5: IVDU Flashcards
Features of calcific aortic stenosis
- Calcification + fibrosis of aortic valve
- Most common heart valve disorder in the West
- Prevalence 2%
- Older age and bicuspid aortic valve (BAV) are risk factors
Presents in 7th-9th decade, patients with BAV present earlier
Causes of calcific aortic stenosis
○ Thought to be associated with ‘wear and tear’
○ Chronic injury due to hyperlipidaemia, HTN, inflammation and factors associated with atherosclerosis cause degeneration of valve leaflets
○ Leads to deposition of hydroxyapatite
The abnormal valves contain cells resembling osteoblasts that synthesise bone matrix proteins and promote deposition of calcium salts
Morphological features of calcific aortic stenosis
○ Gross
§ Hallmark - mounded calcified masses on the outflow surfaces of the cusps that ultimately prevent cuspal opening
§ Free edges of the cusp not involved
○ Microscopic
§ The layered architecture of the valve is largely preserved
§ The calcific process begins in the valvular fibrosa on the outflow surface of the valve, at the points of maximal cusp flexion (near the margins of attachment).
§ Inflammation is variable, and metaplastic bone can be seen
Complications of calcific aortic stenosis
- LV hypertrophy
□ Calcific nodules decrease functional valve area -> outflow obstruction
□ LV pressure rises, producing concentric LV (pressure overload) hypertrophy. - Ischaemia
□ The hypertrophied myocardium tends to be ischaemic (as a result of diminished microcirculatory perfusion, often complicated by coronary atherosclerosis) - Congestive heart failure
□ Both systolic and diastolic myocardial function may be impaired; eventually, cardiac decompensation and CHF can ensue
Which groups are more likely to have a bicuspid aortic valve?
- Most common congenital heart defect
- Problems
○ Stenosis -> heart failure
○ Regurgitation
○ Infective endocarditis
○ Aortic aneurysm and dissection
○ Calcification - At risk groups
○ Some cases of BAV show familial clustering, often with associated aortic or LV outflow tract malformations
○ Loss of function mutations in NOTCH1 (mapping to chromosome 9q34.3) have been specifically associated with BAV in a few families
- Problems
Features of mitral valve prolapse
- (myxomatous degeneration of the mitral valve)
- One or both mitral valve leaflets are ‘floppy’ and protrude into the left atrium during systole.
- Most often an incidental finding but can cause significant complications in a minority
- Valve leaflets balloon upward as the ventricle contracts
Causes of mitral valve prolapse
○ Unknown in most cases.
○ Most are congenital, tends to run in families
○ Increased risk in:
§ CTDs (Marfan syndrome, Ehlers Danlos)
§ Graves disease
§ Skeletal problems (scoliosis)
§ Some types of muscular dystrophy
○ Rarely, it can be caused by damage to the heart muscles itself – for example, as the result of a heart attack
Morphological features of mitral valve prolapse
○ Gross
§ Ballooning of leaflets
§ Affected leaflets often enlarged, thick and rubbery
§ Associated tendinous cords may be elongated, thinned or even ruptured and annulus may be dilated
○ Microscopic
§ Collagen in fibrosa layer is loose and disorganised
§ Increased proteoglycan deposition in spongiosa layer
§ Elastin in arterioles layer disorganised
○ Secondary changes
§ Fibrous thickening of the leaflets, particularly where they rub against each other
§ Linear fibrous thickening of the left ventricular endocardial surface where the abnormally long cords snap or rub against it
§ Thickening of the mural endocardium of LV or atrium as a consequence of friction-induced injury induced by the prolapsing, hypermobile leaflets
§ Thrombi on arterial surfaces of leaflets or the atrial walls
§ Focal calcifications at base of posterior mitral leaflets
Complications of mitral valve prolapse
§ Can progress to mitral regurgitation
§ MR leads to atrial dilation
□ Arrhythmias e.g. AF
□ Thrombus formation and embolization
□ Stroke
§ Increased infective endocarditis risk
□ A deformed mitral valve flap can attract bacteria in the bloodstream. The bacteria attach to the valve
Causes of rheumatic heart disease
- Heart valve damage due to rheumatic fever
○ Mitral > aortic > tricuspid > pulmonary- RF: autoimmune inflammatory response to group A Streptococcal pharyngitis (Strep throat), rarely skin infections, scarlet fever
- Occurs few weeks after Strep infection
○ Takes time to generate immune response - RF is most often a childhood condition (5-15 years)
Pathophysiology of rheumatic heart disease
○ Host response to group A streptococcal antigens cross-react with host proteins: synovium, heart muscle and valves, CNS, skin (molecular mimicry)
○ Antibodies and CD4+ cells against streptococcal M proteins in some cases recognise cardiac self-antigens
○ Approx. 50% develop RHD
○ After initial attack, increased chance of reactivation of disease with subsequent pharyngeal infections
○ Damage to valves is cumulative- Turbulence induced by ongoing valvular deformities leads to additional fibrosis.
○ Familial studies of rheumatic heart disease suggest a vulnerable population with increased risk. Relationships between the development of rheumatic fever and human leukocyte antigen (HLA)-DR subtypes have been found
Morphology of rheumatic heart disease
○ Gross
§ Leaflet thickening, commissural fusion and shortening, and thickening and fusion of the tendinous cords
§ Vegetations (verrucae) along lines of closure of valve leaflets
§ LA dilation in mitral stenosis
§ In rheumatic mitral stenosis, calcification and fibrous bridging across valvular commissures create ‘fish mouth’ stenoses
§ MacCallum plaques, usually in left atrium
○ Microscopic
§ Aschoff bodies: T lymphocytes, plasma cells, plump activated macrophages called Anitschkow cells.
§ Anitschkow cells have abundant cytoplasm and central round-to-ovoid nuclei (occasionally binucleate) in which the chromatin condenses into a central, slender, wavy ribbon (caterpillar cells)
§ Aschoff bodies may be found in any of 3 layers of heart, resulting in pericarditis, myocarditis, endocarditis (pancarditis- seen in acute RF)
§ Rarely seen at autopsy due to long intervals between the initial insult and the development of the chronic deformity
Complications of rheumatic heart disease
○ Heart failure § Over time, heart function declines due to valve disease ○ LA dilation due to mitral stenosis § Arrhythmias- AF § Stroke ○ Pulmonary HTN due to mitral stenosis § Can lead to right heart failure ○ Complications in pregnancy § Increased blood volume
Types of endocarditis
- Aspectic ○ Non-bacterial thrombotic endocarditis ○ Liebman-Sacks endocarditis - Septic ○ Infective endocarditis
Pathophysiology of aseptic endocarditis
§ Haemodynamic instability
□ Malignancy
□ Hyperoestrogenic states
□ Disseminated intravascular coagulation
□ SLE
§ Endothelial injury
□ High velocity jet striking endothelium
□ Flow from high to low pressure chamber
□ Flow across narrow orifice at high velocity
□ Indwelling catheter
Pathophysiology of septic phase
§ Bacteraemia § Colonisation § Growth of vegetation § Infective endocarditis □ Damage to intracardiac structures □ Embolisation - infection and infarction □ Circulating immune complexes □ Haematogenous spread
Risk factors for endocarditis
Structural heart disease Degenerative valve disease Cardiac interventions Congenital heart defects IVDU
Valves affected in endocarditis
○ Non-IVDU - mitral > aortic > tricuspid > pulmonary
IVDU - tricuspid > mitral > aortic > pulmonary
