Hypertrophic cardiomyopathy

Abstract

Hypertrophic cardiomyopathy (HCM) is an inherited disorder of myocardial sarcomeric protein characterised by the presence of myocardial hypertrophy in the absence of any identifiable cardiac or systemic cause. Several sources suggest that myocardial ischaemia in the absence of obstructive coronary artery disease, plays an important role in the pathophysiology and natural history of HCM. Autopsy series have commonly shown left ventricular (LV) fibrosis and transmural scarring. Histological examination of these areas has revealed narrowed, small intramural coronary arteries that may be responsible for reduced coronary flow. Other mechanisms leading to ischaemia include systolic compression of epicardial arteries and an inadequate capillary density relative to muscle mass. Metabolic studies have shown abnormalities of lactate metabolism and coronary sinus pH consistent with the presence of myocardial ischaemia. Imaging studies with thallium-201 and position emission tomography (PET) have shown both reversible and fixed exercise-induced defects in myocardial perfusion. Although the presence of ischaemia is recognised and its pathophysiological importance assumed, the clinical and prognostic significance of ischaemia in individual patients with HCM is not yet known. Ischaemia may influence LV systolic function, ventricular relaxation, induce chest pain and be an important modulator of the arrhythmogenic substrate. There are also a minority of patients with HCM whose symptoms coincide with the development of systolic failure, progressive LV dilatation and wall thinning, and irreversible perfusion defects and diminished coronary flow reserve (CFR) have been demonstrated in this group. The clinical evaluation of ischaemia in patients with HCM by conventional methods remains problematic. Technical difficulties with conventional techniques of assessing ischaemia are compounded by difficulty in interpreting the data obtained in relation to clinical findings. The presence of baseline electrocardiographic abnormalities in many patients complicates the interpretation of ST segment changes at rest and during exercise. ST segment depression during exercise also correlates poorly with symptoms, thallium-201 perfusion abnormalities and metabolic markers of ischaemia. Reversible defects on thallium-201 perfusion imaging correlate poorly with symptoms. Thallium imaging is further complicated by partial volume effects in the presence of asymmetric septal hypertrophy and a lack of data on the kinetics of thallium in hearts affected by HCM. PET has shown diminished CFR and hypoperfusion of the subendocardium in patients with HCM, but expense and the availability of this modality precludes its use to most physicians.