Left Ventricular Outflow Tract

Introduction:

The subvalvular Left Ventricular Outflow Tract (LVOT) is fixed by the interventricular septum of the basal membrane between the aortic valves. Through here passes the systolic flow of blood from the left ventricle (LV) to the ascending aorta.

Left Ventricular Outflow Tract Obstruction (LVOTO) is a generic term for an obstruction that interferes with the ejection of blood from the LV into the aorta. It is a heterogenous defect caused by the contact between the anterior leaflet of the mitral valve and the interventricular septum during systole, which can occur at either the supravalvular, valvular or subvalvular level. It also can include several stenotic lesions of the left ventricular outflow tract (LVOT) which forcefully increases the afterload on the LV and may eventually result in LV failure.

Some of the different sources of LVOTO include:

Subaortic Stenosis – progressive narrowing of the aorta caused by either a localised, fibromuscular build-up around the LVOT, or a more general narrowing of the cardiac muscle, resulting in a lesion out of the LV.

Bicuspid Aortic Valve – abnormal vasculogenesis (blood vessel formation) that causes leaflet stress, leading to calcification, scaring and aortic stenosis.

Supravalvular Aortic Stenosis – hypoplasia (incomplete/underdeveloped) obstructions in the ascending aorta caused by thickening and disorganised elastin fibres, leading to hypertrophy and calcification.

Coarctation of the Aorta – narrowing of the aorta at the ductus arteriosus caused by stenotic lesions that increase systolic pressure, leading to Left ventricular hypertrophy (LVH).

However, in the case of this patient, the LVOTO is most likely secondary to Hypertrophic Obstructive Cardiomyopathy (HOCM). This is a congenital, autosomal-dominant disorder, characterised by disorganisation of the cardiac myocytes leading to hypertrophy of the LV in the absence of abnormal loading conditions. LVOTO is a frequent manifestation which can be a major cause of symptoms such as dyspnoea, chest pain, presyncope, and syncope in HOCM. The obstruction can often be controlled with medical therapy, however, interventional therapy such as septal alcohol ablation or surgical myectomies can be performed when necessary and are discussed in the treatments section.

Pathology:

Hypertrophic Cardiomyopathy (HCM) occurs in approximately 1 in every 500 people, most prevalent in males and is the most common cause of sudden cardiac death (SCD) in the <35-year-old population. There is an autosomal dominant pattern of inheritance, with 60-70% of patients having an affected family member. HCM is a disorder of the myocardium usually caused by mutations of the sarcomere or sarcomere-associated proteins (including β-myosin heavy chain, myosin binding protein C, troponin I and troponin T). This leads to: a disarray of myocytes and myofibrils, myocardial fibrosis and also LV hypertrophy with a wall thickness of >15mm. However, up to 50% of accounted for cases have scattered causes listed in figure 1.

The LV Hypertrophy may be asymmetric, concentric, localised in the apex or also involving the RV. The extent and location of the hypotrophy varies. Sarcomeric hypertrophy is most commonly asymmetric, with 90% seen affecting the interventricular septum (asymmetrical septal hypertrophy), defined as a septal-to-posterior wall ratio of >1.3 (or >1.5 in hypertensive patients). Whilst 3% affects the Apical, 1% midventricular and 1% posteroseptal and lateral. The remaining 5% of cases are classed as symmetrical hypertrophy.

Abnormal mitral valves, such as elongated mitral leaflets or coaptation of the mitral leaflets, are a common abnormality associated with HCM, as well as anteriorly displaced papillary muscles that are shown to reduce the LVOT cross-sectional area and thought to create drag forces on the valve leaflets. The anterolateral displacement of these muscles may contribute to the obstruction of the outflow tract or may produce obstruction even in patients with an almost normal ventricular wall thickness. This displacement of the papillary muscle can produce insufficient flow through the Mitral valve due to repeated contact between the interventricular septum and the anterior leaflet of the mitral valve during Systolic Anterior Motion (SAM). The Venturi effect (anterior leaflet of the mitral valve is sucked against the interventricular septum mid-systole, narrowing the LVOT) may also play a role in accentuating the obstruction as it increases septal wall thickness and intra-ventricular pressure.

Some processes that contribute to the pathophysiology of HCM include:

• Abnormal diastolic function – A major consequence of LV hypertrophy increasing dependence on the aorta for ventricular filling due to reduced LV diastolic volume and reduced stroke volume as LV relaxation is prolonged/incomplete. This can cause arrhythmias such as atrial fibrillation to be poorly tolerated

• Mitral regurgitation – malcoaptation of the mitral leaflets secondary to mitral valve SAM

• Myocardial Ischaemia – a combination of LVH with LVOTO increases the myocardial oxygen demand, precipitating angina in approximately 30% of HCM patients.

Diagnosis:

Symptoms of LVOTO include: chest pain, dyspnoea (laboured breathing), fatigue on exertion, dizziness, palpitations, presyncope / syncope and other symptoms associated with heart failure. Obstruction can contribute to exercise intolerance, angina and syncope. In terms of this patient, he is experiencing chest pain and shortness of breath on exertion, correlating to symptoms associated with HOCM.

It is important to determine if these symptoms are due to the LVOTO or caused by other related conditions such as diastolic dysfunction, myocardial ischemia, or arrhythmias. Approximately 25-30% of patients with HCM have LVOTO caused by SAM at rest, whilst a significant proportion of patients without evidence of resting outflow obstruction can have provoked obstructive gradients during manoeuvres. When categorizing patients with HCM, the three distinct hemodynamic groups are: those with resting outflow tract obstruction (obstructive), those with provocable gradients but no obstruction at rest (latent obstruction), and those with no gradient either at rest or on provocation (non-obstructive). Thus, it is important to provoke a meaningful gradient that can be related to a patient’s symptoms despite the method used. To do this, the baseline gradients and the magnitude of provocable gradients must be quantified.