Cardiomyopathies are structural or functional abnormalities of the myocardium not secondary to congenital, valvular, hypertensive, pulmonary, or coronary heart diseases. Cardiomyopathy has been classified into three types based on anatomic and functional features; hypertrophic, dilated, and restrictive ( Fig. 18-1 ).
- 1.
In hypertrophic cardiomyopathy (HCM), there is massive ventricular hypertrophy with a smaller than normal ventricular cavity. Contractile function of the ventricle is enhanced, but ventricular filling is impaired by relaxation abnormalities.
- 2.
Dilated cardiomyopathy (DCM) is characterized by decreased contractile function of the ventricle associated with ventricular dilatation. Endocardial fibroelastosis (seen in infancy) and doxorubicin cardiomyopathy (seen in children who have received chemotherapy for malignancies) have clinical features similar to those of DCM.
- 3.
Restrictive cardiomyopathy denotes a restriction of diastolic filling of the ventricles (usually infiltrative disease). Contractile function of the ventricle may be normal, but there is marked dilatation of both atria.
Recently, two new ones have been added to the classification, arrhythmogenic cardiomyopathy and left ventricular (LV) noncompaction. The two new types of cardiomyopathies are presented later in this chapter. The original three types of cardiomyopathies are functionally different from one another, and demands of therapy also are different. Table 18-1 summarizes clinical characteristics and treatment of the original three types of cardiomyopathies.
| Clinical Features | Hypertrophic | Dilated | Restrictive |
|---|---|---|---|
| Cause | Inherited (AD in ≈50%) Sporadic (new mutation ±) | Pluricausal (e.g., toxic, metabolic, infectious, alcohol, doxorubicin) | Myocardial fibrosis, hypertrophy, or infiltration (amyloid, hemochromatosis) |
| Inherited form (20%–35% of idiopathic forms) | |||
| Hemodynamic dysfunction | Diastolic dysfunction (with normal systolic function) (abnormally stiff LV with impaired ventricular filling) | Systolic contractile dysfunction (↓ cardiac output, ↓ stroke volume, ↑ LVEDP) | Diastolic dysfunction (rigid ventricular walls impede ventricular filling) |
| Echocardiography (morphology) | Thickened LV (and occasionally RV) wall | Biventricular dilatation (↑LVDD, ↑LVSD) | Biatrial enlargement |
| Small or normal LV chamber dimension | Atrial enlargement in proportion to ventricular enlargement | Normal LV and RV volume | |
| Supernormal LV contractility | Atrial enlargement in proportion to ventricular enlargement | Normal LV systolic function until advanced stage | |
| HOCM, ASH, or both | Apical thrombus (±) | Atrial thrombus (±) | |
| Doppler | Reduced relaxation pattern (see Fig. 18-6 ) | Reduced relaxation pattern (see Fig. 18-6 ) | “Restrictive” pattern (see Fig. 18-6 ) |
| Treatment | β-Adrenoreceptor blockers | Vasodilator therapy | Diuretics |
| Calcium antagonists | Digitalis plus diuretics | Anticoagulants (±) | |
| (Digitalis, catechols, and nitrates contraindicated) | β-Adrenoceptor blockers (±) | Corticosteroids (±) | |
| Anticoagulants | Permanent pacemaker for advanced heart block (±) | ||
| (Diuretics may worsen symptoms) | Antiarrhythmics (±) | ||
| Cardiac transplantation (±) | Cardiac transplantation (±) |
Hypertrophic Cardiomyopathy
Hypertrophic cardiomyopathy is a heterogeneous, usually familial disorder of heart muscle. In about 50% of cases, HCM is inherited as a Mendelian autosomal dominant trait and is caused by mutations in one of 10 genes encoding protein components of the cardiac sarcomere (e.g., β-myosin heavy chain, myosin binding protein C, and cardiac troponin-T). The remainder of the cases occurs sporadically. HCM usually is seen in adolescents and young adults, with equal gender distribution. It is the most common cause of sudden cardiac death in teens and young adults, especially among athletes. It may be seen in children with LEOPARD syndrome (see Table 2-1 ). A usually transient form of HCM occurs in infants of mothers with diabetes, which will be presented under a separate heading in this chapter.
Pathology and Pathophysiology
- 1.
The most characteristic abnormality is the hypertrophied LV, with the ventricular cavity usually small or normal in size. Although asymmetrical septal hypertrophy, a condition formerly known as idiopathic hypertrophic subaortic stenosis ( Fig. 18-2 ), is most common, the hypertrophy may be concentric or localized to a small segment of the septum ( Fig. 18-3 ). Microscopically, an extensive disarray of hypertrophied myocardial cells, myocardial scarring, and abnormalities of the small intramural coronary arteries are present.
FIGURE 18-2
Systolic anterior motion of the mitral valve. A, Diagram of systolic anterior motion in the presence of an asymmetrical septal hypertrophy. The Venturi effect may be important in the production of systolic anterior motion. B, M-mode echocardiography of the mitral valve in a patient with hypertrophic cardiomyopathy. Systolic anterior motion of the anterior leaflet of the mitral valve is indicated by arrows. AO, aorta; IVS, interventricular septum; LA, left atrium; LV, left ventricle; LVPW, LV posterior wall; mv, mitral valve; RV, right ventricle.
FIGURE 18-3
Morphologic variability in hypertrophic cardiomyopathy seen on parasternal short-axis view of two-dimensional echo. In type I hypertrophy, relatively mild left ventricular hypertrophy confined to the anterior portion of the ventricular septum (VS) is present. In type II, hypertrophy of the anterior and posterior septum is present in the absence of free wall thickening. In type III, there is diffuse hypertrophy of substantial portions of both the ventricular septum and the anterolateral free wall (ALFW). In type IV, the M-mode echocardiography beam (M) does not traverse the thickened portions of the left ventricle (LV) in the posterior septum and anterolateral free wall. A or ANT, anterior; AML, anterior mitral leaflet; L, left; LVFW, left ventricular free wall; P or POST, posterior; PML, posterior mitral leaflet; R, right.
(From Maron BJ: Asymmetry in hypertrophic cardiomyopathy: The septal to free wall thickness ratio revisited [editorial]. Am J Cardiol 55: 835-838, 1985.)
- 2.
In some patients, an intracavitary pressure gradient develops during systole, either at subaortic or rarely at mid-cavity. This subset is called hypertrophic obstructive cardiomyopathy (HOCM).
- a.
The subaortic obstruction is commonly caused by systolic anterior motion (SAM) of the mitral valve against the hypertrophied septum (see Fig. 18-2 ). The SAM probably is created by the high outflow velocities and Venturi forces with frequent association of mitral regurgitation (MR).
- b.
Midcavity obstruction is caused by anomalous insertion of anterolateral papillary muscle into the anterior mitral leaflet.
- c.
In so-called apical HCM, hypertrophy is confined to the LV apex without intracavitary obstruction (and with giant negative T waves on the electrocardiogram (ECG). This subtype is present in about 25% of patients in Japan and fewer than 10% in other parts of the world.
- a.
- 3.
The myocardium itself has an enhanced contractile state, but diastolic ventricular filling is impaired by abnormal stiffness of the LV, which may lead to left atrial enlargement and pulmonary venous congestion, producing congestive symptoms (exertional dyspnea, orthopnea, paroxysmal nocturnal dyspnea).
- 4.
A unique aspect of HOCM is the variability of the degree of obstruction from moment to moment; the intensity of the heart murmur varies from time to time. Because the obstruction of the LVOT results from SAM of the mitral valve against the hypertrophied ventricular septum, any influence that reduces the LV systolic volume (e.g., positive inotropic agents, reduced blood volume, or lowering of the systemic vascular resistance) increases the obstruction. On the other hand, any influence that increases the LV systolic volume (e.g., negative inotropic agents, leg raising, blood transfusion, or increasing systemic vascular resistance) lessens the obstruction.
- 5.
A large portion of the stroke volume (≈80%) is ejected during the early part of systole when there is little or no obstruction, producing a sharp upstroke in the arterial pulse, a characteristic finding of HOCM. The obstruction occurs late in systole, producing a late systolic murmur.
- 6.
Patients with severe hypertrophy and obstruction may experience anginal chest pain, lightheadedness, near syncope, or syncope. Patients also are prone to develop arrhythmias, which may lead to sudden death (presumably from ventricular tachycardia or fibrillation). Nearly 30% of children with HCM have myocardial bridging (seen on coronary angiograms) with narrowing of the anterior descending coronary artery, which may have a key role in the development of ventricular arrhythmias. These patients may be more prone to sudden death. (Normally, the large epicardial coronary arteries run on the surface of the heart, with only their terminal branches penetrating the myocardium. When parts of the epicardial artery dip beneath the epicardial muscle so that there is a muscle bridge over the artery, they are called myocardial bridges.)
Clinical Manifestations
History
- 1.
Easy fatigability, dyspnea, palpitation, dizziness, syncope, or anginal pain may be present.
- 2.
Family history is positive for the disease in 30% to 60% of patients.
Physical Examination
- 1.
A sharp upstroke of the arterial pulse is characteristic (in contrast to a slow upstroke seen with fixed aortic stenosis [AS]). An LV lift and a systolic thrill at the apex or along the lower left sternal border may be present.
- 2.
The S2 is normal, and an ejection click is generally absent. A grade 1 to 3 of 6 ejection systolic murmur of medium pitch is most audible at the mid-and lower left sternal borders or at the apex. A soft holosystolic murmur of MR is often present. The intensity and even the presence of the murmur vary from examination to examination.
Electrocardiography
The ECG is abnormal in the majority of patients. Common ECG abnormalities include left ventricular hypertrophy (LVH), ST-T changes, and abnormally deep Q waves (owing to septal hypertrophy) with diminished or absent R waves in the left precordial leads ( Fig. 18-4 ). Occasionally, “giant” negative T waves are seen in the left precordial leads, which may suggest apical HCM. Other ECG abnormalities may include cardiac arrhythmias and first-degree AV block.
Radiography
Mild LV enlargement with a globular-shaped heart may be present. The pulmonary vascularity usually is normal.
Echocardiography
- 1.
Echocardiography is diagnostic. Two-dimensional echocardiography demonstrates the wide morphologic spectrum of the disease; including concentric hypertrophy ( Fig. 18-5 ), localized segmental hypertrophy, and asymmetrical septal hypertrophy (see Fig. 18-3 ). Apical HCM may be missed by two-dimensional echocardiography. (If apical HCM is suspected, a cardiac MRI should be obtained.)
FIGURE 18-5
Parasternal short-axis view of a 14-year-old boy with hypertrophic cardiomyopathy. Marked hypertrophy of the interventricular septum (IVS) as well as the posterior wall of the left ventricle (LVPW) is present. The left ventricle (LV) cavity is small. The IVS is approximately 39 mm, and the LV posterior wall is 26 mm thick. The thickness of both structures does not exceed 10 mm in normal persons.
- 2.
The diastolic LV wall thickness 15 mm or larger (or on occasion, 13 or 14 mm), usually with LV dimension smaller than 45 mm, is accepted for the clinical diagnosis of HCM in adults. For children, z-score of 2 or more relative to body surface area is theoretically compatible with the diagnosis.
The heart of some highly trained athletes may show hypertrophy of the LV wall, making the differentiation between the physiologic hypertrophy and HCM difficult. An LV wall thickness of 13 mm or larger is very uncommon in highly trained athletes, and it is always associated with an enlarged LV cavity (with LV diastolic dimension >54 mm, with ranges 55 to 63 mm). Therefore, athletes with LV wall thickness greater than 16 mm and a nondilated LV cavity are likely to have HCM ( Pelliccia et al, 1991 ).
- 3.
M-mode echocardiography may demonstrate an asymmetrical septal hypertrophy of the interventricular septum (with the septal thickness 1.4 times greater than the posterior LV wall) and occasionally SAM of the anterior mitral valve leaflet in the obstructive type (see Fig. 18-2 ).
- 4.
Mitral inflow Doppler tracing demonstrates diastolic dysfunction with decreased E-wave velocity, increased deceleration time, and decreased E/A ratio of the mitral valve (usually <0.8) ( Fig. 18-6 ). LV systolic function is normal or supernormal.
FIGURE 18-6
Examples of diastolic dysfunction seen in various forms of cardiomyopathy. (See Chapter 5 for further discussion.) A, A-wave velocity (the velocity of a second wave that coincides with atrial contraction); AFF, atrial filling fraction; DT, deceleration time; E, E-wave velocity (the velocity of an early peak); E/A, ratio of E-wave to A-wave velocity; IVRT, isovolumic relaxation time.
- 5.
Doppler peak gradient in the LVOT of 30 mm Hg or greater indicates an obstructive type.
Natural History
- 1.
The obstruction may be absent, stable, or slowly progressive. Genetically predisposed individuals often show striking increases in wall thickness during childhood.
- 2.
Death is often sudden and unexpected and typically is associated with sports or vigorous exertion. Sudden death may occur most commonly in patients between 10 and 35 years of age. The incidence of sudden death may be as high as 4% to 6% a year in children and adolescents and 2% to 4% a year in adults. Ventricular fibrillation is the cause of death in the majority of sudden deaths. Even brief episodes of asymptomatic ventricular tachycardia on ambulatory ECG may be a risk factor for sudden death. Patients with myocardial bridging (occurring in about 30%) may be at risk for sudden death.
- 3.
Atrial fibrillation (AF) may cause stroke or heart failure. AF results from left atrium (LA) enlargement with loss of the atrial “kick” needed for filling the thick LV.
- 4.
In a minority of patients, heart failure with cardiac dilatation (“burned-out” phase of the disease) may develop later in life.
Management
The goal of treatment is to reduce ventricular contractility, increase ventricular volume, increase ventricular compliance, and increase LV outflow tract (LVOT) dimensions. In the obstructive form of the condition, reduction of the LVOT pressure gradient is important. However, unfortunately, most of therapeutic modalities used do not appear to significantly reduce the mortality rate. Surgical implantation of an automatic defibrillator may prove to be a very important modality to reduce sudden death.
Medical
- 1.
General management
- a.
Moderate restriction of physical activity is recommended. Patients with the diagnosis of HCM should avoid strenuous exercise and competitive sports, regardless of age, gender, symptoms, LVOT obstruction, or treatment.
- b.
Digitalis is contraindicated because it increases the degree of obstruction. Other cardiotonic drugs and vasodilators should be avoided because they tend to increase the pressure gradient. Diuretics usually are ineffective and can be harmful. However, judicious use can help improve congestive symptoms (e.g., exertional dyspnea, orthopnea) by reducing LV filling pressure.
- c.
Clinical screening of first-degree relatives and other family members should be encouraged.
- d.
Annual evaluation of adolescence (12–18 years of age) is recommended, regardless of symptoms, with physical examination, ECG, and two-dimensional echocardiography studies.
- a.
- 2.
Patients with symptoms (dyspnea, chest discomfort, disability)
Exertional dyspnea and disability are caused by diastolic dysfunction with impaired filling caused by increased LV stiffness. Chest pain is probably caused by myocardial ischemia of severely hypertrophied LV. Beta-blockers and calcium channel blockers are effective therapies in children with HCM. These agents reduce hypercontractile systolic function and improve diastolic filling.
- a.
A β-adrenergic blocker (e.g., propranolol, atenolol, or metoprolol) appears to be a preferred drug for symptomatic patients with outflow gradient, which develops only with exertion. Beta-blockers reduce the degree of outflow tract obstruction, decrease the incidence of anginal pain, and have antiarrhythmic effects.
In small children, propranolol is the drug of choice because of liquid formulation and low side effect profile. The dosage is 2 to 5 mg/kg/day given in three divided doses, with the heart rate goal of 80 to 100 beats/min. In older children, atenolol is typically used. In patients with excessive LVH and severe LVOT obstruction, a combination therapy with atenolol and verapamil may be considered.
- b.
Calcium channel blockers (principally verapamil) may be equally effective in both the nonobstructive and obstructive forms. Adverse hemodynamic effects may occur presumably as the result of vasodilating properties predominating over negative inotropic effects.
- b.
- 3.
Asymptomatic patients. Prophylactic therapy with either β-adrenergic blockers or the calcium channel blocker verapamil is controversial in asymptomatic patients without LV obstruction. Some favor prophylactic administration of these drugs to prevent sudden death or to delay progression of the disease process; others limit prophylactic drug therapy to young patients with a family history of premature sudden death and those with particularly marked LVH. The efficacy of empiric prophylactic drug treatment with the above agents is unresolved.
- 4.
Drug-refractory patients with obstruction. When standard pharmacologic therapy fails, there are limited options. In small children with persistent LVOT obstruction, the Morrow’s myectomy is the only option. In adults, alcohol septal ablation has been used but not in children. In patients with syncope, ventricular arrhythmias, or other high-risk factors, implantable cardioverter-defibrillator (ICD) implantation should be considered.
- a.
Morrow’s myotomy–myectomy. Transaortic LV septal myotomy -– myectomy (the Morrow operation) is the procedure of choice for drug-refractory patients with LVOT obstruction. This operation is performed through an aortotomy without the benefit of complete direct visualization. Two vertical and parallel incisions are made (≈1 cm apart, 1–1.5 cm deep) into the hypertrophied ventricular septum. A third transverse incision connects the two incisions at their distal extent, and the bar of rectangular septal muscle is excised. Indications for the procedure is the presence of a resting pressure gradient of greater than 50 mm Hg by continuous wave Doppler study in patients who are symptomatic despite medical management.
- a.
The mortality rate, including children, is 1% to 3%. Partial or complete left bundle branch block (LBBB) always results. Symptoms improve in most patients, but patients may later die of congestive symptoms and arrhythmias caused by the cardiomyopathy. Serious complications of the surgery such as complete heart block requiring permanent pacemaker and surgically induced ventricular septal defect have become uncommon (1%–2%).
- b.
Percutaneous alcohol septal ablation. For adult patients with persistent LVOT obstruction, the introduction of absolute alcohol into a target septal perforator branch of the left anterior descending coronary artery produces myocardial infarction within the proximal ventricular septum. This is analogous to surgical myomectomy. A decrease in pressure gradient occurs after 6 to 12 months. A large proportion of patients demonstrate subjective improvement in symptoms and in quality of life. The increasing popularity of the procedure is probably unjustifiable. This procedure should not be considered a routine invasive procedure because selection of the appropriate perforator branch is crucially important.
- b.
The procedure-related mortality rate is 1% to 4%. Permanent pacemaker implantation occurs in 1% to 4%. This procedure commonly results in right bundle branch block (RBBB) rather than LBBB seen with surgical myotomy.
- c.
Pacemaker implantation. Dual-chamber pacing was shown in earlier studies to reduce symptoms and the pressure gradient across the LVOT, but more recent studies did not support earlier findings. There are currently no data to support the contention that pacing improves survival or quality of life. Therefore, pacing is not recommended as the primary treatment for most symptomatic patients with obstruction.
- c.
- 5.
ICD. Recently, HCM has become one of the most frequent indications for ICD implantation in children with proven efficacy to prevent sudden death from arrhythmias. ICD implantation is warranted when risk for sudden death is judged to be unacceptably high. The following are risk factors for sudden death in HCM.
- a.
Prior cardiac arrest (ventricular fibrillation)
- b.
Spontaneous sustained ventricular tachycardia (3 beats/min or more or at least 120 beats/min)
- c.
Family history of premature sudden death
- d.
Unexplained syncope, particularly in young patients
- e.
LV thickness of 30 mm or greater, particularly in adolescents and young adults
- f.
Abnormal exercise blood pressure (attenuated response or hypotension)
- g.
Nonsustained ventricular tachycardia
- a.
Special consideration may be given to adolescents for ICD implantation because it is the period of life consistently showing the greatest predilection for sudden death.
- 6.
Cardiac arrhythmias
- a.
Ventricular arrhythmias may be treated with propranolol, amiodarone, and other standard antiarrhythmic agents guided by serial ambulatory ECG monitoring.
- b.
AF occurs more often in patients with LA enlargement. AF can possibly trigger ventricular arrhythmias in certain patients. For new-onset AF, electrical cardioversion followed by anticoagulation with warfarin (superior to aspirin) is recommended. Amiodarone is generally considered to be the most effective agent for preventing recurrence of AF.
- a.
- 7.
In patients with heart failure from either diastolic or systolic dysfunction, therapy is similar to that for DCM, including an angiotensin-converting enzyme (ACE) inhibitor plus beta-blocker with or without diuretic and digoxin. Enalapril plus carvedilol is the most common ACE-inhibitor–β-blocker combination used.
- 8.
Mitral valve replacement. Mitral valve replacement with a low-profile prosthetic valve may be indicated in selected patients with symptomatic mitral regurgitation. The operative mortality rate is about 6%. About 70% of patients show symptomatic improvement, but complications related to the prosthetic valve occur.
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