Chapter 12/Lecture 8: Arrhythmia, SCD, HTN, Cardiac Valve Dz, Cardiomyopathy, Pericardial Dz, Cardiac Tumors, Transplantation Flashcards
1
Q
SA node damage by ischemic injury leads to what?
A
Sick sinus syndrome —> Bradycardia
2
Q
Irritated atrial myocytes which depolarize independently and sporadically (atrial dilation) lead to variable transmission through which node and cause what?
A
AV node –> Atrial Fibrillation
3
Q
What is the most common inherited arrhythmogenic disease?
A
Long QT syndrome
4
Q
Patients w/ long QT syndrome commonly present how?
A
With stress-induced syncope or sudden cardiac death
5
Q
What are 4 genes implicated in long QT syndrome?
A
- KCNQ1
- KCNH2
- SCN5A
- CAV3
6
Q
Which inherited arrhythmogenic disease presents with syncope or SCD during rest or sleep or after large meals?
A
Brugada syndrome
7
Q
What is the leading cause of SCD?
A
Coronary artery disease
8
Q
The mechanism leading to SCD is most often due to what?
A
Lethal arrhythmia (i.e., asystole or ventricular fibrillation) arising from ischemia-induced myocardial irritability
9
Q
80-90% of pt’s who suffer SCD but are successfully resuscitated do not show what?
A
Enzymatic or ECG evidence of myocardial necrosis
10
Q
In structurally normal hearts, arrhythmias are more often due to what?
A
Mutations in ion channels that cause aberrant repolarization or depolarization
11
Q
What are the 2 criteria for the diagnosis of systemic (left-sided) hypertensive heart disease?
A
1) LV hypertrophy (usually concentric) in the absence of other cardiovascular pathology
2) Clinical hx or pathologic evidence of HTN in other organs (i.e., kidney)
12
Q
In Systemic (left-sided) HHD as the LV wall continues to increase in thickness what associated morphological changes occur?
Enlargement of?
A
↑ interstitial CT –> stiffness = impaired diastolic filling –> LEFT ATRIAL ENLARGEMENT
13
Q
In many pt’s systemic HHD comes to attention due to what signs/sx’s?
A
- New atrial fibrillation induced by left atrial enlargement
- Progressive CHF
14
Q
What are some of the potential long term complications associated with Systemic (left-sided) HHD?
Risk factors for what?
A
- Development of IHD
- Renal damage or cerebrovascular stroke
- Progressive CHF or SCD
15
Q
Isolated pulmonary (right-sided) HHD (cor pulmonale) arises in the setting of what?
A
Pulmonary HTN
16
Q
What is the most common cause of pulmomary HTN (cause of isolated right-sided HHD)?
A
Left-sided heart disease
17
Q
What are the 2 typical causes of chronic cor pulmonale (right-sided HHD)?
A
- Chronic parenchymal disease (ie emphysema)
- Primary pulmonary HTN
18
Q
Acute cor pulmonale (right-sided HHD) may follow what?
A
Massive pulmonary embolism
19
Q
What are the morphological changes seen in the right-side of the heart in the setting of acute vs. chronic cor pulmonale?
A
- Acute = marked RV DILATION, but WITHOUT hypertrophy
- Chronic = RV wall THICKENS
20
Q
What are 5 diseases affecting the pulmonary parenchyma which predispose to cor pulmonale?
A
- COPD
- Diffuse pulmonary interstitial fibrosis
- Pneumoconioses
- CF
- Bronchiectasis
21
Q
Stenosis is failure of a valve to _______ completely, which impedes _______ flow.
A
Stenosis is failure of a valve to open completely, which impedes forward flow.
22
Q
Insufficiency is failure of a valve to _______ completely, which allows _______ flow.
A
Insufficiency is failure of a valve to close completely, which allows reverse flow.
23
Q
Chronic stenosis may cause what type of overload hypertophy vs. chronic insufficiency?
A
- Chronic stenosis = cause pressure overload hypertrophy
- Chronic insufficiency = cause volume overload hypertrophy
*Both leading to CHF
24
Q
What are the 4 most frequent causes of the major functional valvular lesions?
A
- Aortic stenosis
- Aortic insufficiency
- Mitral stenosis
- Mitral insufficiency
25
What is the major etiology causing Mitral Stenosis?
Postinflammatory scarring (**rheumatic heart disease**)
26
What are the 3 major etiologies causing Aortic Stenosis?
- Postinflammatiory scarring (**rheumatic heart disease**)
- **Senile calcific aortic stenosis**
- **Calcification** of **congenitally deformed valve**
27
What are 4 causes of abnormalities of leaflets and commissures leading to mitral regurgitation?
- **Postinflammatory scarring**
- **Infective endocarditis**
- **Mitral valve prolapse**
- **Drugs** (i.e., fen-phen)
28
What is the major etiology responsible for abnormalities of leaflets and commissures leading to Aortic Regurgitation?
Postinflammatory scarring (**rheumatic heart disease**)
29
Abnormalities of the tensor apparatus leading to Aortic Regurgitation may be caused by what 4 etiologies?
- **Syphilitic** aortitis
- **Ankylosing spondylitis**
- Rheumatoid arthritis
- **Marfan Syndrome**
30
When is the typical onset for calcific aortic stenosis and what is it due to?
- Manifests at **60-80 yo**
- **"Wear and tear"** assoc. w/ **chronic HTN, hyperlipidemia**, and **inflammation**
31
Why does calcific aortic stenosis of **congenital** **bicuspid valves** have an **accelerated clinical course** and come to clinical attention sooner than normal vavles?
Bicuspid valves incur **greater** mechanical stress
32
In calcific valvular degneration the affected valves contain what kind of cells, which do what?
**Osteoblast-like cells** --\> synthesize **bone matrix** and promote deposition of **Ca2+ salts**
33
What is the morphological hallmark of nonrheumatic, calcific aortic stenosis (involving either tricuspid or bicuspid valves)?
**Mounded** **calcified masses** in **aortic cusps,** which protrude and prevent complete opening of valve
34
In contrast to rheumatic (and congenital) aortic stenosis, what are 2 major differences seen in nonrheumatic, calcific aortic stenosis?
- Commissural fusion is **NOT** usually seen
- **Mitral valve** = normal
35
What are 3 major sx's that may mark the onset of cardiac decompensation associated w/ Calcific Aortic Stenosis?
- Angina
- CHF
- Syncope
36
Which ventricle is affected in Calcific Aortic Stenosis due to the increased pressure and what is seen?
**Concentric** **LV hypertrophy**
37
What is the prognosis and treatment for Calcific Aortic Stenosis?
- **Poor** prognosis
- Tx requires **surgical valve replacement**
38
SOB and cough 2' to pulmonary congestion may be a feature of which type of calcific valvular degeneration?
Calcific Aortic Stenosis
39
Congenital bicuspid aortic valve (BAV) may have a genetic association due to loss of function mutations in which gene?
***NOTCH1*** on **cr. 9**
40
If present, which site on the cusp is a major site of calcific deposits in those with congenital bicuspid aortic valves (BAV)?
Midline **raphe**
41
Although bicuspid aortic valve (BAV) is usually asymptomatic early in life, what are some of the late complications which may arise?
- **Aortic stenosis** and **regurgitation**
- **Infective endocarditis**
- **Aortic dilation** and/or **dissection**
42
As opposed to the predominantly cuspal involvement in aortic valve calcification, where do calcific deposits occur in the mitral valve?
In the **fibrous annulus**
43
What is the gross morphology of the calcific deposits in mitral annular calcification?
Irregular, stony hard, occassionaly ulcerated **nodules**
44
Calcific nodules seen in mitral annular calcification may provide a site for what complications?
Pt's are at greater risk for what?
- **Thrombus** formation, these pt's have **↑ risk of embolic stroke**
- **Infective endocarditis**
45
Mitral annular calcification is most common in what sex and at what age?
Also in pt's with what underlying complication?
- **Women** \>60 yo
- Pt's w/ **mitral valve prolapse**
46
Mitral valve prolapse has a higher incidence in what gender?
**Females** (**7:1)**
47
Mitral Valve Prolapse is often discovered incidentally by hearing what during ausculation?
**Mid systolic click** sometimes followed by **mid-to-late systolic murmur**
48
What occurs to the valve leaflets in Mitral Valve Prolapse?
"Floppy" leaflets balloon back into the **LA** during **systole**
49
Which heritable disorder of CT is associated with Mitral Valve Prolapse?
Marfan Syndrome
50
The leaflets in Mitral Valve Prolapse become thickened and rubbery due to what?
**Proteoglycan** deposits (**myxomatous degeneration**) and **elastic fiber disruption**
51
The key histo change in the tissue seen in Mitral Valve Prolapse is thickening of which layer and deposition of what?
**Spongiosa layer** w/ deposition of **mucoid (myxomatous) material**
52
2' changes reflecting the stresses and tissue injury incident to the billowing leaflets in mitral valve prolapse include thicking of what 3 structures?
- Fibrous thickening of **valve leaflets**
- Linear fibrous thickening of **LV endocardial surface**
- Thickening of the **mural endocardium** of the LV or LA
53
Majority of patients with Mitral Valve Prolapse are asymptomatic, but a small minority may develop which 4 serious complications?
1. I**nfective endocarditis**
2. Mitral insufficiency
3. **Stroke** or **thromboembolism**
4. **Arrhythmias**
54
How can the diagnosis of mitral valve prolapse be made?
- Auscultation
- **Confirmed** w/ **Echocardiography**
55
What is the most common cause for mitral valve surgery in the US?
Mitral Valve Prolapse
56
Rheumatic heart disease is virtually the only cause of what cardiac disorder?
Mitral Stenosis
57
The pathogenesis of Rheumatic Fever involves host immune responses to what?
**Streptococcal M proteins** cross reacting with **cardiac** (among other) **self-antigens**
58
What are the distinctive lesions found in the heart during acute RF, and what do these lesions consist of?
- **Aschoff bodies**
- Consisting of: **T lymphocytes**, plasma cells, and **plump activated macrophages** called **Anitschkow cells**
59
Which cells are pathognomonic for RF?
Anitschkow cells (aka caterpillar cells)
60
During acute RF, diffuse inflammation and Aschoff bodies may be found in which layers of the heart, resulting in?
Pericarditis, myocarditis, or endocarditis = **Pancarditis**
61
Inflammation of the endocardium and the left-sides valves seen in acute RF results in what type of necrosis?
What is seen overlying these necrotic foci?
- **Fibrinoid necrosis** within the cusps of tendinous cords
- Overlying is **vegetations** called **verrucae**
62
Subendothelial lesions seen in acute RF can induce irregular thickenings in the **left atrium**, known as what?
MacCallum plaques
63
What are the cardinal anatomic changes seen in the leaflet and tendinous cords of the mitral valve with **chronic RHD?**
**- Leaflet thickening** + **commissural fusion** and **shortening**
**- Thickening** and **fusion** of the **tendinous cords**
**-** Results in **MITRAL STENOSIS**
64
In rheumatic mitral stenosis, calcification and fibrous bridging across the valvular commissures create a stenoses named what?
**Fish mouth** or **"buttonhole" stenoses**
65
With tight mitral stenosis seen in RHD what compensatory changes occur in the left atrium and it may harbor what?
**Left atrium** **DILATES** and may harbor **mural thrombi** that can **embolize**
66
With chronic RHD, long-standing congestive changes in the lungs may induce what changes and over time lead to hypertrophy of what?
Pulmonary vascular and parenchymal changes; over time lead to **right ventricular hypertrophy**
67
What is the JONES criteria for establishing diagnosis of RF?
- **J** = joints; **migratory polyarthritis** of **large** joints
- **O** = heart; **pancarditis**
- **N** = nodules; **subcutaneous**
- **E** = erythema marginatum
- **S** = sydenham chorea (involuntary rapid, purposless movements)
68
Acute RF appears how soon after a group A strep infection and most often in which pt population?
- **10 days** to **6 weeks**
- Most often in **children** btw ages **5-15**
69
Which 2 antibodies to streptococcal enzymes may be detected in the sera of pt with RF?
- Anti-**streptolysin O**
- Anti-**DNase B**
70
What are the 2 predominant clinical manifestations and features of each in RF?
Which is more common in affected adults?
- **Carditis** = pericardial friction rubs, tachycardia, and arrhythmias
- **Migratory polyarthritis** = more common **adults**
71
After an initial attack of RF there is an increased vulnerability to what?
**Reactivation** of the dz w/ subsequent **pharyngeal infections** and the same manifestations are likely to appear
72
Pt's with chronic RHD are may potentially suffer from what 3 consequences?
1) Atrial Fibrillation
2) Thromboembolic complications
3) Infective endocarditis
73
Infective endocarditis is an infection of **valves** and **endocardium**, characterized by the formation of what hallmark feature?
**Vegetations** composed of **thrombotic debris** and **organisms**, associated with underying tissue **destruction**
74
How does acute infective endocarditis differ from subacute infective endocarditis in the type of organism involved?
- **Acute IE** = infection by **highly** virulent bacteria (i.e., ***S. aureus****)*
* -* **Subacute IE** = infection w/ **lower** virulence bacteria (i.e., **Viridians strep**)
75
How does the treatment for acute infective endocarditis differ from subacute?
- **Acute** requires **surgery** in addition to **Abx**
- **Subacute** can be cured w/ Abx **alone**
76
What are 5 predisposing conditions which increase the risk of developing infective endocarditis?
- **RH**
- **Mitral valve prolapse**
- Degenerative **calcific valvular stenosis**
- **Bicuspid** aortic valves (w/ or w/o calcification)
- **Artificial (prosthetic) valves**
77
Which organism is most often responsible for infective endocarditis of **native** but **previously damaged** or **abnormal valves?**
*Streptococcus viridians*
78
Which bacteria is responsible for a majority of the mortality associated with infective endocarditis and is common in IV drug abusers?
*S. aureus*
79
Which bacteria is most often the culprit of infectious endocarditis in those with **prosthetic valves**?
**Coagulase-neg. staph** (*S. epidermidis)*
80
Which organisms make up the HACEK group which are sometimes implicated in infective endocarditis?
- **H**emophilus
- **A**ctinobacillus
- **C**ardiobacterium
- **E**ikenella
**-** **K**ingella
81
The most important among the risk factors for infective endocarditis are those that can cause microorganisms to do what?
**Seeding** into **blood stream** (**bacteremia or fungemia**) --\> infections elsewhere, dental/surgical procedures, contaminated needles
82
Which valves are most commonly infected during infective endocarditis?
**LEFT sided = Aortic** and **Mitral**
83
Valves of which side of the heart are most commonly infected in IV drug users with infective endocarditis?
Valves of the **right heart**
84
Vegetations seen in infective endocarditis can occasionally erode into the underlying myocardium and produce what?
**Ring abscess**
85
Vegetations of IE are prone to embolization and abscess development from the infected embolic fragments can lead to what complications?
- **Septic infarcts**
- **Mycotic aneursyms**
**- Pulmonary embolism** (if **right** side valve infected)
86
Microscopically, the vegetations of subacute IE typically exhibit what that is indicative of healing?
With time what else is seen?
- **Granulation** tissue at their bases
- With time = **fibrosis**, **calcification**, and **chronic** inflammatory infiltrate
87
What is the clinical presentation (signs/sx's) of infective endocarditis?
What may be heard upon auscultation in left-sided IE?
- Rapidly developing **fever** + Chills
- Weakness + Malaise
- **Left sided IE** = MURMUR
88
Which renal complication may occur within first few weeks of the onset of infective endocarditis?
Glomerulonephritis
89
Early dx/tx of infective endocarditis has nearly eliminated some previously common immunologic phenomena of long-standing IE, such as what (**list 4 of them**)?
- **Splinter** or **subungal** hemorrhages
- **Janeway lesions** = nontender lesions on the **palms** or **soles**
- **Osler nodules** = subcutaneous nodules in the pulp of **digits**
- **Roth spots** = **retinal hemorrhages** in the eyes
90
What is the etiology for each of these different forms of vegetative endocarditis from left to right?
- RHD
- IE
- Nonbacterial thrombotic endocarditis (NBTE)
- Libman-sacks endocarditis (LSE)
91
Which type of endocarditis is characterized by deposition of small **sterile** vegetations along the **lines of closure** of the leaflets or cusps of cardiac valves?
Nonbacterial Thrombotic Endocarditis (NBTE)
92
Although not invasive or inflammatory, NBTE can be a source of what?
**Systemic emboli** producing infarcts in **brain, heart**, or elsewhere
93
NBTE is often encountered in which patients and is seen occuring concomitantly with what underlying conditions?
- **Debilitated pt's** such as those w/ **cancer** or **sepsis**
- Occurs w/ **DVT's**, **pulmonary emboli**, or findings of **hypercoagulable** state
94
There is a striking association of NBTE with what malignancies?
**Mucinous adenocarcinomas --\> Trousseau syndrome**
95
Endocardial trauma, as from an indwelling catheter, is a well-recognized predisposing condition for what type of endocarditis?
NBTE
96
Which type of endocarditis used to be a common findings in SLE pt's until the use of steroids?
Libman-Sacks disease
97
What is the morphology of the lesions like in Libman-Sacks endocarditis associated with SLE?
Which valves are most often involved?
- Small, single or multiple, **sterile**, **pink vegetations** w/ **warty (verrucous)** appearance on either or **both** sides of valve leaflets
- **Mitral** \> Aortic
98
Histologically how do the vegetations in Libman-Sack endocarditis appear?
Vegetations in this setting are often associated with intense?
- Fine, **granular**, **fibrinous** eosinophilic material w/ **cellular debris**
- Associated with **intense vasculitis** --\> **fibrinoid necrosis** of valve
99
Thrombotic heart valve lesions with **sterile** vegetations or rare fibrous thickening can occur in the setting of what disease that induces a hypercoagulable state?
Antiphospholipid syndrome
100
Using the mnemonic **CARC**inoid, what are the manifestations of carcinoid syndrome?
- **C**utaneous flushing and **dermatitis**
- **A**sthmatic wheezing (**bronchoconstriction**)
- **R**ight-sided valvular heart lesions
- **C**ramping and **diarrhea**
101
Cardiac lesions of carcinoid syndrome ususally only occur after there is a massive burden where?
**Hepatic** metastatic burden
102
Which area of the heart is most often affected in Carcinoid Heart Disease?
**RIGHT-sided** **endocardium** and **valves**
103
Urinary excretion of what correlates with the severity of the cardiac lesions in carcinoid heart disease?
5-HIAA
104
What are the distinctive morphological features of the cardiac lesions seen in carcinoid heart disease?
Composed of smooth m. cells and sparse collagen fibers embedded in what?
**- Glistening white** intimal plaque-like **thickening** of the **endocardial surfaces** of the cardiac chambers and valve leaflets
- Embedded in an **acid mucopolysaccharide-rich matrix** material
105
What is the major complication associated with the use of mechanical prosthetic valves?
**Thromboembolism** --\> **thrombotic occlusion** of the prosthesis or **emboli** released from **thrombi** formed on the valve
106
Due to the major risk of thromboembolism associated with mechanical prosthetic valves, what long-term therapy must be given?
Long-term **anti-coagulation** tx
107
Which type of prosthetic valve (mechanical or bioprostheses) almost always undergoes structural deterioration?
Almost **ALL** bioprostheses eventually become **incompetent** due to **calcification** and/or **tearing**
108
Pt's with mechanical prosthetic valves must be on long-term anticoagulant therapy to prevent thromboembolism, but this puts them at a risk of what complication?
**Hemorrhagic stroke**
109
Infective endocarditis is a potentially serious complication associated with what type of prosthetic valve (mechanical or bioprostheses)?
**Both** :)
110
Although the right side of the heart is most often affected by carcinoid tumors, how may the left side become involved?
- **Atrial** or **septal** defects and **right-to-left flow**
- Elicited by **pulmonary carcinoid tumors**
111
The mechanism of heart failure in dilated cardiomyopathy (DCM) is an impairment in what?
Contractility (**systolic** dysfunction)
112
The mechanism of heart failure in hypertrophic **and** restrictive cardiomyopathy is an impairment in what?
Compliance (**diastolic** dysfunction)
113
Familial cases of dilated cardiomyopathy are linked to mutations in what gene?
Major inheritance pattern?
- Mutations in ***TTN***
- **Autosomal dominant**
114
X-linked forms of DCM may be due to mutations in which membrane-associated protein that is also seen mutated in the most common skeletal myopathies (i.e., Duchenne and Becker muscular dystrophies)?
Dystrophin
115
Alcohol abuse is strongly associated with what cardiomyopathy?
What is the toxic agent(s)?
- **Dilated** cardiomyopathy
- Alcohol and **acetaldehyde** are **directly** toxic to **myocardium**
116
Myocarditis can progress to what type of cardiomyopathy and is often associated with what virus?
- **Dilated** cardiomyopthy
- **Coxsackie B**
117
Familial cases of DCM are due to mutations of genes encoding proteins of what 4 important cellular components/proteins?
- **Cytoskeleton**
- Sarcomere
- Mitochondria
- Nuclear envelope
118
Which cardiotoxic drugs/substances are implicated in dilated cardiomyopathy?
- **Doxorubicin** (chemotherapy drug)
- **Cobalt**
119
Pregnancy-associated HTN, volume overload, and nutritional deficiency may cause what type of cardiomyopathy?
When during pregnancy does it occur?
- Special form of **DCM** = **peripartum cardiomyopathy**
- Occurs **late** in pregnancy or **up to few month post-partum**
120
What is the most common cardiac manifestation associated with **iron-overload** often seen in hereditary hemochromatosis or from multiple transfusions?
Dilated cardiomyopathy
121
What are some of the underlying causes of supraphysiologic stress which can lead to DCM?
- Persistent **tachycardia**, **hyperthyroidism** (ie Graves)
- **Fetuses** of insulin-dependent diabetic mothers
- Excess catecholamines --\> **pheochromocytomas**, **COCAINE**, or **vasopressors** such as **dopamine**
- Emotional duress --\> **takotsubo cardiomyopathy** (aka "broken heart syndrome")
122
What are the common gross morphological features of DCM?
Which type of thrombi are common and valvular alterations?
- **Dilation** of **ALL** chambers (enlarged, heavy, and **flabby**)
- **Mural thrombi** are common
- **NO** primary valvular alterations; **functional regurgitation** due to dilation may be present
123
Takotsubo cardiomyopathy (aka "broken heart syndrome") is due to the release of what?
**Excess catecholamines** following extreme emotional/physio. stress
124
Dilated cardiomyopathy typically manifests during what ages?
Presents with signs/sx's of what?
- **Age** 20-50 yo
- **Slowly** progressive signs/sx's of **CHF** --\> **dyspnea**, **easy fatigability**, and **poor exertional capacity**
125
What serious complications are associated with dilated cardiomyopathy?
- **Thrombus** 2' to stasis --\> **embolism (stroke)**
- **Arrhythmias** --\> sudden cardiac death
126
Arrhythmogenic right ventricular cardiomyopathy (ARVC) shows what characteristic gross morphology of the right ventricle?
**Severely thinned** wall, accompanied by extensive **fatty** infiltration and **fibrosis**
127
Arrhythmogenic right ventricular cardiomyopathy leads to failure of what and is associated with what rhythm disturbances?
- **Right**-ventricular failure
- **Ventricular tachycardia** or **fibrillation** ---\> **sudden death**
128
Arrhythmogenic right ventricular cardiomyopathy (ARVC) has what inheritance pattern?
Autosomal **dominant** w/ **variable penetrance**
129
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a component of what syndrome?
What is seen in this disease?
Due to what mutation?
- **Naxos syndrome**
- Characterized by **ARVC** + **hyperkeratosis** of **plantar palmar skin** surfaces
- Mutations in **desmosome**-associated protein **plakoglobin**
130
Which type of cardiomyopathy has a **100%** genetic cause?
**Hypertrophic** cardiomyopathy
131
Is arrhythmogenic right ventricular cardiomyopathy (ARVC) considered inflammatory or non-inflammatory?
**NON-inflammatory**
132
What is the most common cause of sudden, unexplained death in young athletes?
Hypertrophic Cardiomyopathy
133
Which phase of the cardiac cycle is dysfunctional in Hypertrophic Cardiomyopathy?
**Diastolic** dysfunction
134
How is the gross morphology and contractility of hypertrophic cardiomyopathy different from dilated cardiomyopathy?
- Heart is **thick-walled**, heavy, and **HYPERcontracting** in **HCM**
- Compared to **flabby** + **HYPOcontracting** heart in **DCM**
135
Mutations in genes encoding which functional cellular proteins is most often implicated in Hypertrophic Cardiomyopathy?
Which is most common?
**Sarcomeric** proteins **--\> β-myosin heavy chain** (**most common**)
136
In hypertrophic cardiomyopathy, the poorly compliant left ventricular myocardium leads to abnormal diastolic filling and can lead to intermittent what?
Ventricular **outflow obstruction**
137
Which cardiomyopathy is mostly associated with abnormal cytoskeletal proteins and can be conceptualized as a disease of **abnormal force generation**, **force transmisson**, or **myocyte signaling**?
**Dilated** Cardiomyopathy
138
What is the essential morphological feature of Hypertrophic Cardiomyopathy?
**Massive myocardial hypertrophy**, usually **W/O** ventricular dilation
139
In classic hypertrophic cardiomyopathy what is the disproportionate thickening that is seen?
Ventricular septum **relative to** left ventricle free wall, termed **asymmetric septal hypertrophy**
140
What are the 3 most important histologic features of hypertrophic cardiomyopathy?
1. **Massive** myocyte **hypertrophy**
2. **Haphazard** disarray of **bundles of myocytes** = **Myofiber disarray**
3. **Interstitial** and **replacement fibrosis**
141
Central abnormality of hypertrophic cardiomyopathy is reduced ________ due to impaired diastolic filling
Stroke volume
142
Due to compromised cardiac output and increased pulmonary congestion what type of dyspnea is seen pt's with HCM?
What is heard on auscultation?
- **Exertional** dyspnea
- **Harsh systolic ejection murmur** on auscultation
143
Due to the massive hypertrophy, high LV chamber pressure, and frequently thick-walled intramural arteries seen in HCM, there is often focal what?
Focal myocardial **ischemia**
144
What are the major clinical problems associated with HCM?
- **Atrial fibrillation**
- **Mural thrombus** --\> **emboli** (stroke)
- Cardiac failure, **ventricular arrhythmias** and **sudden death**
145
Reducing septal myocardial mass in HCM may be of some benefit and can be accomplished surgically or through carefully controlled septal infarction using what?
**Catheter**-based infusion of **alcohol**
146
Restrictive cardiomyopathy is characterized by a primary decrease in the compliance of what, resulting in what impairment?
Decreased **ventricular compliance** = **impaired** ventricular filling during **diastole**
147
What are 5 distinct diseases/processes affecting the myocardium which are associated with Restrictive Cardiomyopathy?
- **Radiation fibrosis**
- **Amyloidosis**
- **Sarcoidosis**
- **Metastatic tumors**
- **Inborn errors of metabolism**
148
What is the gross morphology of the ventricles and myocardium in Restrictive Cardiomyopathy?
What type of dilation is common?
- Ventricles = **normal sized**
- Myocardium = **firm** and **noncompliant**
- **BI-ATRIAL dilation** is **common**
149
Which **restrictive** condition is principally a disease of **children** and **young adults** in **Africa** and other tropical areas, characterized by fibrosis of the ventricular endocardium and subendocardium, often involving the **atrial** and **mitral** valve?
Endomyocardial fibrosis
150
Loeffler endomyocarditis results in endomyocardial fibrosis, with large mural thrombi, and what systemic manifestations?
- Peripheral **eosinophilia**
- **Eosinophilic infiltration** in **multiple organs**
151
Which toxic product released by eosinophils initiates endomyocardial necrosis --\> scarring, thrombosis and organization of the thrombus in Loeffler Endomyocarditis?
Major basic protein
152
Many pt's with Loeffler Endomyocarditis have what type of underlying disorder?
Associated w/ chromosomal rearrangements involving what GF?
- Myeloproliferative disorder
- **PDGFR**-α or -β genes
153
Which uncommon heart disease is most often seen in the first 2 years of life and is characterized by fibroelastic thickening of the LV endocardium?
Endocardial fibroelastosis
154
Endocardial fibroelastosis may represent a common morphological end-point due to what 2 insults?
- **Viral infections** (intrauterine exposure to **mumps**)
- Mutations in gene for **tafazzin**
155
What is the most commom cause of Myocarditis in the US?
**Viral infections** --\> **Coxsackie viruses A** and **B**
156
Inflammatory cytokines produced in response to myocardial injury causing **myocardial dysfunction** that is **out of proportion** to the degree of actual myocyte damage is characteristic of?
Myocarditis
157
Most common helminthic disease associated with myocarditis?
*Trichinella spiralis =* Trichinosis
158
Non-infectious causes of myocarditis are due to what conditions?
- **Hypersensitivity** --\> Post-strep (**RF**), **SLE**, **drug hypersensitivity**, and **transplant rejection**
- **Idiopathic** --\> **Giant cell myocarditis**
159
What type of infiltrates are seen in **Hypersensitivity Myocarditis**?
**Perivascular,** composed of **lymphocytes**, **macrophages**, and **high** proportion of **_eosinophils_**
160
Giant-cell myocarditis is characterized by **widespread** inflammatory infiltrates composed of?
**Multinucleate giant cells** + lymphocytes, eosinophils, plasma cells, and macrophages
161
What is the distinct morphology of the myocarditis of **Chagas disease**?
**Parasitization** of **scattered** myofibers by **trypanosomes** w/ **mixed inflammatory infiltrate** (neutrophils, lymphocytes, macrophages, and some eosinophils)
162
Clinical features of myocarditis can mimic what?
Late complication?
- Can mimic **acute MI**
- Late complication = **Dilated Cardiomyopathy**
163
Which chemotherapeutic drugs are cardiotoxic and can cause myocardial disease?
**Anthracyclines**: doxorubicin and daunorubicin
164
Amyloidosis results from the extracellular accumulation of protein fibrils which form?
**Insoluble** β-**pleated sheets**
165
Amyloidosis of the heart can appear as a consequence of what 2 underlying conditions?
- **Systemic** amyloidosis = **myeloma** or **inflammation-assoc.**
- Restricted to heart of **older** pt's w/ **senile cardiac amyloidosis**
166
In senile cardiac amyloidosis the deposits are largely composed of what protein?
Normal function of this protein?
**Transthyretin** = **trans**ports **thy**roxin and **retin**ol-binding protein
167
Cardiac amyloidosis most frequently causes what type of cardiomyopathy when deposits are in the interstitium?
**Restrictive** cardiomyopathy
168
Small, semitranslucent **nodules** resembling **wax drippings** seen on the **atrial** endocardial surface is characteristic of?
Cardiac **amyloidosis**
169
How can the hyaline eosinophilic deposits **of amyloid** in the interstitium, conduction tissue, valves, endocardium, pericardium, and intramural coronary arteries be distinguished from other deposits?
**Congo red stain** --\> **apple-green birefringence**
170
Acute, rapidly developing fluid collections of 200-300 mL in the pericardial sac can cause what fatal complication?
Cardiac Tamponade
171
Serous pericarditis is characteristically produced by what 5 non-infectious inflammatory diseases?
- Rheumatic fever
- SLE
- Scleroderma
- Tumors
- Uremia
172
What are the most frequent types of pericarditis?
**Fibrinous** and **serofibrinous pericarditis**
173
What are the most common causes of Fibrinous and Serofibrinous pericarditis?
- **Acute MI**
- **Postinfarction** (**Dressler**) syndrome
- **Uremia**
- **Chest radiation**
- **RF, SLE**, and **trauma**
174
What are the common sx's of fibrinous pericarditis?
Upon auscultation what's heard?
- **Pain** that is **sharp, pleuritic**, and **position dependent**
- **Fever**
- **LOUD** **pericardial friction rub** = most striking clinical finding
175
Purulent or suppurative pericarditis reflecting an active infection is most often a result of microbial invasion via what 4 routes?
- **Direct extension** from: **empyema**, **lobar pneumonia**, mediastinal infections, or ext. of **ring abscess** thru myocardium
- **Seeding from the blood**
- **Lymphatic extension**
- Direct introduction during **cardiotomy**
176
The intense inflammatory rxn of purulent or suppurative pericarditis eventually causes scarring and commonly leads to what?
**Constrictive pericarditis**
177
The active phase of purulent/suppurative pericarditis can resemble that of fibrinous, but the sx's differ how?
Marked systemic sx's ---\> **Spiking fevers** and **rigors**
178
Hemorrhagic pericarditis is most commonly caused by the spread of what?
**Malignant** neoplasm to the **pericardial space**
179
Caseous pericarditis is of what origin until proven otherwise?
Tuberculosis
180
In chronic/healing pericarditis, fibrosis in the form of mesh-like stringy adhesions completely obliterates the pericardial sac and is known as?
Effect on cardiac function?
- **Adhesive** pericarditis
- **NO** effect on cardiac function
181
**Adhesive mediastinopericarditis** may follow infectious pericarditis, previous cardiac surgery, or mediastinal irradiation leading to what clinical findings/problems?
- **Strains cardiac function**
- **Systolic** **retraction** of rib cage and diaphragm
- **Pulsus paradoxus =** ↓ systolic pressure upon inhalation
- **Increased** cardiac workload may cause **severe cardiac hypertrophy** and **dilation**
182
What are 3 signs of constrictive pericarditis?
1. Distant or muffled heart sounds
2. Elevated jugular venous pressure
3. Peripheral edema
183
What is the most common cardiac manifestation seen in Rheumatoid Arthritis?
May also see what in the myocardium, endocardium, valves, and aortic root?
**- Fibrinous** pericarditis
**- Granulomatous** rheumatoid nodules resembling the **subcutaneous nodules**
184
Rheumatoid valvulitis can lead to what morphological changes of the valves?
Marked **fibrous thickening** + **2' calcification** of aortic valve cusps
185
Myxomas may grow as what 2 distinct types of lesions?
Most often occur where in the heart?
- **Sessile** or **pedunculated**
- **90%** in the **ATRIA**, most often **LEFT-side**; most common in **fossa ovalis** in the **atrial septum**
186
Familial syndromes associated with myxomas are associated with what 2 genes and what are the associated syndromes?
- ***GNAS1*** encoding subunit of **Gs**α = **McCune-Albright syndrome**
- ***PRKAR1A*** encoding subunit of **cAMP**-dependent kinase = **Carney complex**
187
What is the clinical significance of the pedunculated form of Myxoma's?
- Often **mobile** and cause **intermittent obstruction** of **AV valve** during **systole**
- May exert **"wrecking ball" effect**, damaging valve leaflets
188
Major clinical manifestations of Myxomas are due to what and include?
- Valvular **"ball-valve"** obstruction
- **Embolization**
- Constitutional sx's = **fever** and **malaise**
189
Which cytokine elabortated by Myxomas is responsible for the consititutional sx's, such as fever and malaise?
**IL-6**
190
Histologically myxomas are composed of what cells?
Which peculiar structures are characteritics findings?
- **Stellate** or **globular myxoma cells**
- Peculiar **vessel-like** or **gland-like** structures
191
3 most common locations of lipomas in the heart?
- Left ventricle
- Right atrium
- Atrial septum
192
Which benign neoplasm of the heart is described as being "sea-anemone-like" lesions most often identified at autopsy, but may embolize and become clinically important?
Papillary Fibroelastoma
193
Papillary fibroelastomas are usually found on what in the heart?
How do they appear morphologically?
- 80% found on **valves** --\> ventricular surface of **semilunar valves**
- Distinctive **cluster** of **hairlike projections** up to 1 cm in length
194
What is the most frequent primary tumor of the pediatric heart and is commonly discovered at what age?
**Rhabdomyomas**; discovered in **first years** of life
195
50% of Rhabdomyomas are associated with mutations in what genes and disease?
**TSC1** and **TSC2 --\> Tuberous Sclerosis**
196
What is the characteristic gross and histologic morphology of Rhabdomyomas?
Involve which part of the heart most often?
- **Gray-white** masses; usually **multiple** and involve **ventricle**
- Composed of **bizarre**, enlarged **myocytes**
- **"Spider" cells** - thin strands of cytoplasm that stretch from nucleus to the surface membrane
197
Rhabdomyomas are typically discovered due to what complication?
Prognosis?
- **Obstruction** of valvular orifice or cardiac chamber
- Often **regress spontaneously**
198
The most frequent metastatic tumors involving the heart include what 4 types?
- **Carcinomas** of the **lungs** and **breast**
- **Melanomas**
- **Leukemias**
- **Lymphomas**
199
Tumors in what 2 locations most often reach the heart by **venous extension**?
- **Renal cell carcinoma**
- **Hepatic cell carcinoma**
200
What are 3 direct consequnces/effects on the heart caused by noncardiac neoplasms?
- **Pericardial** and **myocardial** metastasis
- **Large vessel obstruction** (i.e., Superior Vena Cava Syndrome)
- **Pulmonary tumor emboli**
201
What are 4 **indirect** consequences/effects on cardiac function produced by noncardiac neoplasms?
- Nonbacterial thrombotic endocarditisi
- Carcinoid heart disease
- Pheochromocytoma-associated heart disease
- Myeloma-associated amyloidosis
202
Clinical sx's associated with noncardiac neoplasms is most often associated with pericardial spread, which can cause what 2 complications?
- Symptomatic **pericardial effusions**
- **Mass-effect** sufficient enough to **restrict** **cardiac filling**
203
What is the major complication associated with cardiac transplantation?
**Allograft rejections**; either **cellular** or **Ab-mediated**
204
What is the single most important long-term limitation for cardiac transplantation?
**Allograft arteriopathy** = late, progressive, diffusely **stenosing intimal proliferation**
205
Allograft arteriography in a cardiac transplant is a problem because it can lead to what complications?
- **Silent MI** (transplant pt hearts are **denervated,** so no **angina** experienced)
- **Progressive CHF**
- **Sudden cardiac death**
206
Which malignancy may arise in cardiac transplant recipient due to chronic T-cell immunosuppression?
**EBV**-associated **B-cell lymphoma**
