Aortic Valve Disease

Etiology

There are 2 common causes of aortic stenosis: calcified (age-related) aortic stenosis and congenital bicuspid aortic valves. Rarely, aortic stenosis and/or aortic regurgitation can be a result of rheumatic heart disease, although this is more commonly a disease of the mitral valve and is generally seen in developing countries. Calcified aortic stenosis is the most common etiology and is believed to occur via progressive endothelial damage over many years. Aortic regurgitation can occur in a chronic or acute setting. Causes of acute aortic regurgitation include type A aortic dissection extending to the valve or damage to leaflets from infectious or noninfectious endocarditis. The same pathologies most commonly cause chronic aortic regurgitation in developing countries, such as aortic stenosis, calcific disease, congenital bicuspid valve issues, and Marfan syndrome. Other less common etiologies include complications following percutaneous aortic balloon valvuloplasties and transcatheter aortic valve replacements (TAVR), as well as a slew of inflammatory disorders including but not limited to systemic lupus erythematosus, rheumatoid arthritis, and Takayasu arteritis. The most prevalent etiology of chronic aortic regurgitation in developing countries is rheumatic heart disease.[1][2]

Epidemiology

Aortic stenosis is a condition more prevalent in the elderly population (fifth through eighth decades). According to a prospective population-based study, the incidence of aortic stenosis was 0.2% during the fifth decade of life, 1.3% during the sixth, 3.9% during the seventh, and 9.8% during the eighth. When comparing the subset of patients with congenital anatomic malformations of the aortic valve to those patients with normal anatomy in those who underwent surgery for isolated aortic stenosis, the fraction of abnormal valves decreased with increasing age. In post-surgery patients less than 50 years of age, two-thirds were found to have a bicuspid valve. In contrast, one-third had unicuspid; ages 50 to 70 saw two-thirds of patients with bicuspid, but one-third had normal tricuspid anatomy. In patients greater than 70 years of age, 60% had tricuspid valve, and 40% had bicuspid. Aortic regurgitation has an estimated prevalence of 4.9%, increasing with age until the sixth decade when incidence decreases. However, this number may be artificially low because up to 75% of aortic stenosis patients may have some degree of regurgitation that goes unreported.[3][4]

Pathophysiology

Narrowing the valve in aortic stenosis occurs due to the fusion of the leaflets or calcifications that cause the valve to have decreased mobility and obstruct the orifice. Calcified aortic stenosis occurs via progressive endothelial damage that can initially cause inflammation and infiltration of macrophages and other inflammatory cells. This inflammation and damage lead to profibrotic factors that establish a collagen matrix, which, unlike bone formation, later calcifies. The most common consequences of aortic stenosis stem from decreased anterograde flow from the left ventricle into the aorta, leading to a backup of blood in the left ventricle and increased left ventricular pressures. This backflow can cause symptoms of heart failure, beginning with left atrial dilation and mitral regurgitation and eventually leading to pulmonary edema and right-sided heart failure. A healthy aortic valve measures 3 to 4 cm; symptoms generally do not precipitate until the valve area is less than 1.0 cm. The more severely stenotic the valve becomes, the more difficult it becomes to maintain adequate cardiac output. The left ventricle undergoes hypertrophy and remodeling, leading to increased left ventricular oxygen demand; this, coupled with decreased cardiac output, can lead to ischemia, arrhythmias, and decreased cerebral perfusion.

Aortic regurgitation leads to retrograde blood flow from the aorta into the left ventricle, increased left ventricular volume, and chamber dilation. Initially, this leads to increased cardiac output, which is maintainable for a prolonged period. However, this increase in cardiac output leads to distention and increased pressure in peripheral arteries, causing increased peripheral systolic pressure. Eventually, this causes worsening of the regurgitation, which can give rise to a rapid decrease in peripheral systolic pressure and, in severe disease, cardiovascular collapse (this phenomenon causes the characteristic wide pulse pressure in severe aortic regurgitation).[5][6][7]

History and Physical

An in-depth history and thorough physical exam are essential and commonly the first line of diagnosis for aortic valvulopathy. Symptoms of aortic stenosis or regurgitation often are not present or are too mild for the patient to notice until the pathology has become severe. Due to this, a careful cardiac physical exam is essential for early detection.

A systolic ejection murmur can often be heard best over the right sternal border at the second intercostal space for aortic stenosis. This murmur peaks early during systole when the disease is mild, and as severity increases, it peaks later; it also tends to radiate to the carotid arteries along with a slowly rising carotid upstroke. Auscultation often reveals a sustained apical impulse as well. In severe disease states, a thrill can sometimes be palpated over the carotid arteries and aortic area. Additional physical exam findings due to complications and sequelae of aortic stenosis include those associated with heart failure and left ventricle remodeling, such as third and fourth heart sounds, pulmonary crackles, jugular venous distention, and pedal edema.

When acute or severe, aortic regurgitation can be suspected when the patient has a wide pulse pressure, and a low-pitched early diastolic murmur is auscultated again over the right sternal border at the second intercostal space. Accentuated P2 may also be noticed due to elevated pressures in the pulmonary vasculature. Chronic aortic regurgitation may illicit a blowing diastolic decrescendo murmur with a positive correlation between the duration of the murmur and the severity of the disease. Often, auscultation of a laterally and inferiorly displaced apical impulse is present and sustained. Often, there is the phenomenon of Corrigan pulse (water hammer), a bounding and forceful pulse that rapidly increases and collapses. Other less common physical exam findings include the de Musset sign, which is subtle head bobbing with a pulse, and the Quincke sign and Muller sign (pulsations on the fingernails and uvula, respectively). Similar physical exam findings to aortic stenosis can also be seen late in disease progression. Acute aortic regurgitation presents differently depending on the etiology. If a patient presents with tearing severe chest pain along with physical exam findings such as variation in blood pressure between the right and left extremities, consider aortic dissection as a cause. If the patient presented with a history of streptococcal infection along with fevers, swollen and tender joints, skin nodules, and a new onset of rash, then rheumatic heart disease would be high on the differential.

Chronic aortic regurgitation and late disease progression of aortic stenosis symptoms generally fall into 2 categories: heart failure and decreased coronary and systemic perfusion. Over time, increased pressures in the left ventricle lead to congestive heart failure; patients may complain of pedal edema, shortness of breath, orthopnea, paroxysmal nocturnal dyspnea, and exertional dyspnea. Patients may state that they require additional pillows at night to sleep because lying flat causes them to be short of breath. Additionally, patients may complain that they have decreased exercise tolerance and the number of city blocks they can walk before feeling short of breath or lightheaded decreases. In severe disease states, patients may present with syncope or may also complain of anginal symptoms.[8][9]

Evaluation

Diagnosis is first suspected based on the patient's subjective history or incidental findings on a physical exam. Once there is suspicion of valvular disease, a 2D echocardiogram with a Doppler study would be the gold standard test. There are 3 major parameters measured to evaluate the competency of the aortic valve during an echocardiogram: the aortic jet velocity, mean aortic valve pressure gradient, and the aortic valve area. These values are used in conjunction with the presence or absence of symptoms to determine the severity of the aortic disease. Other existing comorbidities or sequela can be investigated using imaging such as cardiac contrast tomography (CT) or magnetic resonance imaging scan (MRI), stress testing, and blood cultures for suspected endocarditis or rheumatic disease.[10]

Treatment / Management

There is no medical management that can delay the progression of asymptomatic aortic valve disease. Management is a two-prong approach focusing on optimizing other cardiac comorbidities such as hypertension, coronary artery disease, left ventricular dysfunction, atrial fibrillation, and other arrhythmias and vigilante serial evaluation to monitor for disease progression and early detection of symptoms. Patients with Stage B mild aortic valve disease should have echocardiograms every 3 to 5 years, moderate every 1 to 2 years. For patients with stage C1 severe asymptomatic disease, echocardiography is necessary every 6 to 12 months. Regardless of stage, the development of new symptoms always warrants immediate evaluation.

Valve replacement for aortic stenosis is recommended for asymptomatic patients (evidenced by history or stress testing) with a high-gradient disease or asymptomatic patients with severe aortic stenosis (C2) and a left ventricular ejection fraction less than 50%. Indications for valve replacement for stenotic patients include any patients with severe stenosis (C or D) undergoing other cardiac surgery. New guidelines also show that aortic valve replacement is reasonable in a subset of patients:

• Asymptomatic (C1) with severe aortic stenosis and decreased exercise tolerance or exercise fall in blood pressure
• Symptomatic patients with low flow/low gradient and reduced LVEF (D2) but a low-dose dobutamine stress study showing aortic velocity greater than 4 m/s (or mean pressure gradient greater than 40mm Hg) and a valve area less than 1cm2
• Symptomatic patients with low flow/low gradient severe aortic stenosis (D3) who are normotensive and have LVEF greater than 50%, if clinical, hemodynamic, and anatomic data support valve obstruction as the most likely cause of symptoms
• Moderate aortic stenosis (B) patients undergoing other cardiac surgery; valve replacement may be a consideration for asymptomatic patients with severe aortic stenosis (C1) and evidence of rapid disease progression with low surgical risk.

Valve replacement for the treatment of aortic regurgitation is indicated for symptomatic patients with severe AR regardless of LV systolic function (D), asymptomatic patients with chronic severe AR and evidence of LV systolic dysfunction (EF less than 50%; ie, C2),  and patients with severe AR (C or D) while undergoing cardiac surgery for any other indication. Valve replacement is reasonable for:

• Asymptomatic severe AR patients  and normal LV systolic function (EF greater than 50%) but severe dilation of the left ventricle (left ventricular end-diastolic pressure greater than 50mm Hg; ie, C2)
• Moderate AR patients (B) who are undergoing other cardiac surgery
• Asymptomatic patients with severe AR and normal LV systolic function (C1) but with evidence of progressive severe LV dilation (greater than 65 mm) if the surgical risk is low

Patients whose life expectancy after the replacement is less than 1 year or whose quality of life is not expected to improve would not be candidates for valve replacement. However, if life expectancy is greater than 1 year, and predictions include improvement in the quality of life, there are 2 methods for aortic valve replacement: surgical or transcatheter. Transcatheter aortic valve replacement is only indicated for aortic stenosis, not aortic regurgitation. Electing 1 method over the other is determined by evaluating the morbidity and mortality risk of surgical valve replacement, often utilizing the Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM). If the risk of serious complications or death is greater than 50%, transcatheter aortic valve replacement (TAVR) is the preferred option. If the surgical risk is less than 50%, the consensus has been that SAVR is the preferred method. However, several studies now show no difference in morbidity and mortality 1-year post-op between SAVR and TAVR and that TAVR is safe to use in any patient regardless of the risk level. There is 1 other procedure that sees occasional use for aortic stenosis patients, which is balloon valvuloplasty.[11][12][13][14][15] This procedure involves balloon inflation in the valve orifice to widen the valve, used only as a temporary bridge to valve replacement for hemodynamically unstable patients or for palliative/symptomatic relief in patients who are not surgical candidates. The valve replacement indications are addressed in this topic's staging portion.[15][16][17](A1)

Differential Diagnosis

The differential diagnosis for patients presenting with aortic valve disease symptoms includes but is not limited to:

• Hypertrophic obstructive cardiomyopathy
• Restrictive cardiomyopathy
• Constrictive cardiomyopathy
• Congestive heart failure with reduced ejection fraction (HFrEF)
• Coronary artery disease
• Atrial fibrillation
• Atrial flutter
• Ischemic heart disease
• Pericardial effusion
• Pulmonary hypertension
• Chronic obstructive pulmonary disease
• Restrictive lung diseases
• Symptomatic anemia

Pertinent Studies and Ongoing Trials

Transcatheter aortic valve implantation vs. surgical aortic valve replacement for treating severe aortic stenosis: a meta-analysis of randomized trials showed reduced mortality with TAVR compared to SAVR, with data being most significant in transfemoral TAVR.[18]

Staging

Chronic aortic disease is staged A to D. Stage A (at risk) is a patient with no change in hemodynamics of the valve and no symptoms but the presence of at least 1 risk factor, ie, bicuspid valve, sclerotic valve, history of rheumatic fever, etc. Stage B (progressive) has mild hemodynamic changes with or without left ventricular dilation of early left ventricular diastolic dysfunction, along with the presence of known risk factors, but the patient remains asymptomatic. Stage C1 (asymptomatic severe) includes severe hemodynamic changes on echocardiogram, presence of left ventricular diastolic dysfunction, without decreased left ventricular function, and no symptoms in daily life (however, symptoms may be precipitated with exercise stress testing). Stage C2 has the same hemodynamic parameters as C1 with a depressed left ventricular ejection fraction (under 50%). Stage D1 (symptomatic severe) is the high gradient (Vmax less than 4m/s) with left diastolic dysfunction, left ventricular hypertrophy, and potentially pulmonary hypertension accompanied by angina or heart failure symptoms on exertion. D2 (symptomatic severe) has a low flow/gradient with reduced left ventricular ejection fraction (Vmax greater than 4m/s), decreased left ventricular ejection fraction (under 50%), and symptoms at rest. D3 (severely symptomatic) is the last stage and characteristically presents with a low gradient with normal left ventricular ejection fraction (aka paradoxical low flow), ejection fraction less than 50% is present, but stroke volume is less than 35mL/min; consequence small left ventricular chamber and restrictive diastolic filling. Stage D3 aortic stenosis also has symptoms at rest.[19][20][21]

Prognosis

Prognosis is largely determined by the time of onset of symptoms. Asymptomatic patients who do not progress to symptomatic have a longer life expectancy. The prognosis of patients with severe symptomatic aortic valve disease who do not undergo valve replacement is very poor, with survival at 3 years ranging from approximately 40 to 60%. In contrast, those who underwent valve replacement ranged from 80% to 90%.[22]