Cardio-Path- Cardiomyopathies Flashcards
1
Q
Cardiac diseases due to intrinsic myocardial dysfunction are termed:
A
cardiomyopathies.
2
Q
Cardiomyopathies principally confined to the myocardium:
A
primary cardiomyopathies
3
Q
Cardiomyopathies due to a cardiac manifestation of a systemic disorder?
A
secondary cardiomyopathies
4
Q
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.
A
inflammatory; metabolic; genetic
5
Q
Often, the cardiomyopathy is of unknown etiology or in other words?
A
idiopathic
6
Q
Three clinical, functional, and pathologic patterns are recognized:
A
๏ Dilated cardiomyopathy (DCM). (including arrhythmogenic right ventricular cardiomyopathy)
๏ Hypertrophic cardiomyopathy (HCM)
๏ Restrictive cardiomyopathy
7
Q
Which of the 3 types of cardiomyopathies is most common (90%)?
A
Dilated cardiomyopathy
8
Q
Which cardiomyopathy occurs least frequent?
A
restrictive cardiomyopathy
9
Q
Within each pattern of cardiomyopathy, there is a of clinical severity, and in some cases clinical features overlap among the groups.
A
spectrum
10
Q
What type of cardiomyopathy involves impairment of contractility (systolic dysfunction)?
A
Dilated
11
Q
Which 2 cardiomyopathies involve impairment of compliance (diastolic dysfunction)?
A
hypertrophic and restrictive
12
Q
What is the ejection fraction with dilated cardiomyopathy (DCM)?
A
less than normal, <40%
13
Q
What is the estimated ejection fraction for hypertrophic cardiomyopathy?
A
50-80%
14
Q
What is the estimated ejection fraction between in restrictive cardiomyopathy?
A
45-90%
15
Q
Which cardiomyopathy is characterized by progressive cardiac dilation and contractile (systolic) dysfunction, usually with concurrent hypertrophy?
A
DCM
16
Q
What can happen to valves if there is dilation in atria or ventricles?
A
they can be pulled apart, become dysfunctional or compromised
17
Q
What are the 5 pathways that can lead to end-stage DCM?
A
1๏ Genetic causes
2๏ Infection
3๏ Alcohol or other toxic exposure
4๏ Peripartum cardiomyopathy
5๏ Iron overload
18
Q
As far as genetic causes are concerned, DCM can be caused by mutations in which elements?
A
cytoskeletal,
sarcomeric,
nuclear envelope,
or mitochondrial proteins;
-this leads to poor force generation, transmission, and myocyte signalling
19
Q
As far as genetic causes are concerned, hypertrophic cardiomyopathies can be caused by mutations in which main element:
A
sarcomeric protein
20
Q
What is the common clinical end point for DCM as well as hypertrophic cardiomyopathy?
A
left ventricle
21
Q
What are the 4 phenotypic characteristics of DCM?
A
- hypertrophy
- dilation
- fibrosis
- intracardiac thrombi
22
Q
There is a hereditary basis in of DCM cases.
A
20-50%
23
Q
What is the predominant inheritance pattern in DCM with a hereditary basis?
A
autosomal dominant inheritance
24
Q
Which mutations are most commonly involved in DCM?
A
Mutations affecting cytoskeletal proteins, or proteins that link the sarcomere to the cytoskeleton
25
What is the protein that physically couples the intracellular cytoskeleton to the extracellular matrix.?
dystrophin
26
As contractile myocytes and conduction fibers share a common developmental pathway, congenital abnormalities can be a feature of inherited forms of DCM.
conduction
27
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
28
Virtually all hypertrophic cardiomyopathies are caused by:
genetics (sarcomeric protein mutations)
29
Mutations affecting cytoskeletal proteins, or proteins that link the sarcomere to the cytoskeleton are most commonly involved with which cardiomyopathy?
DCM
30
X-linked DCM is most frequently associated with mutations in which protein?
dystrophin
31
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)
32
Mutations in (the largest known human protein), accounts for approximately 20% of all dilated cardiomyopathy.
titin
33
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
34
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
35
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
36
What is the e principal intermediate filament protein in cardiac myocytes? And is involved with genetic forms of DCM?
desmin
37
Dilated Cardiomyopathy Pathogenesis caused by Infection are usually by which viral culprits?
coxsackievirus B and other enteroviruses
38
During which stage of DCM disease are viral nucleic acid “footprints” like coxsackievirus B and other enteroviruses detected in the myocardium?
late-stage DCM
39
Is it possible for infectious myocarditis to progress to DCM?
yes
40
Which common characteristic is absent from end-stage DCM attributed to viral infections?
inflammation
41
Alcohol abuse is **strongly/slightly** associated with the development of dilated cardiomyopathy
strongly
42
Alcohol and its metabolites have a **direct/indirect** toxic effect on the myocardium
direct
43
Chronic alcoholism can be associated with deficiency, introducing an element of beriberi associated heart disease
thiamine
44
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.**
45
When could DCM occur as related to peri and post partum?
late in gestation, or several weeks to months postpartum
46
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.
47
The primary defect related to peripartum DCM may be impaired within the myocardium leading to ischemic injury.
angiogenesis
48
What can result from hereditary hemochromatosis or from multiple transfusions, and could lead to development of DCM?
iron overload
49
Though iron overload is most common in the development of DCM, it can also cause cardiomyopathy due to interstitial fibrosis
restrictive
50
Why does iron overload contribute to the development of dilated (more common) and restrictive cardiomyopathy?
\* It has been attributed to interference with metal-dependent enzyme systems or to injury caused by iron-mediated production of reactive oxygen species.
51
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
52
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
53
Explain why chamber dilation increases risk of thrombi?
Dilation creates space for statis, stasis creates thrombi, and possibly thromboemboli
54
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.
55
In DCM secondary to **iron overload**, there is a marked accumulation of intramyocardial , which is seen by staining with Prussian blue.
hemosiderin
56
Which stain is used on histological samples to demonstrate iron overload and what does it stain?
hemosiderin is stained blue with Prussian blue
57
The fundamental defect in dilated cardiomyopathy is?
ineffective contraction
58
In end-stage DCM, the cardiac ejection fraction typically is percent
\< 25%
59
Other than ineffective contraction, what other signs are common in DCM?
Secondary mitral regurgitation, and abnormal cardiac rhythms
60
What conditions mimick dilated myocardial myopathy or secondary myocardial dysfunctions?
ischemic heart dz, valvular dz, hypertensive heart dz, and congenital heart dz
61
At what age is dilated cardiomyopathy most commonly diagnosed?
20 and 50
62
It typically manifests with signs of slowly progressive , including **dyspnea**, easy **fatigability,** and **poor exertional capacity**
CHF
63
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.
64
What is the only definitive treatment and what treatment is increasingly utilized?
Cardiac transplantation is the only definitive treatment,
implantation of long-term ventricular assist devices is increasingly utilized.\*
65
Arrhythmogenic right ventricular cardiomyopathy is the subtype of which type of cardiomyopathy?
DMC
66
Which subtype of DMC is an **autosomal dominant disorder** that classically manifests with **right-sided heart failure and rhythm disturbances**, which can cause **sudden cardiac death?**
Arrhythmogenic right ventricular cardiomyopathy
67
Which cardiomyopathy subtype acounts for almost 10% of cases of sudden deaths in athletes have been attributed to this condition?
Arrhythmogenic Right Ventricular Cardiomyopathy
68
What is the inheritance pattern of Arrhythmogenic Right Ventricular Cardiomyopathy?
autosomal dominant
69
Arrhythmogenic Right Ventricular Cardiomyopathy classically manifests with which 2 conditions that can lead to sudden cardiac death?
right-sided heart failure and rhythm disturbances
70
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**
71
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
72
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
73
Concerning arrhythmogenic right ventricular cardiomyopathy, Myocyte death may be caused by detachment, particularly during strenuous
desmosomal; exercise.
74
Which type of cardiomyopathy is characterized by myocardial **hypertrophy**, **defective diastolic filling**, and - in a third of cases - **ventricular outflow obstruction?**
hypertrophic cardiomyopathy (HCM)
75
How would you describe the heart wall of someone with Hypertrophic cardiomyopathy (HCM)?
thick-walled, heavy, and hypercontractile.
76
function usually is preserved in hypertrophic cardiomyopathy, but the myocardium **does not relax** and therefore exhibits primary dysfunction.\*
Systolic; diastolic
77
What other conditions could cause hypertrophy of heart and ventricular stiffness?
amyloid deposition) and ventricular hypertrophy (eg, aortic stenosis and hypertension).
78
Most cases of HCM are caused by what type of mutations in one of several genes encoding proteins that form the contractile apparatus?
missense mutations
79
What is the usual pattern of genetic transmission in HCM?
**autosomal dominant** with variable expression
80
Nearly percent of HCM cases are caused by genetics (problems with sarcomeric proteins).
100%
81
Gene mutations in HCM mainly effect what type of proteins and with what effect?
affect sarcomeric proteins and **increase** myofilament function.
82
What is the result of gene mutations that affect sarcomeric proteins and increase myofilament function, as in the case of HCM?
This results in myocyte hypercontractility,
increased energy use,
and a net negative energy balance.
83
Which sarcomeric protein is most frequently inolved with HCM? And what are the other two commonly involved?
**, β-myosin heavy chain** is most frequently involved, followed by **myosin-binding protein C** and **troponin T.\***
**note: mutations in these 3 genes** account for 70% to 80% of all cases of HCM.
84
Though mutations affect the same genes in DCM and HCM, the effect is different; how do these effects differ?
DCM the mutations **depress** motor function, as opposed to the **gain of function** seen in HCM.
85
Hypertrophic CM is marked by massive myocardial hypertrophy **with/without** ventricular dilation.
without
86
Classically, there is disproportionate thickening of the ventricular relative to the left ventricle free wall (asymmetric septal hypertrophy), in cases of HCM.
septum
87
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)
88
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**
89
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.**
90
Histologically, what are the characteristic features of HCM?
marked **myocyte hypertrophy**, haphazard **myocyte disarray**, and **interstitial fibrosis** (light pink areas on slide)
91
At what age does HCM present?
at any age, but typically manifests during the **post-pubertal growth spurt**
92
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
93
Approximately 25% of HCM patients have dynamic obstruction to the left ventricular outflow by the leaflet of the mitral valve
anterior
94
As concerning HCM, with reduced cardiac output and a secondary increase in pulmonary venous pressure, what signs are expected?
exertional dyspnea, with a harsh systolic ejection murmur.
95
HCM is an important cause of cardiac death
sudden
96
In almost a third of cases of sudden cardiac death in athletes less than 35 years of age, the cause is
HCM.
97
The most common cause of sudden cardiac death in young athletes is:
Hypertrophic Cardiomyopathy
98
A combination of **massive hypertrophy**, **high left ventricular pressures**, and **compromised intramural arteries** frequently leads to , even in the absence of coronary artery disease.
MI with angina
99
Major clinical problems associated with can include **atrial fibrillation** with mural thrombus formation, **ventricular fibrillation** leading to sudden cardiac death, **infectious endocarditis** of the mitral valve, and **congestive heart failure.**
HCM
100
Most patients of HCM are improved by what type of therapy?
therapy that promotes ventricular relaxation
101
What 2 treatments can can relieve the outflow tract obstruction associated with HCM?
Partial surgical excision or alcohol-induced infarction of septal muscle
102
Though almost 100% of the causes for HCM are genetic, what are the other 3 rare causes?
Fridreich ataxia, storage diseases, infants of diabetic mothers
103
Which cardiomyopathy is characterized by a primary decrease in ventricular compliance, resulting in impaired ventricular filling during diastole (the wall is stiffer).
Restrictive cardiomyopathy
104
Restrictive cardiomyopathy may be **idiopathic** or associated with **systemic diseases that affect the myocardium,** eg,:
radiation fibrosis,
amyloidosis,
sarcoidosis,
or products of inborn errors of metabolism
105
There a 3 forms of restrictive cardiomyopathy:
* Amyloidosis
* Endomyocardial fibrosis
* Loeffler endomyocarditis
106
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
107
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
108
What type of amyloidosis that causes restrictive cardiomyapathy is described:
deposition of normal (or mutant) forms of **transthyretin** (a liver-synthesized circulating protein that transports thyroxine and retinol) in the hearts of older adult patients results in a restrictive cardiomyopathy
senile cardiac amyloidosis,
109
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
110
What does fibrous tissue do to the heart chambers as in the case of restrictive cardiomyopathy endomyocardial fibrosis?
markedly diminishes the volume and compliance of affected chambers, resulting in a restrictive physiology.
111
What restrictive cardiomyopathy subtype is related to nutritional deficiencies and/or inflammation related to helminthic infections (eg, hyper-eosinophilia)?
Endomyocardial fibrosis
112
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
113
In the case of Loeffler Endomyocarditis, eosinopnil granule contents, especially MBP, probably causes endocardial and myocardial .
necrosis
114
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
115
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**
116
What happens to the atria in restrictive cardiomyopathy, as a result of restricted ventricular filling and pressure overloads?
Both atria are typically dilated
117
What is a prominant feature in microscopic examination of restrictive cadiomyopathy?
interstitial fibrosis
note: fibrosis is the light pink
118
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.
119
What are the main 3 causes of restrictive cardiomyopathy?
amyloidosis, radiation induced fibrosis, and idiopathic
120
