Hypertrophic cardiomyopathy (HCM) is a relatively common disorder estimated to affect between 0.2% and 0.5% of the global population.¹ The condition is characterized by abnormal thickening of the cardiac walls that leads to heart failure, atrial fibrillation, and sudden death due to ventricular arrhythmias. HCM has an autosomal-dominant etiology and results from a mutation in genes that encode for 1 of the 9 sarcomere proteins, leading to structural and functional abnormalities in myofibril and myocytes.^2,3

The common presentation types include obstructive HCM, which manifests as thickening of the interventricular septum, and nonobstructive HCM, which is characterized by thickening of the left ventricle. Both presentation types produce the same net effect of reduced blood flow from the heart to the rest of the body. Symptoms of both HCM types include dyspnea, angina, and syncope, and there is often a family history of sudden cardiac death.

HCM is highly heterogeneous with diverse pathophysiologies and clinical courses. In most patients, the presentation can be asymptomatic.¹

Given the availability of improved treatment options for symptomatic obstructive and nonobstructive HCM,^5,6 accurate diagnosis is critical. Several tools can be used for the diagnosis of HCM, but understanding of this disease is poor. Significant disparities in diagnosis reported across various demographic and socioeconomic groups may reflect a low index of suspicion for HCM in certain populations, resulting in missed opportunities for accurate diagnosis and treatment of this disease.⁷

Clinical Manifestation and Prevalence

Although the majority of patients with obstructive HCM are asymptomatic, a minority of patients experience symptoms and have clinical presentations that include chest pain, shortness of breath, fatigue, arrhythmias, dizziness, lightheadedness, swelling, and syncope.⁸

The symptoms result from increased demand for blood flow to the body as a result of the thickened heart muscle and alterations in the cardiac conduction system.⁵

A study by Maron and colleagues reported a prevalence of HCM of 2 per 1000 in the general adult population.⁹ This prevalence is consistent with reported estimates that in the United States, HCM affects between 600,000 and 1.5 million people.¹⁰ Although most patients present with HCM in their second or third decade of life, some may present between their fourth and sixth decades.³

Studies conducted in Germany and Korea show that the prevalence of HCM increases with age and that its incidence increases over time.^11,12 The study conducted in Germany used data from the Institute for Applied Health Research and found the prevalence of HCM among patients aged 0 to 9 years to be lower than that in patients 80 years of age and older (7.4 per 100,000 persons vs 298.7 per 100,000 persons). In all age categories, the prevalence of HCM was higher in men compared with women (Figure 1).¹¹

The study conducted in Korea, which evaluated data from the National Health Insurance Services database, found that among patients with newly diagnosed HCM, the total incidence rate increased steadily from 4.15 per 100,000 person-years in 2010 to 5.6 per 100,000 person-years in 2016; the incidence rate was approximately 1.7-fold higher in males throughout the study period compared with females (Figure 2).¹²

In the United States, although rates of diagnosis of obstructive HCM are higher among men (specifically White men), there are data supporting increased prevalence in women. There are also data indicating that women often present at an older age with worse symptoms and a higher risk of disease progression to heart failure or death.⁷ Traditionally, HCM was considered a condition most commonly responsible for sudden cardiac death in young athletes.¹³ Given that HCM can be asymptomatic during childhood, the diagnosis can be missed and individuals may die by sudden cardiac death.⁶

Patients diagnosed with HCM during childhood have been reported to have a higher annual mortality rate compared with patients diagnosed as older children or during middle or old age.^7,14,15  In one study, the annual sudden death mortality average in patients with HCM aged between 9 and 13.9 years was 7.2% compared with 1.7% in patients aged 16 years and older.¹⁴ Diagnosis of HCM in older children, young adults, or older individuals is associated with lower rates of sudden death.⁷

Although information from the HCM database in the United States suggests a lower rate of obstructive HCM among African American men (presumably because of lower rates of diagnosis), data from the National Collegiate Athletic Association (NCAA) show that African American basketball players who are men represent the most likely demographic to be affected by, and die from, obstructive HCM. Authors of a recent study suggest that there is a higher overall incidence of obstructive HCM among African Americans.⁷ The social determinants of health and healthcare — including income, education, insurance, and geography — may hinder access to services such as routine screening, diagnostic evaluation, and long-term follow-up.⁷

The healthcare cost of HCM is enormous. A study conducted in the United States using real-world population claims data found that the mean annual cost of healthcare resource utilization was approximately $20,000 higher for patients with obstructive HCM and approximately $35,000 higher for patients with symptomatic obstructive HCM compared with that of matched control groups without HCM.¹⁶ Over a 1-year follow-up period, mean healthcare costs for patients with HCM were nearly $37,000 higher than those of matched controls due predominantly to inpatient costs.¹⁶ Early diagnosis can reduce the economic burden of obstructive HCM.

Diagnosis of HCM

Early screening, prompt diagnosis, and ongoing monitoring of individuals with or at risk for obstructive HCM can improve health outcomes. In the United States, approximately 13% of an estimated 750,000 cases of HCM have been diagnosed.¹ Sometimes, diagnoses are incidentally being made after a heart murmur is detected during a physical examination or in a patient with abnormal findings on electrocardiogram (ECG) or a family history suggestive of the condition. Given that HCM is an inherited disorder, current evidence-based recommendations support genetic testing, including cascade testing of relatives. Individuals who are affected should be offered genetic counseling.¹

A diagnosis of HCM is based on medical and family history, physical examination, and diagnostic tests. The physical examination and family history are essential first steps in determining HCM signs, symptoms, or risk for HCM, with level of risk evaluated by identification of relatives who have HCM or associated conditions such as heart failure or cardiac arrest. The American Heart Association identifies several diagnostic tests for HCM.⁸

HCM is typically diagnosed using an echocardiogram to measure the thickness of the heart muscle and blood flow from the heart. Transesophageal echocardiogram may also be used, although this minimally invasive procedure involves insertion of a probe in the throat while the patient is under sedation.⁸

It is essential to determine whether obstruction is present in symptomatic patients, either at rest or during exertion. Comprehensive 2-dimensional and Doppler echocardiography are needed to identify the presence of an obstruction, as well as its location and severity.

A diagnosis of HCM is confirmed if left ventricular wall thickness is at least 15 mm and this thickness cannot be explained by other conditions such as hypertension, valvular problems, congenital disease, or infiltrative cardiomyopathies. The diagnosis can also be confirmed if left ventricular wall thickness is at least 13 mm in patients who are genotype-positive or are relatives of individuals with HCM.¹ It should be noted that although abnormal results seen on a 12-lead ECG are not specific for HCM, certain findings such as localized or widespread repolarization changes, prominent precordial voltages and left axis deviation, P-wave abnormalities, and inferior and/or lateral Q waves should raise suspicion for the disorder.¹ Cardiac magnetic resonance imaging (MRI) can provide superior morphologic and tissue characterization and volumetric assessment compared with ECG. Use of MRI may help to differentiate myocardial thickening due to HCM from thickening due to other causes, thereby guiding appropriate management.¹⁷ Cardiac MRI is recommended for¹⁸:

Differential Diagnosis

Myocardial thickening due to many causes may mimic HCM phenotypes. Systemic hypertension and aortic stenosis are the most common causes of acquired left ventricular hypertrophy that can be confused with HCM. Physiologic remodeling due to physical fitness can also manifest with left ventricular wall thickening; however, wall thickness rarely exceeds 15 mm in this setting. Furthermore, in physiologic remodeling, diastolic function is normal and left ventricular cavity sizes are generally larger compared with typical left ventricular cavity sizes in HCM.¹

Several conditions can mimic HCM (Table 1).¹⁷ The use of heart murmurs to differentiate HCM from non-HCM-related conditions is outlined in Table 2.^17,20 

Genetic Testing

Although genetic testing is not required for the diagnosis of HCM, testing for disease-associated genetic variants should be offered to patients who have an atypical presentation on screening or when another genetic condition is suspected. Genetic testing can also facilitate the identification of first-degree family members who may be at risk of developing HCM.¹ Next-generation sequencing technologies, despite their limitations, allow faster and increasingly affordable gene-based diagnostic tests that may help clinicians to differentiate HCM from mimics of the condition and thus potentially facilitate early identification of at-risk individuals for clinical evaluation and surveillance prior to disease onset.^1,21

Addressing Disparities in the Diagnosis of Obstructive HCM

Early diagnosis and management of obstructive HCM improves health outcomes and reduces the incidence of sudden cardiac death. The previously mentioned racial and gender disparities are rooted in the lack of robust data to confirm anecdotal evidence of higher rates of sudden cardiac death among African American men and other minority populations, as well as the worse HCM outcomes observed among women.⁶ Clinicians should have a high index of suspicion for an increased risk of obstructive HCM in specific populations and are recommended to increase the level of screening and diagnostic evaluations accordingly.

Summary

HCM is an inherited disorder, current evidence-based recommendations support genetic testing, and affected individuals should be offered genetic counseling.

The symptoms of obstructive HCM — including dyspnea, angina, and syncope — are associated with suboptimal left ventricular blood flow due to thickening of the ventricular wall. For diagnostic evaluation, it is essential to obtain a family history and perform a physical examination that includes echocardiography and an ECG. In some patients, cardiac MRI can provide additional diagnostic information to guide appropriate management.

Posted by Haymarket’s Clinical Content Hub. The editorial staff of Cardiology Advisor had no role in this content’s preparation.
                                                                                                                                  Reviewed January 2022