Hypertrophic cardiomyopathy differential diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Soroush Seifirad, M.D.[2]

Overview

Cardiomyopathy must be differentiated from athlete heart (which is often confused with HCM on echocardiography), hypertrophy due to hypertension or aortic stenosis; as these have common clinical features, including thickened myocardium on imaging and high QRS voltage on EKGs. On the basis increased LV to aortic gradient, hypertrophic cardiomyopathy must be differentiated from sever volume depletion, subaortic stenosis, and valvular aortic stenosis.

Differentiating Hypertrophic cardiomyopathy from other Diseases

Cardiomyopathy must be differentiated from athlete heart (which is often confused with HCM on echocardiography), hypertrophy due to hypertension or aortic stenosis; as these have common clinical features, including thickened myocardium on imaging and high QRS voltage on EKGs. On the basis increased LV to aortic gradient, hypertrophic cardiomyopathy must be differentiated from sever volume depletion, subaortic stenosis, and valvular aortic stenosis.

Differentiating Hypertrophic cardiomyopathy from other diseases on the basis of increased LV to aortic gradient

On the basis increased LV to aortic gradient, hypertrophic cardiomyopathy must be differentiated from sever volume depletion, subaortic stenosis, and valvular aortic stenosis.

Sever volume depletion:

• These patients may develop hyperdynamic ventricular function in an effort to maintain cardiac output in the setting of normal LV systolic function.
• Here is the sequence of events in this setting:

• Hyperdynamic LV function
• Vigorous blood ejection at a higher velocity than normal
• An increased intracavitary gradient
• This may be mistaken for an increased LVOT gradient.

Subaortic stenosis:

• A congenital abnormality typically caused by a thin membrane of tissue in the LVOT
• Fixed subaortic stenosis can usually be distinguished from HCM and valvular AS by echocardiography or invasive cardiac catheterization.
• There is no systolic anterior motion of the mitral valve, and generally the ventricular wall thickness is normal. Nevertheless, chronic long-standing LV hypertension may finally lead to concentric LVH.
• The aortic valve leaflets are usually normal, but in decades these patients may develop aortic valve damage as well.

Valvular aortic stenosis:

• In addition to potentially causing LVH, narrowing of the aortic valve opening can lead to a significant pressure gradient between the LV and the aorta.
• similar to subaortic stenosis, valvular AS can be distinguished from other pathology by echocardiography or invasive cardiac catheterization.

Differentiating Hypertrophic cardiomyopathy from other diseases on the basis of hypertrophy

Cardiomyopathy must be differentiated from athlete heart (which is often confused with HCM on echocardiography), hypertrophy due to hypertension or aortic stenosis; as these have common clinical features, including thickened myocardium on imaging and high QRS voltage on EKGs.

Athlete's heart

Quite often, HCM can be mistaken for a condition known as athlete’s heart. Both involve the growth of the myocardium, however, the latter generally is not correlated with incidences of SCD. While HCM can be linked to family history, an athlete’s heart arises purely as a function of intense exercise (usually at least an hour a day, every day. Since the body is operating at high training levels, the heart adapts and grows in order to pump blood more efficiently. The stoppage of exercise for three months generally leads to a decrease in wall/septum thickness in those with an athlete’s heart, whereas those with HCM exhibit no decline.

People with an athlete’s heart do not exhibit an abnormally enlarged septum, and the growth of heart muscle at the septum and free ventricular wall is symmetrical. The asymmetrical growth seen in HCM results in a less-dilated left ventricle. This, in turn, leads to a smaller volume of blood leaving the heart with each beat.

	Athlete's Heart	HCM
Septum thickness	<15 mm	>15 mm
Symmetry	Yes (for septum and LV wall)	No (septum much thicker
Family history	None	Possibly
Deconditioning	Reduction within 3 months	None

Several criteria can be used to distinguish these two entities:

The degree of left ventricular wall thickness

• In athlete's heart the LVH is symmetric and less than or equal to 12 mm
• Rarely the LV thickness can be 14-16 mm and this makes it difficult to distinguish from HOCM. Athletes who engage in strength training may develop this pattern, athletes who engage in endurance training do not.
• If the degree of thickening is out of proportion to the type and intensity of exercise, this suggests HOCM

The pattern of left ventricular wall thickness

• Athleste's heart is symmetric
• HOCM is more often asymmetric, but may in some cases be symmetric

The left ventricular cavity size

• HOCM has smaller LV cavitary dimensions

Aortic stenosis

Aortic stenosis must be differentiated from other cardiac or pulmonary causes of dyspnea, weakness, and dizziness. Furthermore, when left ventricular outflow tract obstruction is present, it is critical to identify whether the obstruction is subvalvular, valvular or supravalvular and whether there is hypertrophic cardiomyopathy (HOCM) or not.

Differentiating Aortic Stenosis from other Diseases

Pulmonary Causes of Dyspnea

Aortic stenosis can be differentiated from pulmonary causes of dyspnea by the presence of:

• A narrow pulse pressure
• A harsh late-peaking systolic murmur heard best at the right second intercostal space with radiation to the carotid arteries
• A delayed slow-rising carotid upstroke (pulsus parvus et tardus)
• Signs of heart failure on examination

Aortic Sclerosis

While a murmur may be heard in aortic sclerosis, there is no fusion of the commisures and no significant obstruction to antegrade blood flow across the aortic valve. As a result, the S2 is normal in aortic sclerosis and the carotid upstroke is normal (i.e. pulsus parvus et tardus is absent).

Mitral Regurgitation

The murmur of aortic stenosis is harsh and best heard at the right second intercostal space while the murmur of mitral regurgitation is blowing, soft and best heard at the apex.

Hypertrophic Obstructive Cardiomyopathy

In HOCM the murmur is dynamic and varies with maneuvers. Moreover, there is a bifid or spoke and dome pattern of the carotid upstroke.

Valvular, Subvalvular and Supravalvular Aortic Stenosis

Differentiating Valvular Aortic Stenosis from Subvalvular Aortic Stenosis

Aortic insufficiency is more often present with subvalvular aortic stenosis (in 50% to 75% of cases). Symptoms associated with subvalvular aortic stenosis begin earlier in life (in childhood or adolescence) than symptoms associated with valvular aortic stenosis.

Differentiating Valvular Aortic Stenosis from Supravalvular Aortic Stenosis

Supravalvular aortic stenosis is an uncommon congenital anomaly caused by a narrowing in the ascending aorta or by the presence of a fibrous diaphragm just above the aortic valve. It presents in early adulthood. Although the aortic valve is not stenotic, doppler shows an increased pressure gradient. 50% of patients with supravalvular aortic stenosis have a characteristically greater pulse and systolic blood pressure in the right carotid and brachial arteries than in the left. The systolic murmur is maximal below the right clavicle and radiates primarily to the right carotid artery. There is not an ejection click nor a diastolic murmur.

Differentiating hypertrophic cardiomyopathy and valvular aortic stenosis

Diseases	Clinical manifestations						Para-clinical findings
	History and Physical examination
							Lab Findings		Echocardiography			Histopathology
	Murmur of AI	Pulse pressure after PVC	Valsalva maneuver	Carotid pulsation	Family history	Deconditioning	ECG	Gene mutations MYH7 TNNT2 TPM1	Aortic valve calcification	Dilated ascending aorta	Ventricular hypertrophy
Hypertrophic cardiomyopathy	No	Decreased	Increased intensity of murmur	Brisk, jerky, or bisferiens pulse (a collapse of the pulse followed by a secondary rise)	+	None	LVH* LAD Arrhythmia	Yes	No	Rare	Asymmetric Often involving the septum Septum thickness>15 mm	Myocardial disarray
Aortic stenosis	Common	Increased	Decreased intensity of murmur	Normal or tardus et parvus	+/-	None	LVH LAD	No	Common	Common	Concentric LVH	Hyperthrophy
Athlete's Heart	No	No	No	Normal	-	Reduction within 3 months	LVH	No	No	No	Symmetric Septum thickness<15 mm	Hyperthrophy

*A 12 lead EKG is strongly recommended at the time of the initial diagnosis of hypertrophic cardiomyopathy. Common findings on an EKG in these patients include tall R waves, deep Q waves, inverted T waves, ST segment abnormalities and 'strain pattern' in the chest leads. The deep Q waves indicate septal hypertrophy and similarly deeply inverted T waves indicate apical hypertrophy.

Other differential diagnoses

Hypertensive heart disease

• Long-standing HTN is the most common cause of LVH

• Most of the LVH due to HTN cases will present beyond adolescence when HCM is most commonly identified.
• The magnitude of hypertrophy seen in hypertension, however, rarely leads to wall thicknesses in excess of 1.5 cm.
• Hypertension is usually suspected in persons with an extended history of elevated blood pressures (10 or more years), particularly in those with other evidence of end-organ damage due to hypertension (eg, retinopathy, nephropathy).

Anderson-Fabry disease

(X-linked deficiency of the lysosomal enzyme alphagalactosidase)