Overview
Definition:
Hypertrophic Cardiomyopathy (HCM) is a genetic heart muscle disease characterized by unexplained left ventricular hypertrophy (LVH) in the absence of other causes like hypertension or valvular disease
It is a leading cause of sudden cardiac death (SCD) in young athletes and a common cause of heart failure in adults
Genetic mutations in sarcomeric proteins are the primary cause, leading to myocyte disarray, fibrosis, and diastolic dysfunction.
Epidemiology:
HCM affects approximately 1 in 500 individuals worldwide
It is the most common inherited cardiac condition
In pediatrics, the prevalence is similar, though diagnosis can be delayed due to less pronounced symptoms
Autosomal dominant inheritance is most common, with a 50% risk of transmission to offspring
However, incomplete penetrance and variable expressivity are significant challenges in screening.
Clinical Significance:
Identifying individuals with a family history of HCM is crucial for early diagnosis, risk stratification, and timely intervention to prevent life-threatening complications such as ventricular arrhythmias, heart failure, and SCD
Proactive screening allows for genetic counseling, lifestyle modifications, and pharmacological or device-based therapies to improve outcomes and reduce mortality in affected families.
Screening Approach
Family History Taking:
A detailed family history is paramount, inquiring about known cases of HCM, unexplained sudden death (especially in young individuals or athletes), syncope, dyspnea, chest pain, or palpitations in first-degree relatives (parents, siblings, children) and other relatives
Specific attention should be paid to the age of onset and cause of death
Family pedigrees are invaluable tools.
Risk Stratification:
Based on family history, a tiered approach to screening is employed
Affected relatives of a known HCM patient are considered high risk
Individuals with a personal history of unexplained syncope, exertional dyspnea, or those experiencing SCD at a young age in the family should also be prioritized
Absence of symptoms does not exclude disease due to variable expressivity.
Genetic Testing:
Targeted genetic testing for known familial mutations is the most efficient approach if a pathogenic variant has been identified in a family member
If no familial mutation is known, broad gene panel testing encompassing sarcomeric protein genes (e.g., MYH7, MYBPC3, TNNT2, TPM1) can be considered
Genetic counseling is essential before and after testing.
Regular Surveillance:
For individuals identified as at-risk due to family history, regular clinical surveillance is recommended
This typically includes annual clinical evaluations with ECG and echocardiography to detect cardiac remodeling and functional changes early
The frequency and intensity of surveillance may be adjusted based on age, genetic status, and clinical findings.
Clinical Presentation In Pediatrics
Symptoms:
Many affected children are asymptomatic, especially in early stages or with milder forms
When symptomatic, presentations can include: exertional dyspnea
chest pain, especially with exertion
syncope or pre-syncope
palpitations
fatigue
exercise intolerance
in infants, poor feeding or failure to thrive.
Signs:
Physical examination may reveal: a harsh systolic ejection murmur, often loudest at the left sternal border, which may increase with Valsalva maneuver and decrease with squatting
An S4 gallop
JVP may be elevated in severe cases
Pulsus alternans may be present in advanced heart failure.
Diagnostic Criteria:
Diagnosis of HCM is based on identifying LVH by echocardiography (maximal wall thickness ≥15 mm in adults, or ≥12 mm in individuals <16 years old with a family history, or ≥10 mm in infants/children with a family history) unexplained by other causes
Genetic testing confirming a pathogenic variant in sarcomeric genes further supports the diagnosis, even with milder hypertrophy.
Diagnostic Approach
History Taking:
Crucial elements include detailed family history of HCM, SCD, arrhythmias, syncope, and unexplained deaths
Personal history of similar symptoms, exercise tolerance, and any previous cardiac evaluations are essential
Red flags include unexplained syncope or near-syncope, particularly with exertion
a family history of SCD at <50 years
and presence of a murmur.
Physical Examination:
Focus on cardiovascular examination: palpation for heaves and thrills
Auscultation for murmurs (note characteristics, maneuvers affecting intensity), gallops (S3, S4), and respiratory sounds
Assess for peripheral edema and signs of poor perfusion
Check for any dysmorphic features suggestive of genetic syndromes.
Investigations:
1
Electrocardiogram (ECG): May show LVH, ST-T wave abnormalities, deep Q waves (mimicking infarction), or arrhythmias
Not specific but can raise suspicion
2
Echocardiography: The cornerstone of diagnosis, demonstrating LVH, assessing diastolic function, septal morphology, LV outflow tract (LVOT) obstruction, and identifying any coexisting valvular abnormalities
3
Cardiac Magnetic Resonance Imaging (CMR): Useful for detailed characterization of LVH, fibrosis assessment, and differentiating HCM from other causes of LVH
4
Holter Monitoring: For detecting arrhythmias, especially ventricular tachycardia, which is a risk factor for SCD
5
Exercise Stress Testing: To assess for exercise-induced LVOT obstruction, arrhythmias, or exertional symptoms
6
Genetic Testing: Crucial for confirming diagnosis and facilitating cascade screening in family members.
Differential Diagnosis:
Conditions to rule out include: athlete's heart, hypertensive heart disease, valvular aortic stenosis, Fabry disease, Danon disease, mitochondrial myopathies, amyloidosis, and other storage diseases
Differentiating features include family history, genetic testing, and specific imaging characteristics.
Management Strategy
Goals Of Care:
Primary goals are to alleviate symptoms, prevent SCD, and improve quality of life
Management is individualized based on symptom severity, presence of LVOT obstruction, arrhythmia burden, and risk factors for SCD.
Medical Management:
Beta-blockers (e.g., propranolol, metoprolol) are first-line to reduce heart rate and myocardial contractility, thereby decreasing LVOT obstruction and symptoms
Calcium channel blockers (e.g., verapamil, diltiazem) may be used, especially if beta-blockers are not tolerated or effective, but caution is advised in the presence of significant LVOT obstruction
Antiarrhythmic drugs (e.g., amiodarone) may be used for significant arrhythmias
Diuretics are used cautiously for heart failure symptoms, avoiding dehydration which can worsen LVOT obstruction.
Device Therapy:
Implantable Cardioverter-Defibrillators (ICDs) are indicated for primary or secondary prevention of SCD in patients deemed at high risk, based on established criteria (e.g., unexplained syncope, significant sustained ventricular arrhythmias, LV wall thickness >30 mm, family history of SCD, abnormal blood pressure response to exercise).
Surgical And Interventional Procedures:
Myectomy (surgical reduction of septal hypertrophy) or alcohol septal ablation (percutaneous transluminal septal myocardial ablation) are considered for symptomatic patients with significant LVOT obstruction refractory to medical therapy
Septal myectomy is generally preferred in younger patients.
Lifestyle Modifications:
Avoiding strenuous competitive sports is often recommended, especially for individuals with significant LVH, LVOT obstruction, or a history of arrhythmias or syncope, to reduce the risk of SCD
Patients should be encouraged to maintain moderate physical activity
Genetic counseling and education about the disease are vital for the patient and family.
Complications
Arrhythmias:
Atrial fibrillation, ventricular tachycardia, and ventricular fibrillation can lead to syncope, heart failure, and SCD
These are particularly common in patients with significant hypertrophy, fibrosis, and a history of syncope.
Heart Failure:
Diastolic dysfunction is a hallmark of HCM, leading to progressive heart failure symptoms
Systolic dysfunction can occur in late stages, especially in the presence of significant fibrosis or previous myocardial infarction.
Sudden Cardiac Death:
The most feared complication, often occurring during or after strenuous physical exertion in individuals with unrecognized or inadequately managed HCM
Factors increasing risk include young age, extensive hypertrophy, LVOT obstruction, arrhythmias, syncope, and family history of SCD.
Prevention Strategies:
Strict adherence to medical management, appropriate use of ICDs in high-risk individuals, judicious risk stratification, and personalized recommendations regarding physical activity are key preventive measures
Regular follow-up with experienced cardiologists specializing in HCM is essential.
Prognosis
Factors Affecting Prognosis:
Prognosis varies widely and is influenced by age of onset, severity of hypertrophy, presence of LVOT obstruction, degree of fibrosis, occurrence of arrhythmias, family history of SCD, and response to therapy
In pediatrics, earlier onset and more severe hypertrophy often portend a poorer prognosis.
Outcomes With Management:
With early diagnosis, appropriate management, and regular surveillance, many individuals with HCM can lead long and relatively normal lives
Risk stratification and timely intervention, particularly ICD implantation in high-risk patients, significantly reduce the incidence of SCD
Symptomatic relief is often achievable with medical therapy.
Follow Up Recommendations:
Lifelong follow-up is necessary for individuals with HCM
This typically includes annual or biannual clinical evaluations, ECG, and echocardiography
For children and young adults, follow-up is often more frequent and may include Holter monitoring, stress testing, and genetic testing of family members
Transition of care to adult cardiology services should be seamless.
Key Points
Exam Focus:
Remember that HCM is the most common inherited cardiac disease and a leading cause of SCD in young adults/athletes
Autosomal dominant inheritance is typical
Screening of family members of affected individuals is critical
Key investigations are ECG and ECHO
Management aims to control symptoms and prevent SCD
ICDs are crucial for risk stratification.
Clinical Pearls:
Always ask about family history of sudden death, especially in young individuals
A murmur that increases with Valsalva is highly suggestive of LVOT obstruction in HCM
Be cautious with vasodilators and diuretics in patients with LVOT obstruction as they can worsen it
Genetic counseling is a vital part of managing HCM families.
Common Mistakes:
Mistaking HCM for athlete's heart or secondary LVH
Underestimating the risk of SCD in asymptomatic individuals with family history
Failing to perform adequate family screening
Incorrect risk stratification for ICD implantation
Inadequate follow-up and surveillance.