Aortic Regurgitation

Aortic regurgitation is a valvular heart disease characterized by the inadequate closure of the aortic valve during diastole, allowing blood to flow back from the aorta into the left ventricle. This condition impairs valve competence and leads to volume overload of the left ventricle, with progressive hemodynamic consequences. It may occur in either acute or chronic form and can originate from structural abnormalities of the valve leaflets or the aortic root.

Etiology, Pathogenesis, and Pathophysiology

The causes of aortic regurgitation fall into two main categories:

• Primary valvular causes, directly affecting the cusps:
  • Rheumatic heart disease: the most common cause worldwide; leads to retraction, commissural fusion, and thickening of the cusps;
  • Infective endocarditis: may cause laceration, perforation, and leaflet destruction;
  • Senile calcific degeneration: typical in the elderly, especially in the presence of bicuspid aortic valve;
  • Connective tissue disorders: Marfan syndrome, Ehlers-Danlos syndrome, osteogenesis imperfecta, pseudoxanthoma elasticum;
  • Blunt chest trauma: rare, but may result in valve rupture in the absence of pre-existing lesions.
• Secondary aortic causes, affecting the valvular support structure:
  • Idiopathic dilation of the aortic root;
  • Type A aortic dissection: causing loss of commissural support;
  • Inflammatory aortitis: syphilis, Takayasu arteritis, rheumatoid arthritis, ankylosing spondylitis;
  • Chronic hypertension: a frequent cause of annular dilation in the elderly;
  • Congenital bicuspid valve: commonly associated with aortic root ectasia and early degeneration.

Aortic regurgitation results in retrograde flow into the left ventricle during diastole, causing volume overload in addition to normal diastolic filling. To maintain an effective stroke volume, the left ventricle undergoes progressive dilation and eccentric hypertrophy, with increased end-diastolic volume and myocardial mass.

This adaptive mechanism follows Laplace’s law, where wall tension is proportional to the product of pressure and radius and inversely proportional to wall thickness. Ventricular dilation stimulates sarcomere replication in series, maintaining intraventricular pressure within functional limits and temporarily preserving systolic function—a phase known as stable compensation.

As the disease progresses, excessive dilation leads to increased wall stress, decreased contractility, and systolic dysfunction, eventually resulting in hemodynamic decompensation.

Loss of diastolic aortic pressure due to blood backflow, combined with increased systolic pressure from augmented stroke volume, produces a markedly widened pulse pressure, a pathognomonic sign of the disease.

In acute aortic regurgitation—caused by endocarditis, trauma, or dissection—the left ventricle has no time to compensate. Rapid elevation of end-diastolic pressure reduces the aorto-ventricular gradient, leading to acute pulmonary congestion, alveolar edema, and cardiogenic shock. In the absence of hypertrophy, the heart cannot manage the overload, making the condition rapidly fatal if untreated.

Four pathophysiological stages have been described in chronic aortic regurgitation:

• Stable compensation: optimal ventricular adaptation, normal systolic function, asymptomatic patient;
• Unstable compensation: early subclinical dysfunction with structural changes (fibrosis), but no symptoms yet;
• Borderline compensation: symptoms appear only with exertion, with evident dysfunction on stress testing;
• Overt ventricular failure: reduced ejection fraction, symptoms at rest, full-blown heart failure.

Clinical Manifestations

Clinical manifestations of chronic aortic regurgitation may remain silent for years due to the adaptive capacity of the left ventricle. Symptoms emerge when mechanical compensation is lost and ventricular dysfunction begins to impair cardiac output.

In the early stages (stable and unstable compensation), patients are either asymptomatic or report only fatigue, palpitations, or a sensation of pulsation in the neck or head (Corrigan’s sign). The first true symptom is typically exertional dyspnea, which may progress to orthopnea and paroxysmal nocturnal dyspnea.

With the onset of systolic dysfunction, angina pectoris may develop (even without coronary artery disease) due to an imbalance between oxygen demand and supply, along with acute pulmonary edema and eventual global heart failure. The condition may deteriorate rapidly if the regurgitation becomes acute.

In acute aortic regurgitation (e.g., endocarditis, dissection, trauma), symptoms present abruptly: worsening dyspnea, massive pulmonary edema, severe hypotension, and cardiogenic shock.

In chronic cases, clinical signs reflect volume overload and increased pulse pressure. Inspection may reveal visible neck or jugular pulsation, head bobbing in sync with the pulse (Musset’s sign), or pulsating tongue (Müller’s sign).

Palpation may detect Corrigan’s pulse (rapid and bounding), hyperdynamic and “water-hammer” in character. The apical impulse is hyperdynamic, displaced downward and laterally.

Auscultation provides the most characteristic findings:

• The hallmark is a high-pitched, decrescendo diastolic murmur along the left sternal border, best heard with the patient leaning forward in held expiration;
• A functional systolic murmur may be present due to increased stroke volume;
• The Austin Flint murmur, a mid-to-late diastolic murmur at the apex, results from interference with mitral inflow caused by the regurgitant jet;
• Third and fourth heart sounds are common in advanced ventricular dysfunction.

In acute regurgitation, peripheral signs are absent (no time for compensation). The pulse is weak, pulse pressure is not markedly widened, and the diastolic murmur may be short and faint.

Diagnosis

Electrocardiography (ECG) is often nonspecific early on but may show signs of left ventricular hypertrophy (increased voltage, left axis deviation). As the disease advances, there may be ST segment and T wave abnormalities (inversion, asymmetry), and eventually left bundle branch block in severe cases.

In acute regurgitation, sinus tachycardia and ST segment changes due to subendocardial ischemia may be present.

Chest X-ray in chronic cases shows cardiomegaly with an elongated third left arch due to left ventricular dilation and signs of pulmonary congestion. In acute forms, it may appear normal or show acute alveolar edema.

Echocardiography is the key diagnostic tool:

• It visualizes the origin of regurgitation, semilunar anatomy, and aortic root dilation;
• It assesses systolic function and wall thickness of the left ventricle;
• Color Doppler quantifies regurgitation using vena contracta, EROA, regurgitant volume (RVol), and regurgitant fraction (RF);
• A vena contracta ≥ 6 mm or an EROA ≥ 30 mm² indicates severe regurgitation.

Aortography, though less frequently used today, remains important preoperatively or when echocardiographic findings are inconclusive. It visually assesses regurgitation by contrast opacification of the left ventricle, graded from 1+ to 4+.

Cardiac magnetic resonance (CMR) offers accurate evaluation of ventricular mass and function and volumetric quantification of regurgitation in patients with suboptimal echocardiographic images.

Treatment

Treatment of aortic regurgitation depends on the form (acute or chronic), the severity of regurgitation, and the presence or absence of left ventricular dysfunction.

In mild to moderate, asymptomatic forms without left ventricular dysfunction (EF > 55%) and with normal aortic root dimensions, periodic echocardiographic follow-up and bacterial endocarditis prophylaxis are sufficient.

In patients with moderate-to-severe regurgitation but preserved ventricular function, the following may be beneficial:

• Arterial vasodilators (e.g., ACE inhibitors, nifedipine) to reduce afterload and slow disease progression;
• Diuretics for pulmonary congestion symptoms, used cautiously to avoid excessive preload reduction;
• Beta-blockers in patients with Marfan syndrome and aortic root dilation to reduce wall stress;
• Positive inotropes (e.g., digoxin) in advanced stages with systolic dysfunction.

Surgical intervention is indicated:

• In all symptomatic patients with severe regurgitation regardless of EF;
• In asymptomatic patients with EF < 55% or left ventricular end-systolic diameter > 50 mm (ESC criteria);
• In cases of aortic root dilation (diameter > 50 mm in Marfan patients, > 55 mm in others);
• In all cases of acute severe regurgitation (e.g., endocarditis, dissection) as a cardiac surgery emergency.

Valve replacement with mechanical or biological prostheses is the treatment of choice. In selected cases, valve repair may be feasible, particularly in high-volume specialist centers.

Prognosis

Prognosis is heavily influenced by the timing of surgical intervention. Asymptomatic patients with normal ventricular function have excellent long-term survival. However, 5-year survival drops dramatically (< 20% in untreated patients) after symptom onset, especially in the presence of systolic dysfunction, angina, or heart failure.

Patients undergoing early surgery (with preserved EF) have a very favorable outcome. In untreated acute forms, aortic regurgitation may be rapidly fatal.

Complications

The main complications of aortic regurgitation include:

• Acute pulmonary edema in decompensated or acute forms;
• Angina and myocardial ischemia even without coronary artery disease;
• Heart failure with progressive ejection fraction reduction;
• Aortic dissection in the presence of marked aortic root ectasia;
• Infective endocarditis with potential valve destruction;
• Ventricular arrhythmias in terminal stages.

References
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