Diagnosis of Hypertrophic Cardiomyopathy: What Every Cardiologist Needs to Know

Anjali Tiku Owens, MD; Nosheen Reza, MD


May 22, 2020

Hypertrophic cardiomyopathy (HCM) is the most common inherited monogenic cardiac disorder, affecting 0.2-0.5% of the population.[1,2] In the United States, 750,000 people are estimated to have HCM; however, only approximately 100,000 people have been diagnosed, signifying a large gap in the recognition and understanding of this disease.[3] As diagnostic and therapeutic paradigms for HCM continue to evolve, cardiovascular clinicians will need to become familiar with the diagnosis of this condition.

History and Physical Examination

Often, patients with HCM remain asymptomatic or mildly symptomatic,[3] and present to medical attention after identification of a suggestive family history, detection of a murmur on physical examination, or an abnormal electrocardiogram (ECG). The most commonly reported symptoms include dyspnea, fatigue, chest discomfort, palpitations, presyncope, and syncope. Important historical clues include progressive exertional intolerance and lightheadedness or syncope during or immediately following exertion or when dehydrated.

A multigeneration family history should be elicited at initial evaluation focusing on relatives with any cardiac diagnoses, "thick" hearts, "heart attack" or stroke early in life, abnormal heart rhythms, permanent pacemakers or implantable cardiac defibrillators, heart failure, or heart transplantation. Reported history of sudden death should trigger focused questions regarding relatives with premature or unexpected death, death associated with exertion, and availability of autopsy or postmortem genetic testing.

On physical examination, the presence of a harsh crescendo–decrescendo systolic murmur at the lower left sternal border, a mid–late systolic apical murmur or holosystolic apical murmur, and/or paradoxically split S2 should alert clinicians to the possibility of HCM.

Making the Diagnosis

The diagnosis of HCM is confirmed with the presence of a left ventricular wall thickness of ≥15 mm that is otherwise unexplained by abnormal loading conditions (e.g., hypertension, valvular, congenital disease) or infiltrative cardiomyopathies. Unexplained left ventricular wall thickness of ≥13 mm is sufficient for diagnosis in relatives of individuals with HCM or those who are genotype positive. The basal septum is the most common location for hypertrophy, and multiple other patterns of asymmetric hypertrophy (reverse septal curvature, sigmoid septum, neutral septum, midventricular, apical) are also seen.

The presence, location, and mechanism of left ventricular obstruction should be identified with serial continuous-wave Doppler interrogation from the left ventricular apex to the base, with care taken to avoid cross-contamination of the left ventricular outflow gradient and mitral regurgitation signals when systolic anterior mitral valve motion is present. The left ventricular outflow tract gradient should be measured at rest. If the peak instantaneous continuous-wave Doppler gradient is <50 mm Hg, then provocative measures including the Valsalva maneuver during rest echocardiography or exercise during treadmill stress echocardiography may elicit a gradient.[4] A peak instantaneous continuous-wave Doppler gradient of ≥30 mm Hg at rest indicates obstructive physiology, and a gradient of ≥50 mm Hg either at rest or with provocation is considered the threshold for septal reduction therapy in symptomatic patients.

Whereas the abnormalities seen on 12-lead ECG are not specific for HCM, findings such as localized or widespread repolarization changes (including T-wave inversions), prominent precordial voltages and left axis deviation (suggestive of ventricular hypertrophy), P-wave abnormalities (suggestive of left atrial enlargement), and inferior and/or lateral Q waves (suggestive of hypertrophied septal depolarization) should raise suspicion for the disorder.

Cardiac magnetic resonance imaging (MRI) provides superior morphologic and tissue characterization and volumetric assessment compared with echocardiography. Cardiac MRI is recommended in: 1) patients for whom echocardiography is inconclusive for making the diagnosis of HCM; and 2) patients with known HCM for whom additional information regarding magnitude and distribution of hypertrophy or anatomy of the mitral valve apparatus would be helpful in decision making regarding septal reduction therapy.[4] Large prospective studies regarding prognostic utility of contrast-enhanced MRI in sudden death risk stratification are ongoing.[5]

Differential Diagnosis

Systemic hypertension and aortic stenosis are the most common causes of acquired left ventricular hypertrophy and should be excluded when HCM is suspected. Physiologic remodeling due to fitness can also manifest with left ventricular wall thickening but can usually be differentiated from HCM by using a combination of imaging and functional testing. With physiologic remodeling, left ventricular wall thickness rarely exceeds 15 mm and left ventricular cavity sizes tend to be larger compared with the typical left ventricular cavity sizes in HCM.[6] Diastolic function, including tissue Doppler measurements, should be normal in cases of physiologic remodeling.

Genetically mediated phenocopies of HCM (e.g., Anderson-Fabry disease [GLA], Danon disease [LAMP2], Pompe disease [GAA], AMPK-mediated glycogen storage disease [PRKAG2], amyloidosis [TTR], Friedreich ataxia [FRDA], myotonic dystrophy [DMPK, ZNF9]) should be considered in the initial evaluation of left ventricular hypertrophy. Patterns of inheritance, multiorgan (especially neurologic, musculoskeletal, renal) involvement, and ECG characteristics such as pre-excitation are useful to differentiate HCM from these disorders.[7]

Genetic Testing and Screening

Patients who undergo genetic testing should also undergo counseling by someone knowledgeable in the genetics of cardiovascular disease so that results and their clinical significance can be appropriately reviewed with the patient. Although genetic testing is not required for diagnosis of HCM, testing for causal/disease-associated genetic variants should be offered to the index patient (i.e., proband) if there is an atypical presentation or when another genetic condition is suspected. In current practice, commercial genetic testing companies typically offer targeted genetic sequencing of 50-100 genes associated with cardiomyopathy.

Genetic testing is also reasonable to facilitate identification of first-degree family members at risk for developing HCM. If a genetic variant causal for HCM is identified in the proband and affected relatives, relatives who do not carry the familial variant can be dismissed from ongoing clinical screening. If genetic testing is not performed or if a causal variant is not identified in the proband, ongoing periodic clinical surveillance of relatives with electrocardiography and echocardiography every 3-5 years is recommended.


Patients with HCM have a wide range of presentation, from asymptomatic with a suggestive family history, murmur, abnormal ECG, or echocardiogram to heart failure symptoms from outflow tract obstruction or restrictive physiology to sudden cardiac death. Echocardiography is the key to diagnosis and MRI may play a future role in sudden death risk stratification. Assessment for genetically mediated phenocopies or physiologic remodeling due to fitness is essential because these diagnoses would alter management. As understanding of the genetic underpinning of HCM grows, genetic testing may offer more insight and should always occur in concert with genetic counseling so that patients and family members can best appreciate the ramifications of the findings.


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