Cardiomyopathy Overview and Key Concepts

Cardiomyopathy Overview

• Cardiomyopathy is a heterogeneous group of diseases affecting the myocardium, leading to:
  • Cardiac dysfunction
  • Arrhythmias
  • Heart failure
  • Sudden cardiac death (SCD)

Learning Outcomes

1. Understand macro and micro differences of main cardiomyopathies.
2. Characterize Hypertrophic Cardiomyopathy (HCM) based on:
   • Morphological aspects
   • Molecular genetic basis
   • Pathogenesis

Classification of Cardiomyopathies

• Primary Cardiomyopathy (causes: genetic, acquired, or mixed)
• Secondary Cardiomyopathy (acquired, develops due to another health condition)

Types of Primary Cardiomyopathies

• Dilated Cardiomyopathy (DCM)
• Restrictive Cardiomyopathy (RCM)
• Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)
• Hypertrophic Cardiomyopathy (HCM)

Dilated Cardiomyopathy (DCM)

• Characterized by:
  • Thinning of heart muscle
  • Left ventricular (LV) dilation
  • Impaired systolic function
• Most cases are familial with autosomal dominant inheritance.

Clinical Features of DCM:

• Reduced exercise capacity
• Fatigue
• Dyspnea
• Paroxysmal nocturnal dyspnea
• Abdominal bloating

Pathophysiology:

• Diffuse inflammation and degeneration of myocardium leading to ventricular dilation.
• Resulting in cardiomegaly and impaired systolic function.

Restrictive Cardiomyopathy (RCM)

• Heart muscle rigidity, preventing relaxation and filling with blood.
• Characteristics include:
  • Reduced diastolic function, with normal systolic function.
  • Can be familial or associated with other health problems.

Clinical Features of RCM:

• Fatigue
• Exercise intolerance
• Dyspnea
• Syncope
• Palpitations

Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)

• Defined by progressive replacement of myocardium with adipose and fibrous tissue, disrupting electrical signals in the heart.
• Most cases are inherited with autosomal dominant transmission.

Hypertrophic Cardiomyopathy (HCM)

• Characterized by thickening of the heart muscle (wall thickness ≥ 15 mm in adults).
• Prevalence ranges from 1:200 to 1:500 globally, most common in individuals aged 30s.

Types of HCM:

1. Obstructive HCM (HOCM)
2. Non-obstructive HCM

Symptoms of HCM:

• Arrhythmia
• Chest pain
• Fatigue
• Fluttering sensation in the chest
• Heart murmur,
• Dizziness
• Fainting
• Shortness of breath
• Swelling in extremities

Complications:

• Risks include arrhythmias, heart failure, and sudden cardiac death (SCD).
  • SCD is often caused by dangerously fast heartbeats and is the most common cause of SCD in individuals under 35 without prior symptoms.

Molecular Genetic Basis of HCM

• Caused by mutations in over 1,400 genes related to cardiac sarcomere proteins, including:
  • MYH7 (β-Myosin heavy chain)
  • MYBPC3 (cardiac myosin binding protein C)
• MYH7 is located on chromosome 14q11-12 and is integral for muscle function.

MYH7 Gene Function:

• Encodes β-Myosin heavy chain, facilitating the actin-myosin interaction essential for muscle contraction and relaxation.

MYBPC3 Gene:

• Located on 11p11.2, it influences calcium-activated actomyosin sliding and muscle contractility.

Pathogenesis of HCM

• HCM is linked to increased cytosolic Ca²+ sensitivity and modifications to sarcomeric proteins leading to LV hypertrophy and potentially heart failure.

Summary of Cardiomyopathy Prevalence

Additional Notes

• Understanding the genetic and functional alterations is critical in diagnosing and managing cardiomyopathies effectively.