Objective:
To observe the
association between clinical
phenotypes of
hypertrophic cardiomyopathy (HCM)
patients and a rare
calcium channel and
regulatory gene variation (Ca2+
gene variation) and to compare clinical
phenotypes of HCM
patients with Ca2+
gene variation, a single
sarcomere gene variation and without
gene variation and to explore the influence of rare Ca2+
gene variation on the clinical
phenotypes of HCM.
Methods:
Eight hundred forty-two non-related
adult HCM
patients diagnosed for the first
time in Xijing
Hospital from 2013 to 2019 were enrolled in this study. All
patients underwent
exon analyses of 96 hereditary
cardiac disease-related
genes.
Patients with
diabetes mellitus,
coronary artery disease, post alcohol septal ablation or septal myectomy, and
patients who carried
sarcomere gene variation of uncertain significance or carried>1
sarcomere gene variation or carried>1 Ca2+
gene variation, with HCM pseudophenotype or carrier of
ion channel gene variations other than Ca2+ based on the genetic test results were excluded.
Patients were divided into
gene negative group (no
sarcomere or Ca2+
gene variants),
sarcomere gene variation group (only 1
sarcomere gene variant) and Ca2+
gene variant group (only 1 Ca2+
gene variant). Baseline data,
echocardiography and
electrocardiogram data were collected for
analysis.
Results:
A total of 346
patients were enrolled, including 170
patients without
gene variation (
gene negative group), 154
patients with a single
sarcomere gene variation (
sarcomere gene variation group) and 22
patients with a single rare Ca2+
gene variation (Ca2+
gene variation group). Compared with
gene negative group,
patients in Ca2+
gene variation group had higher
blood pressure and higher percentage of
family history of HCM and
sudden cardiac death (P<0.05); echocardiographic results showed that
patients in Ca2+
gene variation group had thicker
ventricular septum ((23.5±5.8) mm vs. (22.3±5.7) mm, P<0.05); electrocardiographic results showed that
patients in Ca2+
gene variation group had prolonged QT interval ((416.6±23.1) ms vs. (400.6±47.2) ms, P<0.05) and higher RV5+SV1 ((4.51±2.26) mv vs. (3.50±1.65) mv, P<0.05). Compared with
sarcomere gene variation group,
patients in Ca2+
gene variation group had later
onset age and higher
blood pressure (P<0.05); echocardiographic results showed that there was no significant difference in ventricular septal thickness between two groups;
patients in Ca2+
gene variation group had lower percentage of left ventricular outflow tract
pressure gradient>30 mmHg (1 mmHg=0.133 kPa, 22.8% vs. 48.1%, P<0.05) and the lower early diastolic peak velocity of the
mitral valve inflow/early diastolic peak velocity of the
mitral valve annulus (E/e') ratio ((13.0±2.5) vs. (15.9±4.2), P<0.05);
patients in Ca2+
gene variation group had prolonged QT interval ((416.6±23.1) ms vs. (399.0±43.0) ms, P<0.05) and lower percentage of ST segment
depression (9.1% vs. 40.3%, P<0.05).
Conclusion:
Compared with
gene negative group, the clinical
phenotype of HCM is more severe in
patients with rare Ca2+
gene variation; compared with
patients with
sarcomere gene variation, the clinical
phenotype of HCM is milder in
patients with rare Ca2+
gene variation.