Arrhythmias, SCD, HTN, Cardiac Valve Dz, Cardiomyopathy, Pericardial Dz, Cardiac Tumors, Transplantation Flashcards
Ischemic injury is the most common cause of rhythm disorders including sick sinus syndrome, afib, and heart block. What is sick sinus syndrome?
Bradycardia d/t SA node damage
Condition in which myocytes depolarize independently and sporadically (atrial dilation) with variable transmission through AV node; auscultated as irregularly irregular rhythm
Atrial fibrillation
Heart block occurs as a result of dysfunctional ___ node
What are the 3 degrees of heart block?
AV
3 degrees of heart block:
First degree = prolonged PR interval
Second degree = intermittent transmission
Third degree = complete failure
Arrhythmias may result from abnormalities in ____ junction structure or spatial relationship, such as those that occur in IHD, dilated cardiomyopathies, myocyte hypertrophy, inflammation (myocarditis or sarcoid), amyloid, etc
Gap
Most hereditary conditions resulting in arrhythmia are _____ inheritance. Primary electrical disorders are dx through genetic testing. ______ are diseases associated with mutations in genes that are required for normal ion channel function, often associated with skeletal m. disorders and diabetes
Autosomal dominant; channelopathies
Most common inherited arrhythmogenic disease
Long QT syndrome
[associated with gene defects in KCNQ1, KCNH2, SCN5A, CAV3; results in LOF of K+ channel or GOF of Na channel or caveolin]
4 inherited arrhythmogenic diseases
Long QT syndrome (most common)
Short QT syndrome (GOF in K+ channel)
Brugada syndrome (LOF in Na or Ca channel)
CPVT syndrome (GOF or LOF in diastolic Ca release)
Sudden cardiac death is due to a fatal _____ most often arising from ischemia-induced myocardial irritability; it may occur without symptoms or within 1-24 hours of symptom onset. 80-90% of successively resuscitated pts show ____ on ECG
arrhythmia; Nothing!
80-90% show no lab or ECG changes
_______ precipitates sudden cardiac death in 80-90% of cases
CAD — usually with >75% stenosis of one or more of the 3 main coronary arteries
Unfortunately, SCD may be the first manifestation of IHD; healed remote MIs are seen in about 40%
CAD is the most common cause of sudden cardiac death. What are some other possible causes?
Cardiomyopathy, myocarditis, congenital abnormalities of conduction system, myocardial hypertrophy
Describe changes in the heart with left-sided hypertensive disease
Pressure overload —> left ventricular hypertrophy (concentric thickening)
Diastolic dysfunction can result in left atrial enlargement, which may lead to afib
May lead to CHF
Risk factor for SCD!
Describe right-sided hypertensive disease
Isolated right-sided hypertensive heart disease arises in the setting of pulmonary hypertension
Acute cor pulmonale may arise from a large pulmonary embolus —> marked dilation of RV without hypertrophy
[remember most common cause of pulmonary HTN is LEFT-sided heart dz]
Diseases predisposing to cor pulmonale include diseases of pulmonary parenchyma, diseases of pulmonary vessels, disorders affecting chest movement, and disorders inducing pulmonary arterial constriction. What are some associated diseases of the pulmonary parenchyma?
COPD Diffuse pulmonary interstitial fibrosis Pneumoconiosis Cystic fibrosis Bronchiectasis
Diseases predisposing to cor pulmonale include diseases of pulmonary parenchyma, diseases of pulmonary vessels, disorders affecting chest movement, and disorders inducing pulmonary arterial constriction. What are some associated diseases of the pulmonary vessels?
Recurrent PE Primary pulm HTN Extensive pulmonary arteritis Drug, toxin, radiation-induced obstruction Extensive pulmonary tumor microembolism
Diseases predisposing to cor pulmonale include diseases of pulmonary parenchyma, diseases of pulmonary vessels, disorders affecting chest movement, and disorders inducing pulmonary arterial constriction. What are some associated disorders affecting chest movement?
Kyphoscoliosis
Marked obesity (OSA, pickwickian syndrome)
Neuromuscular dz
Diseases predisposing to cor pulmonale include diseases of pulmonary parenchyma, diseases of pulmonary vessels, disorders affecting chest movement, and disorders inducing pulmonary arterial constriction. What are some associated diseases inducing pulmonary arterial constriction?
Metabolic acidosis
Hypoxemia
Chronic altitude sickness
Obstruction of major airways
What is the difference between valvular stenosis and valvular insufficiency?
Stenosis = valve doesn’t OPEN completely; occurs chronically, impeding FORWARD flow
Insufficiency = valve doesn’t CLOSE completely; may occur acutely or chronically, allowing REVERSED flow
Chronic stenosis may cause _____ overload hypertrophy —> CHF
Chronic insufficiency may cause ____ overload hypertrophy —> CHF
Pressure
Volume
Virtually the ONLY cause of mitral stenosis
Postinflammatory scarring d/t rheumatic heart disease
Causes of mitral regurgitation
Abnormalities of leaflets and commissures: postinflammatory scarring, infective endocarditis, mitral valve prolapse, drugs (fen-phen)
Abnormalities of tensor apparatus: rupture of papillary muscle, papillary muscle dysfunction/fibrosis, rupture of chordae tendinae
Abnormalities of LV and/or annulus: LV enlargement (myocarditis, dilated cardiomyopathy), calcification of mitral ring
Causes of aortic stenosis
Postinflammatory scarring (rheumatic heart disease)
Senile calcific aortic stenosis
Calcification of congenitally deformed valve
Causes of aortic regurgitation
Abnormalities of leaflets and commissures: postinflammatory scarring (RHD)
Abnormalities of tensor apparatus: degenerative aortic dilatation, SYPHILITIC AORTITIS, ankylosing spondylitis, rheumatoid arthritis, MARFAN
Most common valve abnormality and commonly associated comorbidities
Calcific aortic stenosis — “wear and tear” phenomenon associated with chronic HTN, hyperlipidemia, and inflammation
With calcific aortic stenosis, ____ valves will show an accelerated course. Affected valves contain ____-like cells which deposit substance that creates mounded calcifications in cusps which prevent complete opening of the valve
Bicuspid; osteoblast (deposit osteoid like substance that ossifies)
Symptoms and clinical features of calcific aortic stenosis
Angina, CHF, or syncope
Increased pressure causes LVH
Most pts with aortic stenosis will die within 5 years of developing angina, within 3 years of developing syncope, and within 2 years of CHF onset
Mitral annular calcification involves calcific deposits in the fibrous annulus. It normally does NOT affect valve function. However, nodules may becomes sites for ______ formation or _____ _____. It is most common in females > males, > 60 yrs, and with pts who have ________
Thrombus; infective endocarditis; mitral valve prolapse
Most bicuspid aortic valves are prone to calcification. Patients can remain relatively asymptomatic until stenosis reaches a critical point when _____ rapidly ensues. The dense white nodules of calcification are present on both valve surfaces
CHF
[while bicuspid aortic valves are especially susceptible, an aortic valve does not need to be bicuspid to calcify. Sometimes in older adults, a normal aortic valve will undergo calcification = “senile calcific aortic stenosis”]
Mitral valve prolapse often occurs in those with ____ syndrome or as a complication of other cuases of regurgitation like dilated hypertrophy. On auscultation, a _____ may be noted
Marfan; mid-systolic click
Mitral valve prolapse occurs when valve leaflets prolapse into the ____ during systole. It affects 2-3% of adults in the US with a female predominance. Leaflets become thickened and rubbery due to disorganized ______ deposits, aka ______ degeneration, and elastic fiber disruption
LA; proteoglycan; myxomatous
Symptoms and complications associated with mitral valve prolapse
Most are asymptomatic but a minority may experience pain mimicking angina and/or dyspnea
Serious (but rare) complications may include: Infective endocarditis Mitral insufficiency Thromboembolism Arrhythmias
Rheumatic fever is a multisystem inflammatory disorder occurring 10 days to 6 weeks following pharyngeal infection with _________; acute rheumatic fever may include a carditis component, and over time may evolve into ____________
Group A streptococcus
Chronic rheumatic heart disease
Pathogenesis of rheumatic fever
Immune response to streptococcal M proteins, which cross react with cardiac (among other) self-Ags
Lab tests used to dx acute rheumatic fever
ASO and anti-DNase B
General clinical features of rheumatic fever
Pancarditis Migratory polyarthritis Subcutaneous nodules Rash (erythema marginatum) Syndenham chorea
Specific cardiac features of acute rheumatic fever
Pancarditis featuring Aschoff bodies
Inflammation and fibrinoid necrosis of endocardium and left-sided valves, with verrucae (vegetations)
[Repeated strep infections will cause these features to recur!]
Cardiac findings with chronic rheumatic heart disease
Mitral leaflet thickening, fusion and shortening of commissures, fusion and thickening of tendinous cords, resulting in mitral stenosis, neovascularization
LA enlargement may lead to afib or thromboembolic events
Pulmonary congestion/RHF
Infective endocarditis
Surgical repair/prosthetic valve replacement
Where do the verrucae tend to line up in rheumatic fever?
Along lines of valve closure
Central wavy ribbon of chromatin in macrophages is characteristic of ____ cells in acute RHD
Anitschkow
Infective endocarditis is an infection of valves and endocardium, characterized by ____ consisting of microbes and debris, associated with underlying tissue destruction.
What is the difference between acute and subacute IE?
Vegetations
Acute: rapidly progressing, destructive infection of previously normal valve; requires surgery in addition to abx. Necrotizing, ulcerative destructive lesions, ring abscesses, emboli —> septic infarcts or mycotic aneurysm
Subacute: slower-progressing infection of previously deformed valve (such as chronic RHD); can often be cured with abx alone. Granulation tissue, fibrosis, calcification, chronic inflammatory cells, vague flu-like sxs
Predisposing conditions to infective endocarditis
Valvular abnormalities — RHD, prosthetic valves, MV prolapse, calcific stenosis, bicuspid AV
Bacteremia — another site of infection, dental work, surgery, contaminated needle, compromised epithelium
Classic features of infective endocarditis
Friable, bulky destructive valvular vegetations; pts present with fever, weight loss, fatigue
Left-sided vavles more commonly affected - usually hear murmur (right-sided valves — think IV drug users)
Friability leads to septic emboli (PE if right sided valve)
Vegetations are mixtures of fibrin, inflammatory cells, and organisms; subacute vegetations may have granulation tissue component
Organisms typically involved in infective endocarditis
S.viridans —> valve abnormalities
S.aureus —> normal valves, abnormal valves, IV drug abusers
S.epidermidis —> prosthetic valves
HACEK: Hemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella
In summary: vegetative endocarditis manifesting as —
Warty, line of closure = _____
Large, irregular = _______
Small, line of closure = ______
Both sides of valve affected = ____
RHD
IE
NBTE
LSE (libman sacks endocarditis — think lupus)
Name some of the vascular lesions and immunologic phenomena that constitute minor diagnostic criteria for infective endocarditis
Vascular lesons: arterial petechiae, subungual/splinter hemorrhages, Janeway lesions
Immunologic phenomena: osler nodes, roth spots
Disease characterized by small, sterile thrombi on cardiac valve leaflets along the line of closure that are loosely attached, non-invasive, and do not elicit an inflammatory reaction but may be a source of emboli; associated with malignancy (especially mucinous adenocarcinomas), sepsis, or catheter-induced endocardial trauma
Nonbacterial thrombotic endocarditis (NBTE)
Systemic disorder marked by flushing, diarrhea, dermatitis, and bronchoconstriction d/t release of bioactive compounds such as serotonin
Carcinoid syndrome
[5-hydroxyindoleacetic acid levels correlate with severity of cardiac lesions]
50% of pts with systemic carcinoid syndrome develop cardiac manifestations. Describe carcinoid heart disease
Affects right endocardium and valves; the left side is protectd d/t pulmonary vascular bed degradation of mediators
[lesions appear similar to pts taking fen-phen or ergot alkaloids for migraine as they affect systemic serotonin metab]
Gross and histologic findings associated with carcinoid heart dz
Grossly: glistening white intimal plaque-like thickenings of the endocardial surfaces of the cardiac chambers and valve leaflets
Histo: intimal thickening (acid mucopolysaccharide-rich)
Complications of cardiac valve prostheses
Thrombosis/thromboembolism
Anticoagulant-related hemorrhage
Prosthetic valve endocarditis
Structural deterioration — wear, fracture, poppet failure in ball valves, cuspal tear, calcification
Inadequate healing (paravalvular leak), exuberant healing (obstruction), hemolysis
Most common cardiomyopathy and its associated mechanism of heart failure
Dilated cardiomyopathy — causes impairment of contractility (systolic dysfunction) — also has most significant change in EF —> <40%
[indirect myocardial dysfunction includes IHD, valvular heart disease, hypertensive heart disease; congenital heart disease]
Causes of dilated cardiomyopathy
Genetic Alcohol Peripartum Myocarditis Hemochromatosis Chronic anemia Doxorubicin toxicity Sarcoidosis Idiopathic
What 2 types of cardiomyopathy result from impairment of compliance (diastolic dysfunction)?
Hypertrophic cardiomyopathy — presents like hypertensive heart disease or aortic stenosis
Restrictive cardiomyopathy — presents like pericardial constriction
LV EF and causes of hypertrophic cardiomyopathy
LV EF = 50-80%
Causes: genetic, friedrich ataxia, storage diseases, infants of diabetic mothers
LV EF and causes associated with restrictive cardiomyopathy
LV EF = 45-90%
Causes: amyloidosis; radiation-induced fibrosis; idiopathic
Dilated cardiomyopathy = progressive cardiac dilation and systolic dysfunction, usually with dilated hypertrophy
What are the genetic components of dilated cardiomyopathy?
Thought to be familial in 30-50% of cases
TTN (titin) mutations may account for 20% of all cases
Usually autosomal dominant
Risk factors and associations in the pathogenesis of dilated cardiomyopathy
Alcohol is strongly linked to DCM
Myocarditis
Cardiotoxic drugs/substances like doxorubicin and iron overload (may occur with hereditary hemochromatosis (HFE mutation))
Morphology of dilated cardiomyopathy
Dilation of all chambers
Mural thrombi are common
Functional regurgitation of valves
Clinical Presentation of dilated cardiomyopathy
Usually manifests between ages 20-50
Progressive CHF —> dyspnea, exertional fatigue, decreased EF (<25% end stage)
Arrhythmias
Embolism
Cardiomyopathy associated with excess catecholamines following extreme emotional or psychological stress; occuring in women 90% of the time, typically ages 58-75
Takotsubo cardiomyopathy
What cardiomyopathy is associated with apical ballooning of the left ventricle with abnormal wall motion and contractile dysfunction?
Takotsubo cardiomyopathy
Hypertrophic cardiomyopathy is considered 100% genetic. What is the associated phenotype?
Marked hypertrophy as well as asymmetrical septal hypertrophy
MYOFIBER DISARRAY
Fibrosis
LV outflow tract plaques
Thickened septal vessels
Describe myocardial findings and inheritance pattern associated with arrhythmogenic right ventricular cardiomyopathy (ARVC)
Right ventricular failure and arrhythmias — myocardium of the right ventricular wall is replaced by ADIPOSE and FIBROSIS —> ventricular tachycardia or fibrillation —> sudden death
Familial, autosomal dominant (defective cell adhesion proteins in desmosomes that link adjacent cardiac myocytes)
Arrhythmogenic right ventricular cardiomyopathy with hyperkeratosis of plantar palmar skin surfaces
Naxos syndrome
Naxos syndrome = Arrhythmogenic right ventricular cardiomyopathy with hyperkeratosis of plantar palmar skin surfaces. This is caused by mutations in the gene encoding the desmosome-associated protein ______
Plakoglobin
Hypertrophic cardiomyopathy is a genetic disorder leading to myocardial hypertrophy and diastolic dysfunction —> reduced stroke volume and often ventricular outflow obstruction. It is due to numerous mutations involving _____ proteins, most commonly ______
Sarcomeric; beta-myosin heavy chain
Consequences of hypertrophic cardiomyopathy
Foci of myocardial ischemia may occur
Left atrial dilation and mural thrombus
Diminished CO and increased pulmonary congestion —> exertional dyspnea (may be seen in athletes!)
Arrhythmias
Sudden death!
In what type of cardiomyopathy are the ventricles usually normal sized but BOTH atria can be enlarged?
Restrictive cardiomyopathy
Describe restrictive cardiomyopathy
Decreased ventricular compliance (increased stiffness) —> diastolic dysfunction (impaired filling), while systolic function of LV remains normal
May be secondary to deposition of material within the wall (amyloid) or increased fibrosis (radiation)
Ventricles are usually of normal size but both atria can be enlarged
Describe restricive cardiomyopathy associated with amyloid deposition
Extracellular deposition of proteins which form an insoluble beta pleated sheet — stains with congo red stain —> apple green birefringence
May be systemic (myeloma) or restricted to the heart (usually transthyretin)
Note: certain mutated version fo transthyretin are more amyloidogenic; amyloid can involve different parts of the heart, but when deposits are in the interstitium of the myocardium, a restrictive cardiomyopathy results
In the US, myocarditis is most commonly due to a virus. What are the most common viruses implicated? What are some other infectious causes?
Most common = Coxsackie A and B
Other infectious causes = Trypanosoma cruzi (Chagas disease), various bacteria and fungi
Describe myocarditis caused by trypanosoma cruzi
10% die during acute attack
May progress to cardiac insufficiency in 10-20 years
Parasitization of scattered myofibers; mixed inflammatory cell infiltrate (PMN, lymphocytes, macrophages, and occasional eosinophils)
Noninfectious causes of myocarditis
Immune mediated reactions including RF, SLE, drug hypersensitivity (see eosinophils on histology!! Vs. parasites if caused by chagas)
Pericardial disease is characterized by > 50 mL of fluid surrounding the heart. What is the difference between slow vs. fast accumulation?
Slow accumulation of <500 mL may remain symptomatic as long as it is slow enough — may see globular enlargement of the heart shadow on CXR
An acute, rapid gain of 200-300 mL —> cardiac tamponade
Most common types of pericardial disease
Fibrinous and serofibrinous — associated with AMI, postinfarction (Dressler’s), uremia, chest irradiation, RF, SLE, trauma, etc.
Fibrinous = dry, finely granular
Serofibrinous = yellow-brown, turbid fluid w/ WBCs, RBCs, and fibrin
Symptoms of fibrinous or serofibrinous pericarditis
Pain (sharp, pleuritic, and positional)
Fever
+/- CHF
Most striking feature = loud pericardial friction rub!
Primary cardiac tumors are rare, what are some examples?
Myxoma Fibromas Lipomas Papillary fibroelastomas Rhabdomyomas Angiosarcomas
Most common primary, pedunculated or sessile, cardiac tumor; usually located in region of fossa ovalis
Myxoma
Familial syndromes associated with myxomas have activating mutations in the ____ gene, in association with ______ syndrome; OR null mutations in ______ as part of the _____ complex
GNAS1; McCune-Albright
PRKAR1A; Carney
Describe appearance of myxoma
Globular hard mass, mottled with hemorrhage; may also be soft, translucent, papillary, or villous with a gelatinous appearance
Symptoms associated with myxoma
“Ball-valve” obstruction — meaning sxs may be positional
The pedunculated form causes intermittent obstruction during systole of AV valve; or “wrecking ball” causing damage to the valve leaflets
Constitutional sx: elaboration of IL-6 by some myxomas
Auscultation may reveal positional “tumor plop”
Describe major complications associated with heart transplants
Allograft rejection (requires routine endomyocardial bx to monitor)
Allograft arteriopathy = most important long-term compl. —late, progressive, diffusely stenosing intimal proliferation, silent MI (denervated transplanted heart = no angina)
EBV associated B-cell lymphoma — d/t chronic T-cell immunosuppression
