Which feature makes dynamic hypertrophic obstructive cardiomyopathy significant?

1 What is hypertrophic cardiomyopathy?

Hypertrophic cardiomyopathy (HCM) is a primary cardiac disorder characterized by myocardial hypertrophy and a nondilated left ventricle (LV) in the absence of an accountable increase in cardiac afterload (i.e., aortic stenosis or systemic hypertension). Historically, and due to the fact that two basic phenotypes (i.e., with and without obstruction to outflow, discussed later) exist within the HCM spectrum, there has been a confusing array of names, such as idiopathic hypertrophic subaortic stenosis (IHSS) or muscular subaortic stenosis. Currently, hypertrophic cardiomyopathy is the preferred term.

Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy is relatively common, with a prevalence estimated at 1 in 500. It is an autosomal dominant disorder associated with various forms of left ventricular hypertrophy; the risk that an affected patient will transmit the disease to offspring is 50%. Additionally, hypertrophic cardiomyopathy mutations are highly penetrant. Preconception genetic counseling is recommended.156

The complications that result from hypertrophic cardiomyopathy can be separated into two categories: mechanical and electrophysiologic. The mechanical consequences relate to left ventricular outflow tract obstruction, mitral regurgitation, diastolic dysfunction, and development of heart failure. The electrophysiologic complications include atrial and ventricular arrhythmias and, most important, the risk for sudden cardiac death. The myocardial ischemia observed in patients with hypertrophic cardiomyopathy, often at ages younger than expected, is caused by supply-demand mismatch rather than coronary atherosclerosis. Hypertrophic cardiomyopathy is associated with disorganized myocardial architecture, myocardial disarray, and fibrosis (Fig. 41.7).

One of the hallmarks of hypertrophic cardiomyopathy is the dynamic left ventricular outflow tract obstruction. The obstruction gradient typically increases after a premature ventricular contraction. One-third of patients have left ventricular outflow tract obstruction at rest, one-third have a physiologically provocable gradient, and one-third have no gradient (nonobstructive form of hypertrophic cardiomyopathy). A gradient of 30 mm Hg or more is clinically significant.235

Pregnant women with hypertrophic cardiomyopathy may have dyspnea, fatigue, angina, palpitations, and/or syncope. Symptoms of congestive heart failure are rarely seen in patients in sinus rhythm; these symptoms are more frequently encountered when atrial fibrillation is present.

On physical examination, the classic obstructive systolic murmur is heard at the apex (grade 3/6 to 4/6), and it radiates to the left sternal border. Although most patients will have a displaced and forceful left ventricular impulse, the presence of a murmur depends on the degree and type of obstruction. The intensity of a hypertrophic cardiomyopathy murmur increases with the Valsalva maneuver or standing (decreased preload or afterload causes more obstruction), and it decreases with squatting (increased afterload causes less obstruction). Invasive arterial pressure monitoring allows recognition of abifid arterial pulse waveform.

The ECG is abnormal in the vast majority of patients and demonstrates an increase in voltage, T-wave inversions, and pathologic Q waves. ECG abnormalities correlate poorly with the severity of hypertrophic cardiomyopathy.157 Transthoracic echocardiography is indispensable for making the diagnosis, determining prognosis, and guiding management decisions.156 Diagnostic criteria include a septal thickness greater than 15 mm, although it should be emphasized that individuals may carry the genotype without evidence of increased wall thickness (so-called “subclinical hypertrophic cardiomyopathy”).156 Systolic anterior motion of the mitral valve has a specificity of 98% for hypertrophic cardiomyopathy. Left ventricular outflow tract obstruction is apparent during Doppler interrogation; the continuous wave tracing has a classic “dagger-shaped” contour (Fig. 41.8). In addition, echocardiography allows identification of various morphologic variants and assessment of the extent of hypertrophy. A wall thickness of 30 mm or greater is associated with a high risk for sudden cardiac death.236 Patients with a gradient of 50 mm Hg or greater are at highest risk for complications.156

1 What is hypertrophic cardiomyopathy?

Hypertrophic cardiomyopathy (HCM) is a primary disorder of the cardiac muscle characterized by inappropriate myocardial hypertrophy of a nondilated left ventricle (LV) in the absence of a cardiovascular or systemic disease (i.e., aortic stenosis or systemic hypertension). Historically, HCM has been known by a confusing array of names, such as idiopathic hypertrophic subaortic stenosis (IHSS), muscular subaortic stenosis, and hypertrophic obstructive cardiomyopathy (HOCM). Presently, hypertrophic cardiomyopathy is the preferred term because only a small percentage of patients actually have left ventricular outflow tract (LVOT) obstruction.

Idiopathic Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy, which is usually inherited as an autosomal dominant trait with variable penetrance but sometimes is caused by a spontaneous mutation, is being recognized with increasing frequency. The phenotypes vary greatly. Left ventricular outflow tract obstruction may or may not be present, and the hypertrophy may be either symmetric or asymmetric. The chief symptoms are angina, dyspnea, arrhythmia, and syncope. Sudden death is a feature mostly confined to patients in whom the diagnosis is established in childhood or youth, patients with a history of syncope or ventricular arrhythmia, and patients with a family history of hypertrophic cardiomyopathy and sudden death. Recent research has shown that certain specific genetic defects place patients at great risk for sudden death.

When the disease is first detected in older adults, the course is more benign and sudden death is rare. Left ventricular hypertrophy is often apparent on clinical examination and ECG and is invariably present on the echocardiogram. The echocardiographic findings are often diagnostic and include marked thickening of the ventricular septum, usually with less thickness of the other walls of the left ventricle (asymmetric hypertrophy), and abnormal systolic anterior movement of the mitral valve (Fig. 52.17,Video 52.9A, andVideo 52.9B). The internal dimensions of the left ventricle are normal to small, and its contractility is increased.

An important feature in many cases is obstruction of the space between the ventricular septum and the anterior leaflet of the mitral valve. This space constitutes the left ventricular outflow tract. Outflow obstruction by the anterior mitral valve leaflet is worsened by increased inotropy, decreased heart size, and diminished peripheral vascular resistance. The normal fall in peripheral vascular resistance that accompanies pregnancy tends to increase outflow tract obstruction, although this effect may be compensated for by the physiologic increase in blood volume. In addition, vena caval obstruction in late pregnancy and blood loss at delivery, both of which may result in hypotension, can have a similar deleterious effect. Outflow tract obstruction may also be worsened by the increases in circulating catecholamine levels frequently encountered during labor and delivery. The Valsalva maneuver during the second stage of labor may greatly diminish heart size and increase outflow tract obstruction. Despite all these problems, however, most pregnant women with hypertrophic cardiomyopathy do tolerate labor and delivery.96

Introduction

Hypertrophic cardiomyopathy (HCM) is characterized by unexplained myocardial hypertrophy, that is, hypertrophy that has developed in the absence of other attributable etiology, myocyte disarray, and myocardial fibrosis (Fig. 23.1). In large part, through cardiac imaging and molecular research, our understanding of the pathophysiology, epidemiology, and prognosis of HCM in the last several decades has rapidly advanced. Echocardiography is an essential tool for examining the morphologic diversity, dynamic remodeling, hemodynamic changes, and complex disturbances of cardiac function associated with HCM. Current American Society of Echocardiography (ASE) Guidelines recommend an initial comprehensive echocardiographic evaluation of all patients with or suspected of having HCM (Table 23.1), including the assessment of cardiac structure, systolic and diastolic function, pulmonary artery pressures, valvular function, and dynamic outflow evaluation.1

This chapter reviews the echocardiographic evaluation and findings in HCM relevant to patient care and clinical investigation. Echocardiography is often the key to establishing the diagnosis of HCM and describing morphologic variants; characterizing natural history and heterogeneous phenotypic expression; evaluating pathophysiology, including obstructive physiology and diastolic abnormalities; and guiding therapeutic interventions including surgical septal myectomy and alcohol septal ablation

Abstract

Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiomyopathy and is a disease characterized by substantial heterogeneity in both phenotypic expression and clinical course. Although HCM is associated with normal longevity in the majority of patients, a small but important subset of patients remain at risk for a number of adverse disease-related events, including advanced heart failure and sudden death. Cardiovascular magnetic resonance (CMR), with high spatial resolution and tomographic imaging capability, can provide relevant diagnostic and prognostic information that impacts the noninvasive clinical evaluation of HCM patients. The diagnosis of HCM is reliably made with CMR with precise left ventricular (LV) wall thickness measurements and can identify areas of focal LV hypertrophy not well visualized by transthoracic echocardiography, as well as aiding in the differentiation of HCM from other cardiovascular diseases with LV hypertrophy. CMR has also expanded our appreciation for the diversity of HCM phenotypic expression to include morphologic abnormalities of the right ventricle, high-risk LV apical aneurysms, massive hypertrophy, as well as structural abnormalities of the mitral valve and subvalvular apparatus, which contribute to LV outflow obstruction, findings that may impact management strategies. Additionally, contrast-enhanced CMR with late gadolinium enhancement (LGE) allows for the noninvasive characterization of abnormal myocardial substrate in HCM (i.e., fibrosis), with extensive LGE representing a marker for increased risk for potentially life-threatening ventricular tachyarrhythmias and heart failure progression with systolic dysfunction. As a result, CMR has emerged as an increasingly dominant complementary imaging technique in the contemporary evaluation of nearly all HCM patients.

Abstract

Hypertrophic cardiomyopathy (HCM) is one of the most common forms of inherited cardiomyopathies and is characterized by increased ventricular wall thickness without apparent cause. HCM can present at any age, but left ventricular hypertrophy may not develop until adolescence or later. Although disease course is highly variable, there is an increased risk of sudden cardiac death and cardiovascular morbidity. No medical treatment has yet been reliably demonstrated to alter disease progression. Current treatment is focused on symptom palliation and providing implantable cardioverter defibrillators to patients deemed at high risk of sudden cardiac death. HCM is often caused by mutations in sarcomere genes, highlighting the importance of family screening. When definitive, genetic testing can guide family management. Other conditions can lead to a similar cardiac appearance and require differentiation from HCM to provide optimal care.

Midventricular Obstruction and Apical Aneurysms

Hypertrophic cardiomyopathy with midventricular obstruction is far less common than HCM associated with SAM and LVOT obstruction.70 The echocardiographic features of this condition include (1) midventricular obliteration caused by septal hypertrophy and apposition with the mid-LV wall segments (and often the papillary muscles), (2) a midventricular gradient of at least 30 mm Hg at rest recognized by color and PW Doppler, and (3) absence of leaflet SAM.70 One study of 490 patients with HCM in Japan detected midventricular obstruction in 46 patients (9%), coupled with apical aneurysm formation in 13 patients (i.e., 28% of the patients with midventricular obstruction and 3% of the overall cohort). There was a higher incidence of adverse HCM-related outcomes in patients with midventricular obstruction.70 An echocardiographic and magnetic resonance study of 1299 patients with HCM revealed apical aneurysms in 2%.71 Most apical aneurysms (68%) were small (greatest width or length <2 cm) or medium (2–4 cm) in size. There were nine patients with apical aneurysms who had resting midventricular obstruction (74 ± 42 mm Hg) without SAM.71 Patients with medium or large (>4 cm) apical aneurysms had an increased risk of HCM-related complications.71

Definition

Hypertrophic cardiomyopathy (HCM) is defined as left ventricular (LV) hypertrophy in the absence of abnormal loading conditions (valve disease, hypertension, congenital heart defects) sufficient to explain the degree of hypertrophy.1 Although asymmetrical septal hypertrophy was first described in the late 19th century, it was only after landmark reports by Sir Russell Brock (later Lord Brock) in 1957 and Donald Teare in 1958 that HCM became established as a clinical entity. Subsequent clinical, angiographic, and echocardiographic studies defined the characteristic morphologic and clinical features of the disease. Advances in molecular techniques have resulted in the current view of HCM as a disease primarily of the cardiac sarcomere.