Cardio-Path- Cardiomyopathies Flashcards
Cardiac diseases due to intrinsic myocardial dysfunction are termed:
cardiomyopathies.
Cardiomyopathies principally confined to the myocardium:
primary cardiomyopathies
Cardiomyopathies due to a cardiac manifestation of a systemic disorder?
secondary cardiomyopathies
Cardiomyopathies are a diverse group that includes disorders (eg, myocarditis), immunologic diseases (eg, sarcoidosis), systemic disorders (eg, hemochromatosis), muscular dystrophies, and disorders of myocardial fibers.
inflammatory; metabolic; genetic
Often, the cardiomyopathy is of unknown etiology or in other words?
idiopathic
Three clinical, functional, and pathologic patterns are recognized:
๏ Dilated cardiomyopathy (DCM). (including arrhythmogenic right ventricular cardiomyopathy)
๏ Hypertrophic cardiomyopathy (HCM)
๏ Restrictive cardiomyopathy
Which of the 3 types of cardiomyopathies is most common (90%)?
Dilated cardiomyopathy
Which cardiomyopathy occurs least frequent?
restrictive cardiomyopathy
Within each pattern of cardiomyopathy, there is a of clinical severity, and in some cases clinical features overlap among the groups.
spectrum
What type of cardiomyopathy involves impairment of contractility (systolic dysfunction)?
Dilated
Which 2 cardiomyopathies involve impairment of compliance (diastolic dysfunction)?
hypertrophic and restrictive
What is the ejection fraction with dilated cardiomyopathy (DCM)?
less than normal, <40%
What is the estimated ejection fraction for hypertrophic cardiomyopathy?
50-80%
What is the estimated ejection fraction between in restrictive cardiomyopathy?
45-90%
Which cardiomyopathy is characterized by progressive cardiac dilation and contractile (systolic) dysfunction, usually with concurrent hypertrophy?
DCM
What can happen to valves if there is dilation in atria or ventricles?
they can be pulled apart, become dysfunctional or compromised
What are the 5 pathways that can lead to end-stage DCM?
1๏ Genetic causes
2๏ Infection
3๏ Alcohol or other toxic exposure
4๏ Peripartum cardiomyopathy
5๏ Iron overload
As far as genetic causes are concerned, DCM can be caused by mutations in which elements?
cytoskeletal,
sarcomeric,
nuclear envelope,
or mitochondrial proteins;
-this leads to poor force generation, transmission, and myocyte signalling
As far as genetic causes are concerned, hypertrophic cardiomyopathies can be caused by mutations in which main element:
sarcomeric protein
What is the common clinical end point for DCM as well as hypertrophic cardiomyopathy?
left ventricle
What are the 4 phenotypic characteristics of DCM?
- hypertrophy
- dilation
- fibrosis
- intracardiac thrombi
There is a hereditary basis in of DCM cases.
20-50%
What is the predominant inheritance pattern in DCM with a hereditary basis?
autosomal dominant inheritance
Which mutations are most commonly involved in DCM?
Mutations affecting cytoskeletal proteins, or proteins that link the sarcomere to the cytoskeleton
What is the protein that physically couples the intracellular cytoskeleton to the extracellular matrix.?
dystrophin
As contractile myocytes and conduction fibers share a common developmental pathway, congenital abnormalities can be a feature of inherited forms of DCM.
conduction
d-sarcoglycan, dystrophin, desmin, mitochondrial proteins, titin, Lamin A/C, actin, myosins, and troponin
are all key proteins involve with which genetically based cardiomyopathy?
DCM
note: focus on the red words
Virtually all hypertrophic cardiomyopathies are caused by:
genetics (sarcomeric protein mutations)
Mutations affecting cytoskeletal proteins, or proteins that link the sarcomere to the cytoskeleton are most commonly involved with which cardiomyopathy?
DCM
X-linked DCM is most frequently associated with mutations in which protein?
dystrophin
Actin, B-myosin heavy chain, myosin binding protein C, myosin light chains, and troponins are proteins involved with which cariomyopathy?
hypertrophic cardiomyopathy
note: blue words (only hypertrophic) and green labels (DCM and hypertrophic)
Mutations in (the largest known human protein), accounts for approximately 20% of all dilated cardiomyopathy.
titin
Which protein spans the sarcomere and connects the Z and M bands thereby limiting the passive range of motion of the sarcomere as it is stretched?
titin
Which sarcomeric protein acts like a spring, domains that unfold when the protein is stretched and refold when the tension is removed, thereby impacting the passive elasticity of striated muscle?
titin
Uncommon forms of DCM are caused by mutations of mitochondrial proteins involved in or fatty acid β-oxidation, presumably leading to defective generation.
oxidative phosphorylation; ATP
What is the e principal intermediate filament protein in cardiac myocytes? And is involved with genetic forms of DCM?
desmin
Dilated Cardiomyopathy Pathogenesis caused by Infection are usually by which viral culprits?
coxsackievirus B and other enteroviruses
During which stage of DCM disease are viral nucleic acid “footprints” like coxsackievirus B and other enteroviruses detected in the myocardium?
late-stage DCM
Is it possible for infectious myocarditis to progress to DCM?
yes
Which common characteristic is absent from end-stage DCM attributed to viral infections?
inflammation
Alcohol abuse is strongly/slightly associated with the development of dilated cardiomyopathy
strongly
Alcohol and its metabolites have a direct/indirect toxic effect on the myocardium
direct
Chronic alcoholism can be associated with deficiency, introducing an element of beriberi associated heart disease
thiamine
Exposure to what other toxic substances (other than alcohol) can cause DCM to develop?
toxic agents, such as cobalt, and particularly doxorubicin (Adriamycin), a chemotherapeutic drug.
When could DCM occur as related to peri and post partum?
late in gestation, or several weeks to months postpartum
DCM related to peripartum pathogenesis has an etiology that is multifactorial. What factors are involved that could lead to DCM?
pregnancy-associated HTN,
volume overload,
nutritional deficiency,
metabolic derangements (eg, gestational diabetes), a
nd/or immunologic responses.
The primary defect related to peripartum DCM may be impaired within the myocardium leading to ischemic injury.
angiogenesis
What can result from hereditary hemochromatosis or from multiple transfusions, and could lead to development of DCM?
iron overload
In the case of dilated cardiomyopathy, the heart is characteristically is (up to 2-3 x the normal weight) and flabby, with of all chambers.
enlarged; dilation
Due to the dilation of chambers in DCM, are often present and may be a source of thromboemboli.
mural thrombi
note: white arrow pointing to mural thrombi
Explain why chamber dilation increases risk of thrombi?
Dilation creates space for statis, stasis creates thrombi, and possibly thromboemboli
Describe the nonspecific histological characteristics of DMC heart tissue?
Most myocytes exhibit hypertrophy with enlarged nuclei, but many are attenuated, stretched, and irregular. • There is variable interstitial and endocardial fibrosis, with scattered areas of replacement fibrosis.
In DCM secondary to iron overload, there is a marked accumulation of intramyocardial , which is seen by staining with Prussian blue.
hemosiderin
Which stain is used on histological samples to demonstrate iron overload and what does it stain?
hemosiderin is stained blue with Prussian blue
The consequences of DMC are devastating, One half of patients die within 2 years and only 25% survive longer than 5 years. Death is usually due to which 2 consequences?
progressive cardiac failure or arrhythmia.
Morphologically, what happens to the right ventricular wall in Arrhythmogenic Right Ventricular Cardiomyopathy?
right ventricular wall is severely thinned owing to myocyte replacement by fatty infiltration and lesser amounts of fibrosis
Why is the right ventricular wall is severely thinned in Arrhythmogenic Right Ventricular Cardiomyopathy and how does that compromise pumping?
owing to myocyte replacement by fatty infiltration and lesser amounts of fibrosis; less muscle means contraction issues
Concerning Arrhythmogenic Right Ventricular Cardiomyopathy, Many of the causative mutations involve genes encoding junctional proteins, as well as proteins that interact with the eg, the intermediate filament desmin.
desmosomal; desmosome
Which type of cardiomyopathy is characterized by myocardial hypertrophy, defective diastolic filling, and - in a third of cases - ventricular outflow obstruction?
hypertrophic cardiomyopathy (HCM)
How would you describe the heart wall of someone with Hypertrophic cardiomyopathy (HCM)?
thick-walled, heavy, and hypercontractile.
Hypertrophic CM is marked by massive myocardial hypertrophy with/without ventricular dilation.
without
Classically, there is disproportionate thickening of the ventricular relative to the left ventricle free wall (asymmetric septal hypertrophy), in cases of HCM.
septum
What happens to the ventricular cavity in cases of HCM?
ventricular cavity loses its usual round-to-ovoid shape and is compressed into a “banana-like” configuration.
Note about diagram:
septal muscle bulges into the left ventricular outflow tract, giving rise to a “banana-shaped” ventricular lumen, and the left atrium is enlarged. The anterior mitral leaflet has been moved away from the septum to reveal a fibrous endocardial plaque (arrow)
Concerning HCM, As the ventricular septum is enlarged, The anterior mitral leaflet contacts the septum during ventricular systole, which can affect ventricular outflow in which 2 ways?
a plaque in the left ventricular outflow tract and thickening of the mitral leaflet
What changes correlate with functional left ventricular outflow tract obstruction due to systolic anterior motion of the mitral valve in cases of HCM?
The anterior mitral leaflet contacts the enlarged septum during ventricular systole, producing a plaque in the left ventricular outflow tract and thickening of the mitral leaflet.
Histologically, what are the characteristic features of HCM?
marked myocyte hypertrophy, haphazard myocyte disarray, and interstitial fibrosis (light pink areas on slide)
As concerning HCM, despite having massive left ventricular hypertrophy, HCM demonstrates markedly reduced stroke volume as a consequence of impaired diastolic filling. Explain why?
Though there is hypertrophy of muscle, the overall chamber size is smaller
Which cardiomyopathy is characterized by a primary decrease in ventricular compliance, resulting in impaired ventricular filling during diastole (the wall is stiffer).
Restrictive cardiomyopathy
What pathology is caused by the deposition of extracellular proteins that form insoluble β-pleated sheets? And appear apple green under polarized light with Congo Red stain?
amyloidosis
Cardiac amyloidosis can occur in the setting of amyloidosis, eg, multiple myeloma, or can be predominantly restricted to the heart, eg, amyloidosis.
systemic; senile cardiac
Which restrictive cardiomyopathy is principally a disease of children and young adults in Africa and other tropical areas that is characterized by dense diffuse fibrosis of the ventricular endocardium and subendocardium, often involving the tricuspid and mitral valves?
Endomyocardial fibrosis
What restrictive cardiomyopathy subtype is related to nutritional deficiencies and/or inflammation related to helminthic infections (eg, hyper-eosinophilia)?
Endomyocardial fibrosis
Which cardiomyopathy subtype exhibits endocardial fibrosis, typically associated with formation of large mural thrombi and is characterized by peripheral hyper-eosinophilia and eosinophilic tissue infiltrates?
Loeffler Endomyocarditis
In the case of Loeffler endomyocarditis, release of eosinophil granule contents, especially major basic protein, probably causes endocardial and myocardial necrosis, followed by:
scarring and subsequent thrombus formation
In the case of restrictive cardiomyopathy, describe the ventricles?
The ventricles are of approximately normal size or only slightly enlarged, the cavities are not dilated, and the myocardium is firm
What happens to the atria in restrictive cardiomyopathy, as a result of restricted ventricular filling and pressure overloads?
Both atria are typically dilated
What is a prominant feature in microscopic examination of restrictive cadiomyopathy?
interstitial fibrosis
note: fibrosis is the light pink
While gross morphologic findings are similar for restrictive cardiomyopathy of various causes, endomyocardial biopsy often can reveal a specific etiology according to the slides:
amyloidosis.
