PREVALENCE AND EPIDEMIOLOGY

The incidence of HCM is reported to be as high as 1/500 individuals, making it the most common genetically inherited cardiovascular disease.¹ Nevertheless, HCM is thought to represent no more than 1% of cardiac outpatients,¹ suggesting that many genetically affected individuals remain asymptomatic for most or all of their lives.

ETIOLOGY AND PATHOPHYSIOLOGY

HCM is inherited as an autosomal dominant trait with variable penetrance. The distribution of hypertrophy in HCM is variable, with septal, right ventricular, left ventricular, septal, apical, midventricular, or concentric patterns. Asymmetric hypertrophy of the ventricular septum is by far the most common.² Histologically, HCM is characterized by myofibrillar disarray.¹

MANIFESTATIONS OF DISEASE

Imaging Techniques and Findings

Ultrasound

Patients clinically suspected to have hypertrophic cardiomyopathy are initially referred for echocardiography.² Asymmetric septal hypertrophy is the most common finding. Septal thickening of 13 to 15 mm or more and a septal-to-posterior wall ratio of 1.5 : 1 or higher have been the usual definitions of septal hypertrophy.⁷ In general, however, any abnormal hypertrophy noted on echocardiography that is not otherwise explained raises the suspicion of HCM.

Computed Tomography

Computed tomography (CT) has been shown to demonstrate morphologic and functional abnormalities in HCM (Fig. 64-1). Multidetector helical CT allows the acquisition of multiphase imaging relatively free of motion, as well as three-dimensional reformations. Reports applying electrocardiographically gated helical CT to the assessment of HCM are encouraging.⁸ However, CT has disadvantages, including the use of ionizing radiation and iodinated contrast agent, as well as limited contrast resolution.

FIGURE 64-1 CT for hypertrophic cardiomyopathy. Contrast-enhanced CT image shows asymmetric septal hypertrophy (arrow) in a patient with hypertrophic cardiomyopathy.

Magnetic Resonance Imaging

MRI with electrocardiographic gating provides excellent depictions of cardiac anatomy in hypertrophic cardiomyopathy. MRI can be used for accurate identification of the site and extent of ventricular hypertrophy and subaortic stenosis, and for quantification of myocardial mass.⁹ MRI also differentiates septal hypertrophy from septal neoplasm, an important distinction, because the two entities may present with similar symptoms.¹⁰

MRI can be used for precise and reproducible quantification of left ventricular function, including the measurement of stroke volume, ejection fraction, and mass. MRI can also be used to assess the presence and functional significance of mitral regurgitation and left ventricular outflow tract obstruction.¹¹ The response of left ventricular outflow tract obstruction to therapy, including septal myectomy and percutaneous transluminal septal wall ablation, has also been demonstrated with MRI.¹² Abnormal systolic wall thickening, a sign of myocardial dysfunction, may be seen in patients with HCM using MRI.¹¹ In addition, MRI is able to identify associated perfusion abnormalities, such as impaired global perfusion, diminished coronary flow reserve, and isolated perfusion deficits.¹³ MRI also may be used to detect abnormal myocardial architecture caused by fibrosis or necrosis.¹⁴

In patients with suspected HCM not fully assessed by echocardiography, MRI offers improved detection of disease. Specifically, echocardiography is often of limited value in the assessment of the anterior and lateral left ventricular wall and of the ventricular apex.¹⁵ Without the limits of acoustic windows inherent in echocardiography, MRI demonstrates myocardial thickening regardless of location. In addition, the high reproducibility of MRI is an advantage compared with echocardiography in monitoring regression or progression of left ventricular mass in response to therapy.

Morphology

MRI readily shows the location and extent of ventricular hypertrophy. Patients are referred for MRI when echocardiography is nondiagnostic because of a poor acoustic window or when echocardiographic evaluation of myocardial segments is incomplete. End-diastolic ventricular thickness of 1.5 cm or more on MRI scans is a commonly used indicator of HCM in patients without hypertension, aortic stenosis, or other explanations for hypertrophy.¹⁶ Asymmetric hypertrophy is demonstrated by calculating a ratio of wall thickness, such as septal to posterolateral thickness.¹⁶ Electrocardiographically gated black blood and white blood steady-state free precession MRI sequences in the short- and long-axis planes ensure that all myocardial segments are clearly visualized (Table 64-1; Fig. 64-2).¹⁷

TABLE 64-1 Selected Magnetic Resonance Imaging Sequences Used for Hypertrophic Cardiomyopathy

Sequence	Indications and Use	Imaging Plane
Black blood (double-inversion recovery)	Distribution of hypertrophy Identification of intramural cardiac mass

Coronal

Axial

Steady-state free precession cine

Cardiac function and wall motion

LVOT obstruction (signal void)

Mitral valve motion and regurgitation

Measurement of myocardial mass

Short axis

Long axis (four-chamber view)

LVOT, left ventricular outflow tract.

FIGURE 64-2 Normal cardiac anatomy. Steady-state free precession cine MR short-axis and horizontal long-axis images of the heart define the various cardiac regions affected by hypertrophic cardiomyopathy. A, Short-axis images. The left ventricle is divided into five equal segments—anteroseptal (AS), posteroseptal (PS), anterior free wall (AFW), lateral free wall (LFW), and posterior free wall (PFW). B, Horizontal long-axis images are divided into three segments—septum, apex, and free wall.

Asymmetric septal hypertrophy is the most common distribution of hypertrophy in HCM.¹ MRI readily demonstrates septal hypertrophy in patients with HCM (Fig. 64-3).¹¹ Other patterns, such as apical hypertrophy (Fig. 64-4), midventricular hypertrophy, concentric hypertrophy (Fig. 64-5), and right ventricular hypertrophy (Fig. 64-6) are also well visualized by MRI.¹⁵ In particular, the usefulness of MRI for apical HCM has been emphasized.¹⁶ Defining the location of hypertrophy is of clinical importance because some forms of HCM, such as apical HCM, have a more favorable prognosis and because treatment may depend on the distribution of hypertrophy.²

FIGURE 64-3 Asymmetric septal hypertrophy. Steady-state free precession cine MRI in the long-axis (A) and short-axis (B) planes demonstrate hypertrophy (arrows) of the interventricular septum, with a maximal thickness of 1.7 cm and septal-to-posterior wall ratio of 1.8.

FIGURE 64-4 Apical HCM. This axial black blood image shows hypertrophy of the apical region of the left ventricle, with a maximal thickness of 3.1 cm. A wall thickness of 1.5 cm or more indicates hypertrophy. The septum and free wall are within normal limits.

FIGURE 64-5 Concentric hypertrophy. This axial black blood MRI scan reveals hypertrophy of the entire left ventricle, with a septal thickness of 2.3 cm, apical thickness of 3.4 cm, and left ventricular free wall thickness of 2.7 cm.

FIGURE 64-6 Right ventricular involvement of HCM. Sagittal (A) and axial black blood (B) MRI scans images show marked RV hypertrophy (asterisks) and concentric left ventricular hypertrophy.

Ventricular mass can be used as a predictor of prognosis in patients with HCM.¹³ The myocardial mass can be calculated accurately with MRI (Fig. 64-7).¹⁷ Echocardiographically derived masses are the product of several measurements entered into a formula that relies on geometric assumptions regarding cardiac morphology. Given the variable nature of hypertrophy encountered with HCM, these assumptions are often incorrect and lead to erroneous mass values.¹⁴ Importantly, the interstudy reproducibility of left ventricular mass measurement with MRI is less than 5%,¹⁸ so MRI is the procedure of choice for monitoring left ventricular mass over time and in response to therapy.

FIGURE 64-7 Quantification of left ventricular mass. Myocardial mass is obtained by multiplying the myocardial volume by the myocardial specific gravity (1.05 g/mL). To estimate the myocardial volume of the left ventricle, cine MR images are selected at end-diastole from the cardiac apex to the cardiac base. The epicardium and endocardium are then outlined on each image. The area enclosed between the epicardium and endocardium is multiplied by the slice thickness, and the values are summed across the entire ventricle, yielding the total left ventricular volume. The normalized left ventricular mass (left ventricular mass index) equals mass divided by body surface area. In this 69-year-old woman, left ventricular mass = 149 g, left ventricular mass index = 55 g/m². Normal left ventricular mass index = 78 g/m² ± 17 g/m² in men and 61 g/m² ± 14 g/m² in women.

Cardiac Neoplasms

Focal hypertrophic cardiomyopathy can be difficult to distinguish from an intramural cardiac mass on echocardiography. MRI can be used to differentiate HCM from a neoplasm.^10,19 Images obtained using MR tagging can identify active myocardial contraction; whereas focal HCM may exhibit decreased systolic thickening or abnormal wall motion, the absence of identifiable contraction suggests a neoplasm.¹⁹ Gadolinium-enhanced MRI can also distinguish a cardiac mass from HCM (Fig. 64-8).¹⁰

FIGURE 64-8 Differentiation of cardiac neoplasm from septal hypertrophy. A, B, Asymmetric hypertrophic cardiomyopathy. A, Axial black blood MR image demonstrates septal thickening (arrow). B, Gadolinium-enhanced axial black blood image shows only mild enhancement of the septal wall (arrow), consistent with the diagnosis of hypertrophic cardiomyopathy. C, D, Angiosarcoma. C, Axial black blood MR image illustrates increased thickness of the septum (arrow). D, Gadolinium-enhanced axial black blood MR image demonstrates marked septal enhancement (arrow), consistent with neoplasm. Endomyocardial biopsy established the diagnosis of angiosarcoma.

Cardiac Function

MRI permits the quantitative analysis of cardiac function in patients with HCM. Compared with echocardiography, MRI assessment of cardiac function has the advantages of high reproducibility and operator independence. MRI is therefore ideal for patient monitoring. Stroke volume, ejection fraction, and cardiac output may all be calculated (Fig. 64-9). Although often clinically insignificant, mild diastolic dysfunction is the most common functional abnormality seen in HCM, often with an increased ejection fraction in the setting of decreased stroke volume and cardiac output.¹ Patients with end-stage HCM may exhibit systolic dysfunction caused by progressive myocardial fibrosis, which can cause ventricular wall thinning and dilation.²

FIGURE 64-9 Calculation of ejection fraction, stroke volume, and cardiac output. Shown are end-diastolic (A) and end-systolic (B) images from the cardiac apex to the base. These are cine MR images obtained in the short-axis plane. The endocardium is outlined on each image. The area that is outlined is multiplied by the slice thickness and summated across all the slice locations; the sum, from apex to base, yields the total ventricle chamber volume at end-systole and end-diastole. From these values, one can determine the stroke volume (end-diastolic volume minus end-systolic volume), ejection fraction (stroke volume divided by end-diastolic volume), and cardiac output (stroke volume multiplied by heart rate). In this patient, end-diastolic volume = 89 mL and end-systolic volume = 13 mL, stroke volume = 76 mL, ejection fraction = 86%, and cardiac output = 4.6 L/min. Normal ejection fraction for men = 69% and for women = 70%.²⁹

Abnormal wall motion may be noted in some patients with HCM. MRI scans obtained using myocardial tagging can demonstrate reduced wall motion in areas of hypertrophy and impaired systolic thickening.²⁰ Cine MR images can also be used to show impaired systolic thickening (Fig. 64-10).²¹

FIGURE 64-10 Impaired systolic thickening in HCM. End-systolic and end-diastolic images are selected at the region of maximal hypertrophy. Systolic thickening can be expressed as fractional thickening (end-systolic thickness/end-systolic thickness) or as a percentage ([end-systolic thickness − end-diastolic thickness]/end-diastolic thickness ). End-diastolic (A) and end-systolic (B) short-axis cine MR images at the cardiac base. A, Maximal end-diastolic septal wall thickness is 2.1 cm (white line). B, Maximal end-systolic septal thickness is 2.2 cm (white line). Fractional thickening = 1.1 and percentage thickening = 6%, which is markedly reduced. Normal septal thickening at the cardiac base is approximately 49%.

Myocardial Perfusion

MRI can be used to demonstrate impaired myocardial perfusion and perfusion reserve in patients with HCM.¹³ First-pass gadolinium MRI allows the direct visualization of impaired perfusion. First-pass images both before and after administration of coronary vasodilator agent are analyzed to determine perfusion reserve. First-pass gadolinium imaging has correlated decreased perfusion reserve to both the site and extent of ventricular hypertrophy.¹³

Viability

Delayed hyperenhancement MRI can be used to differentiate viable myocardial tissue from areas of fibrosis that presumably result from previous ischemia and infarction.¹⁴ Because gadolinium chelate contrast agent cannot cross cell membranes, it accumulates in regions of fibrosis because of slow distribution kinetics and expansion of extracellular space.^22,23 MRI performed 10 to 15 minutes following contrast agent administration may demonstrate this accumulation of gadolinium–diethylenetriamine penta-acetic acid (Gd-DTPA; Fig. 64-11). In HCM, delayed hyperenhancement has been shown in the most hypertrophied areas.¹⁴ Areas of delayed hyperenhancement exhibit reduced systolic wall thickening, an indicator of decreased myocardial function.²⁴ The presence and severity of delayed hyperenhancement in HCM may be related to a worse prognosis.

FIGURE 64-11 Delayed hyperenhancement in HCM. Gadolinium chelate contrast agent cannot cross cell membranes and therefore builds up in regions of fibrosis. To demonstrate delayed hyperenhancement, MRI scans are obtained approximately 10 to 15 minutes following the intravenous administration of gadolinium chelate contrast agent. A, B, Delayed hyperenhancement in asymmetric septal HCM. A, Cine MR image in the cardiac short-axis shows asymmetric septal hypertrophy, with maximum hypertrophy in the anterior interventricular septum and anterior free wall (asterisk). B, Delayed hyperenhancement image obtained 12 minutes after contrast administration in the same patient demonstrates persistent enhancement in the region of maximal hypertrophy (arrows). C, D, Delayed hyperenhancement in apical HCM. C, MR examination in the horizontal long axis illustrates a patient with apical hypertrophic cardiomyopathy (asterisk). D, Delayed hyperenhancement MRI scan obtained 10 minutes after contrast administration demonstrates delayed hyperenhancement at the cardiac apex (arrow).

(From Bogaert J, Goldstein M, Tannouri F, et al. Late myocardial enhancement in hypertrophic cardiomyopathy with contrast-enhanced MRI. AJR Am J Roentgenol 2003; 180:981-985.)

Coronary Flow Reserve

Abnormal coronary vasculature and a mismatch between myocardial mass and coronary circulation are thought to be responsible for impaired coronary flow reserve and intermittent myocardial ischemia.¹ The result of these processes is myocyte death, with subsequent fibrosis. The areas of scarring in the setting of acute ischemia, hypotension, or intense physical exertion may be the arrythmogenic substrate responsible for sudden cardiac death by ventricular tachycardia or ventricular fibrillation.¹

Quantification of coronary flow reserve is possible with MRI.²⁴ Velocity-encoded cine phase contrast MRI through the coronary sinus permits measurement of coronary flow. Patients with HCM have impairment of coronary flow reserve.²⁴

Left Ventricular Outflow Tract Obstruction

In patients with asymmetric septal HCM, left ventricular outflow tract obstruction can result from severe septal hypertrophy or systolic anterior motion of the anterior mitral leaflet. Patients with left ventricular outflow tract obstruction may suffer from angina, dyspnea, or syncope, even on minimal exertion. Identification of left ventricular outflow tract obstruction is an important clinical goal, because patients may benefit from invasive therapy such as septal myectomy or percutaneous septal wall ablation. The severity of outflow tract obstruction is reflected in the pressure gradient across the outflow tract. Surgical or transcathether septal myomectomy is often advocated when the pressure gradient is more than 30 mm Hg.⁶

Because of its high reproducibility and interobserver agreement, MRI is superior to echocardiography for patient monitoring in left ventricular outflow tract obstruction. This is especially true when the feasibility and subsequent efficacy of medical or surgical management must be evaluated. MRI can identify left ventricular outflow tract obstruction in a number of ways. Obstruction is frequently visualized on steady-state free precession cine MR images as a signal void, representing a high-velocity jet in the outflow tract (Fig. 64-12). MRI can directly depict the outflow tract region, and decreased outflow tract area in patients can be quantified.¹²

FIGURE 64-12 Left ventricular outflow tract obstruction. Signal void on cine MR images represents a high-velocity jet, implying a flow obstruction or stenosis. The blood in the area of the signal void moves out of the imaging plane too quickly to produce a signal. Asymmetric HCM often causes an obstruction in the left ventricular outflow tract, which causes a signal void on cine MRI scans. A, Left ventricular outflow tract cine MR image at late systole demonstrates a signal void (arrow) in the left ventricular outflow tract, proximal to the level of the aortic valve. B, Early diastolic image at the same level shows the location of the aortic valve (arrow).

Systolic anterior motion of the anterior mitral valve leaflet is the most common cause of left ventricular outflow tract obstruction in patients with septal HCM; it also leads to mitral regurgitation. Cine MR images in the horizontal long-axis plane can depict the anterior mitral leaflet adjacent to or near the septum in systole.²¹ Mitral regurgitation is visualized with MRI as a systolic signal void emanating from the mitral valve into the left atrium (Fig. 64-13).¹⁷ MRI can be used for qualitative or quantitative characterization of the severity of regurgitation.²⁵

FIGURE 64-13 Mitral regurgitation occurs in patients with asymmetric septal HCM as a consequence of systolic anterior motion of the mitral valve. The presence of mitral regurgitation also implies that a pressure gradient exists in the left ventricular outflow tract. Mitral regurgitation is seen on steady-state free precession cine MRI scans as a signal void that represents a high-velocity jet. In this patient, horizontal long-axis cine MRI scanning in early systole clearly demonstrates a signal void at the level of the mitral valve, extending into the left atrium (arrow).

Therapy

Invasive therapy for left ventricular outflow tract obstruction is considered when medical management has failed to control symptoms in patients with severe heart failure (NYHA Class III or IV) and a significant outflow tract pressure gradient.²⁶ Current options include surgical myotomy or myectomy of the septal wall and alcohol septal myocardial ablation.^1,26

Surgical myotomy or myectomy is a proven technique, with subjective improvement of symptoms in 70% of patients and a mortality of less than 2%. However, there are few centers skilled in these techniques, and many patients are not candidates for surgery given the advanced nature of their disease.¹ Following surgical myotomy or myectomy, MRI can verify improvement of outflow tract obstruction by demonstrating reduction of the signal void in the outflow tract and decrease of the systolic anterior motion of the mitral valve. Moreover, left ventricular function and mass can be measured and compared with presurgical values.

Alcohol septal myocardial ablation is a technique whereby a septal perforator branch of the left anterior descending artery is selectively catheterized and injected with ethanol, causing limited septal infarction.²⁷ Preliminary studies have shown that this technique has been successful, as judged by a reduction in the pressure gradient across the outflow tract and by symptomatic improvement.²⁸ MRI offers a useful method to evaluate patients selected for alcohol septal myocardial ablation (Fig. 64-14). A perfusion defect and delayed hyperenhancement are noted after treatment, clearly demonstrating the location and extent of infarcted myocardium. Hypokinesis of the septal wall is readily displayed on cine MR images following intervention.

FIGURE 64-14 MR evaluation of alcohol septal myocardial ablation. A, B, First-pass MRI. A, First-pass perfusion MRI performed before alcohol septal ablation demonstrates normal myocardial perfusion in the septal wall. B, Following septal ablation, a significant perfusion deficit is noted in the septal wall (arrowheads), depending on patient chosen). C, D, Delayed hyperenhancement MRI. C, MRI performed 10 minutes after administration of gadolinium chelate demonstrates no areas of enhancement before intervention, implying a normal, viable myocardium. D, There is dramatic late hyperenhancement in the septal wall (arrowheads) following alcohol septal ablation, indicating nonviable myocardium.

Angiography

Cardiac catheterization is also performed in cases of HCM, most often to address a particular clinical concern. Catheterization may be performed to determine the magnitude of outflow tract obstruction caused by septal hypertrophy by measuring pressures proximal and distal to the obstruction.¹² Also, catheterization is performed when invasive therapy, such as myectomy or percutaneous transluminal septal wall ablation, is being considered.¹³ Angiographic ventriculograms may reveal a characteristic deformity of the left ventricle at end-systole in some forms of HCM, such as the apical form.¹

SYNOPSIS OF TREATMENT OPTIONS

Surgical and Interventional

In patients with hypertrophic cardiomyopathy, surgical treatment via septal myectomy has traditionally been used.⁵ Percutaneous transluminal septal myocardial ablation with ethanol has shown promising success in the treatment of significant outflow obstruction.^9,10

KEY POINTS

Echocardiography is the initial imaging modality for the evaluation of HCM

MRI offers comprehensive assessment of the morphologic and functional characteristics of HCM.

The ability to delineate uncommon patterns and locations of hypertrophy is an advantage of MRI.

MRI is capable of delineating myocardial perfusion and viability, coronary flow abnormalities, and pre- and post-treatment evaluation