1. D . B A S E M E L S A I D E N A N Y
L E C T U R E R O F C A R D I O L O G Y
A I N S H A M S U N I V E R S I T Y
Aortic stenosis

2. 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.

5. 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

6. 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

8. 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}

9. --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

13. 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 stressprogress 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

14. AHA 2014

17. 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

18. 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.

19. 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.

20. 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

22. 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.

23. --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).

24. 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

25. =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.

28. 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 stenosis
3-Endocarditis:
-Can occur in patients with AS, particularly those with a congenitally bicuspid aortic
valve
-Antibiotic prophylaxis is no longer recommended
4-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 clearance
5-Embolic events — Isolated case reports have described cerebral or systemic embolic
events due to calcium emboli
6-CAD: age> 50 y

29. 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 .

31. 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

33. 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

37. --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 VAV
where 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

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

39. Moderate
Aortic velocity=3.0-4.0 M/sec
Mean PG=25-40 mmHg
AVA=1.0-1.5 cm2

40. -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.

41. AHA 2014
Class IIa
1. Low-dose dobutamine stress testing using echocardiographic or
invasive hemodynamic
measurements 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; and
d. 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)

43. 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 IIa
1. Exercise testing is reasonable in selected patients
with asymptomatic severe VHD to 1) confirm
the absence of symptoms, or 2) assess the
hemodynamic response to exercise, or 3) determine
Prognosis . (Level of Evidence: B)

44. --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

45. 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 outputcaution.
-Beta blockers reduce contractility which may pose a risk for the overloaded
left ventricleavoided 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

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

47. AHA 2014
Class I
1. 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 IIb
1. 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 Benefit
1. 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)

48. 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

50. AHA 2014
The patient and family should be sufficiently
educated 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.

51. Heart Valve Centers of Excellence
1) are composed of experienced healthcare providers with
expertise 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 outcome
registries;
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 success
rates.

61. -- 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

64. Date of download:
12/13/2013
Copyright © The American College of Cardiology.
All rights reserved.

65. Algorithm for Management of Patients With AS
Algorithms 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.

66. 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.

67. 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 of
the consequences of the different valve lesions, i.e. symptoms
or presence of LV dilatation or dysfunction
--The decision to intervene on multiple valves should take into
account the extra surgical risk
--The choice of surgical technique should take into account the
presence of the other VHD.

68. Thank you