Hypertrophic cardiomyopathy: A complex disease
ABSTRACT
Hypertrophic cardiomyopathy (HCM) is a complex cardiovascular disease with wide phenotypic variations. Despite significant advances in imaging and genetic testing, more information is needed about the roles and implications of these resources in clinical practice. Patients with suspected or established HCM should be evaluated at an expert referral center to allow for the best multidisciplinary care. Research is needed to better predict the risk of sudden cardiac death in those judged to be at low risk by current risk-stratification methods.
KEY POINTS
- Obstruction of the left ventricular outflow tract is a key pathophysiologic mechanism in HCM.
- Because most of the genetic variants that contribute to HCM are autosomal dominant, genetic counseling and testing are suggested for patients and their first-degree relatives.
- Transthoracic echocardiography is the first-line imaging test, followed by magnetic resonance imaging.
- Beta-blockers are the first-line drugs for treating symptoms of HCM.
- An implantable cardioverter-defibrillator can be considered for patients at risk of sudden cardiac death.
- When medical therapy fails or is not tolerated in patients with severe symptoms of obstructive HCM, surgery to reduce the size of the ventricular septum can be considered. Alcohol septal ablation is an alternative.
Ambulatory electrocardiographic monitoring in all patients at diagnosis
Ambulatory electrocardiographic monitoring for 24 to 48 hours is recommended for all HCM patients at the time of diagnosis, even if they have no symptoms. Any evidence of nonsustained ventricular tachycardia suggests a substantially higher risk of sudden cardiac death.28,29
In patients with no symptoms or history of arrhythmia, current guidelines suggest ambulatory electrocardiographic monitoring every 1 to 2 years.9,21
Two risk-stratification models
The North American model was the first risk-stratification tool and considers 5 risk factors.9 However, if this algorithm were strictly followed, up to 60% of HCM patients would be candidates for cardioverter-defibrillator implantation.
The European model. This concern led to the development of the HCM Risk-SCD (sudden cardiac death), a risk-stratification tool introduced in the 2014 European Society of Cardiology HCM guidelines.30 This web-based calculator estimates a patient’s 5-year risk of sudden cardiac death using a complex calculation based on 7 clinical risk factors. If a patient’s calculated 5-year risk of sudden cardiac death is 6% or higher, cardioverter-defibrillator implantation is recommended for primary prevention.
The HCM Risk-SCD calculator was validated and compared with classic risk factors alone in a retrospective cohort study in 48 HCM patients.30 Compared with the North American model, the European model results in a lower rate of cardioverter-defibrillator implantation (20% to 26%).31,32
Despite the better specificity of the European model, a large retrospective cohort analysis showed that a significant number of patients stratified as being at low risk for sudden cardiac death were ultimately found to be at high risk in clinical practice.31 Further research is needed to find the optimal risk-stratification approach in HCM patients at low to intermediate risk.
GENETIC TESTING, COUNSELING, AND FAMILY SCREENING
Genetic testing is becoming more widely available and has rapidly expanded in clinical practice. Genetic counseling must be performed alongside genetic testing and requires professionals trained to handle the clinical and social implications of genetic testing. With this in mind, genetic testing can provide a definitive means of identifying family members at risk of HCM.
Given the autosomal dominant nature of HCM, screening for HCM is recommended in all first-degree relatives of an affected patient. Genetic testing may be a means to achieve this if a pathogenic mutation has been identified in the affected patient. However, serial electrocardiographic and transthoracic echocardiographic monitoring is an acceptable alternative in those without a clear genetic mutation association or in those who do not want to undergo genetic testing. If these first-degree relatives who do not undergo genetic testing are adult athletes or adolescents, they should undergo surveillance monitoring, with echocardiography and electrocardiography, whereas adults not participating in athletics should be monitored every 5 years.9,21
As genetic counseling and testing become more widely available, more patients are being found who harbor a mutation but have no phenotypic manifestations of HCM on initial presentation. Clinical expression varies, so continued monitoring of these patients is important. Expert guidelines again recommend serial electrocardiography, transthoracic echocardiography, and clinical assessment every 5 years for adults.9
Recent data suggest that up to 40% of HCM cases are nonfamilial, ie, their inheritance is sporadic with no known family history and no sarcomeric gene mutation evident on screening.33,34 The clinical course in this subgroup seems to be more benign, with later clinical presentations (age > 40) and lower risk of major adverse cardiovascular events.
MANAGEMENT
Conservative management
Asymptomatic HCM can usually be managed with lifestyle modifications.
Avoiding high-risk physical activities is the most important modification. All HCM patients should be counseled on the risk of sudden cardiac death and advised against participating in competitive sports or intense physical activity.35 Aerobic exercise is preferable to isometric exercises such as weightlifting, which may prompt the Valsalva maneuver with worsening of left ventricular outflow tract obstruction leading to syncope. A recent study showed that moderate-intensity aerobic exercise can safely improve exercise capacity, which may ultimately improve functional status and quality of life.36
Avoiding dehydration and excessive alcohol intake are also important in maintaining adequate preload to prevent an increasing left ventricular outflow tract gradient, given the dynamic nature of the left ventricular outflow tract obstruction in HCM.
