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
what is a key anatomical AND histological finding of hypertrophic cardiomyopathy? what is the clinical significance of this?
recall hypertrophic cardiomyopathy is of GENETIC cause, AD mutation in sarcomere proteins —> reduced LV compliance
anatomical: asymmetrical septal hypertrophy (ventricle may be banana shaped) - causing LV outflow tract obstruction!
historical: cardiomyocyte disarray
a patient’s CXR shows asymmetrical enlargement of the ventricular septum, and a tissue biopsy from the same patient’s heart shows cardiomyocyte disarray
from these two findings alone, what is most likely?
hypertrophic cardiomyopathy: GENETIC cause, AD mutation in sarcomere proteins —> reduced LV compliance
anatomical: asymmetrical septal hypertrophy (ventricle may be banana shaped) - causing LV outflow tract obstruction!
Histological: cardiomyocyte disarray
**LV hypertrophy develops in ABSENCE of causative factors (because it is GENETIC)
what clinical symptoms manifest from hypertrophic cardiomyopathy?
hypertrophic cardiomyopathy: GENETIC cause, AD mutation in sarcomere proteins —> reduced LV compliance
asymmetrical septal hypertrophy —> outflow tract obstruction
—> light-headed, exercise intolerance, syncope (fainting), palpitations/atrial fibrillation (due to high atrial pressure), microinfarcation (focal ischemia)
what kind of murmur is associated with hypertrophic cardiomyopathy?
hypertrophic cardiomyopathy: GENETIC cause, AD mutation in sarcomere proteins —> reduced LV compliance
systolic crescendo-decrescendo murmur at lower left sternal border - heard as heart is ejecting blood across the obstruction of the asymmetric septum
unique: murmur gets louder with maneuvers that DECREASE volume in the heart (increased volume improves obstruction via pressure of blood)
will also hear S4 due to stiff LV
Your patient has hypertrophic cardiomyopathy. You know the murmur (caused by asymmetrical septum obstruction) gets louder with maneuvers that LOWER blood volume.
Which of these would decrease blood volume in the heart?
a. Valsalva
b. Handgrip
c. Hot bath
d. Squatting
e. Standing
f. Inotrope
g. Diuretic
decrease heart volume:
a. valsalva (suck in abdomen)
c. hot bath
e. standing
f. inotrope (via increased SV)
g. diuretic
increase heart volume (would make most murmurs loader):
ice bath, squatting, vasodilator
Increase afterload: handgrip
Your patient just learned they have hypertrophic cardiomyopathy. What lifestyle changes should you advise them? Why might you consider prescribing a beta blocker or calcium channel blocker (or both)?
hypertrophic cardiomyopathy: GENETIC cause, AD mutation in sarcomere proteins —> asymmetric septal hypertrophy —> LV outflow tract obstruction
need to avoid episodes of low volume (makes obstruction worse) - stay hydrated, avoid exercise
beta blocker - increases time for diastole, more time to fill, more volume in heart
calcium channel blocker - less contractility = more volume in heart
how would hypertrophic cardiomyopathy affect the following parameters?
a. LV mass
b. LV cavity size
c. LV EF
d. LV diastolic function
hypertrophic cardiomyopathy: GENETIC cause, AD mutation in sarcomere proteins —> asymmetric septal hypertrophy —> LV outflow tract obstruction
a. LV mass: increase
b. LV cavity size: decreased
c. LV EF: preserved (but low SV)
d. LV diastolic function: impaired (heart can’t fill well bc it is stiff)
what cardiac disorder does this describe?
- reduced compliance of both ventricles
- impaired diastolic filling
- normal ventricle size
- massive atrium
restrictive cardiomyopathy: BOTH ventricles have reduced compliance, causing BOTH atrium to be massively enlarged
ventricles are stiff and hard to fill, but are of normal size and walls may not be thickened because it is caused by infiltrative disease between cells, rather than cellular hypertrophy
what is the cause of restrictive cardiomyopathy?
restrictive cardiomyopathy: BOTH ventricles have reduced compliance, causing BOTH atrium to be massively enlarged
due to infiltrative disease between cells, NOT cellular hypertrophy (so ventricular walls and chamber size are normal)
interstitial infiltrate may be due to amyloidosis (transthyretin), hemochromatosis, scleroderma, Fabry disease, glycogen storage disease, sarcoidosis, others
what is amyloid and how does it present histologically?
amyloid = abnormal folding of proteins, deposit as beta sheet fibrils
with congo red stain, amyloids appear apple-green
AL protein vs ATTR protein amyloids
amyloid = abnormal folding of proteins, deposit as beta sheet fibrils
can be caused by Ig light chains (such as in multiple myeloma) —> AL protein
can also be caused by transthyretin (serum protein, synthesized by liver, transports thyroxin and retinal binding protein) —> ATTR protein
*note that transthyretin amyloids can be caused by WT (senile) or mutant misfolding
what type of amyloid is the cause of most amyloidosis restrictive cardiomyopathies?
restrictive cardiomyopathy: BOTH ventricles have reduced compliance, causing BOTH atrium to be massively enlarged
95% of amyloidosis due to transthyretin misfolding - serum protein, synthesized by liver, transports thyroxin and retinal binding protein
—> misfolded ATTR protein deposits interstitially, causes ventricles to become stiff, pressure backup causes atrial enlargement
why does it make sense that right heart failure dominates in restrictive cardiomyopathy?
restrictive cardiomyopathy: due to interstitial infiltrate, BOTH ventricles have reduced compliance (stiff), causing BOTH atrium to be massively enlarged
R heart failure dominates because right side of heart is lower pressure system while left side is meant for high pressure - so R heart fails first because it cannot tolerate the pressure
therefore, symptoms are of RHF: JVD (Kussmaul sign) , lower extremity edema, hepatomegaly, ascites, etc
Pt presents with exercise intolerance, a-fib, ascites, and a Kussmaul sign. S4 and pulmonary rales are heard, and ECG shows low voltage in limb leads. Heart biopsy with congo red stain appears apple-green.
What do you expect to find on chest x-ray?
Kussmaul sign: JVD distends during inspiration, when normally it should flatten because it should be easier for blood to enter heart on inspiration
Congo red stain that shows apple green indicates amyloids
pt shows signs of right heart failure (fails before left because it can’t tolerate the pressure)
these all indicate restrictive cardiomyopathy: due to interstitial infiltrate, BOTH ventricles have reduced compliance (stiff), causing BOTH atrium to be massively enlarged - CXR would show massive bi-atrial enlargement (“owl eyes”)
what does a positive Kussmaul sign indicate?
JVD distends during inspiration, when normally it should flatten because it should be easier for blood to enter heart on inspiration
indicates elevated right side heart pressure
how would restrictive cardiomyopathy affect the following parameters?
a. LV mass
b. LV cavity size
c. LV EF
d. LV diastolic function
a. LV mass: normal (stiff R/L ventricles due to infiltrate, not hypertrophy)
b. LV cavity size: normal (atrium are massive)
c. LV EF: preserved (but low SV)
d. LV diastolic function: impaired (stiff ventricles can’t fill well)
how would athlete’s heart affect the following parameters?
a. LV mass
b. LV cavity size
c. LV EF
d. LV diastolic function
a. LV mass: increased
b. LV cavity size: normal or increased
c. LV EF: preserved
d. LV diastolic function: normal
how would athlete’s heart vs hypertrophic cardiomyopathy affect the following parameters?
a. LV mass
b. LV cavity size
c. LV EF
d. LV diastolic function
athletes heart: increased LV mass, normal/increased LV cavity, preserved EF, normal LV diastolic function (filling)
hypertrophic cardiomyopathy (seen in some athletes who suddenly collapse - GENETIC cause): increased LV mass, decreased LV cavity, preserved EF (but low SV), impaired LV diastolic function (filling)
