Introduction
Left ventricular outflow tract obstruction (LVOTO) refers to the limitation of blood flow out of the left ventricle. The level of obstruction can be valvular, sub-valvular, or supravalvular. It can include anatomic stenotic lesions anywhere from left ventricle (LV) outflow to descending aorta. Hemodynamically, LVOTO has been defined as a peak instantaneous gradient at LV outflow of at least 30 mmHg, either at rest or on provocation.[1] While traditionally defined in patients with hypertrophic cardiomyopathy, LVOTO is known to have several causes.
LVOTO constitutes 6% of congenital heart diseases, and in most cases, the cause of LVOTO is congenital.[2] It can occur in isolation or accompany other congenital heart diseases.[3] Dynamic LVOTO can also be seen in critically ill patients, whereby the use of inotropes in patients with intravascular volume depletion results in hypovolemia.[4]
In general, there is an obstruction to forward flow, which increases afterload and, if untreated, can result in hypertrophy, dilatation, and eventual failure of the left ventricle.
Issues of Concern
Following are the significant etiologies of LVOTO, with a brief overview of clinical features and respective management options.
Subaortic Stenosis
Subaortic stenosis (SAS) is a narrowing below the level of the aortic valve. It follows aortic valve stenosis as the most common cause of LVOTO. [5] SAS may occur due to a fibrous ring encircling the LVOT or, more commonly, due to a discrete ridge below the aortic valve. The obstruction may be focal or more diffuse, resulting in a tunnel leading out of the left ventricle. In complex subaortic stenosis, there is an abnormal adherence of the anterior leaflet of the mitral valve to the septum and the presence of endocardial tissue in the LVOT. Complex LVOTO is commonly seen in patients with ventral septal defects (VSDs). The clinical course of SAS is progressive, with increasing obstruction and progression of aortic regurgitation seen in more than 80% of untreated patients.
Clinical presentation varies with the degree of obstruction. Patients with mild to moderate degrees of obstruction are usually asymptomatic, and the diagnosis of SAS is made while the patient is being evaluated for a murmur or on imaging for evaluation of other congenital heart defects. Older patients with a progressively worsening degree of obstruction can manifest with exertional dyspnea, angina or syncope.
On examination, a harsh systolic ejection murmur is heard along the left sternal border, with or without a thrill. Patients may also have systolic click if the SAS is associated with a bicuspid aortic valve (BAV). A decrescendo-blowing murmur of aortic regurgitation can be appreciated.
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 and 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 also considered 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 so that further aortic valve damage can be avoided. 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 fibro-myectomy with concomitant aortic valve repair if significant aortic regurgitation is present. SAS can recur and requires reoperation in up to 20% of cases.[6][7]
Bicuspid Aortic Valve stenosis
Bicuspid aortic valve (BAV) stenosis is one of the most common congenital cardiovascular malformations, present in about 1% to 2% of the population. It is more common in males. Patients with BAV make up more than 50% of cases with clinically significant aortic stenosis. BAV can be inherited, and family clusters have been documented. In inherited cases, inheritance patterns are usually autosomal dominant with variable penetrance. A mutation in the NOTCH1 gene has also been described.[8]
BAVs arise from abnormal cusp formation and vasculogenesis, which results in the formation of one smaller cusp and one larger cusp. More commonly, the right and left coronary cusps are fused. BAVS 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, leading to accelerated valvular changes, including scarring, calcification, aortic stenosis, and regurgitation. The condition is associated with aortopathy and an increased risk of aortic dissection.
Aortic stenosis is the most common complication of BAV. The clinical presentation resembles that of degenerative aortic stenosis. The patient may present with angina, syncope, or heart failure. On examination, there is a mid-systolic murmur which increases in severity as the degree of stenosis worsens. Concomitant aortic regurgitation results in an early diastolic murmur. The ejection click, which is characteristic of a normally functioning BAV, diminishes or becomes inaudible with a progressive degree of AS.
Transthoracic echocardiography may show reduced systolic excursion of calcified bicuspid aortic valves. Doppler echocardiography can reveal increased gradients across the obstructive valve. Color Doppler may show forward turbulence (AS) or a backward flow (AR). It is important to document the presence (or absence) of coarctation of the aorta on a suprasternal view due to its association with BAV. CTA and CMR have good sensitivity and specificity for the evaluation and diagnosis of BAV. CTA particularly helps in aortic valve and vascular assessment before transcatheter intervention for BAV stenosis.[9][10]
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 increase exercise tolerance may also be considered for surgery. Severe aortic regurgitation 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 of aortic dissection or rapid progression (aortic growth rate >0.5 cm/year), and/or concomitant coarctation of the aorta. Balloon valvuloplasty may decrease the gradient and improve symptoms in those without a calcified valve.[11][12]
Supravalvular Aortic Stenosis (SVAS)
Supravalvular aortic stenosis (SVAS) is the least common lesion amongst the LVOT obstruction spectrum, contributing to 8 to 14% of cases.[5][13] SVAS can occur in the following four settings. It can occur as a part of Williams syndrome, including intellectual disability, hypercalcemia, short stature, and 'elfin' facies. At least 70% of patients with William syndrome may have SVAS.[14] The occurrence pattern of SVAS can also be familial, sporadic, or associated with familial hypercholesterolemia.[15] In most cases, the underlying cause is a mutation of the elastin gene on chromosome 7.
There are three anatomic types: hourglass type, membranous type, and diffuse hypoplasia of the ascending aorta. SVAS may be associated with aortic valve abnormalities, coarctation of the aorta and ostial stenosis of branches of the aorta, or coronary artery stenosis. Hourglass type is the most common type, in which there is 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, ultimately leading to 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.[16]
Clinically, patients with SVAS associated with William syndrome may have features of the systemic disease such as failure to thrive, intellectual impairment, elfin facies, gastrointestinal problems, and urinary tract abnormalities. Physical findings of isolated SVAS are like 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 sino-tubular junction. There may be left ventricular hypertrophy. Doppler echocardiography reveals an increased gradient across the stenosis. Additionally, MRI can define the extent and severity of stenosis, along with defining co-existing vascular stenosis. Invasive 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 sino-tubular junction, or aortoplasty. The prognosis is good following the surgical intervention.[17]
Coarctation of the Aorta
Coarctation of the aorta refers to a narrowing of the aortic lumen. The location of narrowing is mostly at the point of insertion of ductus arteriosus, just distal to the left subclavian artery. 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. Ultimately left ventricular hypertrophy develops due to increased afterload. Over time, collaterals are established to circumvent the obstruction.[18]
Clinical presentation varies with age. Severe coarctation may manifest in neonates as cardiogenic shock and heart failure soon after the closure of the patent ductus arteriosus. Adults may initially present with systemic arterial hypertension. It may be asymptomatic and discovered on evaluation of a heart murmur or other congenital structural heart disease. 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 difference of at least 10 mmHg between the upper and lower extremities. A delay or decrease in the 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 due to 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-rays or CT due to extensive collateral formation bypassing the area of coarctation. A figure of "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.[19] MRI and angiogram may also be performed before or at the time of intervention if indicated.
There can be two management strategies: surgical or catheter-based (with or without a stent). Neonates aged less than four months are surgical candidates, as there are higher chances of recurrence after balloon angioplasty. For patients weighing more than 25kg weight, catheter-based intervention is recommended, given that adult-size stent placement is technically possible. This excludes patients with complex anatomy, such as excessive vessel tortuosity. 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.[20][21][22]
Hypertrophic Cardiomyopathy (HCM)
HCM is an autosomal dominant disease with equal prevalence in males and females. It is caused by a genetic mutation of cardiac sarcomeres. The disease is characterized by disorganized myocytes, interstitial fibrosis, and hypertrophied left ventricle.[23] The most common pattern of hypertrophy is the involvement of the basal anterior septum and anterior wall. About two-thirds of patients with HCM have an obstructive form. In most patients with HCM, due to elongated leaflets, there is a systolic anterior motion of the anterior mitral valve leaflet (SAM). The SAM creates dynamic LVOT obstruction. The narrower diameter of the LVOT due to increased septal wall thickness contributes to this obstruction.
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. On precordial examination, a harsh crescendo-decrescendo murmur is heard at the apex. This murmur varies in intensity with different physiological states. There is an increase in intensity with Valsalva, or nitrates, and a decrease in intensity with squatting or hand grip.
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 is the most important tool for diagnosis. It establishes the presence, location, and degree of hypertrophy. It also establishes the presence of SAM and the degree of LVOT obstruction. It defines the mechanism of mitral regurgitation.
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.[24][25][26]
Enhancing Healthcare Team Outcomes
There are many causes of left ventricular outflow tract obstruction (LVOTO). Thus the condition is best managed by an interprofessional team that includes a pediatrician, cardiologist, cardiac sonographer, cardiac surgeon, internist, and cardiac nurses. Most cases of LVOTO in newborns and children are congenital, whereas, in adults, the cause may be a bicuspid aortic valve or degenerative aortic stenosis. In almost all cases, symptomatic patients need surgery because the obstruction is mechanical. The outcome depends on the patient's age, comorbid condition, and severity of the heart disease.
The entire healthcare team must communicate openly with all team members to address any concerns that arise promptly. This includes meticulous record keeping, ensuring that anyone on the interprofessional team who examines the patient record has the most updated and accurate information on which to base clinical decisions. Nurses will also be crucial in monitoring the patient cond coordinating with the appropriate specialists, particularly if the patient's condition deteriorates. This interprofessional approach will be the best method to achieve optimal patient outcomes. [Level 5]
Left Ventricular Outflow Tract Obstruction