What is aortic regurgitation, its assessment, pharmacology, and pathophysiology?

Aortic Regurgitation: Assessment, Pathophysiology, and Pharmacology

Aortic regurgitation (AR) is defined as the backward flow of blood from the aorta into the left ventricle during diastole due to imperfect functioning or incompetence of the aortic valve, requiring surgical intervention when symptomatic or when left ventricular dysfunction develops. 1

Pathophysiology

Aortic regurgitation results from either primary valve leaflet disease, aortic root pathology, or a combination of both mechanisms:

• Mechanisms (El Khoury classification) 1:

  • Type I: Normal leaflet motion with aortic root dilatation
  • Type II: Excessive leaflet motion (prolapse)
  • Type III: Restrictive leaflet motion

• Hemodynamic consequences:

  • Acute AR: Sudden volume overload leads to increased left ventricular end-diastolic pressure, pulmonary edema, and potentially cardiogenic shock 2
  • Chronic AR: Gradual left ventricular adaptation with eccentric hypertrophy, progressive dilation, and eventually systolic dysfunction 1

• Common etiologies 1:

  • Bicuspid aortic valve (most common congenital cause)
  • Aortic root dilatation/annulo-aortic ectasia
  • Degenerative valve disease
  • Connective tissue disorders (e.g., Marfan syndrome)
  • Infective endocarditis
  • Failed bioprosthetic valves
  • Complications of transcatheter interventions

Assessment

Clinical Evaluation

• Acute AR presentation:

  • Sudden pulmonary edema
  • Hypotension
  • Tachycardia
  • Signs of cardiogenic shock

• Chronic AR findings:

  • Wide pulse pressure
  • Bounding peripheral pulses
  • Diastolic murmur at left sternal border
  • Displaced and hyperdynamic apical impulse
  • Symptoms of heart failure in advanced stages

Diagnostic Imaging

• Echocardiography (primary diagnostic modality) 3, 1:

  • Transthoracic echocardiography (TTE) as first-line
  • Transesophageal echocardiography (TEE) when TTE is non-diagnostic
  • 3D echocardiography for complex valve lesions

• Criteria for severe AR 3, 1:

  • Vena contracta >0.6 cm
  • Effective regurgitant orifice area (EROA) ≥0.3 cm²
  • Regurgitant volume ≥60 mL/beat
  • Holodiastolic flow reversal in descending aorta
  • Doppler jet width ≥65% of LVOT
  • Pressure half-time <200 ms
  • Regurgitant fraction ≥50% on CMR
  • Evidence of LV dilatation

• Additional imaging modalities:

  • Cardiovascular magnetic resonance (CMR): Assesses biventricular volumes, systolic function, and regurgitant fraction 1
  • Computed tomography (CT): Evaluates aortic root dimensions and excludes dissection in acute AR 3
  • Cardiac catheterization: Reasonable when echocardiographic findings are discordant with symptoms 3

Pharmacological Management

Acute AR

• Medical stabilization (bridge to urgent surgery) 3:
  • Afterload reduction with vasodilators
  • Inotropic support if hypotensive
  • Note: Intra-aortic balloon counterpulsation is contraindicated 3
  • Antibiotics if endocarditis is the cause

Chronic AR

• Asymptomatic patients with hypertension:

  • ACE inhibitors or dihydropyridine calcium channel blockers are recommended 3, 2

• Symptomatic patients with LV dysfunction not candidates for surgery:

  • Guideline-directed medical therapy for heart failure 3:
    • ACE inhibitors
    • Angiotensin receptor blockers (ARBs)
    • Sacubitril/valsartan

• Medication considerations:

  • β-blockers should be used with caution due to potential negative effects 2
  • Goal of vasodilator therapy: Significant decrease in systolic arterial pressure 4

Monitoring and Intervention Timing

• Follow-up intervals 3:

  • Mild AR: Every 3-5 years
  • Moderate AR: Every 1-2 years
  • Severe asymptomatic AR: Every 6-12 months
  • If significant changes in LV size/function: Every 3-6 months

• Indications for surgical intervention 3, 1:

  • Symptomatic severe AR: Surgery indicated regardless of LV function
  • Asymptomatic severe AR with:
    • LVEF <50-55%
    • LVESD >50 mm or >25 mm/m²
    • LVEDD >65 mm
    • Progressive decline in LVEF on serial studies

Clinical Pearls and Pitfalls

• Pitfalls to avoid:

  • Delaying surgery in acute severe AR (medical emergency)
  • Missing progressive LV dysfunction in asymptomatic patients
  • Waiting for symptoms to develop before intervening (may lead to irreversible LV damage)

• Important considerations:

  • Severe AR carries significant mortality (75% of patients die or require AVR within 10 years) 1
  • Even asymptomatic severe AR has up to 19% mortality within 6.6 years 1
  • Surgical options now include valve repair, replacement, or transcatheter interventions 3
  • Patients with bicuspid valves require additional surveillance of the aorta 1

By understanding the pathophysiology, proper assessment techniques, and appropriate pharmacological management, clinicians can optimize outcomes for patients with aortic regurgitation and intervene before irreversible ventricular damage occurs.