中华心血管病杂志最新文献

Objective: To investigate the impact and potential mechanisms of Sorbin and SH3 domain-containing protein 2 (Sorbs2) on ventricular arrhythmias in mice. Methods: In the animal experiments, mating was performed using six 8-week-old Sorbs2^+/- mice (3 males and 3 females) weighing 20-22 g. Wild-type (Sorbs2^+/+, n=8) and homozygous (Sorbs2^-/-, n=6) offspring were selected as experimental subjects through genotyping. Echocardiography was performed at 16 weeks of age to record cardiac function parameters in both groups. Resting-state and caffeine-dobutamine-induced electrocardiograms were also conducted. Real-time quantitative reverse transcription polymerase chain reaction was used to detect Sorbs2 messenger RNA expression in the heart, liver, spleen, lung, kidney, brain, small intestine, and skeletal muscle tissues of wild-type mice. Western blotting was employed to measure the protein expression levels of Sorbs2 and voltage-dependent sodium channel alpha subunit 1.5 (Na_v1.5) in myocardial tissues from both groups. In the cell experiments, H9C2 cells were transfected with Sorbs2 small interfering RNA as the si-Sorbs2 group, with a corresponding si-negative control group established. Western blot was performed to detect the protein expression levels of Sorbs2 and Na_v1.5 in both groups. Results: Sorbs2 was abundantly expressed in cardiac tissue. Compared with wild-type mice, homozygous mice exhibited larger left ventricular end-systolic diameter, along with lower left ventricular ejection fraction and fractional shortening (P all<0.05). Resting-state electrocardiograms revealed no spontaneous arrhythmias in either group; however, homozygous mice showed shorter RR intervals but longer QRS and QTc intervals versus wild-type mice (P all<0.05). Following caffeine and dobutamine induction, homozygous mice demonstrated a higher incidence of ventricular arrhythmias, longer arrhythmia duration, and higher ventricular arrhythmia scores than wild-type mice (P all<0.05). Western blot analysis revealed that Na_v1.5 protein expression was markedly lower in myocardial tissues of homozygous mice compared to wild-type mice. Similarly, si-Sorbs2-transfected H9C2 cells exhibited lower Na_v1.5 protein levels compared to the si-negative control group (P<0.05). Conclusion: Sorbs2 plays a critical role in maintaining normal cardiac electrophysiological function. Deficiency of Sorbs2 may lead to impaired cardiac function and increased susceptibility to ventricular arrhythmias in mice, which could be associated with reduced expression of Na_v1.5 protein.

Objective: To analyze the electrocardiogram (ECG) data of congenital long QT syndrome (LQTS) patients, and to identify the ECG parameters for prediction of life-threatening arrhythmic events (LAEs). Methods: This cohort study enrolled patients diagnosed with congenital LQTS at the Department of Cardiology, Beijing Tsinghua Changgung Hospital from September 2014 to May 2023. Baseline clinical and ECG data were collected. Patients were followed with LAEs as the primary endpoint. Based on the occurrence of LAEs, patients were divided into two groups: the event group and the event-free group. Cox regression analysis was used to identify independent predictors of LAEs in LQTS patients. Results: A total of 293 patients diagnosed with congenital LQTS were included, aged 32.5 (19.0, 41.8) years, including 201 females (68.6%). Sixty-six patients experienced LAEs and 227 patients did not. Compared to the event-free group, the event group had a younger onset age (13.0 (5.5, 20.5) years vs. 26.0 (13.0, 35.0) years), a slower heart rate (69.0 (59.5, 76.5) beats/min vs. 77.0 (67.0, 88.0) beats/min), a higher proportion with family history of sudden cardiac death (30.3% vs. 14.5%), as well as longer QT intervals (500.0 (467.0, 594.0) ms vs. 428.0 (402.0, 470.0) ms) and QTc intervals (544.0 (502.5, 589.0) ms vs. 489.0 (480.0, 504.0) ms). Additionally, the event group had higher peak T-wave alternans value (65.0 (42.5, 85.3) μV vs. 44.0 (36.0, 54.0) μV), a higher proportion of patients with documented torsades de pointes (TdP) or ventricular fibrillation (VF) on 24-hour Holter monitoring (39.3% vs. 4.9%), and higher rates of pharmacological treatment (100.0% vs. 9.7%) and device therapy or left cardiac sympathetic denervation (45.5% vs. 2.2%) (all P<0.05). Multivariate Cox regression analysis identified that the heart rate<60 beats/min (HR=2.0, 95%CI: 1.0-3.7) and QTc interval ≥500 ms (HR=2.9, 95%CI: 1.5-5.6) on 12-lead ECG, as well as peak T-wave alternans value ≥55.5 μV (HR=3.2, 95%CI: 1.3-7.8) and documented TdP or VF (HR=2.0, 95%CI: 1.1-3.7) on 24-hour Holter monitoring were independent predictors of LAEs in LQTS patients (all P<0.05). Conclusion: Heart rate <60 beats/min and QTc interval ≥500 ms on 12-lead ECG, along with peak T-wave alternans value ≥55.5 μV and documented TdP or VF on 24-hour Holter monitoring, have been identified as independent predictors of LAEs in patients with LQTS. These ECG parameters may serve as valuable early indicators of sudden cardiac death in LQTS patients.

Objective: To explore the relationship between retinol-binding protein (RBP) levels and disease severity in patients with transthyretin cardiac amyloidosis (ATTR-CA), as well as its impact on therapeutic response to tafamidis. Methods: This retrospective study utilized data from the China National Rare Disease Registry System and included ATTR-CA patients treated with tafamidis between January 2018 and September 2022. Patients were stratified into two groups based on baseline RBP levels: the normal RBP group (≥36 mg/L) and the reduced RBP group (<36 mg/L). Baseline characteristics and clinical data after one year of treatment were collected and compared between the groups. Within the reduced RBP group, patients were further subclassified by changes in RBP levels after treatment (ΔRBP=post-treatment RBP-baseline RBP) into ΔRBP>0 and ΔRBP<0 subgroups. Worsening of global longitudinal strain (GLS) after treatment was defined as the primary outcome, logistic regression analysis was used to identify risk factors influencing therapeutic response to tafamidis in ATTR-CA patients. Results: A total of 52 ATTR-CA patients were included (aged (58.5±12.0) years, 46 males (88%)). Among 39 patients who completed one-year tafamidis treatment, no statistically significant difference was observed in RBP levels post-treatment versus baseline ((27.0±14.3) mg/L vs. (25.9±15.4) mg/L, P=0.261). Compared to the normal RBP group, the reduced RBP group had significantly higher estimated glomerular filtration rate-adjusted N-terminal pro-B-type natriuretic peptide levels (2 316.0 (1 161.5, 6 027.8) ng/L vs. 806.2 (349.5, 1 735.8) ng/L), higher left ventricular mass index ((164.4±46.5) g/m² vs. (123.9±31.8) g/m²), and lower left ventricular ejection fraction ((50.8±11.3)% vs. (58.8±6.2)%) (all P<0.05). Among 31 patients in the reduced RBP group who completed one-year tafamidis treatment, 23 were classified as ΔRBP>0 and 8 as ΔRBP<0. The ΔRBP<0 group exhibited greater GLS worsening than the ΔRBP>0 group (0.7 (-0.1, 1.4)% vs. -0.4 (-1.4, 0.2)%, P=0.027). Multivariate logistic regression analysis revealed that ΔRBP<0 was an independent risk factor for GLS worsening (OR=8.584, 95%CI 1.186-62.150, P=0.033) in ATTR-CA patients. Conclusion: ATTR-CA patients with reduced RBP levels exhibit more severe left ventricular structural and functional impairment compared to those with normal RBP levels. Decline in RBP during treatment (ΔRBP<0) is associated with poorer response to tafamidis treatment. Monitoring RBP dynamics may assist clinicians in assessing disease severity and therapeutic response in ATTR-CA patients.