Cardiac pathology 2 Flashcards
Valvular heart disease - stenosis
valve doesn’t open completely, occurs chronically
◦ Impedes forward flow
◦ Chronic stenosis may cause pressure overload hypertrophy → CHF
Valvular heart disease - insufficiency
valve doesn’t close completely, may occur acutely or
chroncally
◦ Allows reversed flow
◦ Chronic insufficiency may cause volume overload hypertrophy → CHF
Calcific aortic stenosis
◦ Most common valve abnormality
◦ Prevalence increases with age (usually manifest at 60-80 years)
◦ “wear and tear” associated with chronic HTN, hyperlipidemia, inflammation
◦ Bicuspid valves show an accelerated course
◦ Affected valves contain osteoblast-like cells, which deposit an
osteoid-like substance → ossifies
◦ Mounded calcifications in cusps prevent complete opening of the valve
◦ Pressure overload hypertrophy, CHF
Mitral annular calcification
◦ Calcific deposits occur in the fibrous annulus
◦ Normally does not affect valve function
◦ Nodules may become sites for thrombus formation or infective endocarditis
◦F > M
◦ > 60 years
◦ Mitral valve prolapse
Mitral valve prolapse
Valve leaflets prolapse back into LA during systole
Affects 2-3% adults in US, with a 7:1 F:M, usually incidental (mid systolic click)
Leaflets become thickened and rubbery, due to proteoglycan deposits (myxomatous degeneration) and elastic fiber disruption
May also occur as a complication of other causes of regurgitation (dilated hypertrophy)
Most are asymptomatic, a minority may experience:
◦ Pain mimicking angina
◦ dyspnea
Serious (but rare) complications may include: ◦ Infective endocarditis ◦ Mitral insufficiency ◦ Thromboembolism ◦ Arrhythmias
Rheumatic fever and rheumatic heart disease
multisystem inflammatory disorder following pharyngeal infection with group A streptococcus
Incidence decreased with more rapid diagnosis and treatment of strep infections
Acute rheumatic fever may include a carditis component, and over time may evolve to chronic rheumatic heart disease.
Rheumatic fever/heart disease pathogenesis
immune response to streptococcal M proteins cross reacts with cardiac (among other) self- antigens.
Acute RF occurs 10 days to 6 weeks after a grp A strep infection
◦ Anti-streptolysin O; anti-DNase B RF can include:
◦ Pancarditis, migratory polyarthritis, subcutaneous nodules, rash, Sydenham chorea
Cardiac features of acute RF
◦ Pancarditis, featuring Aschoff bodies
◦ Inflammation and fibrinoid necrosis of endocardium and left-sided valves, with verrucae (vegetations)
◦ Repeated streptococcal infections will cause these features to recur
◦ Chronic RHD: mitral leaflet thickening, fusion and shortening of commisures, fusion and thickening of tendinous cords, resulting in mitral stenosis
◦ LA enlargement → atrial fib/thrombosis; pulmonary congestion/RHF
Acute infective endocarditis
rapidly progressing, destructive infection of a previously normal valve
◦ Requires surgery in addition to antibiotics
Subacute infective endocarditis
slower-progressing infection of
a previously deformed valve (such as in chronic RHD)
◦ Can often be cured with antibiotics alone
Infective endocarditis predisposing conditions
◦ 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
◦ Left-sided valves are more commonly affected (right-sided valves often involved in IV drug abusers)
◦ Friability leads to septic emboli
◦ Vegetations are mixtures of fibrin, inflammatory cells, and organisms
◦ Subacute vegetations may have a granulation tissue component
Infective endocarditis presentation
Patients may present with nonspecific symptoms
◦ Fever, weight loss, fatigue
Murmurs are usually present with left-sided lesions
Organisms 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)
Nonbacterial thrombotic endocarditis
◦ Small, sterile thrombi on cardiac valve leaflets, along the line of closure
◦ May be a source of emboli
◦ Associated with malignancies (especially mucinous adenocarcinomas), sepsis, or catheter-induced endocardial trauma
Dilated cardiomyopathy - pathogenesis
Progressive cardiac dilation and systolic dysfunction, usually with dilated hypertrophy
Pathogenesis:
◦ Thought to be familial in 30-50% of cases (TTN mutations may account for 20% of all cases); usually autosomal dominant.
◦ Alcohol is strongly linked to DCM
◦ Myocarditis
◦ Cardiotoxic drugs/substances: doxorubicin, cobalt, iron overload
Dilated cardiomyopathy morphology
dilation of all chambers
mural thrombi are common functional regurgitation of valves
Dilated cardiomyopathy - presentation
usually manifests between ages 20-50
progressive CHF → dyspnea, exertional fatigue, ↓ EF
arrhythmias
embolism
Takotsubo cardiomyopathy
“Broken heart syndrome”
Excess catecholamines following extreme emotional or psychological stress
◦ >90% women, ages 58-75
◦ Symptoms and signs similar to acute myocardial infarction
◦ Apical ballooning of the left ventricle with abnormal wall motion and contractile dysfunction
Arrhythmogenic right ventricular cardiomyopathy
Right ventricular failure and arrhythmias
◦ Myocardium of the right ventricular wall replaced by adipose and fibrosis
◦ Causes ventricular tachycardia and fibrillation, sudden death Familial (usually autosomal dominant)
Hypertrophic cardiomyopathy
A genetic disorder leading to myocardial hypertrophy and diastolic dysfunction, leading to reduced stroke volume and often ventricular outflow obstruction
Numerous mutations known, involving sarcomeric proteins
◦ Most commonly β-myosin heavy chain
Morphology: massive myocardial hypertrophy, often with marked septal hypertrophy. Microscopically, myocyte disarray.
Consequences of extensive hypertrophy
◦ Foci of myocardial ischemia may occur
◦ Left atrial dilation and mural thrombus
◦ Diminished cardiac output and increased pulmonary congestion leads to exertional dyspnea
◦ Arrhythmias
◦ Sudden death
Restrictive cardiomyopathy
Decreased ventricular compliance (increased stiffness), leading to diastolic dysfunction.
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.
Amyloid
Extracellular deposition of proteins which form an insoluble β-pleated sheet.
May be systemic (myeloma) or restricted to the heart (usually transthyretin)
◦ Certain mutated versions of 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.
Myocarditis
Inflammation of the myocardium, most commonly due to a virus.
◦ Coxsackie A and B viruses are most common
Other infectious causes include
◦ Trypanosomes (Chagas disease)
◦ Various bacteria and fungi
Noninfectious causes include
◦ Immune mediated reactions, including RF, SLE, drug hypersensitivity
Congenital heart disease
“Sporadic genetic abnormalities are the major known causes of congenital heart disease.”
◦ The single most common genetic cause of congenital heart disease is trisomy 21
◦ About 40% patients with Down syndrome have at least one heart defect
Atrial septal defect
Usually asymptomatic until adulthood
The left-to-right shunting causes volume overload on the right side, which may lead to
◦ Pulmonary hypertension
◦ Right heart failure
◦ Paradoxical embolization
◦ May be closed surgically, with normal survival
Ventricular septal defect
Most common form of congenital heart disease
Effects depend on size, and presence of other heart defects
Many small VSDs close spontaneously
Large VSDs may cause significant shunting, leading to
◦ Right ventricular hypertrophy
◦ Pulmonary hypertension, which can ultimately reverse flow through the shunt, leading to cyanosis
Patent ductus arteriosis
May fail to close when infants are hypoxic, and/or have defects associated with increased pulmonary vascular pressure (VSD)
PDA produces a harsh, machinery-like murmur
Effect is determined by the shunt’s diameter
◦ Large shunts can increase pulmonary pressure and eventually shunt reversal and cyanosis
Tetralogy of Fallot
Four cardinal features:
◦ VSD
◦ Obstruction of RV outflow tract ◦ Aorta overrides the VSD
◦ RV hypertrophy
Heart is enlarged and “boot shaped” because of the right ventricular hypertrophy
Clinical severity depends on the degree of subpulmonary stenosis
◦ Mild stenosis: L to R shunt. Classic TOF is R to L shunting with cyanosis
Transposition of the great arteries
Results in two separate circuits, incompatible with life after birth unless a shunt is present for mixing of blood from the two circuits
◦ Approximately one third have a VSD
◦ Two thirds have a patent foramen ovale or PDA
◦ Right ventricle becomes hypertrophic (supports systemic circulation) and the left ventricle atrophies.
◦ Without surgery, patients will die within a few months
Coarctation of the aorta
Narrowing of the aorta, generally seen with a PDA (infantile form), or without a PDA (adult form).
Degree of narrowing is variable, with variable clinical effect
Coarctation with PDA manifests at birth: may produce cyanosis in the lower half of the body
Coarctation without PDA – usually asymptomatic
◦ Hypertension in upper extremities, hypotension in lower extremities
◦ Claudication and cold lower extremities
◦ May eventually see concentric LV hypertrophy
