Lefeng Wang

A Missense Mutation in the CHRM2 Gene Is Associated With Familial Dilated Cardiomyopathy

Circulating autoantibodies against the M2-muscarinic acetylcholine receptor (CHRM2) have been detected in patients with dilated cardiomyopathy (DCM). However, it has yet to be determined whether the pathogenesis of familial DCM may be linked to the genetic variability of the CHRM2 gene. The coding regions of the CHRM2 gene were examined by direct DNA sequencing. Plasma concentrations of autoantibodies against CHRM2 were determined by ELISA in 7 unrelated DCM families. Linkage analysis demonstrated cosegregation of the microsatellite markers, D7S509 and D7S495 that flank the CHRM2 gene, with the familial form of DCM. A novel missense mutation (C722G) replacing cysteine with tryptophane (Cys176Trp) was identified in the CHRM2 gene in all affected members but was absent in unaffected members. Additionally, 139 sporadic DCM patients and 450 normal volunteers were screened for the same mutation, but none were identified. Among the 12 affected members with familial DCM, 5 patients had died suddenly and 7 experienced ventricular arrhythmia, atrioventricular conduction block, and heart failure. All mutation carriers were positive for autoantibodies against CHRM2. Survival analysis disclosed that prognosis in patients who were mutation carriers with familial DCM was poorer than that seen in patients who were noncarriers with sporadic DCM ((P<0.05). We have identified a novel missense mutation (C722G) in the CHRM2 gene associated with familial DCM. We also show that this variant correlates with the presence of autoantibodies against CHRM2. Patients with C722G mutation have more progressive disease, characterized by sudden death, arrhythmia, and heart failure.

Two-year clinical outcomes of patients with overlapping second-generation drug-eluting stents for treatment of long coronary artery lesions: comparison of everolimus-eluting stents with resolute zotarolimus-eluting stents.

ObjectiveThe aim of this study was to compare the 2-year clinical outcomes of overlapping second-generation everolimus-eluting stents (EES) with those of overlapping resolute zotarolimus-eluting stents (R-ZES) in the treatment of long coronary artery lesions. Materials and methodsThis retrospective analysis included 256 patients treated with overlapping EES (n=121) and R-ZES (n=135) for long coronary artery lesions (total stent length per lesion ≥34 mm). Study endpoints included major adverse cardiac events (MACE) defined as the composite of cardiac death, myocardial infarction, and target-vessel revascularization (TVR), as well as target-lesion revascularization and definite stent thrombosis separately at 2 years. ResultsIn the two groups, the mean age was older and the average number of disease vessel was higher in the R-ZES group. The mean lesion length and total stent length per lesion were longer in the R-ZES group. EES were more frequently implanted in the left anterior descending coronary artery. No significant differences in the estimated MACE (5.8% for EES vs. 8.1% for R-ZES; P=0.548) or TVR (3.4% for EES vs. 4.0% for R-ZES; P=0.806) rates were noted between the two groups at 2-year follow-up. The incidence of definite stent thrombosis was low and similar in both groups (0.83% for EES vs. 0% for R-ZES; P=0.473). No significant differences were noted with respect to MACE or TVR between the two groups following propensity score matching. ConclusionStent overlap with second-generation EES or R-ZES was associated with low rates of MACE, TVR, and stent thrombosis at 2-year follow-up. Our results suggest that the use of overlapping EES or R-ZES in long coronary lesions is associated with good long-term clinical outcomes. These results need to be validated with randomized controlled trials.

Interaction Between Vitamin D and Lipoprotein (a) on the Presence and Extent of Coronary Heart Disease

BACKGROUND Given both lipoprotein (Lp)(a) and vitamin D have been found to be associated with coronary heart disease (CHD) risk and a biochemical link between vitamin D and cholesterol on atherosclerosis has been proposed, we hypothesised there could exist an interaction between Lp(a) and vitamin D on the severity of CHD. METHODS Lp(a) and 25-OH vitamin D were measured in the plasma of 348 consecutive patients (mean age 62.4±10.5 years; 56.3% male) undergoing coronary angiography at our Heart Center. A multivariate logistic regression model was used to estimate the odds ratios (ORs) of CHD. RESULTS Of these patients, CHD was identified in 212 (60.9%). A multivariable logistic regression model showed multivariable-adjusted ORs (95% CI) of CHD for patients with Lp(a)≧30mg/dl and vitamin D <10 ng/ml, Lp(a) <30mg/dl and vitamin D <10 ng/ml, and Lp(a)≧30mg/dl and vitamin D ≧10 ng/ml were 4.62 (2.04-10.46), 1.79 (1.00-3.17), and 1.70 (0.88-3.31), respectively, compared with those with Lp(a) <30mg/dl and vitamin D ≧10 ng/ml; the multivariable-adjusted ORs of a higher Gensini Score for the above three corresponding groups were 3.48 (1.84-6.60), 1.59 (0.96-2.65), and 1.55 (0.86-2.79), respectively. The interaction term between Lp(a) and vitamin D in each of the above two models was significant (p=0.004 and p=0.005, respectively). CONCLUSIONS Among patients undergoing coronary angiography, there existed an interaction between Lp(a) and vitamin D on the severity of CHD. Future cohort studies are warranted to confirm this finding.

Long-term outcomes following very late stent thrombosis of drug-eluting stent

BACKGROUND Long-term outcomes of very late stent thrombosis (VLST) after implantation of drug-eluting stents (DES) are still unclear. The aim was to evaluate the long-term outcomes after VLST of DES, and to analyze the related factors of long-term outcomes in these patients. METHODS From January 2006 to February 2013, patients with angiographically defined VLST were studied. The clinical characteristics, angiography and interventional data, and anti-platelet therapy protocols were analyzed. The patients were divided into two groups according to the occurrence of major adverse cardiac events (MACE) during follow-up. The clinical and interventional data between the two groups were compared. RESULTS Sixty-two patients were enrolled consisting of 55 males and 7 females with an average age of 58.6±10.2 (41-82) years. The mean time from first implantation of DES to occurrence of VLST was 38.7±18.1 (12.5-84) months. One patient died in hospital. Sixty-one patients survived to discharge, and MACE occurred in 17 patients after a median follow-up of 32.1±19.1 (median: 44, range 5-88) months. The total MACE rate was 29.0% (18/62), and Kaplan-Meier survival analysis showed the estimated MACE-free survival was 45.1%. The rate of implantation of an additional first-generation DES during the first VLST in the group with events was higher (44.4% vs.11.4%, respectively, p=0.007). The percentage of continuous dual antiplatelet therapy (DAPT) at the longest available follow-up was higher in the event-free group (27.8% vs. 75.0%, respectively, p=0.001). Multivariable Cox regression analysis revealed that the only independent predictors for freedom of MACE during long-term follow-up was continuous DAPT at the longest available follow-up [hazard ratio (HR)=0.30, 95% CI: 0.09-0.97, p=0.04]. CONCLUSIONS Long-term outcomes after VLST were unfavorable. Implantation of an additional first-generation DES might be avoided, and DAPT should be continued.

Efficacy and safety of a biodegradable polymer sirolimus-eluting stent in primary percutaneous coronary intervention: a randomized controlled trial.

Introduction With long-term follow-up, whether biodegradable polymer drug-eluting stents (DES) is efficient and safe in primary percutaneous coronary intervention (PCI) remains a controversial issue. This study aims to assess the long-term efficacy and safety of DES in PCI for ST-segment elevation myocardial infarction (STEMI). Material and methods A prospective, randomized single-blind study with 3-year follow-up was performed to compare biodegradable polymer DES with durable polymer DES in 332 STEMI patients treated with primary PCI. The primary end point was major adverse cardiac events (MACE) at 3 years after the procedure, defined as the composite of cardiac death, recurrent infarction, and target vessel revascularization. The secondary end points included in-segment late luminal loss (LLL) and binary restenosis at 9 months and cumulative stent thrombosis (ST) event rates up to 3 years. Results The rate of the primary end points and the secondary end points including major adverse cardiac events, in-segment late luminal loss, binary restenosis, and cumulative thrombotic event rates were comparable between biodegradable polymer DES and durable polymer DES in these 332 STEMI patients treated with primary PCI at 3 years. Conclusions Biodegradable polymer DES has similar efficacy and safety profiles at 3 years compared with durable polymer DES in STEMI patients treated with primary PCI.

Predictive Nomogram of RAGE Genetic Polymorphisms and Metabolic Risk Factors for Myocardial Infarction Risk in a Han Chinese Population

We investigated the association of 4 well-characterized polymorphisms in receptor for the advanced glycation end-product (RAGE) gene with myocardial infarction (MI) risk and the changes in metabolic risk factors among 717/612 patients/controls, with the aim of constructing a predictive nomogram. The genotype/allele distributions differed significantly between the 2 groups for T-429C (P genotype/allele = .004/.001) and G1704T (P < .001/.001). T-429C was significantly associated with MI risk, especially under a recessive model (adjusted odds ratio: 2.24, 95% confidence interval: 1.33-3.79, P = .003). For G1704T, significance was detected under additive (1.37; 1.12-1.67; P = .002) and recessive (3.86; 2.27-6.57; P < .001) models. There were significant differences in blood pressure and low-density lipoprotein cholesterol (LDL-C) across T-429C genotypes and in total cholesterol and LDL-C across G1704T genotypes. The overall best multifactor dimensionality reduction model included dyslipidemia, G1704T, and T-429C. Further predictive nomogram on 2 significant polymorphisms, blood pressure and lipids, showed a better predictive capability (concordance index = 0.716, P < .001). Altogether, we identified 2 polymorphisms of RAGE, T-429C and G1704T, which interacted with metabolic risk factors associated with the occurrence of MI. We also constructed a genetic–metabolic nomogram that can better predict MI risk.

Modification of the association between smoking status and severity of coronary stenosis by vitamin D in patients suspected of coronary heart disease

AbstractGiven both smoking and vitamin D are associated with coronary heart disease (CHD) via inflammation and smoking may interfere with the local antiinflammatory effects of vitamin D. We hypothesized that the relationship between smoking and severity of CHD may be modified by vitamin D.A cross-sectional study was conducted. 25-OH vitamin D values were determined in 348 consecutive patients (mean age 62.4 ± 10.5 years; 56.3% male) undergoing coronary angiography at the Heart Center of Chaoyang Hospital affiliated to Capital Medical University between the period of September 2014 and May 2015. We categorized the patients into 2 groups based on 25-OH vitamin D levels, that is, severe hypovitaminosis D (25-OH vitamin D < 10 ng/mL) and higher vitamin D (25-OH vitamin D > =  10 ng/mL). Multivariable logistic regression models were used to estimate odds ratios (ORs) of severe coronary stenosis or higher Gensini score across three smoking status, that is, never smokers, former smokers, and current smokers in severe hypovitaminosis D and higher vitamin D groups, respectively.Of these patients, we identified 212 (60.9%) cases of severe CHD and 161 (46.3%) cases of severe hypovitaminosis D. Multivariable logistic regression model showed the ORs of severe CHD were 1.94 (95% confidence interval [CI]: 0.47, 7.98) for former smokers and 2.62 (95% CI: 0.83, 8.24) for current smokers, compared with never smokers in group with severe hypovitaminosis D (P-trend = 0.005). In contrast, smoking was not found to be significantly associated with severe CHD in group with higher 25-OH vitamin D (P-trend = 0.115). We found a significant interaction between smoking status and vitamin D on presence of severe CHD (P-interaction = 0.015). In terms of Gensini score as a dependent variable, similar results were identified.Our finding indicated the association between smoking and severity of CHD appeared to be substantially stronger among patients with severe hypovitaminosis D as compared with those with higher vitamin D levels. This suggests vitamin D sufficiency may have a protective effect against the damaging effects of smoking on coronary artery. Future cohort studies are warranted to confirm this finding.

The association of eight potentially functional polymorphisms in five adrenergic receptor-encoding genes with myocardial infarction risk in Han Chinese

Adrenergic receptors play a key role in activating the sympathetic nervous system, which often accompanies with the development of myocardial infarction (MI). Here, we aimed to test the association of eight potentially functional polymorphisms in five adrenergic receptor-encoding genes with MI risk. Genotypes were available for 717 MI patients and 612 controls. There were no detectable deviations from the Hardy-Weinberg equilibrium for all study polymorphisms. Allele frequencies differed remarkably for ADRA2B D/I (P<0.001), ADRB1 Ser49Gly (P=0.002), ADRB2 Gln27Glu (P=0.005), and ADRB3 Trp64Arg (P<0.001) polymorphisms, even after the Bonferroni correction. Systolic blood pressure was significantly lower in ADRA2B II genotype carriers than in the DD genotype carriers (P=0.006), while plasma high-density lipoprotein cholesterol was significantly higher in patients carrying ADRA2B I allele and ADRB1 49Ser allele than in patients with the DD genotype and 49Gly/49Gly genotype, respectively (P=0.018 and 0.033). Overall best interaction model consisted of ADRA2B D/I, ADRB1 Ser49Gly, dyslipidemia and hypertension, with the highest testing accuracy of 0.627 and the maximal 10-fold cross-validation consistency (P=0.017). Finally, a nomogram was depicted based on four significant polymorphisms and metabolic risk factors, and it had a better predictive utility and was internally validated with a discrimination C-index of 0.723 (P<0.001). Altogether, we identified two polymorphisms, ADRA2B D/I and ADRB1 Ser49Arg, which not only altered genetic susceptibility to MI, but also impacted on blood pressure and plasma lipid changes, and their combination with metabolic risk factors constituted the overall best interaction model.

Long-term prognosis of patients with acute myocardial infarction due to unprotected left main coronary artery disease: a single-centre experience over 14 years.

INTRODUCTION Acute myocardial infarction (AMI) due to unprotected left main coronary artery (ULMCA) disease is clinically catastrophic although it has a low incidence. Studies on the long-term prognosis of these patients are rare. METHODS From January 1999 to September 2013, 55 patients whose infarct-related artery was the ULMCA were enrolled. Clinical, angiographic and interventional data was collected. Short-term and long-term clinical follow-up results as well as prognostic determinants during hospitalisation and follow-up were analysed. RESULTS Cardiogenic shock (CS) occurred in 30 (54.5%) patients. During hospitalisation, 22 (40.0%) patients died. Multivariate logistic regression analysis showed that CS (odds ratio [OR] 5.86; p = 0.03), collateral circulation of Grade 2 or 3 (OR 0.14; p = 0.02) and final flow of thrombolysis in myocardial infarction (TIMI) Grade 3 (OR 0.05; p = 0.03) correlated with death during hospitalisation. 33 patients survived to discharge; another seven patients died during the follow-up period of 44.6 ± 31.3 (median 60, range 0.67-117.00) months. The overall mortality rate was 52.7% (n = 29). Kaplan-Meier analysis showed that the total cumulative survival rate was 30.7%. Cox multivariate regression analysis showed that CS during hospitalisation was the only predictor of overall mortality (hazard ratio 4.07, 95% confidence interval 1.40-11.83; p = 0.01). CONCLUSION AMI caused by ULMCA lesions is complicated by high incidence of CS and mortality. CS, poor collateral blood flow and failure to restore final flow of TIMI Grade 3 correlated with death during hospitalisation. CS is the only predictor of long-term overall mortality.

An Extremely Effective and Safe Approach of Guiding Catheter Crossing over Spasmodic Radial or (and) Brachial Artery in Patients Whose Percutaneous Coronary Intervention Was Undergone via Radial Artery Access

Objective: Percutaneous coronary intervention (PCI) via the radial artery access has more advantages than that of femoral artery access, while radial or (and) brachial artery have tendency to be spasmodic. We sought to investigate the effectiveness and safety of guiding catheter crossing over spasmodic radial or (and) brachial artery segments by the aid of PCI wire and balloon compared with traditional anti-spasmodic approach. Methods: The clinical data of 168 patients with coronary artery disease (CAD) (group A), whose PCI was performed via radial artery access with radial or (and) brachial artery spasm or (and) dissection and guiding catheter passing through spasmodic segments successfully by the aid of PCI guiding wire and balloon were analyzed retrospectively, simultaneously, the other 73 patients (group B) who used conventional approach to cross over the spasmodic radial or (and) brachial artery segments were treated as the control. The success rate, the time consumption and the complication were compared between the two groups. Findings: There was no significant difference in the spasmodic site between the two groups (all p value > 0.05). The success rate in group A was significantly higher than that in group B (168(100%) vs 28 (38.4%), p < 0.0001). As for those of successful crossover in the two groups, the time consumption of guiding catheter crossing over spasmodic segment in group A was shorter than that in group B (p < 0.0001). The incidence of forearm hematoma in group A was lower than that in group B (7(4.2%) vs 14 (19.2%), p < 0.0001). Conclusions: It is more effective and safer for guiding catheter crossing over spasmodic or (and) dissected radial or (and) brachial artery segments by the aid of PCI guiding wire and balloon than using the routine approach of administration of anti-spasm drugs for trans-radial PCI.