侯翠红
中国医学科学院阜外医院 心血管内科
OBJECTIVES:Patient reported outcomes in Implantable Cardioverter Defibrillator (ICD) patients can describe the experience of living with heart disease and with an ICD. However, very little is known about patient outcomes among Chinese patients which may limit effective patient discussions and interventions for these patients. The purposes of this study were to examine device related experiences (e.g., device acceptance, shock anxiety) in Chinese ICD patients and identify potential variables that influence health related quality of life (HRQOL) and to compare HRQOL outcomes to healthy and heart failure populations.METHODS:This study used a cross-sectional research design with serially recruited ICD patients (N = 100) from clinics in China. Participants completed surveys including: the 12-Item Short-Form Health Survey Questionnaire (SF-12), Florida Patient Acceptance Survey (FPAS), Florida Shock Anxiety Scale (FSAS), Type D Scale (DS-14), and general information questionnaire.RESULTS:Participants were 100 ICD patients in China with a mean age of 53.32(SD = 13.70). The mean scores of the SF-12 physical component summary (PCS) and mental component summary (MCS)of ICD patients (43.55 and 47.07, respectively) were lower than the Chinese general population (P<0.001) and general health, social functioning, and role emotional scores were lower than chronic heart failure patients (P<0.001). Multiple linear regression analysis indicated that LVEF, positive shock history, age and shock anxiety were significant predictors of physical function and accounted for 24.5% of the adjusted variance. Type D personality, shock history, and shock anxiety were predictors of the mental health component and accounted for 25.9% of the variance. Shock history, age, type D personality, and shock anxiety significantly predicted device acceptance (FPAS-Total) and accounted for 32% of variance.CONCLUSIONS:ICD patients reported health outcomes were generally lower than the Chinese general population and patients with heart failure in relation to general health, social functioning, and role emotional. Both generic and disease specific HRQOL were influenced by both medical and psychosocial predictors. This suggests that current Western society based comprehensive models of patient HRQOL and patient care needs may extend to Chinese patients with ICDs.
Heart & lung : the journal of critical care 2021
BACKGROUND:Pacing the cardiac conduction system has been explored in patients with conduction system disease, but comprehensive comparisons between different pacing modalities are not well investigated.OBJECTIVE:To compare pacing characteristics and ventricular synchrony between His-bundle pacing (HBP) and left bundle branch pacing (LBBP) in patients with atrioventricular block (AVB).METHODS:Fifty pacemaker-indicated patients with AVB were enrolled. Twenty-five patients underwent HBP, and another 25 patients underwent LBBP. Success rate, procedural and fluoroscopy duration, pacing parameters, and echocardiographic data were perioperatively assessed and at 3-month follow-up.RESULTS:HBP was successful in 19 of 25 (76.0%) patients, whereas LBBP was successful in 22 of 25 (88.0%) patients. Compared with HBP, LBBP capture threshold was significantly lower (0.76 ± 0.25 V/0.4 ms vs. 1.27 ± 0.61 V/1.0 ms, P = 0.003) and R-wave amplitude was significantly higher with LBBP (11.7 ± 6.6 vs. 4.9 ± 2.4 mV, P < 0.001) at implant. The mean procedural time (74.3 ± 17.8 vs. 63.2 ± 12.3 min, P = 0.029) and fluoroscopy duration (10.3 ± 4.5 vs. 6.8 ± 2.2 min, P = 0.005) were significantly longer in the HBP group compared to LBBP. At 3-month follow-up, pacing capture threshold remained more stable in LBBP than in HBP group while left ventricular synchrony was similar between both groups.CONCLUSION:Despite similar impact on ventricular synchrony compared with HBP, LBBP featured a significantly lower pacing capture threshold, higher R-wave amplitude, and less time to achieve similar success rate in patients with AVB. These findings indicate LBBP as a physiological pacing strategy for AVB patients.
Journal of interventional cardiac electrophysiology : an international journal of arrhythmias and pacing 2021
BACKGROUND:Titin-truncating variants (TTNtv) have been recognized as the most prevalent genetic cause of dilated cardiomyopathy. However, their effects on phenotypes of left ventricular non-compaction cardiomyopathy (LVNC) remain largely unknown.HYPOTHESIS:The presence of TTNtv may have an effect on the phenotype of LVNC.METHODS:TTN was comprehensively screened by targeted sequencing in a cohort of 83 adult patients with LVNC. Baseline and follow-up data of all participants were collected. The primary endpoint was a composite of death and heart transplantation. The secondary endpoint was heart failure (HF) events, a composite of HF-related death, heart transplantation, and HF hospitalization.RESULTS:Overall, 13 TTNtv were identified in 13 patients, with 9 TTNtv located in the A-band of titin. There was no significant difference in baseline characteristics between patients with and without TTNtv. During a median follow-up of 4.4 years, no significant difference in death and heart transplantation between the two groups was observed. However, more HF events occurred in TTNtv carriers than in non-carriers (P = 0.006). Multivariable analyses showed that TTNtv were associated with an increased risk of HF events independent of sex, age, and baseline cardiac function (hazard ratio: 3.25, 95% confidence interval: 1.50-7.01, P = 0.003). Sensitivity analysis excluding non-A-band TTNtv yielded similar results, but with less strength.CONCLUSIONS:The presence of TTNtv may be a genetic modifier of LVNC and confer a higher risk of HF events among adult patients. Studies of larger cohorts are needed to confirm our findings.
Clinical cardiology 2019
BACKGROUND:Robust data regarding genotype-phenotype correlations in left ventricular noncompaction cardiomyopathy (LVNC) are lacking.METHODS:About 72 cardiomyopathy-related genes were comprehensively screened in a cohort of LVNC patients using targeted sequencing. Baseline and follow-up data were collected. The primary endpoint was a composite of death and heart transplantation.RESULTS:A total of 83 unrelated adult patients were included in analyses. Following stringent classification according to the American College of Medical Genetics and Genomics (ACMG) guidelines, 36 pathogenic variants of 14 genes were detected in 32 patients. Among them, 12 patients carried at least one nonsarcomere variant (NSV). At baseline, NSV carriers had a higher frequency of atrial fibrillation, but lower left ventricular ejection fraction, than did noncarriers. During a median follow-up of 4.2 years, NSV carriers experienced a higher rate of the primary endpoint compared with noncarriers. There was no significant difference in the rate between carriers of sarcomere variant (SV) and noncarriers, as well as between carriers of SV and NSV. The presence of NSV was associated with an increased risk of the primary endpoint independent of age, sex, and cardiac function (hazard ratio: 3.61, 95% confidence interval: 1.42-9.19, p = .002).CONCLUSION:NSV may act as a genetic modifier and worsen the clinical phenotype in patients with LVNC.
Molecular genetics & genomic medicine 2019
Background Left ventricular noncompaction cardiomyopathy ( LVNC ) is a genetically and phenotypically heterogeneous disease. This study aims to investigate the genetic basis and genotype-phenotype correlations in a cohort of Chinese patients with LVNC . Methods and Results A total of 72 cardiomyopathy-associated genes were comprehensively screened in 83 adults and 17 children with LVNC by targeted sequencing. Pathogenicity of the detected variants was determined according to their prevalence and American College of Medical Genetics and Genomics recommendations. Baseline and follow-up clinical data were collected. The primary end point was a composite of death and heart transplantation. Overall, 42 pathogenic variants were identified in 38 patients (38%), with TTN , MYH 7, MYBPC 3, and DSP being the most commonly involved genes. At baseline, genotype-positive adults had higher rates of atrial fibrillation and family history, and lower left ventricular ejection fraction, compared with genotype-negative adults. During a median follow-up of 4.2 years, more primary end points occurred in genotype-positive adults than in genotype-negative adults (50.0% versus 23.5%; P=0.013). Multivariable analysis demonstrated that genotype-positive status was associated with higher risks of death and heart transplantation, independent of age, sex, and cardiac function at baseline in patients with LVNC (adjusted hazards ratio, 2.49; 95% confidence interval, 1.15-5.37; P=0.020). Conclusions Our study revealed a distinct genetic spectrum in Chinese patients with LVNC , with variants in TTN , MYH 7, MYBPC 3, and DSP being the most common. The presence of pathogenic variants is an independent risk factor for adverse outcomes and may aid in risk stratification in adult patients. Larger studies are needed to confirm these findings.
Journal of the American Heart Association 2018
Right ventricular apical (RVA) pacing can lead to progressive left ventricular dysfunction and heart failure (HF), even in patients with normal cardiac structure and function. Our study conducted candidate gene screening and lentivirus transfected neonatal rat cardiomyocytes (NRCMs) to explore the genetic and pathogenic mechanisms of RVA pacing induced cardiomyopathy in third degree atrioventricular block (III AVB) patients. We followed 887 III AVB patients with baseline normal cardiac function and RVA pacing. After a median follow-up of 2.5 years, 10 patients (four males, mean age 47.6 ± 10.0 years) were diagnosed with RVA pacing induced HF with left ventricular ejection fraction (LVEF) reducing dramatically to 37.8 ± 7.1% (P < 0.05). Candidate genes sequencing found cardiomyopathy associated genetic variations in all ten HF patients and six SCN5A variations in 6 of 20 control patients. Transfected NRCMs of Lamin A/C mutations (R216C and L379F) disrupted Lamin A/C location on nucleus membrane and finally resulted in increased apoptotic rate after serum starvation. In conclusion, cardiomyopathy associated genetic variations play an essential role in occurrence of newly onset HF in the III AVB patients with RVA pacing. RVA pacing, serving as extra stimulator, might accelerate the deterioration of cardiac structure and function.
Scientific reports 2017
Background Patient activity (PA) has been demonstrated to predict all-cause mortality. However, the association between PA and cardiac death is unclear. Aims The aims of this study were to determine whether PA can predict cardiac death and what is the cut-off of PA to discriminate cardiac death, as well as the mechanism underlying the relationship between PA and survival in patients with home monitoring. Methods This study retrospectively analysed clinical and implantable cardioverter-defibrillator/cardiac resynchronization therapy defibrillator device data in 845 patients. Data regarding PA and PP variability during the first 30-60 days of home monitoring were collected, and mean values were calculated. The primary endpoint was cardiac death, and the secondary endpoint was all-cause mortality. Results The mean PA percentage was 11 ± 5.8%. Based on receiver operating characteristic curve analysis, we determined that a PA cut-off value of 7.84% (113 min) can predict cardiac death. During a mean follow-up period of 31.1 ± 12.9 months (ranging from three to 60 months), PA ≤ 7.84% was associated with increased risks of cardiac death in an unadjusted analysis; after adjusting in a multivariate Cox model, the relationship remained significant between PA≤7.84% and cardiac death (hazard ratio = 3.644, 95% confidence interval = 2.424-5.477, p < 0.001). Moreover, a significant correlation was observed between PA and PP variability ( r = 0.601, p < 0.001). Conclusions A baseline PA ≤ 7.84% was associated with a higher risk of cardiac death in patients who have survived more than three months after implantable cardioverter-defibrillator/cardiac resynchronization therapy defibrillator implantation. PA had a sizable effect on heart rate variability, reflecting autonomic function.
European journal of preventive cardiology 2017
AIMS:Two LMNA mutations (R644C and R190W) have been associated with familial and sporadic left ventricular non-compaction (LVNC). However, the mechanisms underlying these associations have not been elucidated.METHODS AND RESULTS:Genomic DNA was isolated from peripheral blood leucocytes and analysed by direct sequencing. Human embryonic kidney 293 cells were transfected with either wild type or mutant LMNA and SCN5A for whole-cell patch-clamp experiment and fluorescence microscopy. Point mutation modeling for mutant LMNA was also performed. One novel LVNC-associated mutation (V445E) in β2 sheet of immunoglobulin (Ig)-like fold was found in the proband and his father. We also found that the peak current of sodium channel was markedly reduced in mutant LMNA compared with WT while the activation, inactivation, and recovery curves were not significantly altered. The mutant lamin A/C were aggregated into multiple highlighted particles. Three β sheets and multiple side chains in Ig-like fold were altered due to the replacement of a valine by glutamic acid.CONCLUSION:Our data associated a novel lamin A/C mutation (V445E) with a sudden death form of familial LVNC. The reduced sodium current in mutant LMNA may account for the advent of malignant ventricular arrhythmias. The altered structures of three β sheets and side chains may partially explain the aggregation of lamin A/C protein subjacent to the nuclear envelope.
Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology 2016
Several genetic variants have been associated with early repolarization syndrome (ERS). However, the lack of functional validations of the mutant effects has limited the interpretation of genetic tests. In the present study, we identified and characterized a novel sodium channel, voltage gated, type V alpha subunit (SCN5A) mutation that was associated with ERS. A 67-year-old male proband suffering from recurrent syncope underwent a documented electrocardiogram (ECG) for polymorphic ventricular tachycardia (VT). It was noted that baseline 12-lead ECG exhibited a predominantly elevated ST-segment which mimicked acute myocardial ischemia in lead V2-V6, and the ECG also demonstrated J waves in lead Ⅱ, Ⅲ, aVF and V2-V6. Using genetic analysis, we noted that the proband carried a novel heterozygous missense mutation of A1055G in the SCN5A gene. Whole-cell configuration of patch-clamp analysis revealed that the mutation significantly decreased peak sodium current (INa) density and shifted the steady-state inactivation curve of INa to a more negative potential. Confocal imaging suggested that in the mutant channel a defect of protein expression both on the cell membrane and in cytoplasm was present. The present study demonstrated that a novel heterozygous missense mutation of A1055G in SCN5A led to 'loss-of function' of the sodium channels, and we suggest that it accounts for the arrhythmogenic characteristics of ERS.
International journal of molecular medicine 2016
Aims. The molecular mechanisms of Chinese traditional medicine Wenxin Keli (WXKL) were unknown. This study was aimed at exploring the effects of WXKL on the gene expression profile and pathological alteration of rabbits with myocardial infarction. Methods. Twenty male adult rabbits were randomly divided into 4 groups: sham, model, WXKL, and captopril groups. Model, WXKL, and captopril groups underwent the ligation of the left anterior descending coronary artery while sham group went through an identical procedure without ligation. WXKL (817 mg/kg/d), captopril (8 mg/kg/d), and distilled water (to model and sham groups) were administered orally to each group. After 4 weeks, the rabbits were examined with echocardiography and the hearts were taken for expression chip and pathological staining (H&E, Masson, and Tunel) studies. Results. The data revealed that WXKL downregulated genes associated with inflammation (CX3CR1, MRC1, and FPR1), apoptosis (CTSC and TTC5), and neurohumoral system (ACE and EDN1) and upregulated angiogenesis promoting genes such as RSPO3. Moreover, the results also showed that WXKL improved cardiac function and prevented histopathological injury and apoptosis. Conclusion. The present study demonstrated that WXKL might play an important role in inhibiting inflammation, renin-angiotensin system, and apoptosis. It might be a promising Chinese medicine in the treatment of patients with myocardial infarction.
Evidence-based complementary and alternative medicine : eCAM 2016
