Routine orthostatic LVOT gradient assessment in patients with basal septal hypertrophy and LVOT flow acceleration at rest: please stand up

A 70-year-old female with exertional dyspnoea was found to have basal septal hypertrophy (BSH), or a ‘basal septal bulge’, with evidence of mild left ventricular outflow tract obstruction (LVOT) at rest on her initial echocardiogram. She was usually fit and well with no significant past medical history. She had no history of hypertension. She had never smoked. There was no family history of hypertrophic cardiomyopathy (HCM). A cardiac MRI did not demonstrate any typical features of HCM. ECG showed sinus tachycardia with a rate of 101 bpm but was otherwise unremarkable. She was referred for exercise echocardiography to assess for latent LVOT obstruction. Prior to commencing exercise, her LVOT gradient was re-assessed at rest. Her LVOT gradients were 30 mmHg at rest, 49 mmHg during Valsalva and 91 mmHg on standing. A diagnosis of significant latent LVOT obstruction was made and the patient was started on bisoprolol, a cardioselective beta-blocker. Bisoprolol was slowly uptitrated from 1.25 mg to 5 mg once daily, following which the patient reported a significant improvement in her symptoms with an improved exercise capacity. Follow-up echocardiography demonstrated a dramatic reduction in LVOT gradient, with a maximum of 11 mmHg assessed both with Valsalva and on standing. This case is a reminder that patients with a ‘common’ basal septal bulge can develop significant LVOT obstruction, the symptoms of which may respond to pharmacological therapy. Orthostatic assessment of LVOT gradient using echocardiography should be considered during standard LVOT obstruction provocation manoeuvres such as a Valsalva. Learning points: Differentiation between basal septal hypertrophy (BSH) and hypertrophic cardiomyopathy (HCM) may be challenging. Key factors favouring HCM include a positive family history of HCM or sudden cardiac death, septal thickness >15 mm/posterior wall thickness >11 mm, systolic anterior motion of the anterior mitral valve (SAM), late gadolinium enhancement on cardiac MRI, a causative genetic mutation associated with HCM and an abnormal ECG. Significant LVOT obstruction may develop in patients with BSH and is potentially responsive to pharmacotherapy. Standing reduces venous return, resulting in decreased LV volume. Compensatory mechanisms to maintain cardiac output involve sympathetic nervous system activation leading to increased LV contractility and subsequent increased LVOT gradient. Significant LVOT obstruction may be unmasked by an orthostatic posture. Orthostatic LVOT gradient assessment should be part of the routine echocardiographic assessment of all patients with an increased LVOT gradient at rest. The post-prandial state has been associated with increased LVOT gradient due to splanchnic dilatation and the consequent increased cardiac output required to maintain blood pressure. Post-prandial status should therefore be considered when assessing LVOT gradient. Keywords: basal septal hypertrophy, orthostatic LVOT assessment, latent LVOT obstruction, provocable gradient Background The 2015 European Society of Cardiology (ESC) guidelines recommend provocation testing to assess for latent LVOT obstruction in all patients with exertional symptoms who have either hypertrophic cardiomyopathy (HCM) or isolated basal septal hypertrophy (BSH) (1). LVOT obstruction is a major cause of symptoms in HCM and has been associated with a worse prognosis (1). BSH, often referred to as a ‘sigmoid septum’ or a ‘ventricular septal bulge’, is common in elderly patients, particularly those with hypertension. The differentiation between this very common finding and genetically inherited HCM can be difficult. Canepa et al. proposed that a family history of HCM or sudden cardiac death, presence of symptoms, septal thickness >15 mm/posterior wall thickness >11 mm, systolic anterior motion of the anterior mitral valve (SAM) and LVOT obstruction, late gadolinium enhancement on cardiac MRI, a genetic mutation associated with HCM and an abnormal ECG all make HCM more likely versus BSH (2). Importantly patients with BSH can have latent LVOT obstruction and there is evidence demonstrating improvement in symptoms with pharmacological treatment (3). Aortoseptal angulation has also been shown to be predictive of latent outflow tract obstruction, with smaller angles in patients with provocable LVOT obtruction (4). In most echo departments, standard outpatient provocation testing involves measuring the LVOT gradient at rest and following a Valsalva manoeuvre. If no significant gradient is induced in a symptomatic patient, stress testing is usually implemented at this stage. Shah et al. demonstrated that 2/3rd (62.1%) of patients who had no previous documented LVOT obstruction (LVOT gradient ≤30 mmHg) developed LVOT obstruction during exercise (5). Approximately 20% of these patients went on to have invasive treatment with subsequent improvement in symptoms (5). It is recognised that following a meal mesenteric vasodilatation occurs, resulting in reduced peripheral vascular resistance. As a compensatory mechanism, heart rate and stroke volume increase to maintain blood pressure (6). Using radionucleotide imaging, Kelbaek et al. demonstrated post-prandial increases in cardiac output of 62% due to increased heart rate and stroke volume (6). This post-prandial haemodynamic change is well recognised to increase LVOT gradient and exacerbate symptoms (7). Protocols used for the assessment of latent LVOT obstruction should therefore take into consideration post-prandial status. LVOT gradient is sensitive to preload. Bedside manoeuvres that affect preload will therefore change the outflow gradient. Squatting increases preload and therefore reduces the gradient through the outflow tract, whereas standing up reduces preload and has the opposite effect. The reduction in venous return caused by standing up also results in decreased LV volume. Compensatory mechanisms to maintain cardiac output involve sympathetic nervous system activation leading to increased LV contractility, which also contributes to increased LVOT gradient (8). A number of studies have demonstrated increased LVOT gradient in the standing versus the supine position (7, 8, 9). Crucially, most patients will be in a fully upright position when symptoms are usually experienced. Orthostatic assessment of LVOT gradient is therefore more representative of ‘real-life’ haemodynamics and is commonly employed during stress testing to look for outflow obstruction.