Makindo Medical Notes

Related Subjects: |Dilated Cardiomyopathy |Hypertrophic cardiomyopathy (HCM - HOCM) |Peripartum cardiomyopathy |Restrictive Cardiomyopathy |Takotsubo Cardiomyopathy

Hypertrophic Cardiomyopathy (HCM) may first present during adolescence with cardiac arrest or sudden cardiac death. This condition involves various genetic mutations. If no mutation is identified within a family, it is essential to screen first-degree relatives using ECG and echocardiography.

About

• Characterized by left ventricular hypertrophy (LVH) with a maximal wall thickness >15 mm.
• Primarily results in diastolic dysfunction, as the stiffened ventricle struggles to fill adequately.
• Increased risk of supraventricular tachycardia (SVT) and ventricular tachycardia (VT), occurring in about 1 in 500 adults.
• Differentiating HCM from aortic stenosis can be clinically challenging due to overlapping features.

Aetiology

• HCM can be sporadic or inherited, with autosomal dominant transmission being the most common pattern.
• Involves mutations in cardiac sarcomere proteins, affecting the contractile function of the heart muscle.
• Rare cases can have autosomal recessive, X-linked recessive, or de novo mutations.

Genetics

• HCM is associated with mutations in at least 10 different sarcomeric protein genes, which include:
  • Beta-Myosin Heavy Chain (MYH7)—one of the most common mutations.
  • Myosin Binding Protein C (MYBPC3)—also frequently mutated.
  • Other mutations involve alpha-tropomyosin, cardiac troponin T, cardiac troponin I, titin, and actin.
• Genetic testing can help identify specific mutations, guiding family screening and risk assessment.

Pathology

• HCM is characterized by myocyte disarray (disorganized cardiac muscle cells), myocyte hypertrophy, and interstitial fibrosis.
• Septal hypertrophy is common and can lead to obstruction of the left ventricular outflow tract (LVOT).
• Apical hypertrophy is more common in Japan and can result in different clinical presentations.

Septal Hypertrophy

The degree of outflow obstruction and hypertrophy does not reliably correlate with the risk of sudden cardiac death (SCD).

Associations

• Mitral valve prolapse
• Phaeochromocytoma
• Noonan's syndrome, Wolff-Parkinson-White (WPW) syndrome

Clinical Presentation

• Often asymptomatic, detected during family screening or after an event in a relative.
• Symptoms include:
  • Exertional chest pain (angina)
  • Palpitations due to arrhythmias
  • Jerky pulse; only 20% have LVOT obstruction.
  • Exertional dyspnoea due to diastolic dysfunction.
  • Syncope or pre-syncope, particularly during physical activity.
  • Sudden cardiac death, especially in young athletes.

Risk Factors for Sudden Cardiac Death (SCD)

Complications

• Symptomatic LVH with progressive diastolic dysfunction
• Arrhythmias (atrial fibrillation, malignant ventricular arrhythmias)
• Refractory heart failure
• Sudden cardiac death

Examination Findings

• Irregular pulse if atrial fibrillation is present.
• JVP may show a prominent 'a' wave due to stiff atrial contraction.
• Double or triple apical impulse.
• Pan-systolic murmur due to mitral regurgitation.
• Late systolic murmur due to LVOT obstruction, which becomes louder with standing or Valsalva and softer with squatting.

Investigations

• ECG: Findings may include deep T wave inversion, ST changes, "pseudo-infarction" Q waves, LAD, and LVH. May also show left or right atrial enlargement.
• Transthoracic Echo: Identifies:
  • Asymmetrical septal hypertrophy (ASH), mitral regurgitation (MR).
  • Systolic anterior motion (SAM) of the mitral valve.
  • Diastolic dysfunction, including restrictive filling patterns.
• Cardiac MRI: Offers detailed imaging of myocardial structure and assessment of fibrosis (LGE).
• Coronary Angiography: To exclude coronary artery disease in symptomatic patients.

ECG Example

Pharmacologic Management

• Beta-blockers: First-line therapy for symptom relief, especially for exertional angina and dyspnoea.
• Calcium Channel Blockers: Verapamil is often used when beta-blockers are contraindicated.
• Disopyramide: An antiarrhythmic with negative inotropic effects, useful for reducing LVOT gradients.
• Avoid vasodilators, diuretics, and high-dose nitrates in HCM with LVOT obstruction, as they can exacerbate obstruction.

Non-Pharmacologic Management

• Septal Myectomy: Surgical removal of part of the hypertrophied septum to relieve severe LVOT obstruction.
• Alcohol Septal Ablation: A catheter-based procedure to reduce septal thickness using a controlled myocardial infarction.
• Implantable Cardioverter-Defibrillator (ICD): Recommended for high-risk patients to prevent SCD.

Lifestyle Modifications

• Avoid competitive sports and intense physical exertion, which can trigger arrhythmias or SCD.
• Regular follow-up to monitor disease progression and adjust treatment as needed.
• Genetic counseling and family screening are important for first-degree relatives.

Screening for Families with Known HCM

• Genetic testing for known mutations, as some are associated with a higher risk of SCD.
• If no known mutation is identified, first-degree relatives should undergo ECG and echocardiography.
• Children of affected parents should be screened every 3 years until puberty, and then annually until age 20.
• If no HCM is identified by early adulthood, it is unlikely to develop later in life.

References

• ACC/AHA Hypertrophic Cardiomyopathy Guidelines
• ESC Guidelines on Hypertrophic Cardiomyopathy