HYPERTROPHIC CARDIOMYOPATHY: RELATIONSHIP BETWEEN MYOCARDIAL ISCHEMIA,FIBROSIS AND CLINICAL STATUS

Hypertrophic cardiomyopathy (HCM) is a genetic disorder that is typically inherited in an autosomal dominant fashion. There are defects in several of the genes encoding for the sarcomeric proteins, such as myosin heavy chain, actin, tropomyosin, and titin. Multiple mutations have been identified, with genotype-specific risks for mortality and degree of hypertrophy. The disorder has a variable clinical presentation and carries a high incidence of sudden death. HCM is the leading cause of sudden cardiac death in young population. However, many patients may remain stable over long periods of time and then suddenly they may present adverse events: unexpected death, embolic stroke, and the consequences of heart failure. The disease is characterized by an inappropriate myocardial hypertrophy, often asymmetrical, and occurs with no obvious inciting hypertrophy stimulus. Hypertrophy can occur in any region of the left ventricle but frequently involves the interventricular septum, which sometimes results in an obstruction of flow through the left ventricular outflow tract (LVOT). At histology, myocardial disarray and islands of fibrosis are considered hallmarks of this disease. The systolic function of LV is preserved until the end-stage of the disease, but the thickened myocardium with fibrosis increases the stiffness of LV chamber causing impaired diastolic relaxation which produces atrial enlargement and may promote atrial fibrillation. At the end stage, the loss of myocites, replaced by gross scar, is sufficient to determine a manifest systolic LV dysfunction. Myocardial scars create a potentially arrhythmogenic substrate and may increase susceptibility to ventricular tachycardias/fibrillation. Indeed, gross macroscopic scarring is frequently present on post-mortem examination in HCM patients who died suddenly, suggesting a possible causal association between fibrosis and malignant arrhythmias. In most patients with HCM, dense focal myocardial fibrosis can also be visualized noninvasively with the use of gadolinium-enhanced cardiac magnetic resonance imaging (LGE-CMR). Recently, some studies demonstrated the prognostic role of fibrosis, expressed as late gadolinium enhancement (LGE), as predictor of myocardial death. In addiction is also possible to quantify extent of LGE in the myocardium of these patients. The diagnosis of HCM is usually performed at relatively young age when not significant stenosis are present in the main coronary arteries. Despite this, many studies showed the importance of myocardial ischemia, probably also due to microvascular disease, as cause of myocardial fibrosis and symptoms and as a trigger of ventricular arrhythmias. Infact the assessment of myocardial ischemia in selected patients with HCM (with preserved LV function) may represent a prognostic tool for identifying those patients at risk for profound disease progression. CMR also allows to evaluate myocardial perfusion and quantify non invasively myocardial blood flow. It’s now clear the importance to study both and individually myocardial fibrosis and ischemia, and to evaluate the relationship between myocardial scar, myocardial blood flow and clinical expression of the disease.