D.BASEM ELSAID ENANYLECTURER OF CARDIOLOGY

AINSHAMS UNIVERSITY

Aortic stenosis

ETIOLOGY OF VALVULAR AS

-Congenitally abnormal valve with superimposed calcification (unicuspid or bicuspid){USA, Europe}-Calcific disease of a trileaflet valve {USA, Europe}-Rheumatic valve disease {worldwide}-Rare causes include metabolic diseases (eg, Fabry's disease), systemic lupus erythematosus, Paget disease, and alkaptonuria, chronic kidney disease

Calcific involvement starts at the base of the leaflets and moves into the body of the leaflets. Rheumatic disease is a leaflet edge inflammatory disease where fibrosis and calcium deposition occurs and then spreads to the body of the leaflet.

Subvalvular disease

-Thin membrane (the most common lesion) (elective surgical resection even if mild gradient to avoid turbulant damage to AV)

-Thick fibromuscular ridge-Diffuse tunnel-like obstruction-Abnormal mitral valve attachments-Accessory endocardial cushion tissue--Dynamic component that is primarily seen in the genetic disease hypertrophic cardiomyopathy

Supravalvular disease

--The majority of patients (60 to 75 %) have an hourglass deformity= discrete constriction of a thickened ascending aorta at the superior aspect of the sinuses of Valsalva--More diffuse narrowing for a variable distance along the ascending aorta is seen in the remaining patients-- High frequency of supravalvular AS in patients with Williams syndrome {which is due to a mutation in the elastin gene}, homozygous familial hypercholesterolemia and occurs infrequently in heterozygotes

Pathogenesis

--Rheumatic valve disease is characterized by fusion of the commissures between the leaflets, usually with MV--Calcific aortic valve disease is characterized by aortic valve leaflet thickening and calcification : lipid accumulation, inflammation, and calcification leaflets do not open fully with ventricular ejection{disease process is accelerated by abnormal shear or mechanical stress on the leaflet bicuspid aortic valves about 10 years earlier than in patients with trileaflet valves}

--Many of the risk factors for atherosclerosis are also associated with aortic valve sclerosis {it is not clear whether statin therapy can slow disease progression in patients with calcific AS}--Genetic factors play a role in selected patients mutations in the signaling and transcriptional regulator NOTCH1

PATHOPHYSIOLOGY

--Normal area= 3.0 to 4.0 cm2 in adults--Calcific aortic valve disease without a significant gradient (defined as an aortic jet velocity ≤2.5 m/sec) is called aortic valve sclerosis--Increased systolic pressure in the ventricular chamber concentric hypertrophy as a mechanism to maintain normal wall stressprogress less compliant and left ventricular end-diastolic pressure can become elevated {+IS fibrosis}--Most patients with AS develop symptoms before the onset of left ventricular systolic dysfunction

AHA 2014

Symptoms

--Asymptomatic for a prolonged period--Once even mild cardiac symptoms develop, prompt surgical intervention is needed--Most common symptoms are decreased exercise tolerance and dyspnea on exertion. ---Care should be taken to avoid attributing noncardiac symptoms to aortic stenosis: dyspnea may be due to deconditioning or lung disease, ankle edema has many causes other than heart failure, and nonanginal chest or shoulder pain is not a symptom of AS. --Typical symptoms

1-Dyspnea and HF:--Due to:diastolic dysfunction, and an inability of the left ventricle to increase the cardiac output during exercise because the stiff aortic valve obstructs flow--Once overt HF occurs shortness of breath, easy fatigability, debilitation, and other signs and symptoms of a low cardiac output state, AF.

2-Dizziness and syncope:--Due to decreased cerebral perfusion:-Exercise-induced vasodilation in the presence of an obstruction with fixed cardiac output can result in hypotension-A transient bradyarrhythmia that can occur during or immediately after exertion-Abnormalities in the baroreceptor response with an ensuing failure to appropriately increase the blood pressure-An arrhythmia, such as atrial fibrillation; ventricular arrhythmias are uncommon.

3-Angina pectoris:--Two-thirds of patients with severe AS.--Approximately one-half of these patients have underlying coronary artery disease.--Remaining patients left ventricular hypertrophy:-Increased left ventricular oxygen demand as a result of increased left ventricular mass; the myocardial oxygen uptake per gram is normal-Compression of intramyocardial coronary arteries from prolonged contraction and impaired myocardial relaxation-Reduced diastolic coronary perfusion time during tachycardia-Reduced coronary flow reserve

Physical examination

--Carotid pulse:"parvus and tardus", ie, it is small or weak and rises slowly best appreciated in the carotid artery {delay can be appreciated by simultaneous palpation of the apex and the carotid artery}. There may also be an associated carotid artery thrill or coarse vibration ("shuddering") due to the marked turbulence of blood flow across the stenotic valve--The cardiac palpation, percussion:Sustained and is initially normal in location displaced late (left ventricular failure)Palpable fourth heart sound (S4) due to vigorous left atrial contraction into the noncompliant ventricle. In addition, a systolic thrill may be felt at the base of the heart (second intercostal space) or at the sternal notch, especially during full expiration with the patient leaning forward.

--Cardiac auscultation:1-Sounds:-S2 is soft and single since A2 is delayed and tends to occur simultaneously with P2. The S2 may become paradoxically split when the stenosis is severe.The presence of a normal split S2 is the most reliable finding to exclude severe AS in adults.-S1 is usually normal. However, an aortic ejection click, which is more commonly heard with a congenital bicuspid valve, may be heard after S1 early in AS when the leaflets are still somewhat compliant and mobile.-Vigorous left atrial contraction can lead to a fourth heart sound (S4).

2-Murmur:-Systolic "ejection" murmur. It is typically heard best at the base of the heart in the "aortic" area (second intercostal space on the right) where it has a harsh quality. -The murmur is transmitted well and equally to the carotid arteries. Diminished intensity in one carotid artery may indicate the presence of a stenosis in that vessel-A loud murmur (grade 4 or greater) has a high specificity for severe aortic stenosis. However, most patients with severe stenosis have a grade 3 murmur and many have only a grade 1 or 2 murmur.-Late peaking murmur is consistent with severe AS-May also radiate to the apex of the heart where it may have a different quality (musical due to high frequency vibrations) and may be louder, suggesting that the patient also has mitral regurgitation. This is known as the Gallavardin phenomenon.-In almost all patients, AS is associated with a small degree of aortic regurgitation

=Functional murmurs should be systolic, short, soft (typically less than 3/6), early peaking (never passing mid-systole), predominantly circumscribed to the base, and associated with a well-preserved and normally split-second sound. They should have an otherwise normal cardiovascular examination and often disappear with sitting, standing, or straining (as, for example, following a Valsalva maneuver).=Isometric hand grip is carried out by asking the patient to lock the cupped fingers of both hands into a grip and then trying to pull them apart. The resulting increase in peripheral vascular resistance intensifies MR (and ventricular septal defect) while softening instead AS (and aortic sclerosis). Hence, a positive hand grip argues strongly in favor of MR.

OTHER CLINICAL MANIFESTATIONS

1-Sudden cardiac death:The risk of sudden death is reduced by valve replacement, so prompt valve replacement is generally recommended for symptomatic aortic stenosis. 2-Arrhythmias:-AF:Uncommon in isolated AS, often with HF. AF can be life-threatening in severe AS -Ventricular arrhythmias:VPBs and NSVT are common in patients with aortic stenosis3-Endocarditis:-Can occur in patients with AS, particularly those with a congenitally bicuspid aortic valve-Antibiotic prophylaxis is no longer recommended4-Bleeding tendency:-Increased risk of bleeding appears to be due to an acquired von Willebrand syndrome, mechanical disruption of von Willebrand multimers during turbulent passage through the narrowed valve and from a von Willebrand factor interaction with platelets that triggers platelet clearance5-Embolic events — Isolated case reports have described cerebral or systemic embolic events due to calcium emboli6-CAD: age> 50 y

Electrocardiogram

-- LV hypertrophy -- Intraventricular or atrioventricular conduction abnormalities are uncommon severe hypertrophy, extension of calcium from the valve and valve ring into the interventricular septum, or concomitant heart disease.--Ventricular and supraventricular arrhythmias are also uncommon underlying left ventricular dysfunction.--Atrial fibrillation is usually a late arrhythmia, primarily occurring in association with heart failure, mitral valve disease .

Chest radiograph

--Usually normal--A rounding of the left ventricular apex suggests left ventricular hypertrophy.--Calcification of the aortic leaflets and aortic root is present in most adults with hemodynamically significant AS

Echocardiography

--No single finding on physical examination or combination of findings has both a high sensitivity and high specificity for excluding severe AS--The aortic leaflets are often thickened and calcified, and have a reduced excursion with a small aortic orifice during systole {also in heart failure or other conditions that cause a reduction of blood flow across the aortic valve}.--Bicuspid aortic valve two leaflets (and two commissures) of the open valve. A bicuspid valve may appear trileaflet on diastolic images if a raphe is present--LV is concentrically or uniformly hypertrophied

--Doppler echocardiography permits measurement of jet velocity and calculation of the left ventricular-aortic gradient and the valve area, other lesions {AR, MR}--Q = AOT x VOT = AVA x VAVwhere AOT = area of the LV outflow tract, VOT = peak velocity in the outflow tract, AVA = area of the stenotic aortic valve, VAV = maximum velocity across the aortic valve. --Doppler echocardiography provides the most reliable noninvasive estimation of the pulmonary artery pressure increased in AS because of the chronic elevation in left ventricular diastolic filling pressure{>50 mmHg occurs in approximately 15%}--Aorta: in bicuspid AV, dilatation of the aortic root and/or ascending thoracic aorta in the majority of patients aneurysm formation and dissection--Every year for severe aortic stenosis, every one to two years for moderate aortic stenosis, and every three to five years for mild aortic stenosis

dimensionless index vLVOT/vAV . Severe AS is present if this ratio isless than 0.25

Moderate Aortic velocity=3.0-4.0 M/secMean PG=25-40 mmHgAVA= 1.0-1.5 cm2

-By “normalizing” the CO, the gradient can then be reassessed. If the gradient rises to more than 40 mmHg then severe AS is present and the patient should undergo operation. -However, if there is normalization of the CO and the gradient is still 30 mmHg, then this is only mild AS and operation is not warranted.-In addition, dobutamine challenge allows one to assess for contractile reserve as evidence by an increase in stroke volume of 20% or more. The presence of contractile reserve in this patient population has been shown to have lower mortality when undergoing AVR. Although both those with and without contractile reserve benefited from valve replacement, overall mortality was lower in those with contractile reserve.

AHA 2014

Class IIa1. Low-dose dobutamine stress testing using echocardiographic or invasive hemodynamicmeasurements is reasonable in patients with stage D2 AS with all of the following , (Level of Evidence: B):a. Calcified aortic valve with reduced systolic opening;b. LVEF less than 50%;c. Calculated valve area 1.0 cm2 or less; andd. Aortic velocity less than 4.0 m per second or mean pressure gradient less than 40 mm Hg.2. Exercise testing is reasonable to assess physiological changes with exercise and to confirm the absence of symptoms in asymptomatic patients with a calcified aortic valve and an aortic velocity 4.0 m per second or greater or mean pressure gradient 40 mm Hg or higher (stage C) . (Level of Evidence: B)

Other investigations

--Cardiac catheterization:If echo not conclusive--CT the role of quantitation of valve calcium in clinical decision making has not been defined

AHA2014:Class IIa1. Exercise testing is reasonable in selected patients with asymptomatic severe VHD to 1) confirmthe absence of symptoms, or 2) assess the hemodynamic response to exercise, or 3) determinePrognosis . (Level of Evidence: B)

--Patients with symptomatic AS who require temporary or indefinite nonsurgical management:-Comorbid conditions: Such as malignancy or temporary(eg, infection).-High risk patients : transcatheter aortic valve implantation-Patient refusal: Adequate discussion of estimated risks. -Patients awaiting valve replacement:Those with frank heart failure, angina, or syncope should be hospitalized while awaiting valve replacement. -Pregnancy

Medical management

--No endocarditis prophylaxis--Severe mild physical activity {avoid syncope}--Medical therapy for coronary artery disease, and atrial fibrillation --HTN:-Diuretics reduce preload, on which the patient may depend for maintenance of cardiac outputcaution.-Beta blockers reduce contractility which may pose a risk for the overloaded left ventricleavoided in patients with symptomatic aortic stenosis and heart failure.-Vasodilators (such as hydralazine, nitroglycerin, and nifedipine) in the presence of a fixed valvular stenosis may reduce systemic blood pressure and reduce coronary artery perfusion pressure caution-ACEI small dose , gradual titration--Prevention and treatment of concurrent conditions {eg.influenza, fever, volume status}--+ve inotropic agents such as dobutamine must be used with caution; tachycardia (with reduced cardiac output) and myocardial ischemia(O2 demand)--Nitruprusside: may be if no hypotension, critically ill

--HF if low gradient AS proved to be mild or moderate routine ttt of HFIf not surgery--BB in dilated Aortic root

AHA 2014

Class I1. Hypertension in patients at risk for developing AS (stage A) and in patients with asymptomatic AS (stages B and C) should be treated according to standard GDMT, started at a low dose, and gradually titrated upward as needed with frequent clinical monitoring . (Level of Evidence:B)Class IIb1. Vasodilator therapy may be reasonable if used with invasive hemodynamic monitoring in the acute management of patients with severe decompensated AS (stage D) with New York Heart Association (NYHA) class IV heart failure (HF) symptoms. (Level of Evidence: C)Class III: No Benefit1. Statin therapy is not indicated for prevention of hemodynamic progression of AS in patients with mild-to-moderate calcific valve disease (stages B to D) . (Level of Evidence: A)

Noncardiac surgery

--Percutaneous balloon valvotomy critically ill awaiting surgery , pregnant symptomatic{risky}--ACC/AHA guidelines concluded that most asymptomatic patients with severe AS can undergo urgent noncardiac surgery at relatively low risk with careful intraoperative and postoperative management, including monitoring of anesthesia and careful attention to fluid balance Balloon valvotomy was not recommended; aortic valve replacement should be considered if preoperative correction of AS is warranted----Control heart rate (particularly in MS), to avoid fluid overload as well as volume depletion and hypotension (particularly in AS)--European 2012

AHA 2014

The patient and family should be sufficientlyeducated by the Heart Valve Team about all alternatives for treatment so that their expectations can be met as fully as possible using a shared decision-making approach.

Heart Valve Centers of Excellence

1) are composed of experienced healthcare providers withexpertise from multiple disciplines; 2) offer all available options for diagnosis and management, including complex valve repair, aortic surgery, and transcatheter therapies; 3) participate in regional or national outcomeregistries; 4) demonstrate adherence to national guidelines; 5) participate in continued evaluation and quality improvement processes to enhance patient outcomes; and 6) publicly report their available mortality and successrates.

-- Despite the lack of evidence, a combination of low-dose aspirin and a thienopyridine is used early after TAVI and percutaneous edge-to-edge repair, followed by aspirin or a thienopyridine alone

Date of download: 12/13/2013

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Algorithm for Management of Patients With ASAlgorithms for the management of (A) severe aortic stenosis (AS) and (B) moderate AS. The text in black refers to the recommendations proposed in the American College of Cardiology/American Heart Association (ACC/AHA) and European Society of Cardiology (ESC) guidelines whereas the text in red and between [ ]? represents the new emerging parameters that may eventually contribute to improving the assessment and management of AS. However, these new parameters will need to be further validated in future studies. AVR = aortic valve replacement; BNP = brain natriuretic peptide; BP = blood pressure; CABG = coronary artery bypass graft surgery; CAD = coronary artery disease; CT = computed tomography; echo = echocardiography; EOA = effective valve orifice area; FU = follow-up; LV = left ventricular; VPeak = peak aortic jet velocity.

CABG+moderate or mild AS

The 2006 ACC/AHA guidelines reached the following conclusions, according to the severity of the stenosis:

-The weight of evidence was in favor of concurrent aortic valve replacement in patients with moderate AS.-The evidence was less well established in patients with mild AS who had findings, such as moderate to severe valve calcification, suggesting possible rapid progression of the stenosis.

Other valvular lesions

--When either stenosis or regurgitation is predominant, management follows the recommendations concerning the predominant VHD--Interaction between the different valve lesions ex. associated MR may lead to underestimation of the severity of AS--Indications for intervention are based on global assessment ofthe consequences of the different valve lesions, i.e. symptomsor presence of LV dilatation or dysfunction--The decision to intervene on multiple valves should take intoaccount the extra surgical risk--The choice of surgical technique should take into account thepresence of the other VHD.

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