Hypertrophic Cardiomyopathy Workup

Updated: Jan 05, 2016
  • Author: Sandy N Shah, DO, MBA, FACC, FACP, FACOI; Chief Editor: Henry H Ooi, MD, MRCPI  more...
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Approach Considerations

Two-dimensional (2-D) echocardiography is diagnostic for hypertrophic cardiomyopathy (HCM). In general, a summary of echocardiography findings includes abnormal systolic anterior leaflet motion of the mitral valve, LV hypertrophy, left atrial enlargement, small ventricular chamber size, septal hypertrophy with septal-to-free wall ratio greater than 1.4:1, mitral valve prolapse and mitral regurgitation, decreased midaortic flow, and partial systolic closure of the aortic valve in midsystole.

No specific laboratory blood tests are required in the workup of HCM; however, routine laboratory tests may assist in the evaluation of the etiology and/or exacerbating factors contributing to the LV dysfunction. Genetic testing is not widely available at present, but it is becoming increasingly available in this disease setting. In research situations or in larger pedigrees, genotyping is informative for the identification of additional family members once the proband's genotype has been determined.


Laboratory Studies

First-line laboratory tests are similar in adults and children. [14]  Routine laboratory studies may aid in the evaluation of the etiology and/or exacerbating factors underlying the left ventricular (LV) dysfunction.

  • Hemoglobin level: Anemia exacerbates chest pain and dyspnea
  • Fasting glucose levels
  • Renal function tests: Impaired renal function may be seen with severe LV dysfunction
  • Liver function tests (LFT)
  • Brain natriuretic peptide (BNP), N-terminal proBNP (NT-proBNP), and troponin T levels: Elevated BNP, NT-proBNP, and troponin T levels are associated with a higher risk of cardiovascular events, heart failure, and death
  • Thyroid function tests: In patients on amiodarone, thyroid studies should be obtained at the time of diagnosis and monitored every 6 months 

Additional laboratory tests can be performed after a specialist evaluation, as needed.


Two-Dimensional Echocardiography and Doppler Studies

As stated, 2-D echocardiography is diagnostic for hypertrophic cardiomyopathy (HCM). Color Doppler flow studies typically reveal mitral regurgitation. [15]

Spectral continuous-wave Doppler studies in patients with obstructive HCM reveal an elevated flow velocity across the LV outflow tract. Severe obstructive HCM typically has a flow velocity greater than 4 m/s, and a gradient across the LV outflow tract of greater than 50 mm Hg is considered severe.

Echocardiography also typically reveals diastolic dysfunction with reduced LV compliance and a mitral valve ratio of E wave to A wave of less than 1 (usually < 0.8). Systolic function is typically well preserved and normal, and, in fact, the LV ejection fraction is usually normal or high at the time of diagnosis. The LV diameter is at the lower limit of normal or smaller than normal.

A study by Peteiro et al suggests that assessing exercise capacity and LV systolic function during exercise echocardiography may aid in determining the risk stratification among patients with hypertrophic cardiomyopathy. [16]

Tissue Doppler imaging is quite useful as a screening tool in patients with morphologically normal ventricles and in differentiating HCM from other causes of LV hypertrophy (ie, athletic heart hypertrophy).

The hallmarks of the obstructive type of HCM consist of systolic anterior motion of the anterior mitral valve leaflet, septal wall thickness of >15 mm, and asymmetrical septal hypertrophy with a ratio of septal wall thickness to posterior wall thickness of greater than 1.4:1.

The septum not only is relatively thicker than the posterior wall, it is also typically at least 4-6 mm thicker than normal for each age group. Massive hypertrophy with septal wall thickness of greater than 25 mm has been noted in rare cases, particularly in infants with glycogen storage defects, as are observed in patients with Pompe disease.

An unusual echocardiographic pattern consisting of a ground-glass appearance has been noted in portions of the hypertrophied myocardium in some patients. This pattern may be related to the abnormal cellular architecture and myocardial fibrosis that have been observed in pathologic studies.

A narrowing of the LV outflow tract occurs in many patients with HCM. This contributes to the creation of a pressure gradient in a small number of patients.

The hallmark of HCM associated with a pressure gradient is the abnormal systolic motion of the anterior leaflet of the mitral valve (ie, systolic anterior motion) and, in rare cases, the systolic motion of the posterior leaflet.

Several other echocardiographic findings may be present in patients with HCM. For example, a small LV cavity may be present secondary to marked hypertrophy of the myocardium and encroachment into the LV cavity. Moreover, reduced septal motion and thickening during systole may occur, particularly of the upper septum, resulting from disarray of the myofibrillar architecture and abnormal contractile function.

The motion of the posterior wall may be normal or increased, and the rate of closure of the mitral valve in middiastole may be reduced secondary to a decrease in LV compliance or abnormal transmitral flow during diastole. In addition, mitral valve prolapse, a rare echocardiographic occurrence in HCM, may be present.

Partial systolic closure or, more commonly, coarse systolic fluttering of the aortic valve related to turbulent blood flow in the outflow tract may occur. Abnormalities in diastolic function may be demonstrated by echocardiography and Doppler recordings in approximately 80% of patients with HCM, independent of the presence or absence of a systolic pressure gradient.

The presence of mitral regurgitation virtually always is confirmed by Doppler echocardiography in patients with HCM who have a systolic gradient.


Chest Radiography and Radionuclide Imaging

Chest radiography

Chest radiograph (CXR) findings are variable. The cardiac silhouette may range from normal to markedly increased in size. Left atrial enlargement frequently is observed, especially when significant mitral regurgitation is present. This is manifested by a "double-density" appearance on CXR.

Radionuclide imaging

Radionuclide imaging with thallium or technetium may show reversible defects, mostly in the absence of coronary artery disease. Thallium or technetium scintigraphy may reveal defects in myocardial perfusion, even in the setting of angiographically normal coronary arteries.

These reversible defects evident on radionuclide scanning are more common in children and adolescents with a history of sudden death or syncope, which suggests that myocardial ischemia is a significant factor in the mechanism of the demise of younger patients with HCM.


Cardiac MRI

Cardiac MRI imaging is very useful in the diagnosis and assessment of hypertrophic cardiomyopathy (HCM), with ideal image quality covering both ventricles completely for localization of hypertrophy. Cardiac MRI is particularly useful when echocardiography is questionable, particularly with apical hypertrophy.

Cines, oriented in the plane of the LV outflow tract, typically show obstruction, and velocity mapping is useful in the assessment of peak velocities. Systolic anterior motion of the mitral valve is clearly seen on cardiac MRI.

Improvement in obstruction after septal ablation or myomectomy can be demonstrated, as can the location and size of the associated infarction, which are useful for planning repeat procedures.

Cardiac MRI tagging identifies abnormal patterns of strain, shear, and torsion in cases of HCM, demonstrating significant dysfunction in hypertrophic areas of the ventricle. Cardiovascular MR spectroscopy reveals bioenergetic defects in HCM patients with varying genetic mutations, a fact that supports the hypothesis that the underlying substrate for HCM may be inefficient energy utilization.

The accuracy of the phenotypic determination of HCM by cardiac MRI is helpful for family screening, and genetic linkage studies for causative mutations are improved in power.

The use of gadolinium contrast in cardiac MRI is very useful in differentiating HCM from other causes of cardiac hypertrophy and other types of cardiomyopathy, such as amyloidosis, athletic heart, and Fabry disease (alpha-galactoside deficiency).

Late gadolinium enhancement occurring in HCM represents myocardial fibrosis. The greater the degree of late gadolinium enhancement, the more likely that the particular HCM patient has 2 or more risk factors for sudden death and the more likely the patient has or will develop progression of ventricular dilation toward heart failure, thereby indicating a poorer prognosis.

Most patients with HCM have no gadolinium enhancement; a common benign pattern is 2 stripes running along the junction of the right ventricle insertion into the left ventricle.

More extensive gadolinium enhancement can be dense and plaquelike or diffuse. The greater the gadolinium enhancement, the higher the risk of heart failure or sudden death, presumably from reentrant tachycardias and systolic failure from myocyte replacement.

Fabry disease (alpha-galactoside deficiency), which occurs in approximately 4% of HCM patients, often shows unusual lateral wall gadolinium enhancement on cardiac MRI.



Common electrocardiographic findings include ST-T wave abnormalities and LV hypertrophy. Other findings observed on ECG include axis deviation (right or left), conduction abnormalities (P-R prolongation, bundle-branch block), sinus bradycardia with ectopic atrial rhythm, and atrial enlargement. One mutation has been identified that is associated with hypertrophic cardiomyopathy (HCM) and Wolff-Parkinson-White syndrome.

Uncommon findings include an abnormal and prominent Q wave in the anterior precordial and lateral limb leads, short P-R interval with QRS suggestive of preexcitation, atrial fibrillation (poor prognostic sign), and a P-wave abnormality, including left atrial enlargement.

Findings on Holter monitoring and event electrocardiography commonly include atrial and ventricular ectopy, sinus pauses, wandering atrial pacemaker, atrial tachycardia, atrial fibrillation and/or flutter, and nonsustained ventricular tachycardia.

Comprehensive cardiovascular MRI examination can find the presence of scar and may be a good independent predictor of all-cause and cardiac mortality in low or asymptomatic patients with HCM. [17]


Cardiac Catheterization

Although not required for the diagnosis of hypertrophic cardiomyopathy, a diagnostic cardiac catheterization is useful to determine the degree of outflow obstruction, cardiac hemodynamics, the diastolic characteristics of the left ventricle and LV anatomy, and, of particular importance, the coronary anatomy. Cardiac catheterization is also reserved for situations when invasive modalities of therapy, such as a pacemaker or surgery, are being considered.

Therapeutic cardiac catheterization interventions, utilized in well selected cases of hypertrophic cardiomyopathy, include transcatheter septal alcohol ablation to relieve the LV outflow obstruction by intentional infarction of a portion of the interventricular septum.

Cardiac catheterization frequently reveals diminished diastolic LV compliance and, in cases of obstructive hypertrophic cardiomyopathy, a systolic intracavitary pressure gradient within the body of the left ventricle, related to subaortic systolic anterior motion of the mitral valve abutting the markedly hypertrophied septum. The subaortic pressure gradient may be quite labile and may vary between 0 and 175 mm Hg in the same patient under different conditions.

The arterial pressure tracing found on cardiac catheterization may demonstrate a "spike and dome" configuration similar to the carotid pulse recording. As a consequence of diminished left ventricular compliance, the mean left atrial pressure and, particularly, the a wave, in the left atrial pressure pulse and left ventricular end-diastolic pressures are usually elevated.

Artifactual outflow gradients may occur if the left ventricular catheter becomes entrapped in the trabeculae of a markedly hypertrophied left ventricle.

Cardiac output may be depressed in patients with long-standing severe gradients, but in the majority of patients, it is normal. Occasionally, cardiac output is elevated in patients with markedly hyperdynamic LV systolic function.

Hemodynamic abnormality in hypertrophic cardiomyopathy (HCM) is not limited to the left side of the heart. Approximately one fourth of patients demonstrate pulmonary hypertension. It is usually mild, but in some cases, it can be moderate to severe, due (at least in part) to elevated mean left atrial pressures resulting from diminished LV compliance. A pressure gradient in the right ventricular outflow tract occurs in approximately 15% of patients who have obstruction to LV outflow and appears to result from markedly hypertrophied right ventricular tissue. Right atrial and right ventricular end-diastolic pressures may be slightly elevated.

Outflow gradient variability

A feature characteristic of HCM is the variability and lability of the LV outflow gradient. A patient may demonstrate a large gradient on one occasion and have none at another time. In some patients without a resting gradient, it may be temporarily provoked.

Three basic mechanisms involved in the production of dynamic gradients include increased contractility, decreased preload, and decreased afterload. In many patients with HCM, the gradient is midventricular and may be intensified by increased contractility, which exerts a direct muscular sphincter action.

The stimuli that provoke or intensify LV outflow tract gradients in HCM generally improve myocardial performance in normal subjects and in patients with most other forms of heart disease. Conversely, reductions in contractility or increases in preload or afterload, which increased LV dimensions, reduce or abolish the LV outflow gradient.

One of the most potent stimuli for enhancing the LV outflow gradient is postextrasystolic potentiation, which may occur after a spontaneous premature contraction or be induced by mechanical stimulation with a catheter. The resultant increase in contractility in the beat after the extrasystole is so marked that it produces an increase in the outflow gradient. A characteristic change often occurs in the directly recorded arterial pressure tracing, which, in addition to displacing a more marked spike and dome configuration, exhibits a pulse pressure that fails to increase as expected or actually decreases (the so-called Brockenbrough-Braunwald phenomenon).

This is one of the more reliable signs of dynamic obstruction of the LV outflow tract. In some patients, the postextrasystolic murmur is attenuated despite an increase in the outflow gradient, apparently because, in this setting, the murmur mirrors to a greater degree changes in the severity of mitral regurgitation than changes in the outflow tract gradient.

Left ventriculography

Left ventriculography typically shows a hypertrophied ventricle and the presence of an outflow gradient. The anterior leaflet of the mitral valve moves anteriorly during systole and encroaches on the outflow tract. Associated with this motion is mitral regurgitation, which is a constant finding in patients with gradients. The LV cavity is often small, and systolic ejection is typically vigorous, resulting in virtual obliteration of the ventricular cavity at end systole. In patients with apical involvement, the extensive hypertrophy may convey a spade-like configuration to the left ventricular angiogram.

Other findings

In patients older than age 45 years, obstructive coronary artery disease may be present, although the symptoms of ischemic pain are indistinguishable from those of patients with normal coronary angiograms and HCM. The left anterior descending and septal perforator coronary arteries may demonstrate phasic narrowing and associated abnormalities of flow during systole


Electrophysiologic Studies

A diagnostic electrophysiology study using programmed electrical stimulation may identify conduction abnormalities, sinus node dysfunction (SND), and the potential for inducible arrhythmias.

The prognostic correlation of inducible arrhythmias with spontaneous clinical arrhythmias and/or sudden death is not entirely clear. Several studies have shown a relationship between electrophysiologic results and risk stratification for sudden cardiac death, but other studies have not been able to demonstrate a direct relationship.


Histologic Findings

Myocardial hypertrophy and gross disorganization of the muscle bundles result in a characteristic whorled pattern; cell-to-cell disarray and disorganization of the myofibrillar architecture within a given cell occur in almost all patients with hypertrophic cardiomyopathy (HCM).

Fibrosis is prominent and may be extensive enough to produce grossly visible scars. Abnormal intramural coronary arteries, with a reduction in the size of the lumen and thickening of the vessel wall, are common in patients with HCM, occurring in more than 80% of cases. This abnormality most frequently occurs in the ventricular septum and accompanies extensive fibrosis in the affected walls of the heart.