Aortic Stenosis

Epidemiology

Prevalence: 3% of those over age 65 years old (10% in age > 80 years old) in U.S.
Most significant cardiac valve disorder in the developed world

Causes
Valvular

Congenital Bicuspid Valve (Most common)
1. Twice as common in men
2. Slow increase in stenosis (progressive sclerosis)
  1. Childhood: mild stenosis and asymptomatic
  2. Ages 20-40: moderate stenosis develops
  3. Over age 40: severe stenosis develops
Atherosclerosis (Calcific Aortic Valve Stenosis)
1. Normal aortic tricuspid valve becomes calcified and rigid with age
2. Gradually develops, typically presenting over age 70 years
3. Rarely severe
Rheumatic Fever
1. Slowly progressive stenosis
Subacute Bacterial Endocarditis
Other acquired aortic valve stenosis causes
1. Systemic Lupus Erythematosus
2. Fabry Disease
3. Paget's Disease of Bone
4. Rheumatoid Arthritis
5. Radiation exposure
Other congenital aortic valve stenosis causes
1. Unicuspid aortic valve
  1. Very rare congenital defect presenting with Aortic Stenosis at a young age
  2. May be initially misdiagnosed as a bicuspid valve
2. Williams Syndrome
3. Shanes Complex
4. Supravalvular Aortic Stenosis
  1. May be associated with Williams Syndrome or other congenital supravalvular Aortic Stenosis
5. Subvalvular Aortic Stenosis
  1. May be associated with Hypertrophic Cardiomyopathy or other congenital subvalvular Aortic Stenosis
References
1. Baloor and Nayak (2018) Exam Preparatory Manual for Undergraduate Medicine, Jaypee Brothers Medical Publication

Pathophysiology
Course

Initial: Long asymptomatic latent period
Course
1. Increased Left Ventricular Outflow Obstruction and flow restriction with increased left ventricular pressures
2. Next: Left Ventricular Hypertrophy (left ventricular wall thickening with preserved LV volume)
3. Next: Diastolic Dysfunction (resistance to LV filling with preserved systolic function)
4. Next: Systolic Dysfunction and Congestive Heart Failure
5. Next: Increased myocardial oxygen demand, Coronary Artery compression and secondary Angina
6. Next: Hypotension and Syncope in response to Exercise

Symptoms

Mild to Moderate stenosis
1. Asymptomatic
Severe Obstruction
1. Dyspnea (most common presenting symptom)
  1. Dyspnea on exertion progresses to Dyspnea at rest
2. Other presenting symptoms
  1. Syncope
  2. Exercise induced Angina
  3. Congestive Heart Failure

Signs

Classic Murmur
1. Harsh, late-peaking, crescendo-decrescendo Systolic Murmur
2. Medium pitch
3. Heard best at right upper Sternum (second intercostal space)
4. May also be heard at apex (esp. elderly)
5. May radiate into Carotid Artery region
Mild Aortic Stenosis
1. Loud ejection click (best heard at apex)
2. Short, early Systolic Murmur (at right second intercostal space)
3. Loud A2 heart sound (best heard at aortic area)
Moderate Aortic Stenosis
1. Ejection click (best heard at apex)
2. Early Systolic Murmur (loudest at right second intercostal space)
  1. Transmitted to Supraclavicular, Carotids, Apex
  2. Harsh
  3. Systolic ejection murmur that peaks later in systole
  4. Ends well before A2 heart sound
3. Arterial Pulse altered
  1. Upstroke of the pulse has shudder
  2. Delayed, prolonged, low-volume carotid pulsation (Pulsus parvus et tardus)
    1. Test Sensitivity 70% and Test Specificity 98% in Aortic Stenosis
    2. Roldan (1996) Am J Cardiol 77(15): 1327-31 [PubMed]
4. Apex impulse may be abnormal, accentuated
  1. Slightly sustained
  2. Presystolic Shoulder ("a wave") precedes major systolic impulse
5. Systolic thrill may be palpated at base
6. S4 Gallup Rhythm
Severe Aortic Stenosis
1. Ejection click NO longer present
2. A2 heart sound is markedly diminished
3. Systolic Murmur
  1. Variable loudness (may be quiet despite severity)
  2. Long, nearly holosystolic
  3. Harsh (especially at aortic area)
4. Carotid pulse very abnormal
  1. Very slow and long upstroke (Pulsus parvus et tardus)
  2. Overall very weak pulse
5. Brachioradial delay
  1. Right brachial pulse and right radial pulse are simultaneously palpated
  2. Radial pulse is felt after the brachial pulse in severe Aortic Stenosis (also in MR with severe CHF)
    1. Leach (1990) Lancet 335(8699):1199-201 [PubMed]
6. Apical impulse abnormal
  1. Strong and sustained for all of systole

Signs
Most significant findings

Precautions
1. Pulse changes may be masked by atherosclerosis or Hypertension
2. Murmur may be less prominent with reduced LV function
3. Murmur may radiate to apex but not carotids in elderly
High Positive Likelihood Ratio (rule-in diagnosis)
1. Pulsus parvus et tardus (low pulse volume and slow rate of rise of carotid or brachial pulse)
Low Negative Likelihood Ratio (most likely to rule-out diagnosis)
1. Absence of late peaking murmur (early peaking murmur is typically benign)
2. Lack of radiation to right carotid or clavicle
3. Normally split Second Heart Sound (S2)

Classification
Aortic Stenosis Severity

Aortic jet velocity (transaortic velocity)
1. Normal: <2.0 m/sec
2. Mild: 2.0 to 2.9 m/sec
3. Moderate: 3.0 to 3.9 m/sec
4. Severe: >4.0 m/sec
Mean pressure gradient
1. Normal: <10 mmHg
2. Mild: 10-20 mmHg
3. Moderate: 20-40 mmHg
4. Severe: >40 mmHg
5. Critical: >50 mmHg
Aortic valve area
1. Normal: 3 to 4 cm2
2. Mild: 1.5 to 2 cm2
3. Moderate: 1 to 1.5 cm2
4. Severe: <1 cm2
5. Critical: <0.8 cm2

Associated Conditions

AV Node Block (often concurrent with Aortic Stenosis)
Aortic Coarctation
Aortic Dissection

Diagnotics
Electrocardiogram

Precautions
1. Electrocardiogram may only be abnormal in moderate to severe Aortic Stenosis
Common findings
1. Left atrial enlargement
2. Left Ventricular Hypertrophy
  1. Peak systolic gradient (PSG) has been correlated to the QRS amplitude (LVH criteria)
  2. Kishore (1990) Indian Heart J 42(1): 62-5 [PubMed]
Other findings
1. T Wave reduction in leads I, avL, V5, V6
2. Left Anterior Hemiblock or Left Bundle Branch Block
3. Complete AV Block

Imaging

Chest XRay
1. Precautions
  1. Chest XRay is a low yield test in Aortic Stenosis diagnosis
  2. Chest XRay is primarily used to evaluate presenting symptoms (Dyspnea, Syncope, Chest Pain)
2. Findings (unreliable)
  1. Apical Contour abnormal suggests large left ventricle
  2. Prominent ascending aorta
  3. Aortic valve calcification
  4. Left Ventricular Hypertrophy may appear as a boot-shaped heart
Echocardiogram
1. Most important study in the evaluation of suspected Aortic Stenosis
2. Frequency
  1. Initial presentation
  2. Once Aortic Stenosis is diagnosed, repeat echo per monitoring schedule based on severity (see below)
3. Indications
  1. Loud (grade 3), unexplained Systolic Murmur (esp. holosystolic, late systolic)
  2. Single Second Heart Sound
  3. History of bicuspid aortic valve
  4. Symptoms suggestive of Aortic Stenosis
  5. New murmur associated with new symptom presentation (Dyspnea, Syncope, Angina)
4. Findings
  1. Aortic Stenosis diagnosis
    1. Aortic Stenosis grading with aortic valve gradient, orifice size, jet velocity
    2. Aortic Stenosis complications (LV hypertrophy, Diastolic Dysfunction, Systolic Dysfunction)
  2. Other aortic valve disorders
    1. Bicuspid aortic valve
    2. Mildly obstructed valve
    3. Thickened, sclerotic valve (aortic sclerosis)
  3. Other valve disorders presenting similarly to Aortic Stenosis (Dyspnea, Syncope, Angina)
    1. Acute Mitral Regurgitation
      1. May be seen with Myocardial Infarction with papillary Muscle rupture
      2. Chronic Mitral Regurgitation may be associated with Aortic Stenosis (worse prognosis)
    2. Prosthetic valve disorders (e.g. valvular regurgitation or obstruction)
Cardiac Catheterization (Angiogram)
1. Can directly measure left ventricular pressure gradient

Differential Diagnosis

Supravalvular Aortic Stenosis
Membranous supravalvular Aortic Stenosis
Hypertrophic Cardiomyopathy (IHSS)
Mitral Regurgitation

Management
General Measures

Asymptomatic Aortic Stenosis progression is not prevented by any specific measures
SBE Prophylaxis is no longer recommended (until aortic Valve Replacement, or history of prior endocarditis)
Manage comorbid conditions
Maintain adequate hydration (Preload dependent)
Avoid strenuous Exercise or activity in moderate to severe Aortic Stenosis
1. Limit activity in high Dynamic Sports and high Static Sports
2. No restriction needed for mild Aortic Stenosis
Reduce Cardiovascular Risk
1. See Cardiac Risk Management
2. Tobacco Cessation
3. Consider Aspirin prophylaxis
4. Consider Statin for lipid lowering
5. Control Hypertension (40% of patients)
  1. ACE Inhibitors
  2. Amlodipine (Norvasc)
  3. Diuretics (slowly titrate from low dose)
  4. Avoid peripheral alpha blockers (risk of Syncope)
Manage comorbid Atrial Fibrillation (5% of patients) with rate control
1. See Atrial Fibrillation Rate Control
2. Use with caution Beta Blockers and Calcium Channel Blockers
  1. Risk of exacerbating Left Ventricular Systolic Dysfunction

Management
Symptomatic and severe, Critical Aortic Stenosis (>40 mmHg across valve or aortic jet velocity >4.0 m/s)

Admit symptomatic severe Aortic Stenosis and plan aortic Valve Replacement
Consult Cardiothoracic surgery and interventional cardiology
1. Consider valvuloplasty as a temporizing measure in Unstable Patients
Maintain euvolemia with hydration
1. Aortic Stenosis is a Preload dependent disorder
Maintain normal Heart Rate
1. Tachycardia and Bradycardia are poorly tolerated
Approach: Hypertension
1. See SCAPE management below
2. Preferred agents
  1. ACE Inhibitors
  2. Amlodipine (Norvasc)
  3. Nitroprusside
    1. Consider in Critical Aortic Stenosis and ejection fraction <35%
    2. Khot (2003) N Engl J Med 348(18): 1756-63 [PubMed]
3. Agents to use with caution
  1. Diuretics
    1. Indicated for Congestive Heart Failure with hypervolemia
    2. Use with caution (lowers LV filling pressure)
  2. Use Nitroglycerin only with caution
    1. Indicated for Congestive Heart Failure with hypervolemia
    2. Monitor Blood Pressure carefully
    3. Volume expansion may be required
  3. Use Beta Blockers with caution
    1. Indicated for rate control in Supraventricular Tachycardia
    2. Risk of Congestive Heart Failure
4. Agents to avoid
  1. Peripheral Alpha Adrenergic Antagonists
Approach: Hypervolemia (CHF)
1. Nitroglycerin and Diuretics may be used, but monitor closely for Hypotension
2. In Critical Illness, may require ECMO or intraortic balloon bridging to aortic Valve Replacement
Approach: Hypovolemia
1. Hypotension is high risk in Aortic Stenosis
  1. MAP below 65 mmHg decreases coronary perfusion and decreases Cardiac Function
2. May administer small fluid boluses in cycles with reassessment after each bolus
  1. HIgh risk for Fluid Overload (fine balance)
  2. Employ Vasopressors early
  3. Follow Point Of Care Cardiac Ultrasound (Cardiac Function, inferior vena cava)
3. Vasopressors (Phenylephrine, Vasopressin, Norepinephrine)
  1. Administer at lowest effective dose for shortest period
  2. Vasopressors that do not effect Heart Rate are preferred (unless concurrent Bradycardia)
    1. Vasopressin and Phenylephrine constrict Afterload and improve Coronary Artery filling
  3. Start Vasopressin 0.04 units/min
  4. Add Phenylephrine or Norepinephrine as needed
    1. Alternatively, may increase Vasopressin to 0.06 units/min if used as single Vasopressor
Approach: Sympathetic Crashing Acute Pulmonary Edema (SCAPE)
1. Fentanyl may suppress sympathetic overdrive
2. Noninvasive Ventilation (CPAP)
3. Consider vasodilators for Afterload reduction with caution
  1. Clevidapine
    1. Preferred for rapid on and off activity (contrast with longer acting Nicardipine)
      1. Able to be rapidly turned off in case of Hypotension
    2. Preferred for maintained Preload (contrast with venodilation with Nitroglycerin)
Approach: Advanced Airway
1. Start with Noninvasive Ventilation (CPAP)
  1. Use Fentanyl as needed to facilitate patient comfort with CPAP
  2. May be sufficient Ventilatory management to avert Mechanical Ventilation
2. Endotracheal Intubation
  1. Attempt Dissociative Awake Intubation or Awake Nasotracheal Intubation
  2. Use Ketamine for induction agent
  3. Avoid Paralytic Agent (loss of sympathetic drive and apnea)
References
1. Weingart and Swaminathan in Swadron (2022) EM:Rap 22(3): 2-4

Management
Aortic Valve Replacement Indications

Synopsis
1. Aortic valve area <1 cm2 is criteria for stenosis unless completely normal cardiovascular testing
Criteria 1: Severe Aortic Stenosis (see classification above) and
1. Aortic jet velocity: >4 m/sec
2. Mean gradient: >40 mmHg
3. Aortic valve area: <1 cm2
Criteria 2: One of criteria below
1. Symptomatic Aortic Stenosis
2. Possible symptomatic Aortic Stenosis (esp. elderly) with abnormal stress test
  1. Symptoms or Hypotension
  2. Left Ventricular ejection fraction <50%
  3. Dobutamine Stress Echo with <=1 cm valve area or aortic jet velocity >=4 m/s
3. Heart Surgery (e.g. CABG) is already planned (consider AVR even if moderate Aortic Stenosis)
4. Left ventricular ejection fraction <50%
5. Severe aortic valve calcification or rapid progression (e.g. 0.3 m/s increase per year)
6. Low-flow, low gradient severe Aortic Stenosis may initially be misdiagnosed as moderate Aortic Stenosis
  1. Most common in older women with Hypertension
7. Asymptomatic but near Critical Aortic Stenosis
  1. Aortic valve gradient >60 mmHg
  2. Aortic valve orifice <0.6 cm2
  3. Aortic jet velocity >5.0 m/s
  4. Nishimura (2005) Mayo Reviews Lecture, Rochester

Precautions
Surgical evaluation should be prompt for severe Aortic Stenosis

Do not Exercise Stress Test severe Aortic Stenosis with symptoms (high risk for adverse events)
1. Consider stress test only if symptomatic status is unclear
Risk of sudden death
Valve Replacement may be indicated even if ejection fraction low
Valve Replacement is not effective if low ejection fraction and low valve gradient
Carabello (2002) N Engl J Med 346:677-82 [PubMed]

Complications

Monitoring
Echocardiogram Frequency

Mild Aortic Stenosis: Every 3-5 years
Moderate Aortic Stenosis: Every 1-2 years
Severe Aortic Stenosis: Every 6-12 months

Prognosis
Prior to Valve Replacement

Mild Aortic Stenosis: Good (slow progression)
1. Anticipate active and asymptomatic for 10-50 years
Asymptomatic severe Aortic Stenosis
1. At 5 years, 72% will die or have symptoms
2. Recent data suggests sudden death rate is high
3. Pellikka (2005) Circulation 111:3290-5 [PubMed]
Symptomatic severe Aortic Stenosis: Poor prognosis
1. Most patients will have symptom progression
2. Anticipate death within 3 years in most patients
3. Even mild pre-AVR symptoms predict a 2 year mortality >50%

Prognosis
After Aortic Valve Replacement

Consider transcatheter Valve Replacement in those who are at very high surgical risk
Mortality at 30 days post-AVR: 3% (up to 4.5% if CABG performed at the same time)

Resources

Late Aortic Stenosis (University of Washington School of Medicine)
1. https://depts.washington.edu/physdx/audio/lateas.mp3

References

Kondos (1998) CMEA Medicine Review Lecture, San Diego
Long and Gottlieb in Herbert (2022) EM:Rap 22(2): 13-5
Schauer et al. (2016) Crit Dec Emerg Med 30(9):13-9
Assi (1998) Postgrad Med 104(6):99-110 [PubMed]
Bonow (1998) Circulation 98:1949-84 [PubMed]
Bonow (2006) Circulation 114(5): e84-e231 [PubMed]
Carabello (1997) N Engl J Med 337(1):32-41 [PubMed]
Gottlieb (2018) J Emerg Med 55(1): 34-41 [PubMed]
Grimard (2016) Am Fam Physician 93(5): 371-8 [PubMed]
Grimard (2008) Am Fam Physician 78(6): 717-25 [PubMed]
Lester (1998) Chest 113:1109-14 [PubMed]
Otto (2006) J Am Coll Cardiol 47(11): 2141-51 [PubMed]
Shipton (2001) Am Fam Physician 63(11):2201-8 [PubMed]