8.

  Cardiac arrhythmias.

  • a.

    Ventricular arrhythmias are treated with propranolol, amiodarone, and other antiarrhythmic agents, guided by serial ambulatory ECG monitoring.

  • b.

    Atrial fibrillation (AF) occurs more often in patients with LA enlargement. For new-onset AF, electrical cardioversion followed by anticoagulation with warfarin (superior to aspirin) is recommended. Amiodarone is generally considered as the most effective agent for preventing recurrence of AF.

• 9.

  Infants of diabetic mothers

In most cases, the LV hypertrophy spontaneously resolves within the first 6 to 12 months of life. β-Adrenergic blockers, such as propranolol, may help the LVOT obstruction, but treatment usually is not necessary. Digitalis and other inotropic agents are contraindicated because they may worsen the obstruction.

A. Causes

• 1.

  The cause of the condition is idiopathic in about 50% of the cases. Twenty percent to 35% of patients with idiopathic cardiomyopathy have been shown to have inherited familial DCM. Among the familial types, an autosomal dominant inheritance pattern is most frequent (occurring in 30% to 50%); X-linked, autosomal recessive; and mitochondrial inheritance patterns are less common.

• 2.

  Among the known causes of DCM are myocarditis (46%) and neuromuscular diseases (≈25%), followed by familial cardiomyopathy, active myocarditis, and others. The most frequently recognized familial form is Duchenne muscular dystrophy. Some cases of idiopathic dilated cardiomyopathy may be the result of subclinical myocarditis.

• 3.

  Some patients with idiopathic DCM may have tachycardia-induced cardiomyopathy, which is related to chronic tachycardia (usually atrial or supraventricular tachycardia).

• 4.

  Other rare causes of DCM include infectious causes other than viral infection (bacterial, fungal, protozoan, rickettsial), endocrine-metabolic disorders (hyperthyroidism and hypothyroidism, excessive catecholamines, diabetes, hypocalcemia, hypophosphatemia, glycogen storage disease, mucopolysaccharidoses), and nutritional disorders (kwashiorkor, beriberi, carnitine deficiency).

• 5.

  Cardiotoxic agents such as doxorubicin and systemic diseases (such as connective tissue diseases) can also cause dilated cardiomyopathy.

B. Pathology and Pathophysiology

• 1.

  In DCM, a weakening of systolic contraction is associated with dilatation of all four cardiac chambers. Dilatation of the atria is in proportion to ventricular dilatation.

• 2.

  Intracavitary thrombus formation is common in the apical portion of the ventricular cavities and in atrial appendages, and it may give rise to pulmonary and systemic embolization.

• 3.

  Histologic examinations from endomyocardial biopsies show varying degrees of myocyte hypertrophy and fibrosis. Inflammatory cells are usually absent, but a varying incidence of inflammatory myocarditis has been reported.

C. Clinical Manifestations

• 1.

  Fatigue, weakness, and symptoms of left heart failure (e.g., dyspnea on exertion, orthopnea) may be present.

• 2.

  On physical examination, signs of CHF (e.g., tachycardia, pulmonary crackles, weak pulses, distended neck veins, hepatomegaly) may be present. A prominent S3 with or without gallop rhythm is present. A soft systolic murmur of MR or TR may be audible.

• 3.

  The ECG commonly shows sinus tachycardia, LVH, and ST-T changes.

• 4.

  Chest radiographs show generalized cardiomegaly, often with signs of pulmonary venous congestion.

• 5.

  Echo studies are diagnostic and may include unexpected findings in an asymptomatic patient.

  • a.

    The LV and RV are markedly dilated with poor contractility. The LA may be enlarged.

  • b.

    Fractional shortening (FS) and ejection fraction (EF) are reduced.

  • c.

    Intracavitary thrombus and pericardial effusion may be present.

  • d.

    The mitral inflow Doppler tracing demonstrates a reduced E velocity and a decreased E:A ratio: nonspecific signs (see Fig. 11.2 ).

• 6.

  Laboratory tests: The following lab tests may help identify the causes of DCM.

  • a.

    Urine for organic and amino acids, 3-methylglutaconic acid (i.e., Barth syndrome)

  • b.

    Blood studies for complete blood count, comprehensive metabolic panel, lactate, calcium, magnesium, carnitine/acylcarnitine, thyroid function, creatine kinase and its MB fraction (CK-MB), troponin, brain natriuretic peptide (BNP) or its N-terminal fragment (NT-proBNP)

  • c.

    Genetic testing for DCM sequencing and deletion/duplication panels are available from blood, oral rinse or buccal (cheek) swabs.

• 7.

  Although echo study is diagnostic, cardiac catheterization can be helpful (1) to exclude anomalous coronary artery, (2) to predict etiology and prognosis by obtaining endomyocardial biopsy, and (3) to evaluate for possible cardiac transplantation including measurement of pulmonary vascular resistance.

• 8.

  Natural history. Progressive deterioration is the rule rather than the exception for many patients. Cardiac arrhythmias, systemic or pulmonary embolization, and CHF are common causes of death. Review of literature in children has suggested approximately one-third of patients die, one-third recover completely, and one-third improve with some residual cardiac dysfunction.