[Clinical and genetic characteristics of different types of non-obstructive hypertrophic cardiomyopathy].

ABSTRACT

Objective: To analyze the clinical and genetic characteristics of clinical subtypes of non-obstructive hypertrophic cardiomyopathy (HCM). Methods: It was a cohort study. Patients with non-obstructive HCM admitted to Fuwai Hospital, Chinese Academy of Medical Sciences, from January 1999 to April 2019 were enrolled. According to the characteristics of cardiac morphology and function shown by echocardiography, the patients were divided into common type, dilated type, restricted type and reduced ejection fraction type. The clinical data of the patients were recorded, and 8 sarcomere pathogenic genes were screened by full exon sequencing or panel sequencing. Patienst were followed up and cardiovascular endpoint events were recorded. Results: A total of 815 patients with non-obstructive HCM were enrolled, including 27 (3.3%) restricted type, 51 (6.3%) dilated type, 30 (3.7%) reduced ejection fraction type and 707 (86.7%) common type. A total of 704 out of 815 patients underwent genetic testing. Among them, 299 (42.5%) patients carried at least 1 sarcomere gene mutation. MYBPC3 and MYH7 mutation accounted for 42.1% (126/299) and 35.8% (107/299) respectively. 66.7% (16/24) of the patients with restricted type carried sarcomere gene mutation, which was higher than that in patients with dilated type (36.4% (16/44)) and in common type (41.5% (250/602), P=0.015). Among the patients with reduced ejection fraction, 56.7% (17/30) patients carried sarcomere gene mutations, 23.3% (7/30) carried multiple sarcomere mutations, which was higher than that in restricted type (8.3% (2/24)), in dilated type (9.1% (4/44)) and in common type 4.2% ((24/577), P<0.001). MYH7 and MYBPC3 were the main mutation gene types of all clinical subtypes, and the genotypes were similar among groups (all P>0.05). Seven hundred and three out 815 patients were followed up for 2.9 (1.4, 4.0) years. There were 53(7.5%) cardiovascular death. Cardiovascular death occurred in 5.0% (29/578) patients with common type, 13.0% (3/23) patients with restricted type, 16.3% (7/43) patients with dilated type and 46.7% (14/30) patients with decreased ejection fraction. Univariate Cox proportional hazards model analysis showed that the risk of cardiovascular death in patients with restricted, dilated and reduced ejection fraction type was higher than that in patients with common type (P<0.001). After adjusting for gender, age of onset, body mass index, history of hypertension, coronary heart disease and diabetes, multivariate Cox proportional hazards model analysis showed that the HR of cardiovascular death in patients with restricted, dilated and reduced ejection fraction type were 5.454 (95%CI 1.137-26.157, P=0.034) and 6.597 (95%CI 1.632-26.667, P=0.008) and 9.028 (95%CI 2.201-37.039, P=0.002) respectively, as compared to patients with common type. Conclusions: Most of the patients with non-obstructive HCM are common type, featured by mild clinical manifestations and good prognosis. Although the proportion of restricted type and dilated type is relatively low, and cardiac systolic function is mostly preserved, the clinical phenotype and prognosis of these patients are similarly severe and poor as patients with reduced ejection fraction. The genotypes are similar in different clinical subtypes, but the proportion of patients with sarcomere gene mutation is higher in restricted type, and the proportion of patients with multiple sarcomere gene mutation is higher in decreased ejection fraction type.