Imaging in Hypertrophic Cardiomyopathy 

Hypertrophic cardiomyopathy (HCM) consists of genetically abnormal, usually hypercontractile and asymmetric myocardium that may obstruct output and cause sudden death if the hypertrophy is localized in the upper septum.

See the image below depicting hypertrophic cardiomyopathy.

The disease includes asymmetric septal hypertrophy and idiopathic hypertrophic subaortic stenosis (IHSS), but the term HCM is preferred because the majority (75%) of patients do not present with obstruction at rest,^[1] and 30% do not exhibit asymmetric hypertrophy.

Echocardiography

Two-dimensional echocardiography is the usual method of diagnosis. Echocardiography can be used to confirm the size of the heart, the pattern of ventricular hypertrophy, the contractile function of the heart, and the severity of the outflow gradient. It has the advantages of high resolution and no known risk. Criteria for echocardiographic diagnosis of hypertrophic cardiomyopathy (HCM) have been proposed.^[2] Initial studies of 3-dimensional echocardiography suggest that this technique is superior to 2-dimensional echocardiography for the evaluation of HCM.^{[3, 4]}

Echocardiography may at times be limited by poor acoustic windows, incomplete visualization of the left ventricular wall, and inaccurate evaluation of left ventricular mass. Echocardiography is less accurate than MRI in evaluating wall thickness, especially of the anterolateral LV; it is also less accurate in assessing regional wall motion abnormalities, aneurysms, and delayed enhancement.^[5]

Magnetic resonance imaging

The high contrast resolution of ECG-gated MRI provides excellent information about cardiac anatomy. Spin-echo MRI or cine magnetic resonance angiography (MRA) can be used to demonstrate ventricular anatomy and wall thickness. Cine MRA is used to evaluate ventricular function, ventricular end-diastolic and end-systolic volumes, valvular dysfunction, and outflow tract obstruction. In some cases, the signal intensity through the thickened myocardium varies.

A major development in MRI is myocardial tagging, which involves localized radiofrequency (RF) saturation of myocardial tissue before image acquisition to permit monitoring of the progressive distortion of the myocardial wall during the cardiac cycle.^[6] It can provide unique information about regional myocardial strain and function, and it is particularly useful in diseases with regional heterogeneity such as HCM.

Electrocardiography

Findings on 12-lead ECG are abnormal in 75-95% of HCM patients.^[7] Common abnormalities are LVH and widespread, deep, Q waves, which suggest an old myocardial infarction. Many patients have arrhythmias, both atrial and ventricular. ECGs are useful principally for suggesting the possibility of HCM in relatives of HCM patients and in athletes undergoing preparticipation screening.

Chest radiography

The cardiac silhouette can vary from normal to markedly enlarged in rare cases.

Thallium-201 myocardial imaging

This test, particularly with single photon emission CT (SPECT) for cross-sectional imaging, can be used to assess myocardial perfusion and the relative thickness of the IVS and free ventricular walls. Gated radionuclide ventriculography permits evaluation of ventricular size, ejection fraction, and septal and wall motion.

Positron emission tomography

This test can be used as an early diagnostic tool.

ECG-gated CT

This test can be used to evaluate the patterns of LVH and wall motion in HCM.

Cardiac catheterization and angiography

These can be performed to evaluate hemodynamic and morphologic abnormalities associated with HCM, along with associated coronary artery anomalies. However, these are invasive procedures and should be used only if other tests cannot provide adequate information or if alcohol ablation of septal branches is planned.

Electrophysiologic studies

The role of EPS in identifying HCM patients at risk of sudden death is controversial.^[8] The predictive value of inducible sustained ventricular arrhythmias during EPS is low.^[9]

Magnetic resonance spectroscopy

This is a tool for the evaluation of cardiac metabolism with direct measurement of ischemia-induced changes of high-energy phosphates and intracellular pH.^[10] The technique is still in the research phase.

Chest radiographic findings of hypertrophic cardiomyopathy are variable and nonspecific, but the clinical context may suggest HCM as the cause of cardiomegaly. The cardiac silhouette can be normal or enlarged. In most cases, cardiomegaly is due to left ventricular hypertrophy and/or left atrial enlargement.^[8] Significant mitral regurgitation leads to left atrial enlargement.

Electron-beam CT (EBCT) is an excellent method for observing irregular wall hypertrophy, apical morphology, and wall motion dynamics.^[11] This modality is seldom used, however, because it entails exposure to radiation and contrast medium and provides less information than MRI. The criterion for LV wall hypertrophy is an LV wall thicker than 13 mm. Right ventricular hypertrophy is considered when the right ventricular wall is thicker than 6 mm.

Wall thickening during systole can be calculated with EBCT. Most patients (71%) have decreased wall thickening at the hypertrophic site and normal or increased thickening at the nonhypertrophic site.^[11]

Late enhancement of the myocardium on EBCT has been reported in approximately 47% of HCM patients^[12] ; this finding suggests the presence of abnormal tissue with a capillary architecture different from that of normal myocardium. The degree of regional wall thickening also is significantly less in areas of late enhancement, which reflects the abnormal myocardial architecture.^[13]

Spin-echo MRI and cine MRA

Cardiac morphology can be evaluated by using either ECG-gated spin-echo MRI or cine MRA. The 2 most common views are 4 chamber and short axis.^[14] See the images below.

Spin-echo MRI can be used to accurately characterize the distribution and degree of myocardial hypertrophy. MRI correlates well with 2-dimensional echocardiography in demonstrating asymmetric septal hypertrophy, and MRI can visualize apical and posterolateral myocardial hypertrophy that is not always evident on 2D echograms.^[15] . MRI reliably provides accurate, comprehensive data that can be used to calculate hypertrophic scores.^[16]

The hypertrophy in HCM is usually asymmetric and is typically most evident in the anteroseptal myocardium.^[5] In patients with asymmetric septal hypertrophy, the basal IVS at end diastole is disproportionately thickened, and the ratio of IVS thickness to posterolateral wall thickness is significantly increased.

Patients with asymmetric septal hypertrophy also have decreased systolic myocardial thickening, probably due to disarray and disorganization of myocardial fibers.^[17] Long-axis MRIs accurately show the typical spade-shaped deformity of the LV cavity and the apical distribution of myocardial hypertrophy in patients with asymmetric septal hypertrophy.

With MRI, assessment of the thickness of the free wall of the right ventricle and measurement of right ventricular mass are possible; patients with HCM tend to have diffuse hypertrophy of the right ventricular wall and an increased right ventricular wall index.^[18] LV mass can be reliably estimated with spin-echo MRI, ECG-gated MRI, or multilevel cine MRA; however, LV mass, indexed to body surface area, is normal in about 20% of patients with HCM.^[19]

LVH in HCM often decreases the LV volume and increases the ejection fraction, without significantly changing stroke volume. Cine MRA can be used to calculate these parameters. If volume calculation is performed throughout the cardiac cycle, a time-volume curve can be obtained for more detailed functional analysis.

An obstruction of the LV outflow tract (LVOT) resulting in a subaortic pressure gradient can be detected on cine MRA as signal void (ie, an area of low signal intensity in regions where normal cardiac blood flow produces high signal intensity). Although areas of physiologic signal void can be seen on scans in healthy individuals, signal voids are larger and persist longer in the cardiac cycle in patients with pathologic conditions that cause obstruction.^[20] Differentiation of physiologic voids from pathologic ones is rarely difficult. See the image below.

Systolic anterior motion (SAM) of anterior mitral leaflet toward the IVS can be recognized on cine MRAs as a cause of LVOT obstruction. Mitral regurgitation is a common finding in patients with HCM and appears on cine MRAs as a signal void in the left atrium during ventricular systole. It may be associated with mitral valve prolapse (see the images below).

Although healthy individuals may have a small round area of physiologic signal void within the left atrium immediately behind and between the 2 mitral leaflets, in patients with pathologic conditions the signal void is larger and persists longer through ventricular systole. The area and extent of the signal void correlates closely with the grade of mitral regurgitation, as estimated with angiography and echocardiography.^{[7, 21, 22]}

Myocardial structural abnormality from fiber disarray and disorganization can result in abnormal signal intensity. Fattori et al reported areas of reduced signal intensity, probably due to myocardial fibrosis, in 16 (43%) of 37 unselected patients with HCM.^[23] This group also had higher maximum septal thickness (25 mm ± 7 vs 21 mm ± 6) and maximum posterior left wall thickness (15 mm ± 9 vs 7 mm ± 8). In patients with HCM, cine MRA also can be used to demonstrate nonuniform regional LV function (ie, LV asynchrony resulting in abnormal diastolic relaxation).

Cardiovascular MRI with gadolinium enhancement can detect myocardial fibrosis.^[24] Gadolinium hyperenhancement may correlate with progressive ventricular dilation and markers of sudden death.^[25]

Cardiac amyloidosis can resemble HCM; symmetric LV thickening is typical of amyloidosis but also occurs in HCM, and restrictive physiology and poor compliance may be present in both diseases.^[26] However, amyloidosis tissue may be characterized by its diffuse high signal intensity on T2-weighted spin-echo and short–inversion time inversion recovery (STIR) MRI. The signal intensity with echo times of 20 ms and 60 ms is significantly lower in cardiac amyloidosis than in HCM and in normal tissue.^[27] Poorer ventricular wall contractility and lower ECG voltages suggest amyloidosis, and a right atrial free wall > 6 mm thick is a specific marker for the disease.^[27]

Magnetic resonance spectroscopy

Contractile dysfunction in HCM is thought to result from alterations in myocardial metabolism. Proton-decoupled phosphorus-31 nuclear magnetic resonance spectroscopy depicts alterations of myocardial metabolism in asymptomatic patients with HCM.^[28] The ratio of phosphocreatine (PCr) to adenosine triphosphate (ATP) is significantly lower in HCM patients than in healthy control subjects.^[28] In addition, patients with severe hypertrophy of the IVS have a significantly increased inorganic phosphate (Pi)–to-PCr ratio compared with that of control subjects.^{[28, 29, 19]} Both abnormalities are similar to those found in ischemic myocardia. Also, significantly increased phosphomonoester (PME)-to-PCr ratios are present in patients with HCM; this finding indicates altered glucose metabolism.^[28] Myocardial pH is lower in patients with HCM relative to that of control subjects.^[19]

MRI myocardial tagging

MRI myocardial tagging can be used to quantify the severity and extent of subtle regional heart wall motion abnormalities. The 3 stages of myocardial tagging are: (1) placement of a saturation band pattern (either a grid or parallel tag lines) over the myocardium with spatially selective RF pulses; (2) MRI acquisition, during which tag motion is observed; and (3) detection of myocardial tag motion.

The motion of the saturation pattern is then used to compute the regional myocardial function. MR tagging techniques offer 2 fundamental improvements over echocardiography and nontagged MRI in regional function assessment: (1) The same volume of myocardium can be tracked throughout the heart cycle to map function in a specific region, and (2) precise quantitative estimates of myocardial shortening and wall thickening can be computed from the images. The position of a myocardial tag can be estimated within approximately 150 µm.

Maier et al found, with myocardial tagging, that the wall motion of the hypertrophied septum was significantly reduced in HCM,^[30] and Kramer et al showed depressed circumferential myocardial segment shortening in the septum and in the anterior and inferior regions.^[31] Three-dimensional analysis of tagged images showed that although circumferential and longitudinal ventricular strains were reduced in patients with HCM, the magnitude of the maximal contraction strain was reduced only in the basal septum and anterior walls.^[32] This finding suggests that a major portion of the mechanical work in HCM contributes to wall shearing and not cavity reduction. Dong et al reported that the myocardium in patients with HCM is heterogeneously thickened and that the fractional thickening and circumferential shortening of the abnormally thickened myocardium are reduced.^[33]

Echocardiography

A major criterion for the echocardiographic diagnosis of HCM is LV wall thickness of ³13 mm in the anterior septum or posterior wall or ³15 mm in the posterior septum or free wall, in the absence of LV dilatation or other cardiac and systemic causes of increased mass.^[2] However, no definitive criterion or single echocardiographic feature is pathognomonic for HCM.

The typical echocardiographic feature in HCM is hypertrophy of the septum and LV anterolateral free wall (see the images below); however, the degree and pattern of hypertrophy vary. Maximum hypertrophy of the septum often occurs midway between the base and the apex. On echocardiograms, asymmetric septal hypertrophy is defined as a ratio of septal thickness to posterior wall thickness of at least 1.3-1.5. Although the average LV wall is thicker than 20 mm (ie, almost twice the normal thickness), it can vary from 13-15 mm in mild hypertrophy to 50 mm in massive hypertrophy.^[34]

Often, the echocardiographic feature of a ground-glass appearance is noted either visually or by using quantitative texture analysis in both hypertrophied and nonhypertrophied regions of the ventricle.^[35] This feature can be used to distinguish HCM from other causes of secondary hypertrophy.^[36]

Another common echocardiographic feature in HCM is narrowing or obstruction of the LVOT caused by IVS and the anterior leaflet of the mitral valve. The abnormal geometry of LVOT results in a dynamic pressure gradient. Abnormal systolic anterior motion (SAM) of the anterior leaflet (see the images below) and, occasionally, the posterior leaflet of the mitral valve may be present; severe SAM, with septal-leaflet contact, has been proposed as a major diagnostic criterion.^[2] Mitral valve abnormalities in HCM patients include increased leaflet area, elongation of the leaflet, and anomalous insertion of papillary muscle directly into the anterior mitral leaflet.^[37] Recognition of these anatomic abnormalities during the preoperative assessment is important.

Other echocardiographic findings may include a small ventricular cavity, reduced septal motion and systolic thickening, normal or increased motion of the posterior wall, abnormal rate of closure of mitral valve in middiastole (secondary to decreased LV compliance or abnormal transmitral diastolic flow), mitral valve prolapse, and partial systolic closure or coarse systolic fluttering of the aortic valve (see the image below).

Approximately 70% of HCM patients have an LV outflow gradient of ³30 mm Hg (2.7 m/s by Doppler).^[38] Doppler ultrasonography can be used to accurately measure the gradient and to demonstrate the characteristic velocity profile due to dynamic outflow obstruction (see the image below). Distinguishing obstructive from nonobstructive forms of HCM, on the basis of the presence or absence of an LV outflow gradient, may be critical for the selection of management strategies.^[38] Although the gradient may be evident when the patient is at rest, in many cases it is latent and can be identified only with exercise.^[39]

Athlete's heart

In the vast majority of competitive athletes, the LV wall is £12 mm in thickness. Athletes with an LV wall thicker than 16 mm are likely to have pathologic hypertrophy such as HCM. For the minority of athletes whose LV thickness is in the "gray zone" of 13-15 mm, differentiation of physiologic from pathologic hypertrophy can be problematic. Maron et al published criteria that can help in this distinction.^[34] Echocardiographic features that suggest HCM are an unusual pattern of LVH, asymmetry, end-diastolic LV dimension < 45 mm, left atrial enlargement, and abnormal Doppler diastolic indices of LV filling. Other associated features suggestive of HCM are bizarre ECG findings, female sex, and family history of HCM. An end-diastolic LV dimension >55 mm suggests athlete's heart, as does regression of hypertrophy within 3 months after cessation of exercise.^[34]

Dilation of the LV chamber

LV chamber dilatation and systolic dysfunction occur in about 1.5% of patients of HCM per year.^[40] This dilatation can evolve into a phase resembling dilated cardiomyopathy.

Limitations

Prasad et al have reviewed the pitfalls in the echocardiographic diagnosis of HCM, which include the potential for both false-positive and false-negative readings.^[41]

Thallium-201 myocardial tests

²⁰¹ Tl myocardial tests, particularly those with SPECT, permit direct determination of the relative thickness of septum and free wall, and they may be useful in cases in which echocardiography is technically limited. Typically, Tl-enhanced images demonstrate a small LV cavity with marked Tl uptake in the hypertrophied myocardium.

Reversible perfusion defects (see the image below), which presumably reflect myocardial ischemia, are common in HCM without coronary artery disease.^[42] These defects are common in adult patients with HCM and in young patients with a history of syncope and sudden death.^[43] Fixed defects occur in patients with impaired systolic function and likely represent myocardial scarring. Also, technetium-99m–labeled perfusion agents can be used, with similar results.

Gated radionuclide ventriculography

Gated radionuclide ventriculography with bloodpool labeling permits evaluation of the size and diastolic filling of the ventricular cavity and of the motion of the septum and ventricular wall.

Myocardial scintigraphy

Myocardial scintigraphy with iodine-123– m -iodobenzylguanidine (¹²³ I-MIBG) demonstrates decreased uptake and increased clearance in the hypertrophied myocardium, and it has shown that cardiac sympathetic activity correlates with the degree of hypertrophy function in HCM patients.^[44] Scintigraphy results have proved useful for predicting prognosis in HCM.^[45]

Positron emission tomography

In Japanese patients, PET studies performed with¹²³ I-labeled 15-(p -iodophenyl)-3-R,S -methylpentadecanoic acid (BMIPP) suggest that fatty acid metabolism is impaired in areas of myocardium affected by HCM and that BMIPP studies may be useful in classifying HCM and assessing its severity.^[46]

Cardiac catheterization demonstrates decreased LV compliance and, in some patients, a subaortic systolic pressure gradient (see the image below). The pressure gradient may be labile, varying 0-175 mm Hg in the same patient under different conditions.

Increased myocardial contractility can worsen the gradient, particularly in patients with midventricular gradient, because of a direct muscular sphincteric action. Conversely, reduction in contractility or increases in preload or afterload (which increase the LV cavity size) reduce or eliminate the outflow gradient. This dynamic characteristic of HCM distinguishes it from other forms of ventricular outflow obstruction.

The arterial pressure tracing may demonstrate a spike-and-dome configuration. Approximately 25% patients have pulmonary hypertension, at least partly due to decreased LV compliance and elevated left atrial pressure. A right ventricular outflow tract pressure gradient occurs in 15% of patients who have LVOT obstruction, and this likely results from a markedly hypertrophied right ventricle.^[47]

Left ventriculography reveals a hypertrophied ventricle with vigorous ejection. The papillary muscles often are prominent, filling the LV cavity at the end of systole.

In patients with apical involvement, extensive hypertrophy may result in a spadelike configuration of the LV cavity.^[48] Associated mitral regurgitation may be present. Simultaneous right ventriculography in cranially angulated left anterior oblique projections can be performed for optimal evaluation of the IVS. The left septal surface is flat or it bulges into the LV cavity at its middle or lower portion, in contrast to the normal curve toward the right ventricle. See the images below.

Coronary angiographic findings usually are normal, but images may show myocardial bridging. The distance between the coronary arteries on the epicardial surface and the ventricular cavity is increased, indicating myocardial hypertrophy.