The Structural Determinants and Functional Consequences of Left Ventricular Outflow Tract Obstruction in Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is the commonest inherited cardiac condition. Many patients have resting or provocable left ventricular outflow tract (LVOT) obstruction. Symptoms treated with drugs or surgery may improve. There is a need to improve the clinical assessment in individual patients, because of the often poor correlation between symptoms and LVOT gradient, and the association with complications such as stroke, heart failure and sudden cardiac death. In addition, in a proportion of patients with significant LVOT gradients, relief of obstruction does not adequately improve symptoms. Reduced angulation between the inter-ventricular septum and the aorta is a determinant of LVOT obstruction. However, lack of a standardised method of measurement in HCM without recourse to complex 3-D imaging limits the usefulness of this parameter in routine practice. Transthoracic echocardiography is widely available, and can be used to measure aorto-septal angulation. However, data in HCM are lacking. I validated a simple measurement of aorto-septal angulation using 2-D echocardiography and cardiac magnetic resonance imaging and determined its relation to provocable LVOT obstruction in HCM. I showed this technique to be easy, reproducible, comparable to magnetic resonance imaging, and can be quickly calculated using standard echocardiographic software. Patients have a smaller aorto-septal angle than controls, where it is associated with higher peak LVOT gradient. A reduced aorto-septal angle is highly specific for provocable LVOT obstruction and should prompt further evaluation in symptomatic patients without resting gradients. I used a non-invasive technique for measuring cardiac output to determine the relation between LVOT obstruction, cardiac output and peripheral oxygen utilisation in patients with HCM during exercise. I demonstrated that cardiac output response to exercise is impaired, caused largely by failure to appropriately augment stroke volume. LVOT obstruction is associated with greater impairment of stroke volume at peak exercise and is an independent and modifiable predictor of cardiac output reserve. However, heterogenous responses are seen between patients who otherwise appear similar using standard clinical criteria. There is therefore a strong argument for the individualisation of therapy in patients with LVOT obstruction. Invasive therapies to reduce gradients may work better in those with genuine obstruction to the outflow of blood, rather than for example myocardial ischaemia or mitral regurgitation. The non-invasive measurement of haemodynamic indices during exercise is practical, aids understanding of the complex physiological basis behind symptoms and may help to tailor therapy for HCM, and in particular LVOT obstruction

The influence of aortoseptal angulation on provocable left ventricular outflow tract obstruction in hypertrophic cardiomyopathy.

OBJECTIVES: Aortoseptal angulation (AoSA) can predict provocable left ventricular outflow tract obstruction (LVOTO) in patients with symptomatic hypertrophic cardiomyopathy (HCM). Lack of a standardised measurement technique in HCM without the need for complex three-dimensional (3D) imaging limits its usefulness in routine clinical practice. This study aimed to validate a simple measurement of AoSA using 2D echocardiography and cardiac MR (CMR) imaging as a predictor of LVOTO. METHODS: We retrospectively assessed 160 patients with non-obstructive HCM, referred for exercise stress echocardiography. AoSA was measured using resting 2D echocardiography in all patients, and CMR in 29. Twenty-five controls with normal echocardiograms were used for comparison. RESULTS: Patients with HCM had a reduced AoSA compared with controls (113°±12 vs 126°±6), p<0.0001. Sixty (38%) patients had provocable LVOTO, with smaller angles than non-obstructive patients (108°±12 vs 116°±12, p<0.0001). AoSA, degree of mitral valvular regurgitation and incomplete systolic anterior motion (SAM) were associated with peak left ventricular outflow tract gradient (r=0.508, p<0.0001). An angle ≤100° had 27% sensitivity, 91% specificity and 59% positive predictive value for predicting provocable LVOTO. When combined with SAM, specificity was 99% and positive predictive value 88%. Intraclass correlation coefficient of AoSA measured by two observers was 0.901 (p<0.0001). Bland-Altman analysis of echocardiographic AoSA showed good agreement with the CMR-derived angle. CONCLUSIONS: Measurement of AoSA using echocardiography in HCM is easy, reproducible and comparable to CMR. Patients with provocable LVOTO have reduced angles compared with non-obstructive patients. AoSA is highly specific for provocable LVOTO and should prompt further evaluation in symptomatic patients without resting obstruction

Heart rate recovery in patients with hypertrophic cardiomyopathy

Recovery in heart rate (HR) after exercise is a measure of autonomic function and a prognostic indicator in cardiovascular disease. The aim of this study was to characterize heart rate recovery (HRR) and to determine its relation to cardiac function and morphology in patients with hypertrophic cardiomyopathy (HC). We studied 18 healthy volunteers and 41 individuals with HC. All patients underwent clinical assessment and transthoracic echocardiography. Continuous beat-by-beat assessment of HR was obtained during and after cardiopulmonary exercise testing using finger plethysmography. HRR and power spectral densities were calculated on 3 minutes of continuous RR recordings. Absolute HRR was lower in patients than that in controls at 1, 2, and 3 minutes (25.7 ± 8.4 vs 35.3 ± 11.0 beats/min, p <0.001; 36.8 ± 9.4 vs 53.6 ± 13.2 beats/min, p <0.001; 41.2 ± 12.2 vs 62.1 ± 14.5 beats/min, p <0.001, respectively). HRR remained lower in patients at 2 and 3 minutes after normalization to peak HR. After normalization to the difference in HR between peak exercise and rest, HRR was significantly impaired in individuals with obstructive HC at 3 minutes compared with controls. HR at 3 minutes correlated with peak left ventricular outflow tract gradient (B 0.154 beats/min/mm Hg, confidence interval 0.010 to 0.299, p = 0.037) and remained a significant predictor of HRR after multivariable analysis. Spectral analysis showed a trend toward an increased low-frequency to high-frequency ratio in patients (p = 0.08) suggesting sympathetic predominance. In conclusion, HRR is impaired in HC and correlates with the severity of left ventricular outflow tract gradient. Prospective studies of the prognostic implications of impaired HRR in HC are warranted. © 2014 Elsevier Inc. All rights reserved