CV Path Lecture 03

-Mechanical injury
-Autoimmunity
-Infectious
-Inflammation
-Entropy

Severe congenital aortic stenosis

Bicuspid aortic valve

Functionally normally until the patient is in his 50s when it begins to calficy

Calcification and obstruction of a normal valve in the patient's 60s-80s

-Ejection across stenotic aortic valve requires a pressure gradient between the LV and the aorta
-This places a pressure load on the LV
-The more severe the stenosis the greater the necessary gradient
-Stenosis leads to turbulent flow causing a murmur

Pressure gradient = k (Systolic Flow/AVA)^2

AVA = Aortic valve area
Systolic Flow = CO/(HR*SEP)
SEP = Systolic ejection period, the amount of time spent in systole per beat

The greater the flow or the smaller the area the greater gradient that is generated

-The LV pressure load leads to concentric LV hypertrophy (increased wall thickness)
-Increased wall thickness leads to increased LV pressure generation
-Increased wall thickness also normalizes wall stress (stress = LVP/2*thickness)
-The wall stress is a precisely regulated parameter

-LV hypertrophy leads to decreased LV compliance
-Inadequate LV hypertrophy leads to afterload mismatch
-Eventual irreversible depression of contractility occurs with pathological changes of fibrosis

Inadequate hypertrophy for a given amount of obstruction

-Ventricle becomes stiffer
-P-V curve becomes stiffer (greater pressure changes occur for the same volume change)
-At the end of diastole the LV pressure is higher than normal

-Afterload mismatch occurs in a normal heart with severe afterload, but SV and EF are nearly unaffected before that
-Depressed LV function makes the heart more sensitive to afterload and afterload mismatch can occur at lower levels of afterload

EF corrects itself, sometimes within a few hours even in patients with impaired ventricular function

-There is a long period in which the stenosis develops
-There is a long asymptomatic period where the stenosis is established.
-The stenosis can be severe but asymptomatic
-Once the patient develops symptoms that is an inflection point and most patients die within 2-5 years

There is no difference from healthy individuals

-Dyspnea on exertion
-Passing out/almost passing out on exertion
-Angina on exertion that is releived with rest

-Decreased LV compliance leads to increased LVDP which causes increased PCW (wedge pressure)
-Afterload mismatch leads to decreased LVEF (or SV)
-Increased LV ESV
-Increased LV EDV
-Increased LVEDP
-Irreversible decreased LV contractility leads to increased LVEDP

-CO = HR*SV
-The normal response during exercise is that means arterial BP (stays the same) = CO (increased) * total peripheral resistance (decreased)
-With severe AS, the response involves
-Less of increase in CO due to smaller increase in SV
-MAP (decreased) = CO (less increased)*Peripheral resistance (decreased)
-Increased LVP caused LV baroreceptors to further decrease total peripheral resistance
-Less blood to the brain makes patient light headed and potentially pass out

-Increased venous return
-Catecholamine release with increased contractility
-Leads to increased SV and increased HR

-Chest discomfort ccurs when there is an imbalance between myocardial oxygen demand and oxygen supply
-There is increased myocardial oxygen demand due to increased muscle mass and increased afterload
-There is decreased supply of oxygen
-Coronary perfusion pressure (decreased) = Aortic diastolic pressure - LVDP (increased)

Can involve:
-Aortic valve
-Aortic root
-Both

Unlike stenotic lesions, regurgitation can develop acutely or chronically

Most common:
-Infective endocarditis
-Aortic dissection

Also:
-Failed bioprosthesis
-Mechanical valve failure
-Blunt trauma
-Cusp rupture or prolapse (Spontaneous, VSD, myxomatous valve)
-Inflammatory disease
-Post PABV or AV surgery

Aortic dissection is a tear in the intima of the aorta with the blood getting into the medial layer and acting as a jackhammer each time the heart beats, ripping the aorta. If that ripping effects the support of the aortic valve as if often does it causes acute leakage

-Normally CO = SV*HR
-Valve regurgitation
-CO=SV(1-RF)*HR
-RF (regurgitation fraction) = Regurgitation volume/SV
-Normal LV size and complaince limits increase in EDV and SV and therefore CO
-Rapid rise to high level of LV diastolic pressure due to filling of LV from aorta as well as LA. LV diastolic pressure closes MV in diastole and further limits forward flow
-This leads to pulmonary congestion and decreased CO -> death
-Only compensation is increased HR

There are many many etiologies

-Develops slowly enough to allow eccentric LVH.
-This causes increased LV chamber size, changing LV P-V relationship
-The LV can then accommodate a large regurgitant volume at normal diastolic pressure

-The curve is shifted to the right (increased volume required to achieve the same pressure).
-At very high ventricular volumes there is still normal end diastolic pressure

-CO = SV(1-RF)*HR
-CO is maintained because increased eccentric hypertrophy leading to increased SV.
-Normal CO and LVDP allow chronic severe AR to be asymptomatic
-Increased SV leads to increased SBP and widened pulse pressure which causes increased afterload
-Increased LVEDV = increased volume overload

Dyspnea
Angina

-Increased LVEDV can cause LVEDP increase when the ventricle stops performing well . This causes increased LAP
-Afterload mismatch occurs causing increased LVESV. This leads to increased LVEDV causing increased LAP
-There is decreased myocardial contractility causing increased LVEDV which further causes increased LAP
-When you eject the large stroke volume into the aorta you generate a much wider pulse pressure (bigger bolus of blood), so the systolic pressure is more elevated. Because the chamber is large the wall stress increases. Aortic regurgitation is both a volume and a pressure load.

-There is increased demand due to increased afterload
-There is decreased supply due to decreased coronary perfusion pressure (CPP=Ao diastolic pressure - LVDP). Ao diastolic pressure is decreased and LVDP is increased
-One of the compensations for aortic regurgitation is that the peripheral resistance drops in response to the large pulse pressure. The widened pulse pressure is accommodated somewhat by a lower diastolic pressure, rather than a high systolic pressure. If aortic diastolic pressure is low that decreases coronary perfusion.

-Low risk until decreased LVEF or symptoms
-Symptom onset or decreased LVEF leads to progression to death or irreversible LV dysfunction over several (1-5) years

-Pulmonary congestion
-Low CO
-Death (over hours to days)

-Structure of aortic valve
-Towards the lumen there is a dense layer, the fibrosa
-Towards the outside there is a looser layer, the spongiosa

-3 leaflet aortic valve with nodular calcifications
-Calcific aortic stenosis usually occurs in the elderly
-Calcification is at the cusps
-Commissures of valves are normal

-Aortic valve tissue
-Blue is calcification
-There is degeneration and then masses of calcification can occur causing stenosis or insufficiency

-Bicuspid aortic valve
-Arrow is pointing to an incomplete raphe
-There is nodular degeneration and calcification causing stenosis

-Hypertension (causes dilation of the valve ring even though the leaflets are normal)
-Connective tissue disorders
-Marfan's 1 in 5000
-70-85% familial - autosomal dominant
-Fibrilin-1 (15q21) - 500 distinct mutations

-There is a tear in the aortic wall and blood has dissected through
-Dissected blood can reenter the aorta. You are left with 2 lumens, but you can live.
-Dissected blood can go through adventia and death occurs quickly (ruptured aortic aneurysm)
-Blood can go back to the heart and rupture in the pericardial sac, filling the pericardium with blood causing tamponade.

-Medial degeneration without atherosclerosis
-Lumen is at top
-Called cystic medial necrosis (although not necessarily necrotic or cystic)
-There is degeneration in the wall, which weakens the wall and can cause the aorta to dilate and an aneurysm.
-When fully weakened blood can dissect in and this is the path of the dissection.