11 Cardiomyopathy pathology

Question 1

What is a cardiomyopathy?

Answer 1

• disease of the myocardium causing the heart to become enlarged and dilated, thickened and/or stiffened
• weakens the ehart causing it to become inefficient and incapable of pumping blood and maintaingin a normal rhythm
• can lead to heart failure, arrhythmia, or sudden death

**leading indication for heart transplant

Question 2

What are the 3 patterns of cardiomyopathy?

Answer 2

• dilated (DCM)
  
  • most common, 90%
• hypertrophic (HCM)
• restrictive (RCM)
  
  • least common

Question 3

Describe DCM

Answer 3

• most common cardiomyopathy, 90%
• primary indication for heart transplants
• onset usually 30-50 yo (widely variable)
• morphology:
  
  • cardiac dilation
  • contractile disfunction (both ventricles)
  • hypertrophy
  • eventually heart failure

Question 4

Describe the gross morphology of DCM

Answer 4

• 4 chamber dilation (wall thickness may be normal; hypertrophy followed by dilation)
• flabby
• mural thrombi (stagnation of blood)
• valves normal (possibly mitral/tricuspid regurg from dilation of chamber)

Question 5

Describe the histology of DCM

Answer 5

• Stainable iron overload
• No necrosis
• Not specific for DCM:
  
  • myocyte hypertrophy
  • intersitital and endocardial fibrosis (some stretched/irregular fibers)

Question 6

What are the clinical features of DCM?

Answer 6

• congestive heart failure
  
  • edema, orthopnea, paroxysmal nocturnal dyspnea
• reduced cardiac output
  
  • fatigue/dyspnea on exertion
• arrhythmias and/or conduction system disease
• thromboembolic disease
• imaging:
  
  • reduced ejection fraction
  • enlarged left ventricle
  • global hypokinesia

Question 7

What are some causes of DCM?

Answer 7

• ischemic injury (MI, coronary artery disease)
• alcohol/toxins
  
  • alcoholism/beriberi heart disease
  • doxorubicin
• infection
  
  • enteroviruses (e.g. coxsackie B)
• iron overload
• peripartum cardiomyopathy
  
  • multifactorial; pregnancy HTN, volume overload, gestational diabetes, immunologic responses

Question 8

What are the causes of DCM?

Answer 8

• idiopathic
• familial (2+ family members with idiopathic DCM)
  
  • 20-40% have genetic mutation
    (majority autosomal dominant)
  • 10-20% titin (TTN) gene mutation
  • extensive heterogeneity

Question 9

Describe hypertrophic cardiomyopathy

Answer 9

• leading cause of sudden cardiac death in young (<35 yo), esp in young athletes
• unexplained left ventricular hypertrophy in the absence of another cardiac or systemic disease (e.g. HTN, aortic stenosis)
  
  • disproportionate thickening of the septum
  • atrium enlarges due to decreased ventricular compliance

Question 10

Describe HCM histology

Answer 10

• Not specific for HCM:
  
  • marked hypertrophy
  • interstitial fibrosis

Question 11

What are the clinical symptoms of HCM?

Answer 11

**diverse symptoms with variable age of onset

• chest pain, exertional dyspnea, syncope
• A fib (+ mural thrombus formation)
• heart failure, unexpected SCD
• sudden death in young athletes
• majority= asymptomatic

Question 12

How do you diagnose HCM?

Answer 12

• noninvasive imaging (echo, cMRI)
• most commonly asymmetrical hypertrophy, but degree and location can vary
• +/- LVOT obstruction
• abnormal EKG

Question 13

Describe the genetics of HCM

Answer 13

• autosomal dominant (40-60% have identifiable mutation)
  
  • recall, only 10-20% for DCM
• MYH7= classic presentation (MYBPC3= late onset, TNNT2= mild/absent LVH but more arrhythmias/SCD)
• 6% caused by multiple mutations
  
  • more severly affected (severe LCH, rapid progression)
  • earlier onset

Question 14

What is ARVD/C?

Answer 14

• Arrhythmogenic right ventricular dysplasia/cardiomyopathy
• progressive disorder affecting the right ventricle
• characterized by transmural fibrofatty replacement of the myocardium

Question 15

How do patients typically present with AVRD/C?

Answer 15

Heart palpitations, syncope, and death

**4-22% of athletes with SCD

Question 16

Describe the morphology of AVRD/C

Answer 16

• thin and dilated right ventricular wall
• fatty infiltration and interstitial fibrosis

Question 17

How can you diagnose AVRD/C?

Answer 17

1. global/regional dysfunction or structural alterations (echo, MRI, RV angiogram)
2. tissue characterization (biopsy)
3. repolarizatino abnormalities (T wave inversion)
4. depolarization/conduction abnormalities (EKG changes)
5. arrhythmias (VT, PVCs)
6. family history (autosomal dominant disease of desmosomes)

Question 18

Describe the rare autosomal recessive forms of ARVD/C

Answer 18

**cardiocutaneous syndrome

• hyperkeratosis of the palms and soles
• wooly hair
• Plakoglobin (JUP) mutation; Naxos disease
• Desmoplakin (DSP) mutation: Carvajal syndrome
• cardiac phenotype= 100% penetrance by adolescence

Question 19

Describe restrictive cardiomyopathy

Answer 19

• RARE
• normal (or nearly normal) left ventricular wall thickness and ejection fraction
• primarily a disease in compliance
  
  • results in impaired ventricular filling in diastole
• overlaps with DCM and HCM

Question 20

Describe the gross morphology of RCM

Answer 20

• normal ventricles (size, wall thickness)
• bi-atrial dilation
• firm myocardium and interstitial fibrosis

(patchy/diffuse interstitial fibrosis on histology)

Question 21

What are the clinical features of RCM?

Answer 21

• congestive heart failure (right and left)
  
  • severe pulmonary and hepatic congestion
• similar S/S to constrictive pericarditis
• cardiac conduction disease, heart block resulting from focal fibrosis
• possible skeletal myopathy

Question 22

Describe the etiology of RCM

Answer 22

• idiopathic
• secondary to
  
  • post-radiation fibrosis
  • amyloidosis/sarcoidosis
  • metastases
  • Fabry/Pompe
• endomyocardial fibrosis (tropical/African, unknown cause)
• Loeffler eosinophilic endomyocarditis

Question 23

Describe the genetics of RCM

Answer 23

• mainly autosomal dominant
• overlap with HCM and DCM
• disease of the sarcomere, myofilaments
  
  • MYH7, TNNT2, TNNI3, ACTC

Question 24

Describe amyloidosis

Answer 24

• collection of diseases in which a protein-based infiltrate deposits in tissues as beta pleated sheets
• senile cardiac amyloidosis= most common
  
  • transthyretin (prealbumin) deposits in ventricles and atria
  • more common in african americans (4:1) >60 yo

Question 25

What are the clinical features of amyloidosis?

Answer 25

* heart failure, dyspnea, edema * presenting features= angina, syncope * non-specific poor appetite, weight loss * **renal dysfunction** (due to poor CO) * increased risk for cardiac thromboembolism

Question 26

Descibe the gross morphology of amyloidosis

Answer 26

* rubbery texture * interstitial eosinophilic deposition microscopically * **congo red stain** * apple green birefringence under polarized light

Question 27

Describe the genetics of amyloidosis

Answer 27

* mostly autosomal dominant * familial **transthyretin (TTR) amyloidosis** presents with... * neuropathy * cardiomyopathy * nephropathy * ocular (vitreous) disease * V122I variant (late onset in african americans)