Cardiomyopathies 1

Question 1

cardiomyopathy - definition & major categories

Answer 1

*a myocardial disorder in which the heart muscle is structurally and functionally abnormal, in the absence of coronary artery disease, hypertension, valve disease, and congenital heart disease sufficient to cause the observed myocardial abnormality
*note - the left atrium is dilated in all of them, which reflects long-standing increase in preload (LV EDP)
*categories:
-dilated cardiomyopathy
-restrictive cardiomyopathy
-hypertrophic cardiomyopathy
*arrhythmogenic right ventricular cardiomyopathy (ARVC)
-unclassifiable

Question 2

dilated cardiomyopathy - overview

Answer 2

*a condition characterized by the stretching and thinning of one or both ventricles of the heart, leading to impaired contractility
*most common cardiomyopathy
*cardiac ischemia is the most common cause

Question 3

dilated cardiomyopathy - pathogenesis

Answer 3

*myocyte injury → decreased contractility → decreased stroke volume →
1. increased ventricular filling pressures → pulmonary congestion (dyspnea, orthopnea, rales) and systemic congestion (JVD, hepatomegaly, edema)
2. LV dilation → mitral regurgitation
3. decreased forward cardiac output → fatigue, weakness

note - most people with dilated cardiomyopathy present with CHF

Question 4

dilated cardiomyopathy - systolic, diastolic, and RV function

Answer 4

1. systolic dysfunction: decreased LV ejection fraction; LV remodeling occurs as a means to preserve stroke volume/cardiac output
2. diastolic dysfunction: always present in those with systolic dysfunction; contributes significantly to development of symptoms
3. right ventricular function: oftentimes noted to be normal, but as LV failure worsens, can cause RV to start to fail, which is a very POOR PROGNOSTIC SIGN; RV systolic dysfunction is often an exclusion to more advanced therapy

Question 5

dilated cardiomyopathy & wall stress

Answer 5

*hearts with dilated cardiomyopathy are under more wall stress than normal-sized hearts and are more susceptible to ischemia (b/c dilated hearts use more oxygen per gram of tissue than a normal-sized heart)

Question 6

gross appearance of dilated cardiomyopathy

Answer 6

*externally: dilated heart appears more like a ball (normal heart appears more like a cone)
*internally: cords and tendons on the inside of the dilated heart are more visible and appear stretched

Question 7

etiologies of dilated cardiomyopathy

Answer 7

*idiopathic
*coronary artery disease
*myocarditis
*HIV
*peripartum
*alcohol
*drug-induced
*familial

Question 8

ischemic dilated cardiomyopathy

Answer 8

*caused by infarction of a coronary artery

Question 9

viral myocarditis - overview

Answer 9

*one of the most common causes of “idiopathic” cardiomyopathy
*in young adults, up to 20% of all cases of sudden death are due to myocarditis

Question 10

etiologies of viral myocarditis (common viral pathogens)

Answer 10

*coxsackie virus (enterovirus) = most common
*HIV
*other viruses:
-parvovirus B19
-HHV6
-influenza
-adenovirus
-echovirus
-CMV

Question 11

viral myocarditis - risk factors

Answer 11

*immunologic mechanism (develops weeks after the original infection)
*enhanced susceptibility: radiation, malnutrition, steroids, exercise, previous myocardial injury
*tends to be more aggressive and fulminant in infants and pregnant women

Question 12

major risk factors of a myocardial biopsy

Answer 12

1. pericardial effusion
2. ventricular fibrillation

Question 13

cardiac MRI and myocarditis

Answer 13

*looking for a band of brightness along the surface of the heart (scar)
*the white-color at surface of heart (epicardium) indicates scar/injury from viral infection or inflammation

Question 14

HIV cardiomyopathy

Answer 14

*characterized as symptomatic systolic dysfunction associated with a dilated left ventricle
*median survival was less than 3 months prior to the introduction of anti-retroviral meds to treat HIV
*in late 1980s, roughly 1/3 of all HIV-related cardiac deaths were due to dilated cardiomyopathy

Question 15

advances in HIV cardiomyopathy

Answer 15

*with consistent access to antiretroviral medications and early initiation of treatment, myocarditis and dilated cardiomyopathy have virtually disappeared
*burden of cardiac disease in HIV patients now is transitioning toward increasing atherosclerosis and ischemic heart disease

Question 16

peripartum cardiomyopathy

Answer 16

*clear relationship to recent pregnancy:
-symptoms can start during third trimester, and usually start within one to five months postpartum
*no identifiable cause or pre-existing cardiac disease
*exact etiology unclear (maternal autoimmune response, inflammation/myocarditis)
-evidence of inflammation on heart biopsy is a GOOD prognostic sign

Question 17

peripartum cardiomyopathy - risk factors

Answer 17

*maternal age > 30 yo
*twins or triplets
*preeclampsia or pregnancy-induced HTN
*long-term (>4 wks) use of tocolytic tx (tocolytics prevent premature birth in certain situations)
*cocaine use

Question 18

peripartum cardiomyopathy - prognosis

Answer 18

*1/3 recover completely
*1/3 stabilize (never quite normal again, but stable)
*1/3 progress (get worse and worse)
note - high risk for thromboembolism (DVT, arterial thomboembolism, etc)

Question 19

peripartum cardiomyopathy in women with persistent LV dysfunction (do not have complete recovery)

Answer 19

*high risk of death or permanent worsening of cardiomyopathy with subsequent pregnancy
*advice to patient = NEVER GET PREGNANT AGAIN
*surgical sterilization is highly recommended

Question 20

peripartum cardiomyopathy in women with complete recovery

Answer 20

*substantial risk of recurrent cardiomyopathy with subsequent pregnancy and may not return to normal next time
*no clear guidelines due to no way to predict outcomes:
-persistent LV dysfunction: subsequent pregnancy is an unbelievably bad idea
-presumed complete recovery: subsequent pregnancy is still a potentially bad idea

Question 21

peripartum cardiomyopathy - treatment

Answer 21

*guideline-directed medical therapy for CHF
*cannot give ACE inhibitors/ARBs while pregnant or breast feeding
*consider anticoagulation due to higher risk of thromboembolism

Question 22

acute effects of alcohol on LV function in healthy subjects

Answer 22

*light intoxication: LVEF decreased by 5%
*heavy intoxication: LVEF decreased by 11%
*findings suggest that in healthy subjects alcohol intoxication causes a dose-dependent impairment of cardiac contractility

Question 23

alcoholic cardiomyopathy

Answer 23

*caused by long-term, excessive use of alcohol
*cardiac contractility reduced due to the direct effect of ethanol
*usually occurs in males age 30-50
*may be complicated by vitamin deficiencies, particularly B1, which causes tachycardia, vasodilation, and dilated CM in its own right
*treatment:
-abstain from alcohol
-guideline-directed medical therapy for CHF

Question 24

tachycardia-mediated cardiomyopathy

Answer 24

*atrial fibrillation with rapid ventricular response most likely rhythm issue
*rate must be continuously elevated for weeks on end
*prognosis very good if tachycardia can be eliminated
*if you care tachycardia and LVEF normalizes, then you cured tachycardia-mediated cardiomyopathy
*if you cure tachycardia and LVEF stays low: most likely, the tachycardia is a symptom, not the cause

Question 25

familial cardiomyopathy

Answer 25

*a family history of dilated cardiomyopathy without other cause
*in general, genetic testing is not performed b/c it does not change management
*mutations in various proteins identified, including cytoskeletal proteins, myofibrillar proteins, and nuclear membrane proteins

Question 26

Chagas disease

Answer 26

*Chagas disease is a tropical parasitic disease caused by the protist Typanosoma cruzi
*after 8-12 weeks, individuals enter the chronic phase of disease and most do not produce further symptoms
*some people develop further symptoms 10-30 years after initial infection, including enlargement of the ventricles, leading to heart failure
*some experience an enlarged esophagus or an enlarged colon

Question 27

distribution of Chagas disease

Answer 27

*predominantly in Central and South America

Question 28

Chagas disease & cardiac complications

Answer 28

*most common cardiac complications of Chagas disease are:
-LV dilation and dysfunction
-LV aneurysm
-CHF
-thromboembolism
-ventricular arrhythmias
-sudden cardiac death
-cardiac conduction system abnormalities
*CHF usually appears at least 20 years after original infection

Question 29

restrictive cardiomyopathy - overview

Answer 29

*primary problem = very stiff ventricle in the absence of significant hypertension or aortic stenosis
*LV is unable to relax, leading to HFpEF [increased LVEDP and increased RVEDP; s/s of left or right CHF]
*systolic function may or may not be normal
*prognosis is poor for most types

Question 30

restrictive cardiomyopathy - pathogenesis

Answer 30

*rigid myocardium →
1. increased diastolic ventricular pressure → venous congestion → JVD, hepatomegaly, ascites, peripheral edema, dyspnea, orthopnea, rales
2. decreased ventricular filling → decreased cardiac output → weakness, fatigue

*most people with restrictive cardiomyopathy present with CHF

Question 31

types of restrictive cardiomyopathy

Answer 31

1. infiltration of myocardium (amyloid, sarcoid)
2. fibrosis or scarring (scleroderma, Loeffler’s endocarditis)
3. abnormal deposition in myocardium (hemochromatosis [deposition of iron], Fabry’s disease)

Question 32

cardiac amyloidosis restrictive cardiomyopathy

Answer 32

*comprises a group of disorders characterized by the extracellular deposition of ABNORMALLY-FOLDED FIBRILLARY PROTEINS, leading to loss of normal tissue architecture
*CARDIAC AMYLOIDOSIS IS THE POSTER-CHILD for restrictive cardiomyopathy

Question 33

AL amyloidosis restrictive cardiomyopathy

Answer 33

*L, think leukemia/lymphoma
*AL amyloidosis is due to deposition of protein derived from IMMUNOGLOBULIN LIGHT CHAIN FRAGMENTS
*age of onset: 60 yrs
*highest incidence in those with plasma cell dyscrasia in which a monoclonal immunoglobulin is detectable in the serum or monoclonal light chains in the urine

Question 34

AA amyloidosis restrictive cardiomyopathy

Answer 34

*A, think arthritis
*amyloidosis associated with chronic inflammatory states such as rheumatoid arthritis, spondyloarthropathy, or inflammatory bowel disease

Question 35

AF amyloidosis restrictive cardiomyopathy

Answer 35

*F, think Fogey/Familial
*can happen in one of 2 ways:
1. deposition of otherwise normal (wild-type) transthyretin in myocardium and other sites as a consequence of age (age of onset > 75)
2. genetic syndrome involving a mutation in transthyretin which leads to early deposition of transthyretin in the heart and other organs (age of onset 30-50)

Question 36

amyloidosis restrictive cardiomyopathy - diagnostic testing

Answer 36

*fat-pad biopsy showing reflection/refraction of light with Congo Red Stain
*cardiac MRI: significant amount of amyloid deposition changes the magnetic properties of the heart; myocardium turns black before blood
*EKG showing LOW VOLTAGE; may have a pseudo-infarct pattern

Question 37

amyloidosis restrictive cardiomyopathy - echo findings

Answer 37

*thickened walls in LV and RV
*thickened heart valves

Question 38

novel therapies for TTR cardiac amyloidosis

Answer 38

*tafamidis binds to TTR tetramer to slow disease progression
*inotersen and patisiran work by cleaving to and disabling amyloid messenger RNA, a mechanism known as RNA silencing; siRNA drugs produce a reduction in circulating familial and wild-type TTR of ~80%