Abstract
Hypertrophic cardiomyopathy (HCM) is characterized by unexplained myocardial hypertrophy (hypertrophy that develops in the absence of other attributable etiology), myocyte disarray, and myocardial fibrosis. Echocardiographic imaging has played a central role in furthering our understanding of the pathophysiology, epidemiology, and prognosis of HCM. This imaging modality is well suited to evaluate disease progression and to provide pertinent information (morphology, hemodynamic changes, and dynamic assessment of cardiac function) to guide clinicians in the management of HCM. When assessing individuals with unexplained cardiac hypertrophy, echocardiography must be considered in the context of individual demographics, clinical and familial history, electrocardiogram, laboratory findings, and, at times, in conjunction with complementary imaging modalities, such as cardiac magnetic resonance imaging and nuclear imaging, to reach a final diagnosis. This chapter reviews the echocardiographic evaluation and findings in HCM relevant to patient care and clinical investigation: 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 such as surgical septal myectomy and alcohol septal ablation.
Keywords
athlete’s heart, diastolic function, echocardiography, hypertrophic cardiomyopathy, infiltrative and metabolic cardiomyopathies, left ventricular outflow obstruction, systolic anterior motion
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.
| Cardiac Morphology | Presence of hypertrophy and its distribution; report should include measurements of LV dimensions and wall thickness (septal, inferior, and anterior) and location of maximal wall thickness |
| RV hypertrophy and whether RV outflow dynamic obstruction is present | |
| LA volume indexed to body surface area | |
| Cardiac Function | LV ejection fraction |
| LV diastolic function (comments on LV relaxation and filling pressures) | |
| Valvular Function | Mitral valve and papillary muscle evaluation, including the direction, mechanism, and severity of mitral regurgitation; if needed, TEE should be performed to satisfactorily answer these questions |
| Estimation of pulmonary artery systolic pressure | |
| Assessment of Obstruction | Dynamic obstruction at rest and with Valsalva maneuver; report should identify the site of obstruction and the gradient |
| Management Considerations | TEE is recommended to guide surgical myectomy and TTE or TEE to guide alcohol septal ablation |
| Screening at-risk family members for the presence of disease is recommended |
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
Sarcomere Gene Mutations Cause Hypertrophic Cardiomyopathy
HCM is often familial and is in fact the most common inherited cardiomyopathy. Genetic studies on families with HCM helped to establish the paradigm that HCM is a disease of the sarcomere and is caused by autosomal dominant mutations in genes that encode contractile proteins. The sarcomere is the functional unit of contraction of the myocyte and acts as the molecular motor of the heart. Over 1400 mutations have been identified in 11 different components of the sarcomere apparatus. Mutations in the cardiac isoforms of β-myosin heavy chain ( MYH7 ), myosin binding protein C ( MYBPC3 ), and troponin T ( TNNT2 ) are the most frequent, together accounting for over 90% of cases where a genetic mutation has been identified. Genetic testing of known HCM disease genes (predominantly sarcomere genes) typically detects mutations in ∼30% of patients with HCM. However, if a family history of HCM is also present, the yield of genetic testing increases to ∼60%.
Cardiac Morphology
Cardiac morphology in HCM is typically notable for small left ventricular volumes with variable location and degree of hypertrophy. Although asymmetric septal hypertrophy (resulting in reversed septal curvature) is most common and classic ( Fig. 23.2 and 
) , hypertrophy can involve any left ventricle (LV) segment and may be focal or concentric ( Fig. 23.3 ). In classic HCM, in addition to the asymmetric hypertrophy at the basal septum, the left ventricular cavity often has a narrow crescentic shape ( 
). Apical hypertrophy is a well-described morphologic variant of HCM ( Fig. 23.4 ) in which hypertrophy occurs below the level of the papillary muscles in the distal portion of the LV chamber. As such, apical HCM is not associated with left ventricular outflow tract (LVOT) obstruction but may instead cause dynamic obstruction within the mid-to-distal ventricle. The LV often resembles the shape of a spade in diastole (see Fig. 23.4B and 
). First reported in Japan and hence also referred to as “Yamaguchi variant,” the prevalence of apical variant HCM appears to be higher in individuals of Japanese versus Western descent (13%–25% vs. 1%–2%). A family history of HCM and disease-causing sarcomere gene mutations are rarely identified in patients with apical HCM, suggesting that it is a different subtype of disease. While early studies suggested a more benign prognosis for apical HCM, a broad spectrum of clinical outcomes has been described.
Septal morphology is predictive of the presence of sarcomere mutations. The likelihood of positive genetic testing is highest in patients with classic reversed septal curvature, and lowest in patients with a sigmoidal septum (focal upper septal thickening, Fig. 23.5 ). Consistent correlations between the distribution of left ventricular hypertrophy (LVH) and clinical outcomes have not been established. Furthermore, even within families with HCM who share the same underlying sarcomere mutation, LV morphology is often varied.
Cardiac morphology may occasionally not be adequately assessed by echocardiography due to suboptimal visualization of the LV apex, free wall, or endocardial/epicardial borders. In these cases, echocardiographic contrast administration or cardiac magnetic resonance (CMR) imaging should be considered to clarify the LV geometry ( Fig. 23.6 ). Similarly, apical aneurysm ( Fig. 23.7 and 
) is not only a rare consequence associated with obstructive HCM of any morphology that may be visualized with standard echocardiographic techniques, but may also require color Doppler interrogation or LV cavity opacification by echocardiographic contrast to aid with proper identification. The consequences of apical aneurysms are unclear, but they have been suggested to be associated with sudden death, progressive heart failure, and thromboembolic complications in a small patient series.
Standard septal and posterior dimensions, as well as maximum wall thickness and its location, determined after inspecting all imaging views, should be reported (see Table 23.1 ). In general, in the absence of another etiology for LV hypertrophy (i.e., pressure overload or infiltrative processes), a septal wall thickness (IVSd) ≥15 mm or a septal:posterior wall thickness ratio ≥1.3 support a diagnosis of HCM. Modified diagnostic criteria should be considered when evaluating relatives of HCM patients, recognizing the much higher a priori risk for HCM in the family members of patients with diagnosed disease. As summarized in Table 23.2 , more subtle abnormalities, particularly borderline or mild LVH, carry greater significance in this context. Other suggestive features that a sarcomere mutation is present include diastolic abnormalities (decreased early myocardial relaxation velocities, e′, by tissue Doppler interrogation) and electrocardiographic changes (Q waves and marked repolarization changes such as ST segment depression and T wave inversion; see Fig. 23.6D ). Lastly, left atrial (LA) enlargement, measured by anteroposterior linear dimensions or more accurately by volume, appears to be a marker for disease severity and is increased in patients with higher New York Heart Association (NYHA) classes.
| Major Criteria | Minor Criteria | |
|---|---|---|
| Echocardiography | Maximal LV wall thickness ≥13 mm | Anterior septum or posterior wall ≥12 mm |
| Posterior septum or free wall ≥14 mm | ||
| SAM | ||
| Redundant MV leaflets | ||
| Electrocardiography | Voltage criteria for LVH Pathologic Q waves | Complete BBB or (minor) interventricular conduction defect (in LV leads) |
T wave inversion
|
Other incidental findings on echocardiography are common in classic HCM. The aortic leaflets tend to close early in midsystole as mitral-septal contact occurs, which can be observed particularly clearly on M-mode ( Fig. 23.8 ). M-mode also can clearly diagram the systolic anterior motion (SAM) of the mitral leaflets in systole (refer to Fig. 23.13C later). Two-dimensional imaging of the LV may reveal an area of echogenicity and fibrotic thickening at the point of the repetitive SAM-mitral septal contact, which correlates with pathologic findings of a friction plaque. Mitral leaflets are occasionally elongated and/or chordal structures more slack, which may predispose or contribute to SAM. The mitral regurgitation (MR) engendered by SAM is characteristically posteriorly directed (see later).
Left Ventricular Systolic and Diastolic Function
In most cases of HCM, LV ejection fraction is normal or hyperdynamic. However, there is a subset of patients with severe hypertrophy and restrictive physiology, in which LV end-diastolic volumes become reduced, thereby compromising stroke volume despite vigorous LV ejection fraction. Approximately 2%–5% of HCM patients progress to end stage or “burnt out” HCM; about 50% of those affected presenting early, in the first four decades of life. This rare complication of HCM is characterized by a progression from a hypertrophied, nondilated, and hyperdynamic LV to a ventricle with systolic dysfunction (LV ejection fraction <50%). Approximately half of these patients also develop left ventricular cavity enlargement and regression of wall thickness (as illustrated in Fig. 23.9 ). The clinical course of end-stage HCM can vary but is typically highly unfavorable. Advanced heart failure therapies, including cardiac transplantation or mechanical support (left ventricular assist device), are considered when standard medical therapy for systolic heart failure is no longer effective.
Patients with clinically overt HCM typically demonstrate diastolic abnormalities by both standard Doppler interrogation of mitral inflow and tissue Doppler imaging (TDI). However, Doppler methods (see Chapter 15 ) are also useful for evaluating cardiac dysfunction earlier in the subclinical phases. Studies on sarcomere gene mutation carriers have shown that reduced early diastolic relaxation velocity (e′ on TDI), indicative of impaired relaxation, may occur before overt LV hypertrophy ( Fig. 23.10 ). Although these findings help to understand the fundamental biology of HCM, there is no threshold value for e′ that can discriminate at-risk mutation carriers from healthy relatives.
