Issues of Concern
Common Causes of Left Ventricular Outflow Tract Obstruction (LVOTO)
Subaortic Stenosis (SAS)
Subaortic stenosis is narrowing at the level of the aortic valve. It may be due to a discrete ridge or fibrous ring encircling the LVOT. This fibrous membrane may extend onto the aortic valve cusps and make contact with the ventricular side of the anterior mitral leaflet. The obstruction may be focal or more diffuse, resulting in a tunnel leading out of the left ventricle. The discrete form is most common. Complex subaortic stenosis can also be seen which leads to abnormal adherence to the anterior leaflet of the mitral valve to the septum and the presence of endocardial tissue in the LVOT. These types of obstructions are commonly seen in patients with ventral septal defects (VSDs).
If a gradient is present, a systolic ejection murmur is heard along the lower left sternal border, which peaks later with the severity of SAS. The clinical course of SAS is progressive, with increasing obstruction and progression of aortic regurgitation in more than 80% of untreated patients.
Patients may present with one of three symptoms associated with severe valvular aortic stenosis: angina, heart failure, or syncope.
The electrocardiogram is usually normal. However, with isolated forms of LVOT obstruction, left ventricular hypertrophy and left axis deviation may be present.
Transthoracic echocardiography will often demonstrate a focal or diffuse narrowing of the LVOT. Membranes located adjacent to the aortic valve or extending to the anterior leaflet of the mitral valve are more likely to result in a progressive obstruction as well as more likely to cause aortic valve damage with aortic regurgitation. A continuous-wave Doppler peak gradient of greater than or equal to 50 mmHg is considered severe and indicates a poor prognosis if left untreated.
Surgical resection is the intervention of choice and is done via a transaortic approach. Surgical intervention is a consideration in patients with lower gradients (peak pressure gradient less than 50 mmHg) if there is left ventricular systolic dysfunction, moderate to severe aortic regurgitation, or a VSD. Usually, the approach has been to intervene when the mean gradient across the LVOT is more than 30 mmHg to avoid further aortic valve damage. Patients who develop symptoms with exertion and patients planning to become pregnant should be considered for SAS resection if the gradient is greater than or equal to 30 mmHg. Surgery involves fibromyectomy with concomitant aortic valve repair if significant aortic regurgitation is present. SAS can recur and requires reoperation in up to 20% of cases.
Bicuspid Aortic Valve (BAV)
The bicuspid aortic valve is one of the most common congenital cardiovascular malformations, present in about 1% to 2% of the population and more common in males. BAV can be inherited, and family clusters have been documented. In those cases, inheritance patterns are usually autosomal dominant with variable penetrance. A mutation in the NOTCH1 gene has also been described.
BAVs arise from abnormal vasculogenesis and cusp formation, resulting in the formation of one smaller cusp and one larger cusp. More commonly, the right and left coronary cusps are fused. BAV is usually progressive, and most valves function normally until later in life. The abnormal valve formation leads to increased leaflet stress, more turbulent flow, and restricted motion which leads to accelerated valve changes including scarring, calcification, aortic stenosis, and regurgitation. BAV is associated with dilation of the ascending aorta and an increased risk of aortic dissection.
The most common complication of BAV is aortic stenosis. Therefore, clinical features are similar. Patients may present with a midsystolic murmur that increases in harshness and peaks later as the degree of stenosis worsens. Concomitant aortic regurgitation results in an early diastolic murmur. When aortic stenosis is present, patients may complain of chest pain, dyspnea, or have episodes of syncope.
Transthoracic echocardiography may show irregularities in the cusp of the aortic valve along with evidence of progressive thickening and calcification leading to a stenotic valve. Patients with BAV make up more than 50% of cases with clinically significant aortic stenosis.
There are no effective medical therapies to prevent valve deterioration or aortic root dilatation in patients with BAV. Surgical repair is indicated for patients with severe stenosis who are symptomatic or have decreased left ventricular function. Asymptomatic patients who desire to become pregnant or want to increase their exercise tolerance may also be considered for surgery. Severe aortic regurgitation that is associated with symptoms, severe aortic root enlargement, or left ventricular dysfunction should be surgically corrected. For patients who will undergo valve replacement, concurrent aortic root replacement is recommended if the aortic diameter is greater than or equal to 4.5 cm. In those without aortic valve disease, aortic root replacement is recommended when the aortic diameter exceeds 5.5 cm and may be considered in patients with an aortic diameter of 5.0 cm if there is a positive family history or history of rapid progression. Balloon valvuloplasty may decrease the gradient and improve symptoms in those without a calcified valve.
Supravalvular Aortic Stenosis (SVAS)
Supravalvar aortic stenosis (SVAS) is the rarest lesion of the LVOT obstructions. There are three anatomic types: hourglass type, membranous type, and diffuse hypoplasia of the ascending aorta. The most common is the hourglass type with thickening and disorganization of elastin fibers within the aortic media producing a constricting annular ridge at the margin of the sinuses of Valsalva. This leads to reduced elasticity and increased shear stress within the ascending aorta, which incites smooth muscle hypertrophy and increased collagen deposition. The coronary arteries are near the site of outflow obstruction which causes them to be subjected to elevated systolic pressures leading to dilatation, tortuosity, and accelerated atherosclerosis.
SVAS occurs in an autosomally inherited form and in a rare sporadic form. In all three types, the underlying cause has been identified as a mutation of the elastin gene on chromosome 7.
SVAS is associated with William syndrome which is a multisystem disorder with features including failure to thrive, intellectual impairment, elfin facies, gastrointestinal problems, and urinary tract abnormalities.
Physical findings of isolated SVAS are similar to aortic valve stenosis. A systolic murmur is heard which projects to the jugular notch. A hallmark feature of SVAS is that systolic pressure in the right arm is usually higher than in the left arm. The patient may experience symptoms of angina, dyspnea, and syncope.
Electrocardiogram reveals left ventricular hypertrophy when an obstruction is severe. Right ventricular hypertrophy can also be seen if pulmonary arteries are narrowed.
Transthoracic echocardiography may reveal dilated sinuses of Valsalva, and the ascending aorta and arch are usually small or of normal size. The diameter of the aortic annulus is greater than the sinotubular junction.
Angiography is usually done to assess the gradient across the LVOT and to assess the coronary arteries.
Surgical intervention is recommended in symptomatic patients or those with a mean pressure gradient of more than or equal to 50 mmHg. Obstruction can be relieved by excision of focal stenosis with end-to-end anastomosis of the ascending aorta, patch enlargement of the sinotubular junction, or aortoplasty. Prognosis is good following surgical intervention.
Coarctation of the Aorta
Coarctation of the aorta is an aorta narrowing, located at the insertion of the ductus arteriosus just distal to the left subclavian. More diffuse forms of the disease may involve the arch or isthmus. The exact pathogenesis which causes this narrowing is unknown, although multiple theories have been described. The stenotic lesion causes left ventricular outflow tract obstruction resulting in increased systolic pressure in the left ventricle and proximal aorta. Left ventricular hypertrophy and collateral blood flow are mechanisms to try and circumvent this obstruction.
Adults may initially present with systemic arterial hypertension. A patient with systemic arterial hypertension should have upper and lower extremity arterial blood pressures measured. Radial and femoral pulses should also be checked. With coarctation of the aorta, upper limb hypertension is usually present, and there is a systolic pressure differential of at least 10 mmHg between the upper and lower extremities. A delay or decrease in amplitude of the femoral pulse may also be present. A systolic or continuous murmur may be heard on auscultation in the interscapular region or throughout the chest wall from intercostal collateral arteries.
An electrocardiogram may show left ventricular hypertrophy. For more complicated lesions, right ventricular hypertrophy may also be present.
Characteristic rib notching is often present on chest x-ray or CT due to extensive collateral formation bypassing the area of coarctation. A figure “three” sign may also be seen on a chest x-ray due to pre-stenotic and post-stenotic dilatation.
Coarctation of the aorta is best seen on echocardiography via the suprasternal notch view. When performed, this may demonstrate a posterior shelf, well-expanded isthmus, and transverse aortic arch. A high-velocity jet will likely be seen through the coarctation site.
MRI and angiogram may also be performed before or at the time of intervention if indicated.
A surgical repair usually relieves the obstruction with low mortality rates. Stent implantation decreases the risk of aneurysm formation and has good long-term outcomes in both native and recurrent coarctation. For discrete stenoses, balloon angioplasty can be used as a primary intervention, but it is not the best option for long-segment or tortuous forms of coarctation.
Hypertrophic Cardiomyopathy (HCM)
HCM is characterized by disorganized myocytes which lead to hypertrophy of the left ventricle, usually the septum. However, hypertrophy can be extensive involving the LV free wall as well. It is an autosomal dominant disease with equal prevalence in males and females.
About two-thirds of patients have obstructive form. In most patients, LV outflow obstruction occurs via systolic anterior motion (SAM) of the mitral valve in which the elongated leaflets contact the septum in mid-systole due to the high-velocity flow of blood directly on the leaflets. The narrower diameter of the LVOT due to increased septal wall thickness contributes to this obstruction. This leads to increased intraventricular pressures that over time can lead to LV dysfunction.
Symptoms may include chest pain, dyspnea, exertional fatigue, dizziness, palpitation, and other symptoms of heart failure. Patients may experience near-syncope or syncope due to outflow obstruction or arrhythmia. A systolic ejection murmur may be heard at the lower left sternal border and apex that varies with the subaortic gradient.
The most common findings on ECG are left ventricular hypertrophy, T wave inversions, left atrial enlargement, deep and narrow Q waves, and diminished R waves in the precordial leads.
Transthoracic echocardiography usually reveals a thickened septum.
Medical treatment with beta-blockers, calcium channel blockers, and disopyramide has been used for symptomatic patients. Surgical myectomy is the preferred option for patients with severe symptoms refractory to medical therapy or with an LVOT gradient greater than 50 mmHg. Percutaneous alcohol septal ablation is an alternative to myectomy in selected patients. An implantable cardiac device is effectively used for the primary prevention of lethal ventricular tachyarrhythmias.