Cardiomyopathy Flashcards
what are the 3 types of cardiomyopathy (primary disease of myocardium)?
- dilated cardiomyopathy (most common)
- hypertrophic cardiomyopathy (seen with athletes who suddenly collapse - but genetic, NOT the same as athlete’s hypertrophy)
- restrictive cardiomyopathy
*damage is directly on cardiomyocyte
what is the most common pattern of cardiomyopathy?
dilated cardiomyopathy (90%): disease of cardiac muscle (defect in force generation/transmission, myocyte signaling) resulting in reduced systolic function
associated with enlarged LV and decreased LVEF (ejection fraction)
many causes, must exclude ischemia/valve disease/HTN/congenital heart disease for diagnosis (these are more common)
what are 2 genetic (primary) causes of dilated cardiomyopathy?
- titin mutations (AD): anchors actin/myosin to Z line, preventing over-stretch
- dystrophin mutations (X-linked): allows transmission of force during contraction, same mutation as Duchenne muscular dystrophy - dilated cardiomyopathy is most common cause of death in this disease
describe how genetic mutation in dystrophin leads to dilated cardiomyopathy
dystrophin protein allows transmission of force during contraction
without it, myocytes detach during contraction and undergo apoptosis
dead muscle cells are replaced by fat, thus proper conduction/contraction cannot occur —> dilated cardiomyopathy and arrhythmias ensue
*dilated cardiomyopathy is primary cause of death in patients with Duchenne muscular dystrophy
name 4 secondary (non-genetic) causes of dilated cardiomyopathy
(generally, 4 scenarios in which you might suspect dilated cardiomyopathy)
- toxins/metabolites
- peripartum
- stress
- myocarditides (infectious or autoimmune)
the following toxins are associated with what cardiac disease?
- alcohol
- cocaine
- Doxorubin (anthraycline)
- Trastuzumab
- accumulation of cobalt
- selenium depletion
these are all associated with dilated cardiomyopathy (disease of cardiac muscle)
metabolizes of alcohol are directly toxic to cardiomyocytes, and recall that cocaine is a strong beta adrenergic agonist (puts a lot of stress on the heart muscles)
Doxorubin and Trastuzumab (HER2 mAb) are both chemotherapy medications - intercalate DNA to cause strand breakage and induce ROS which causes apoptosis
accumulated cobalt and depleted selenium cause oxidative damage, leading to apoptosis
which 2 trace elements are associated with development of dilated cardiomyopathy?
- accumulation of cobalt
- depletion of selenium
accumulation of cobalt and depletion of selenium are both associated with development of?
dilated cardiomyopathy
due to accumulation of oxidative injury that causes apoptosis of cardiomyocytes
the following metabolic disorders are all associated with what cardiac disease?
- hyper AND hypo-thyroidism
- “beri beri” (thiamine deficiency)
- hypocalcemia
- hemochromatosis (iron-overload)
dilated cardiomyopathy
describe the pathophysiology of peripartum dilated cardiomyopathy
signs/symptoms of HF in last months of pregnancy, up to 5mo post-partum, with no other identifiable cause (must exclude for diagnosis)
due to abnormal processing of prolactin (which rises during pregnancy) - cleavage fragments damage myocardium, causing dysfunction
usually recovery LV function, but subsequent pregnancies are high risk for relapse with worse outcomes
describe Takotsubo cardiomyopathy and its cause
aka stress cardiomyopathy or “broken heart syndrome” - triggered by physical or emotional stress
catecholaminergic surge with microvascular spasm results in transient regional LV systolic dysfunction
causes apical ballooning (LV shaped like a pot) - only base is contracting, not apex
—> chest pain, symptoms of HF, elevated BNP and positive troponins, but REVERSIBLE
Pt is a 66yo F presenting to her GP with chest pain. PE and lab results indicated reduced EF and CO, elevated BNP, and positive for troponins. CXR shows LV systolic dysfunction with apical ballooning. PMH and FHx is unremarkable for cardiac disease. The pt says they have been mourning the loss of their beloved cat.
What is going on?
patient has Takotsubo cardiomyopathy - secondary cause of dilated cardiomyopathy
aka “broke heart syndrome”, triggered by physical or emotional stress, most common in F ~66yo
catecholaminergic surge with microvascular spasm results in transient regional LV systolic dysfunction
causes apical ballooning (LV shaped like a pot) - only base is contracting, not apex
*shows signs/symptoms of HF but is reversible
in what type of patient would you most likely see myocarditis as the cause of dilated cardiomyopathy?
myocarditis usually manifests in otherwise healthy person, with rapidly progressing (and often fatal!) heart failure and arrhythmia
can be autoimmune or infectious, more commonly caused by infection in the US
what is the most common cause of myocarditis in the US?
myocarditis can be caused by infection or autoimmune disease, in the US infection is more common
cardiotropic viruses are most common cause in US: Coxsackievirus group B, Adenovirus C, HIV, Hep C
Pt is a 27yo M presenting to the ER with signs of acute HF and atrial arrhythmia. PMH is unremarkable, FHx is unremarkable for cardiac disease. Pt is admitted but is quickly deteriorating. Labs come back positive for infection.
What kind of infection is most likely, and what is going on?
myocarditis: secondary cause of dilated cardiomyopathy, manifests in otherwise healthy person, can result in readily progressive HF and arrhythmia
in US, infection more common cause than autoimmunity, and typically by a cardiotropic virus:
- coxsackievirus group B
- adenovirus C
- HIV and Hep C
the following infectious pathogens are all known to cause what kind of cardiac disease?
- borrelia species
- corynebacterium diphtheriae
- trypanosoma cruzi
- coxsackievirus group B
- adenovirus C
- HIV and Hep C
these are all infectious agents that can cause infectious myocarditis, a form of secondary dilated cardiomyopathy
myocarditis can be caused by infection of autoimmunity, but most commonly by infection in the US, and usually be cardiotropic viruses
Borrelia and corynebacterium more accurately cause conduction defects such as heart block
Trypanosoma cruzi is a more common cause in Latin America - Chagas’ disease
what is it called when myocarditis is caused by Trypanosoma cruzi infection? describe this illness
Chagas cardiomyopathy: infectious myocarditis (secondary cause of dilated cardiomyopathy), most common cause of non-ischemic cardiomyopathy in Latin America
most are asymptomatic during acute phase, cardiac damage develops 10-30 years later, most likely due to chronic immune response
highly arrhythmogenic, sudden cardiac death is #1 cause of death
Trypanosomes (intracellular parasites) can be seen within cardiomyocytes (a bunch of spots)
Pt is a 45yo immigrant from Latin America presenting with signs of CHF and non-sustained v-tach. PMH and FHx is unremarkable for cardiac illness, and the patient is otherwise healthy. PMH is remarkable for infection of unknown cause when patient was 17yo that resolved without treatment.
What might be going on?
Chagas cardiomyopathy: infectious myocarditis (secondary cause of dilated cardiomyopathy), most common cause of non-ischemic cardiomyopathy in Latin America
most are asymptomatic during acute phase, cardiac damage develops 10-30 years later, most likely due to chronic immune response
highly arrhythmogenic, sudden cardiac death is #1 cause of death
Trypanosomes (intracellular parasites) can be seen within cardiomyocytes (a bunch of spots)
if you’re looking a tissue biopsy from the heart of a patient with dilated cardiomyopathy, what would be an indication that the cause was viral?
lymphocyte infiltration! = viral infectious myocarditis, most common cause of myocarditis in the US
what kind of myocarditis are giant cell and eosinophilic myocarditis?
giant cell myocarditis and eosinophilic myocarditis are forms of autoimmune inflammatory myocarditis (secondary dilated cardiomyopathy)
rare, must rule out other causes
in all forms of dilated cardiomyopathy (primary and secondary), what follows clinically from LV volume overload?
end-stage of all etiologies is the same: LV volume overload leads to decompensation —> dyspnea, fatigue, mitral regurgitation (stretched valve leaflets), arrhythmias (palpitations)
lateral displaced PMI (large heart), high HR but low pulse pressure, S3 heart sound, JVD, ascites, peripheral edema, etc
how are the following parameters altered in dilated cardiomyopathy (same across all etiologies):
a. LV mass
b. LV cavity size
c. LV EF
d. LV diastolic function
a. LV mass: increase
b. LV cavity size: increase
c. LV EF: decrease
d. LV diastolic function: increase (volume load on ventricle is very large)
what is the cause of hypertrophic cardiomyopathy?
GENETIC: AD mutations in sarcomere proteins (myosin binding protein C, beta-myosin heavy chain, troponins)
—> reduced LV compliance associated with myocyte hypertrophy, impaired diastolic filling, LV outflow tract obstruction (due to asymmetrical enlargement of septum) —> reduced CO
in what cardiac disease does LV hypertrophy develop in the absence of causative factors such as HTN, aortic valve disease, systemic infiltrate disease?
what, then, is the cause of the LV hypertrophy?
hypertrophic cardiomyopathy: GENETIC disorder, AD mutations in sarcomere proteins (myosin binding protein-C, beta myosin heavy chain, troponins)
—> reduced LV compliance, associated with myocyte hypertrophy, impaired diastolic filling, LV outflow tract obstruction —> reduced CO
