Genetic testing in the management of relatives of patients with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy is the most common genetic cardiac disease with vast genetic heterogeneity. First-degree relatives of patients with HCM are at 50% risk of inheriting the disease-causing mutation. Genetic testing is helpful in identifying the relatives harbouring the mutations. When genetic testing is not available, relatives need to be examined regularly. We tested a cohort of 99 unrelated patients with HCM for mutations in MYH7, MYBPC3, TNNI3 and TNNT2 genes. In families with identified pathogenic mutation, we performed genetic and clinical examination in relatives to study the influence of genetic testing on the management of the relatives and to study the usefulness of echocardiographic criteria for distinguishing relatives with positive and negative genotype. We identified 38 genetic variants in 47 patients (47 %). Fifteen of these variants in 21 patients (21 %) were pathogenic mutations. We performed genetic testing in 52 relatives (18 of them (35 %) yielding positive results). Genetic testing of one HCM patient allowed us to omit 2.45-5.15 future cardiologic examinations of the relatives. None of the studied echocardiographic criteria were significantly different between the relatives with positive and negative genotypes, with the exception of a combined echocardiographic score (genotype positive vs. genotype negative, 3.316 vs. -0.489, P = 0.01). As a conclusion, our study of HCM patients and their relatives confirmed the role of genetic testing in the management of the relatives and found only limited benefit of the proposed echocardiographic parameters in identifying disease-causing mutation carriers.

Evaluation of the right ventricular function in hypertrophic obstructive cardiomyopathy: a strain and tissue Doppler study.

We investigated the utility of strain, strain rate, and tissue Doppler imaging (TDI) for the evaluation of the right ventricle (RV) impairment in patients with a hypertrophic obstructive cardiomyopathy (HOCM) who underwent a successful alcohol septal ablation (ASA) and were without RV hypertrophy. A group of 19 patients suffering from HOCM with 22 controls was compared. The parameters of TDI were evaluated in mitral and tricuspid annulus. Strain and strain rate derived from TDI were assessed in an apical free wall of RV, as well as in basal segments of the left ventricle. Between both groups, there were significant differences only in isovolumic pre-ejection time (79.2+/-17.3 ms vs. 58.5+/-8.1 ms, p<0.01), isovolumic relaxation time (104.7+/-26.2 ms vs. 77.3+/-24.5 ms, p<0.01), myocardial performance (Tei) index measured from TDI (0.61+/-0.14 vs. 0.49+/-0.09, p<0.01), and early peak diastolic velocity of TDI (10.6+/-1.67 cm/s vs. 12.6+/-2.21 cm/s; p<0.05). Our results suggest the impairment of both systolic and diastolic RV function in patients suffering from HOCM. TDI-related parameters appear to be more sensitive than strain and strain rate for evaluation.

The role of tissue factor in thrombosis and hemostasis.

The tissue factor (TF) is one of the most important regulators of arterial thrombosis. Because arterial thrombosis is the pathophysiologic background of acute coronary syndrome, the possible impact of blocking the arterial thrombosis on its onset is a challenging problem. The investigations of TF brought a new concept of "cell-based coagulation model" which highlighted the question of blood-borne TF as a source of TF in circulating blood. In this review we summarize essential information on the pathophysiology, molecular structure, expression and distribution of TF and we propose a novel concept of blood-borne TF, suggesting the possibilities of inhibition of the coagulation cascade with newly synthetized drugs.