VALVULAR HEART DISEASE

Reactive pulm HTN:

- 40% of cases; medial hypertrophy and intina fibrosis of pulm arterioles - Initially serves a beneficial role bc the increase arteriolar resistance impedes blood flow into the engorged pulm capillaries and thus reduced capillary hydrostatic pressure (protects the pulm capillaries from even higher pressures) - This is at the cost of reduced blood flow through the pulm vasculature and increases pressure in right heart as the RV pumps against this increased resistance - Chronic pressure overload→ hypertrophy of RV → RHF

PE of AS

- A normal aortic valve has a cross-sectional area of 3 to 4 cm^2 and a mean systolic pressure gradient between the LV and aorta of less than 5 mm Hg. - As the valve area decreases in AS, the pressure gradient rises. When the valve area declines to less than 1.0 cm^2, or the mean pressure gradient increases to greater than 40 mm Hg, a patient is considered to have severe aortic stenosis and symptoms typically appear - The key features of advanced AS include (1) a coarse late-peaking systolic ejection murmur and (2) a weakened (parvus) and delayed (tardus) upstroke of the carotid artery owing to the obstructed LV outflow. - Other common findings on cardiac examination include the presence of an S4 (because of atrial contraction into the "stiff" LV) and reduced intensity, or complete absence, of the aortic component of the second heart sound. - On the electrocardiogram, left ventricular hypertrophy is common in advanced AS.

Pathogenesis of rheumatic fever

- Acute rheumatic fever is a hypersensitivity reaction classically attributed to antibodies directed against group A streptococcal molecules that cross-react with host myocardial antigens - antibodies against M proteins of certain streptococcal strains bind to proteins in the myocardium and cardiac valves and cause injury through the activation of complement and Fc receptor-bearing cells (including macrophages). - CD4+ T cells that recognize streptococcal peptides can cross-react with host antigens and elicit cytokine-mediated inflammatory responses. - The characteristic 2- to 3-week delay in symptom onset after infection is explained by the time needed to generate an immune response; streptococci are completely absent from the lesions. - Since only a small minority of infected patients develop rheumatic fever (estimated at 3%), genetic susceptibility to the development of the cross-reactive immune responses is likely in those affected. - The deforming fibrotic lesions are the predictable consequence of healing and scarring associated with the resolution of the acute inflammation.

Morphology of Rheumatic Fever

- Acute rheumatic fever is characterized by discrete inflammatory foci within a variety of tissues. - The myocardial inflammatory lesions—called Aschoff bodies —are pathognomonic for rheumatic fever; these are collections of lymphocytes (primarily T cells), scattered plasma cells, and plump activated macrophages called Anitschkow cells associated with zones of fibrinoid necrosis. - The Anitschkow cells have abundant cytoplasm and nuclei with chromatin that is centrally condensed into a slender, wavy ribbon (so-called "caterpillar cells"). - During acute rheumatic fever, Aschoff bodies can be found in any of the three layers of the heart—pericardium, myocardium, or endocardium (including valves) (pancarditis) The pericardium may exhibit a fibrinous exudate, which generally resolves without sequelae. - The myocardial involvement—myocarditis—takes the form of scattered Aschoff bodies within the interstitial connective tissue. - Valve involvement results in fibrinoid necrosis and fibrin deposition along the lines of closure forming 1- to 2-mm vegetations— verrucae —that cause little disturbance in cardiac function.

Clinical features of RF

- Acute rheumatic fever occurs most often in children; the principal clinical manifestation is carditis. - about 20% of first attacks occur in adults, with arthritis being the predominant feature. - Symptoms in all age groups typically begin 2 to 3 weeks after streptococcal infection and are heralded by fever and migratory polyarthritis—one large joint after another becomes painful and swollen for a period of days, followed by spontaneous resolution with no residual disability. - Although cultures are negative for streptococci at the time of symptom onset, serum titers of antibodies against one or more streptococcal antigens (e.g., streptolysin O or DNAase) usually are elevated. - The clinical signs of carditis include pericardial friction rubs and arrhythmias; myocarditis may be sufficiently severe to cause cardiac dilation and resultant functional mitral insufficiency and CHF. - less than 1% of patients die of acute rheumatic fever. - Carditis is likely to worsen with each recurrence, and the damage is cumulative. - chronic rheumatic carditis usually is not clinically evident until years or even decades after the initial episode of rheumatic fever

Aortic stenosis:

- Among adult patients, there are three major causes of aortic stenosis (AS): (1) degenerative calcification of a previously normal trileaflet aortic valve, (2) calcification of a congenitally bicuspid aortic valve, and (3) rheumatic aortic valve disease. - As with atherosclerosis, risk factors for calcific, degenerative AS include dyslipidemia, smoking, and hypertension - Since the obstruction in AS develops gradually, the LV is able to compensate by undergoing concentric hypertrophy in response to the increased pressure load. - Initially, such hypertrophy serves an important role in reducing LV wall stress - Over time, however, it also reduces the compliance of the ventricle. - The resulting elevation of diastolic LV pressure causes the LA to hypertrophy, which facilitates filling of the "stiffened" LV. - Whereas left atrial contraction contributes only a small portion of the left ventricular stroke volume in normal individuals, it may provide more than 25% of the stroke volume to the stiffened LV in AS patients.

Aortic regurgitation

- Aortic regurgitation (AR), also termed aortic insufficiency, may result either from abnormalities of the aortic valve leaflets or from dilatation of the aortic root. - Primary valvular causes include: (1) bicuspid aortic valve (in some patients AR predominates over aortic stenosis), (2) infective endocarditis (due to perforation or erosion of a leaflet), and (3) rheumatic heart disease (due to thickening and shortening of the aortic valve cusps). - Primary aortic root disease results in AR when the aortic annulus dilates sufficiently to cause separation of the leaflets, preventing normal coaptation in diastole. - In AR, abnormal regurgitation of blood occurs from the aorta into the LV during diastole. - with each contraction, the LV must pump that regurgitant volume plus the normal quantity of blood entering from the LA. . - Hemodynamic compensation relies on the Frank-Starling mechanism to augment stroke volume. - Factors influencing the severity of AR are analogous to those of MR: (1) the size of the regurgitant aortic orifice, (2) the pressure gradient across the aortic valve during diastole, and (3) the duration of diastole - As in MR, the hemodynamic abnormalities and symptoms differ in acute and chronic AR

Calcific aortic stenosis

- Calcific aortic degeneration is the most common cause of aortic stenosis. - In most cases, calcific degeneration is asymptomatic and is discovered only incidentally by viewing calcifications on a routine chest radiograph or at autopsy. - In other patients, valvular sclerosis and/or calcification can be severe enough to cause stenosis, necessitating surgical intervention - In anatomically normal valves, it typically begins to manifest when patients reach their 70s and 80s; onset with bicuspid aortic valves is at a much earlier age (often 40 to 50 years of age) - Although simple progressive age-associated "wear and tear" is often invoked to explain the process, cuspal fibrosis and calcification also can be viewed as the valvular counterparts to age-related arteriosclerosis. - Thus, chronic injury due to hyperlipidemia, hypertension, inflammation, and other factors implicated in atherosclerosis have been proposed as contributors to valvular degenerative changes - The hallmark of calcific aortic stenosis is heaped-up calcified masses on the outflow side of the cusps; these protrude into the sinuses of Valsalva and mechanically impede valve opening; commissural fusion (usually a sign of previous inflammation) is not a typical feature of degenerative aortic stenosis, although the cusps may become secondarily fibrosed and thickened. - An earlier, hemodynamically inconsequential stage of the calcification process is called aortic valve sclerosis. - Cardiac output is maintained only by virtue of concentric left ventricular hypertrophy; the chronic outflow obstruction can drive left ventricular pressures to 200 mm Hg or more. - The hypertrophied myocardium is prone to ischemia, and angina may develop. - Systolic and diastolic dysfunction collude to cause CHF, and cardiac decompensation eventually ensues. - The development of angina, CHF, or syncope in aortic stenosis heralds the exhaustion of compensatory cardiac hyperfunction and carries a poor prognosis

Chronic Mitral Regurgitation

- Chronic MR has multiple primary causes: > myxomatous degeneration of the valve, in which "floppy" leaflets allow regurgitation to occur by bowing excessively into the LA during systole (termed "mitral valve prolapse"). > Other causes of chronic primary MR include rheumatic deformity of the valve, congenital valve defects, and extensive calcification of the mitral annulus, which prevents normal movement of the valve leaflets, thus interfering with valve closure. - Secondary (also termed "functional") chronic MR results from LV enlargement and/or dysfunction as may occur with prior myocardial infarction, chronic ischemic heart disease, or dilated cardiomyopathy - the more gradual development of chronic MR permits the LA to undergo compensatory changes that lessen the effects of regurgitation on the pulmonary circulation > the LA dilates and its compliance increases such that the chamber is able to accommodate a larger volume without a substantial increase in pressure > his adaptation occurs at the cost of reduced forward cardiac output, because the compliant LA becomes a preferred low-pressure "sink" for left ventricular ejection, compared with the aorta. Consequently, as progressively larger fractions of blood regurgitate into the LA, symptoms of chronic MR include those of low forward cardiac output (e.g., weakness and fatigue). - chronic left atrial dilatation predisposes to the development of atrial fibrillation. - the LV also undergoes gradual compensatory dilatation in response to the volume load through eccentric hypertrophy. - Chronic MR: Increased LA size and compliance → Relatively normal LA and pulmonary venous pressures, but decreased forward cardiac output

AR PE:

- Common symptoms of chronic AR include dyspnea on exertion, fatigue, decreased exercise tolerance, and the uncomfortable sensation of a forceful heartbeat associated with the high pulse pressure - Physical examination may show bounding pulses and other stigmata of the widened pulse pressure hyperdynamic LV impulse and a blowing murmur of AR in early diastole along the left sternal border best heard with the patient leaning forward, after exhaling. - In addition, a low-frequency mid-diastolic rumbling sound may be auscultated at the cardiac apex in some patients with severe AR. - Known as the Austin Flint murmur, it is thought to reflect turbulence of blood flow through the mitral valve during diastole owing to downward displacement of the mitral anterior leaflet by the regurgitant stream of AR. - It can be distinguished from the murmur of mitral stenosis by the absence of an OS or presystolic accentuation. - In chronic AR, the chest radiograph shows an enlarged left ventricular silhouette. - This is usually absent in acute AR, in which pulmonary vascular congestion is the more likely finding.

Early manifestation of mitral stenosis:

- Dyspnea (may only be present during physical activity; may occur at rest when valve area is smaller) - Reduced exercise capacity - More severe cases can have orthopnea and paroxysmal nocturnal dyspnea

acute AR

- In acute AR, the LV is of normal size and relatively noncompliant. - Thus, the volume load of regurgitation causes the LV diastolic pressure to rise substantially. - The sudden high diastolic LV pressure is transmitted to the LA and pulmonary circulation, often producing dyspnea and pulmonary edema. - Thus, acute severe AR is usually a surgical emergency, requiring immediate valve replacement.

Mitral regurgitation:

- MR is categorized as: > Primary: due to a structural defect of one or more of the valve components > Secondary: the valve is structurally normal, but regurgitation instead results from left ventricular enlargement. In this case, MR arises from abnormal coaptation and closure of the mitral leaflets owing to dilatation of the mitral annulus by the enlarged LV, and/or spatial separation of the papillary muscles, which places traction of the chordae and attached leaflets - In MR, a portion of the left ventricular stroke volume is ejected backward into the low-pressure LA during systole. - As a result, the forward cardiac output (into the aorta) is less than the LV's total output (forward flow plus backward leak). - the direct consequences of MR include: (1) an elevation of left atrial volume and pressure, (2) a reduction of forward cardiac output, and (3) a volume-related stress on the LV because the regurgitant volume returns to the LV in diastole along with the normal pulmonary venous return. - To meet normal circulatory needs and to eject the additional volume, LV stroke volume must rise. - This increase is accomplished by the Frank-Starling mechanism, whereby the elevated LV diastolic volume augments myofiber stretch and stroke volume. - The hemodynamic consequences of MR vary depending on the degree of regurgitation and how long it has been present. - the LA pressure, or the pulmonary capillary wedge pressure (an indirect measurement of LA pressure), demonstrates a prominent v wave (often referred to as a "cv" wave when it merges with the preceding c wave), reflecting the increased LA filling during systole

Acute Mitral Regurgitation

- Most cases of acute MR are primary in nature and result from sudden damage to components of the valve apparatus. - For example, rupture of an infarcted papillary muscle can occur within days of an acute ST-segment elevation MI, often resulting in severe MR. - Acute MR due to sudden rupture of chordae tendineae can result from infective endocarditis, blunt trauma to the chest, or from degeneration of the chordae owing to connective tissue disorders such as Marfan syndrome - left atrial compliance undergoes little immediate change. > Because the LA is a relatively stiff chamber, its pressure increases substantially when it is suddenly exposed to a regurgitant volume load > This elevated pressure is transmitted backward to the pulmonary circulation and can result in rapid pulmonary congestion and edema, a medical emergency. - Acute MR: Normal LA size and compliance → High LA pressure → High pulmonary venous pressure → Pulmonary congestion and edema

PE of mitral regurgitation

- PE typically reveals an apical holosystolic (also termed pansystolic) murmur that often radiates to the axilla. - The holosystolic nature of the murmur reflects the continued pressure gradient between LV and LA throughout systole - In patients with severe acute MR, the character of the systolic murmur is often different, occurring in early to mid systole with a decrescendo quality. > The length and quality of the murmur are dictated by the systolic pressure gradient between the left ventricle and the relatively noncompliant left atrium. - The chest radiograph may display pulmonary edema in acute MR but in chronic asymptomatic MR more likely demonstrates left ventricular and atrial enlargement, without pulmonary congestion. - Calcification of the mitral annulus may be seen if that is the cause of the MR. - In chronic MR, the electrocardiogram typically demonstrates left atrial enlargement and signs of left ventricular hypertrophy - The characteristic hemodynamic finding is a large v wave in the pulmonary capillary wedge pressure tracing (reflective of LA pressure).

PE findings for mitral stenosis

- Palpation of chest may revela a RV "tap" due to increased RV pressure - Loud S1 in early stages of disease due to higher P gradient bt LA and LV S1 may return to normal or diminish in late disease due to thickening and calcification of leaflets= less mobile - High pitched "opening snap" that follows S2 - Due to sudden tensing of chordae tendineae and stenotic leaflets on opening the abnormal valve - The interval bt S2 and the opening snap is inversely related to the severity of the mitral stenosis: the more severe, the higher the P in the LA and the earlier the stenotic valve is forced to open - The opening snap is followed by a decrescendo murmur (diastolic rumble) caused by turbulent flow across the stenotic valve during diastole - The duration but not the intensity of the diastolic rumble relates to the severity of mitral stenosis - The more severe, the longer it takes to empty the LA and for the gradient bt the LA and LV to dissipate - In patients with systolic rhythm, when the LA contracts during the end of diastole, the P gradient bt the LA and LV rises again, so the murmur briefly becomes louder (presystolic accentuation) > Does not occur if AFib has developed - Other murmurs may coexist with mitral stenosis due to involvement of other valves

Mitral stenosis

- The most common cause of mitral stenosis is prior Rheumatic Fever (50%- 70% of patients with symptoms) > On avg 20 yrs before onset of symptoms - Rare: > calcification of mitral annulus that extends to the leaflets infection endocarditis with lrg > vegetations that obstruct valve orifice > rare congenital stenosis of the valve - Fibrosis thickening and calcification of the valve leaflets - Fusion of the commissures (where the leaflets meet) - Thickening and shortening of the chordae tendineae - Blood flow from te LA to LV is obstructed such that there is an abnormal pressure gradient resulting in the LA pressure increasing - Hemodynamic changes become apparent when the valve reduces in size from 4-6cm^2 to <2cm^2 - The high pressure in the LA is transmitted retrogradely to the pulm vein and capillary pressure= pulm edema - Patient may present with dyspnea and other symptoms of HF - results in pulm HTN (passive and reactive) - Chronic pressure overload in the LA leads to atrial enlargement - LA dilation stretches the atrial conduction fibers and may disrupt the integrity of the cardiac conduction system → AFib

Tricuspid regurgitation

- Tricuspid regurgitation (TR) is usually functional rather than structural in nature; that is, it most commonly results from right ventricular enlargement (e.g., owing to pressure or volume overload) rather than from primary valve disease. - Among patients with rheumatic mitral stenosis, 20% also have significant TR (of whom 80% have functional TR because of pulmonary hypertension with right ventricular enlargement, and 20% have structural TR resulting from rheumatic involvement of the tricuspid valve). - A rare cause of TR is carcinoid syndrome, in which a type of neuroendocrine tumor (usually in the small bowel or appendix, with metastases to the liver) releases serotonin metabolites into the bloodstream; These metabolites are thought to be responsible for the formation of endocardial plaques in the right side of the heart. - The treatment of functional TR is directed at the conditions responsible for the elevated right ventricular size or pressure, and diuretic therapy; surgical repair of the valve is indicated in severe cases. - The most common physical signs of TR are prominent v waves in the jugular veins and a pulsatile liver because of regurgitation of right ventricular blood into the systemic veins. - The systolic murmur of TR is heard at the lower left sternal border. > It is often soft but becomes louder on inspiration.

Rheumatic fever & rheumatic valvular heart disease

- an acute, immunologically mediated, multisystem inflammatory disease that occurs after group A β-hemolytic streptococcal infections (usually pharyngitis, but also occasionally infections at other sites, such as skin). - Rheumatic heart disease is the cardiac manifestation of rheumatic fever. - It is associated with inflammation of all parts of the heart, but valvular inflammation and scarring produce the most important clinical features. - The valvular disease principally takes the form of deforming fibrotic mitral stenosis; rheumatic heart disease is essentially the only cause of acquired mitral stenosis

Three major manifestations occur in patients with advanced AS:

- angina > AS may result in angina because it creates a substantial imbalance between myocardial oxygen supply and demand. > Myocardial oxygen demand is increased in two ways: (1) First, the muscle mass of the hypertrophied LV is increased, requiring greater-than-normal perfusion. (2) Second, wall stress is increased because of the elevated systolic ventricular pressure. > In addition, AS reduces myocardial oxygen supply because the elevated left ventricular diastolic pressure reduces the coronary perfusion pressure gradient between the aorta and the myocardium. - exertional syncope > AS may cause syncope during exertion. > Although left ventricular hypertrophy allows the chamber to generate a high pressure and maintain a normal cardiac output at rest, the ventricle cannot significantly increase its cardiac output during exercise because of the fixed stenotic aortic orifice. > In addition, exercise leads to vasodilatation of the peripheral muscle beds. > Thus, the combination of peripheral vasodilatation and the inability to augment cardiac output contributes to decreased cerebral perfusion pressure and, potentially, loss of consciousness on exertion. -heart failure > LA pumping into a noncompliant V= increase in LA pressure= pulm edema

Williams-Beuren Syndrome

- characterized by mental retardation, hypercalcemia, renovascular hypertension, facial abnormalities, and short stature - have supravalvular aortic stenosis, and some have a more diffuse arteriopathy of the aorta as well as pulmonary artery obstruction. - The genetic abnormality in Williams syndrome is a deletion on chromosome 7 (7q11.23), a region that includes the elastin gene. - Abnormalities in the production of elastin, a critical component of the arterial wall, may be responsible for the observed arteriopathy.

Passive pulm HTN:

- most common; results from raise in LA pressure backing up in pulm circulation; represents an obligatory increase in pulm artery pressure that preserves forward flow in the setting of increased LA and pulm venous pressure

Mitral valve prolapse (myxomatous degeneration of the mitral valve)

- one or both mitral leaflets are "floppy" and prolapse—they balloon back into the left atrium during systole. - Primary mitral valve prolapse is a form of myxomatous mitral degeneration affecting some 0.5% to 2.4% of adults; thus, it is one of the most common forms of valvular heart disease, with women affected almost 7-fold more often than men. - secondary myxomatous mitral degeneration affects men and women equally, and can occur in any one of a number of settings in which mitral regurgitation is caused by some other underlying cause (e.g., IHD). - The basis for primary myxomatous degeneration of the mitral valve is unknown. - an underlying (possibly systemic) intrinsic defect of connective tissue synthesis or remodeling is likely (i.e. Marfan syndrome) - Myxomatous degeneration of the mitral valve is characterized by ballooning (hooding) of the mitral leaflets - The affected leaflets are enlarged, redundant, thick, and rubbery; the tendinous cords also tend to be elongated, thinned, and occasionally rupture - concomitant tricuspid valve involvement is frequent (20% to 40% of cases); less commonly, aortic and pulmonic valves also may be affected. - On histologic examination the essential change is thinning of the valve layer known as the fibrosa layer of the valve, on which the structural integrity of the leaflet depends, accompanied by expansion of the middle spongiosa layer owing to increased deposition of myxomatous (mucoid) material. - Most patients are asymptomatic, and the valvular abnormality is discovered incidentally. - In a minority of cases, patients complain of palpitations, dyspnea, or atypical chest pain. - Auscultation discloses a midsystolic click, caused by abrupt tension on the redundant valve leaflets and chordae tendineae as the valve attempts to close; there is sometimes an associated regurgitant murmur.

chronic AR

- the LV undergoes compensatory adaptation in response to the longstanding regurgitation. - AR subjects the LV primarily to volume overload but also to an excessive pressure load; therefore, the ventricle compensates through chronic dilatation (eccentric hypertrophy, with replication of sarcomeres in series) and, to a lesser degree, increased thickness. - the dilatation increases the compliance of the LV and allows it to accommodate a larger regurgitant volume with less of an increase in diastolic pressure, reducing the pressure transmitted into the LA and pulmonary circulation. - by accommodating the large regurgitant volume, the aortic (and therefore systemic arterial) diastolic pressure drops substantially. - The combination of a high LV stroke volume (and high systolic arterial pressure) with a reduced aortic diastolic pressure produces a widened pulse pressure (the difference between arterial systolic and diastolic pressures), a hallmark of chronic AR

Diagnostic findings in mitral stenosis

ECG: - shows LA enlargement - if pulm HTN has developed, RV enlargement - AFib may be present Chest Xray: - LA enlargement - Pulm vascular redistribution - Interstitial edema - Kerley B lines - RV enlargement and prominence of pulm arteries in cases of pulm HTN Echo: - Major diagnostic tool - Thickening mitral leaflets with abnormal fusion of their commissures with restricted separation during diastole - Diastolic pressure half- time determines mitral valve area and stratified patients into stages: > Normal: 4-6cm^2 > Severe: <1.5cm^2 (LA enlargement and elevated pulm artery pressure) - Very severe: <1.0cm^2 Exercise tests and cardiac cath can also help diagnose and determine severity

Advanced manifestations of mitral stenosis:

Signs of RHF: - Elevated JVP - Hepatomegaly - Ascities - Peripheral edema - Compression of laryngeal N. by enlargement of pulm a or LA may cause hoarseness (Ortner syndrome)

diagnosis of RF

The diagnosis of acute rheumatic fever is made based on serologic evidence of previous streptococcal infection in conjunction with two or more of the Jones criteria: (1) carditis; (2) migratory polyarthritis of large joints; (3) subcutaneous nodules; (4) erythematous annular rash (erythema marginatum) in the skin; and (5) Sydenham chorea, a neurologic disorder characterized by involuntary purposeless, rapid movements (also called St. Vitus dance).

The regurgitant fraction in MR

Volume of mitral regurgitation/ total LV SV - This ratio rises whenever the resistance to aortic outflow is increased (i.e., blood follows the path of least resistance). - For example, high systemic blood pressure or the presence of aortic stenosis will increase the regurgitant fraction. - The extent to which left atrial pressure rises in response to the regurgitant volume is determined by the left atrial compliance.