Cardiomyopathy Flashcards
Define the Frank-Starling law wih regards to cardiomyocytes
Frank-Starling Law
- An optimal separation of cardiomyocytes is necessary for an optimal strength of contraction
Define cardiomyopathy
- Heterogeneous group of myocardial diseases
- Associated with mechanical and/or electrical dysfunction
- Absence of ischaemic, valvular, hypertensive, or congenital heart disease
- Primary (heart only) - genetic/acquire
- Secondary (systemic disease) - e.g., amyloidosis
mech/e =lose ability to pump effectively
Describe elements of the presentation of someone with cardiomyopathy
- Syncope
- Heart failure
- Thromboembolism
- Chest pain
- Arrhythmias
- Fatigue
- Shortness of breath
- Sudden death
Describe classification of cardiomyopahties
WHO
Primary Cardiomyopathies:
- Dilated Cardiomyopathy (DCM)
- Hypertrophic Cardiomyopathy (HCM)
- Restrictive Cardiomyopathy (RCM)
- Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)
- Unclassified – LV noncompaction, mitochondrial myopathies, etc.
-
Cardiomyopathies secondary to systemic conditions
Cardiomyopathies (CM) – lots of causes
- CARDIAC INFECTIONS: Viruses (e.g., Coxsackie B, Parvo, Enterovirus), Others (Chlamydia, rickettsia, bacteria, etc)
- TOXINS: Alcohol, Cobalt, Arsenic, Adriamycin, trastuzumab, Lithium, Catecholamines, etc., Chronic renal failure
- METABOLIC: Hyper/hypothyroidism, Hyper/hypokalemia, Vitamin deficiency, Hemochromatosis, malnutrition, OBESITY
- NEUROMUSCULAR / STORAGE DIS: Friedreich’s ataxia, metabolic storage diseases, Amyloidosis
- Arrhythmia (tachycardia)-induced
- INFILTRATIVE: Sarcoidosis, Radiation-induced fibrosis
- IMMUNOLOGICAL: Myocarditis, Post-transplant rejection, autoimmune diseases
- Pregnancy/peri-partum/post-partum
- Stress: Takotsubo CM
GENETIC mutations can be defects of the cytoskeleton, contractile proteins, or mitochondrial oxidative phosphorylation. Frequently inherited in an autosomal dominant fashion, but X-linked, mitochondrial, or autosomal recessive inheritance seen
Briefly describe dilated cardiomyopathy
- 90% of all CM
- Progressive Cardiac dilatation + hypertrophy (4-chamber)
- Systolic/contractile dysfunction
- Dilatation present for many years
- Presentation with Congestive Heart Failure
Describe the main causes of dilated cardiomyopathy
- GENETIC
- 20-50%
- usually due to mutations in genes for cytoskeletal proteins (dystrophin, laminin, etc.). May be associated with skeletal muscle dystrophies like Duchenne MD
- IDIOPATHIC
- ALCOHOL or other toxins e.g., Adriamycin
- PREGNANCY (+/-Reversible)
- INFECTIONS (Myocarditis-Coxsackie B, Enterovirus)
- IRON OVERLOAD (hemochromatosis/ multiple transfusion)
List possible DDxs for dilated cardiomyopathy
- Ischemic heart disease
- Valvular heart disease
- Congenital heart disease
Describe the fross appearance of dilated cardiomyopathy
Dilated Cardiomyopathy- Gross Appearance
- Large, globular, flabby, heavy heart with dilated chambers, especially ventricles
- Ventricular wall thickness decreased, normal, or increased with mural thrombi
- Subendocardial scars in some
- No significant abnormality of coronary arteries or valves
Describe the histology of dilated cardiomyopathy
- Not specific!
- Most muscle cells hypertrophic with enlarged nuclei, as well as stretched, irregular, and attenuated myocytes
- Variable interstitial and endocardial fibrosis and scarring
pathology is not specific to dilated cardiomyopathy
THEREFORE close clinicopathologic correlation is essential
Describe the clinical features and complications of dilated cardiomyopathy
- Mural thrombi - embolism
- Ventricular arrhythmias
- Congestive heart failure
- Functional valvular dysfunction/incompetence
Briefly describe hypertrophic cardiomyopathy and the genetics
- 1/500 incidence
- Most common cause of sudden cardiac death in young adults
- Genetic causes (50% family history, AD» )
- Hallmark: diastolic dysfunction, preserved systolic function (myocardial hypertrophy)
- 1/3 of cases- intermittent ventricular outflow obstruction
- Often First Diagnosed At Autopsy
Genetics Of Hypertrophic Cardiomyopathy
For interest only
- >100 mutations described, usually in genes coding for sarcomeric proteins (unlike DCM)
- Most common- β Myosin Heavy Chain (70-80%)
Describe the gross pathology of hypertrophic cardiomyopathy
- Massively enlarged and heavy
- Left ventricular hypertrophy (relative RV sparing)- asymmetric septal hypertrophy, often prominent in the subaortic region
- Impaired diastolic filling (atrial dilation)
- Outflow obstruction with LV outflow plaque (endocardial fibrosis due to anterior MV leaflet thickening)
- Thickened septal vessels
List possible DDxs for hypertrophic cardiomyopathy
- DDx:
- Hypertensive heart disease, Amyloidosis, Aortic stenosis
Describe the histology of hypertrophic cardiomyopathy
-extreme myocyte hypertrophy and myocyte disarray-
- Haphazard disarray of bundles of myocytes
- Individual myocytes in a tangled and pinwheel configuration
- Disarray of contractile elements within cells
- Interstitial fibrosis and sometimes scarring
- Intramural coronary artery abnormalities with thickened walls (media disorganization)
Describe the clinical features and complications of hypertrophic cardiomyopathy
- Arrhythmias: Atrial Fibrillation, Ventricular arrhythmias
- Symptoms: Syncope/dizziness (especially during exercise)
- Mural thrombi
- Myocardial ischemia
- Sudden death
Briefly describe the management and treatment of hypertrophic cardiomyopathy
antiarrhythmic drugs, myomectomy, septal ablation, pacemakers, implantable defibrillators, transplant
Describe restrictive cardiomyopathy
- Least common type
- Stiff ventricles causing increased intraventricular pressure and impaired ventricular filling during diastole
- Presents with heart failure but paradoxically normal-sized heart (biatrial dilatation)
Note: Important To Differentiate From HCM or Constrictive Pericarditis
Describe the causes of restrictive cardiomyopathy
Causes
- Idiopathic
- Infiltrative myocardial diseases: Amyloidosis, Sarcoidosis, Radiation fibrosis
- Endomyocardial diseases: Loeffler’s endomyocarditis (eosinophilia), Endomyocardial fibrosis, Endomyocardial fibroelastoses
Describe the pathology of restrictive cardiomyopathy
- Ventricular wall thickness and cavity size often normal
- Atrial dilatation with thrombi may be seen
- Myocardium is firm
- Microscopically, patchy or diffuse interstitial fibrosis
- Disease-specific histology is usually seen
- Modified Trichrome stain (Mallory Azan): marked interstitial fibrosis of cardiac muscle x100 (stains collagen blue)
Cardiac Amyloidosis
- H+E: cardiac muscle with interstitial amyloid deposition (pale pink) x200
- Congo red under polarized light: apple-green birefringence of congo red stain) x200
Primary amyloidosis is more likely to involve the heart.
- Interstitial, pink, amorphous material on H&E.
- Apple green birefringence with Congo Red stain.
Describe the clinical features and complications of restrictive cardiomyopathy
• Signs of R heart failure
• Exercise intolerance
• Dyspnoea
• ↑ venous pressures (elevated JVP, Kussmaul’s sign (JVP rising with inspiration)
• Peripheral oedema
• Enlarged pulsatile liver
• Thromboembolism
• Heart failure
Describe ARVC
Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)
Distinct clinical presentation:
- Right ventricular failure
- Ventricular arrhythmias
- Sudden death (EXERTIONAL)
Can occur on the left side (left-sided HF)
**Causal mutations involve genes encoding desmosomal junctional proteins at the intercalated disc (plakoglobin) and proteins that interact with the desmosomes.
Pathology:
- Dilated, thinned RV
- Gross thinning of dilated RV wall with loss of myocytes and fibrofatty replacement
Describe LVNC
Left Ventricular Non-compaction (LVNC)
- 2/3 Male; genetic mutations- AD, X-linked
- Presumably in utero development in most cases
- Persistence of embryonal sinusoids with maturation arrest (remodelling phase interrupted)
- Spongy left ventricular myocardium with increased trabeculation
- Presents with atrial fibrillation, hydrops fetalis, heart failure, sudden death
