Cardiomyopathies Flashcards
Three major forms cardiomyopathies
Dilated cardiomyopathy (DCM) - includes ARDV
Hypertrophic cardiomyopathy (HCM)
Restrictive cardiomyopathy
Dilated cardiomyopathies details
Most common cardiomyopathy (90%)
Characterized by progressive cardiac dilation and contractile dysfunctions
Usually associated w/ eccentric Hypertrophy and low ejection fractions (systolic HF)
5 pathways that leads to development of DCM
Genetic causes
Infection
alcohol/other toxic exposures
Peripartum cardiomyopathy
Iron overload
Genetic causes for DCM
Is the basis for 20-50% of the DCM cases
Autosomal dominant inheritance patterns w/ over 50 genes being affected
- most common are mutations in genes that affect proteins that link sarcomere to the cytoskeleton
Can be X-linked as well, but in this case almost always revolves around dystrophin protein mutations
Infection in DCM
Most common causative agents are they coxsacklevirus B and enteroviruses
Many cases may not show inflammation in the case of infections
Alcohol/ toxin exposure in DCM
Alcohol abuse is strongly associated with DCM development
- causes thiamine deficiency which leads to wet beriberi heart disease
Other toxic agents include:
- cobalt
- doxorubicin
- chemo drugs
Peripartum cardiomyopathy
Occurs late in gestation of several weeks before postpartum
Etiology is multifactorial including but not limited to the following
- pregnancy associated HTN
- metabolic issues
- autoimmune dysfunctions
- volume overload
- nutritional deficencies
Primary defect is impaired angiogenesis within the myocardium leading to ischemia
Iron overload in DCM
Can be caused by overtransfusion of blood or hereditary hemochromatosis
Can cause restrictive cardiomyopathy as well, but this is rare
DCM heart morphology
Enlarged and flabby with dilation in all 4 chambers
Also often has mural thrombi present
Ventricular thickness can range from smaller than normal to larger than. Normal
DCM histology
Hypertrophied myocytes w/ variable interstitial and endocardial fibrosis (blue staining fibers)
if iron overload is present, hemosiderin (iron) will be present within the cardiac tissue (seen by staining w/ Prussian blue
Clinical features of DCM
Ineffective contraction cardinal feature
Cardiac ejection fraction is less than 25%
Mitral regurgitation and lethal arrhythmias may be present
Mural thrombi may occur intracardiac
50% of patients die within 2 years and 35% survive longer than 5 years total
- death is CHF or lethal arrhythmias
What other pathology often is associated with DCM?
Progressive CHF
Treatment of DCM
Cardiac transplant is the only definitive treatment, however can also use implantation of pacemaker to extend life
Arrhythmogenic right ventricular cardiomyopathy
Autosomal dominant disorder that eventually degrades into right-sided HF and arrhythmias
- leads to SCD if not fixed
- also presents with severally thinned right ventricular wall due to myocytes replacement by fat and fibrosis
- cause for 10% of SCDs in athletes*
Pathogenesis of arrhythmogenic right ventricular
Caused primarily by mutations in desmosomes junctional proteins and filament desmin
Myocyte death is often caused by desmosomes detachment during strenuous exercise
Hypertrophic cardiomyopathy (HCM)
Characterized by the following 4 characteristics:
1) Defective diastolic filling
2) ventricular outflow obstruction
3) myocardial hypertrophy
4) primary diastolic dysfunction
Heart wall becomes thick-walled, heavy and hypercontractile
Pathogenesis of HCM
Most cases are caused by missense mutations in genes associated with contractile apparatus
- often transmitted in autosomal dominant pattern
Also, presents w/ gain-o-function mutations in myofilaments function. (This is opposite of DCM where there is a loss-o-function)
- leads to myocyte hyper-contractility
- most common proteins affected are Myosin heavy chains and troponin T
Morphology of HCM
Marked massive myocardial hypertrophy w/ NO ventricular dilation
- this thickening is often asymmetrical septal hypertrophy (one side, often the left ventricle, is thicker than the other)
- ventricular cavities compress appear “banana-like” in appearance
Often times plaque buildup occurs in the mitral valve and leads to left ventricular outflow obstruction
HCM histology
Marked myocyte hypertrophy w/ haphazard like organization
- also shows interstitial fibrosis throughout the tissue
HCM clinical features
Most commonly found in ages of postpubertal growth spurts (15-21)
- can occur at any age though
Characterized by massive left ventricular hypertrophy w/ markedly reduced SV
- 25% of patients have dynamic obstruction to the left ventricle (mitral valve)
Presents with increased pulmonary venous pressure, exertional dyspnea and a very prominent systolic ejection murmurs
- can show with angina as well if ischemia has set in
primary cause of SCD in athletes
Possible Clinical issues of untreated HCM
HCM untreated can lead to the following:
- atrial fibrillation
- mural thrombi formation
- ventricular fibrillation
- SCD
- CHF
- IE
Treatment of HCM
Pharmacologically by promoting ventricular relaxation
- BBs and CBBs
May need surgery on the mitral valve or the septal muscle if it becomes too prolonged
Restrictive cardiomyopathy
Primary decrease in ventricular compliance and impaired ventricular filling during diastole
- this is due to fibrosis of the myocardium due to a variety of causes
Causes for restrictive cardiomyopathy
Systemic diseases
Radiation on the heart
Amyloidosis
Sarcoidosis
Metabolism abnormalities
3 major forms of restrictive cardiomyopathies
Amyloidosis
- caused by a deposition of extracellular amyloid fibers that produce insoluble B-pleated sheets around myocardium
Endomyocardial fibrosis
- primarily in children and young adults in Africa and other tropical areas
- caused by diffuse fibrosis via nutritional deficiencies of inflammation via parasitic infections
- usually, fibrosis occurs around ventricles, tricuspid or mitral valves
- MOST COMMON form worldwide
Loeffler endomyocarditis
- endocardial fibrosis that often forms large mural thrombi
- caused by hyper-eosinophila and over release of eosinophil granules promoting inflammation and both fibrosis and myocyte death
Restrictive cardiomyopathy morphology
Ventricles are normal size and NOT dialated
Atria are both often dilated
Microscopic examination shows variable degrees of interstitial fibrosis
- if amyloidosis, will also show green amyloid proteins
