Cross-sectional study of retroperitoneal hematoma after invasive intervention in a Chinese population: Prevalence, characteristics, management and outcomes.

The present study aimed to explore the clinical characteristics and management of retroperitoneal hematoma (RPH) after invasive intervention during a 12-year period in China. A retrospective review of patients with RPH after various invasive interventions was conducted at the China National Center for Cardiovascular Diseases. A total of 42 patients with a mean age of 63.1±2.5 years were continuously recruited in the study between January 2007 and September 2018. The incidence, manifestations and management of RPH were analyzed. A total of 20 patients had punctures in the femoral arterial access under the inguinal ligament and 5 patients had punctures above the inguinal ligament. The majority of RPH occurred within 24 h after intervention, while some occurred after postoperative 24 h. Pain was the most common symptom in patients with RPH. All patients who underwent intervention presented a reduction in hemoglobin (HB) concentration. The overall incidence of nosocomial infection was 38.1% and mortality was 7.1%. The findings demonstrated that RPH is a rare complication after invasive intervention of cardiovascular diseases with non-specific clinical manifestations. The reduction of HB concentration was a vital manifestation for RPH. Most RPH cases could be treated by conservative treatment and blood transfusion. A puncture in the femoral arterial access under the inguinal ligament may result in RPH.

Invasive versus conservative strategy in consecutive patients aged 80 years or older with non-ST-segment elevation myocardial infarction: a retrospective study in China.

OBJECTIVE: To investigate whether the very elderly patients with non-ST-segment elevation myocardial infarction (NSTEMI) will benefit from an invasive strategy versus a conservative strategy. METHODS: 190 consecutive patients aged 80 years or older with NSTEMI were included in the retrospective study from September 2014 to August 2017, of which 69 patients received conservative strategy and 121 patients received invasive strategy. The primary outcome was death. Multivariate Cox regression models were used to assess the statistical association between strategies and mortality. The survival probability was further analyzed. RESULTS: The primary outcome occurred in 17.4% patients in the invasive group and in 42.0% patients in the conservative group (P = 0.0002). The readmission rate in the invasive group (14.9%) was higher than that in the conservative group (7.2%). Creatinine level (OR = 1.01, 95% CI: 0.10-1.03, P = 0.05) and use of diuretic (OR = 3.65, 95% CI: 1.56-8.53, P = 0.003) were independent influential factors for invasive strategy. HRs for multivariate Cox regression models were 3.45 (95% CI: 1.77-6.75, P = 0.0003), 3.02 (95% CI: 1.52-6.01, P = 0.0017), 2.93 (95% CI: 1. 46-5.86, P = 0.0024) and 2.47 (95% CI: 1.20-5.07, P = 0.0137). Compared with the patients received invasive strategy, the conservative group had remarkably reduced survival probability with time since treatment (P < 0.001). CONCLUSIONS: An invasive strategy is superior to a conservative strategy in reducing mortality of patients aged 80 years or older with NSTEMI. Our results suggest that an invasive strategy is more suitable for the very elderly patients with NSTEMI in China.

Gender differences in treatment strategies among patients ≥80 years old with non-ST-segment elevation myocardial infarction.

BACKGROUND: This study aims to investigate the gender differences in treatment strategies among non-ST-segment elevation myocardial infarction (NSTEMI) patients ≥80 years old in China. METHODS: A total of 190 consecutive NSTEMI patients ≥80 years old in Fuwai Hospital were included from 2014 to 2017. These patients were grouped by gender, and sub-grouped by conservative treatment or invasive treatment. The clinical characteristics, medical history, discharge drug used, and prognosis were collected and compared between these two treatment strategies. RESULTS: There were significant differences between these two treatment strategies in terms of GRACE grade, history of myocardial infarction (MI), after coronary artery bypass grafting (CABG), III grade, renal dysfunction, anemia, and use of diuretic (P<0.05). In addition, the age, creatinine and Killip class of female patients, and the death and good prognosis of male patients were found to be significantly different between these two treatment strategies (P<0.05). The multivariate logistic regression analysis revealed that the death of males was significantly associated with treatment strategies in the multivariable logistic regression analysis (P<0.05). In addition, the Kaplan-Meier survival analyses revealed that the survival rates of invasive strategy were significantly higher, when compared to that of conservative strategy in males (P=0.001) and females (P=0.015). CONCLUSIONS: There were gender differences in treatment strategies among NSTEMI patients ≥80 years old. The difference in treatment strategies in males was more pronounced than in females, in terms of long-term survival rate.

The expression of Ubc9 and the intensity of SERCA2a-SUMOylation were reduced in diet-induced obese rats and partially restored by trimetazidine.

BACKGROUND: Reduced expression of sarcoplasmic reticulum calcium-transporting ATPase isoform 2a (SERCA2a) has been shown to play a significant role in the cardiac dysfunction of obese animal models. It was reported recently that SUMOylation enhances the stability and activity of SERCA2a. We hypothesized that SERCA2a-SUMOylation might be involved in obesity-mediated reduction of SERCA2a. METHOD AND RESULTS: Trimetazidine (TMZ), the drug that inhibits fatty acid oxidation, was used in diet-induced obese (DIO) rats and palmitic acid (PA)-treated cardiomyocytes. The intensity of SERCA2a-SUMOylation and proteins involved in SERCA2a-SUMOylation were investigated in vivo and in vitro. DIO rats presented cardiac dysfunction, which was alleviated by TMZ treatment. Reductions of SERCA2a protein and the intensity of SERCA2a-SUMOylation were observed in DIO rats and PA-treated cardiomyocytes. These reductions were partially restored by TMZ. However, TMZ itself did not alter the intensity of SERCA2a-SUMOylation in control cardiomyocytes. The variations of protein and messenger RNA levels of Ubiquitin carrier protein 9 are in accordance with the intensity of SERCA2a-SUMOylation. Whereas the other proteins involved in SERCA2a-SUMOylation were not changed by DIO and PA. CONCLUSIONS: TMZ alleviates the DIO- and PA-induced reductions of SERCA2a-SUMOylation. Ubiquitin carrier protein 9 is involved in the reductions.

[Safety and feasibility of carotid artery stenting in patients with coexisting carotid and coronary artery disease].

OBJECTIVE: To evaluate the safety and feasibility of carotid artery stenting (CAS) for treating patients with coexisting carotid and coronary artery disease. METHODS: The clinical data of 237 consecutive patients [(66.1 ± 7.7) years old, 79.7% male] with coexisting carotid and coronary artery disease undergoing CAS in Fuwai hospital from January 2005 to June 2010. The patients were analyzed retrospectively.Indication for CAS was defined as carotid artery diameter reduction of > 60% (symptomatic) or > 80% (asymptomatic) with suitable carotid artery anatomy for stenting. Thirty-day rates of stroke, death and myocardial infarction after CAS were assessed. RESULTS: All patients suffered from coronary artery disease, of whom 87(36.7%) had unstable angina pectoris and 82(34.6%) had recent myocardial infarction (< 30 days). The procedural success rate of CAS was 99.2 % (235/237). Cerebral protection devices were used in 234 patients (99.6%). Among them, 36(15.2%) patients received simultaneous bilateral CAS and 79(33.3%) patients underwent simultaneous percutaneous intervention of other non-coronary arteries.Within 30 days after CAS, 127(53.6%) patients underwent coronary revascularization, including 118(49.6%) coronary artery bypass grafting and 9 (3.8%) percutaneous coronary intervention. The rate of major stroke, minor stroke, death and myocardial infarction from time of CAS to 30 days was 2.1% (5/237), 3.0% (7/237),0.4% (1/237) and 0.4% (1/237) respectively. CONCLUSION: Data from this study indicate that CAS is safe and feasible for treating patients with coexisting carotid and coronary artery disease with a low incidence of periprocedural complication rate.

Clinical and angiographic correlates of left ventricular dysfunction in patients with three vessel coronary disease.

BACKGROUND: Among patients with advanced multivessel coronary disease, left ventricular (LV) function is widely variable, and clinical and angiographic correlates of ventricular dysfunction remain to be defined. METHODS: Among 73 339 patients undergoing diagnostic cardiac catheterization at a single center in China, patients with left ventriculographic assessment were identified with three-vessel coronary disease with or without left main involvement. Clinical and angiographic characteristics were examined among patients with normal or varying extent of LV dysfunction, and predictors of LV impairment (ejection fraction (EF): < 25%, 25% - 40% or > 40%) were determined. RESULTS: Among 11 950 patients identified with three-vessel coronary disease, the sample distribution of LVEF was > 40%, n = 10 776; 25% - 40%, n = 948; < 25%, n = 226. Patients with reduced LV function (< 40%) more commonly were male and had a history of myocardial infarction (MI), diabetes or unstable angina. Hypertension was more frequent in those with LVEF ≥ 40%. In a multivariate Logistic regression analysis, prior MI (odds ratio (OR), 3.37; 95% confidence interval (CI), 2.96 - 3.84) was most predictive of LVEF < 40%, followed by male gender, diabetes, and presentation with unstable angina. For LVEF < 25%, only prior MI was identified as a significant correlate of severe LV dysfunction (OR 4.06, 95%CI 3.06 - 5.39). Following exclusion of patients with previous MI (n = 7416), male gender and diabetes were predictive of LVEF < 40%, yet presentation with unstable angina was the only factor significantly associated with LVEF < 25%. CONCLUSION: Among individuals identified with three-vessel coronary disease with or without left main involvement, previous MI was the most significant risk factor of LV dysfunction.

[Clinical analysis of simultaneous bilateral carotid stenting for treating patients with bilateral atherosclerotic carotid stenosis].

OBJECTIVE: To evaluate the safety and feasibility of simultaneous bilateral carotid stenting for treating patients with bilateral atherosclerotic carotid stenosis. METHODS: The clinical data of 39 consecutive patients with bilateral atherosclerotic carotid stenosis undergoing simultaneous bilateral carotid artery stenting in Fuwai hospital from January 2005 to December 2009 were collected and analyzed retrospectively. The reduction of the angiographic diameter stenosis after stenting and clinical outcomes of 30 days after stenting including hyperperfusion syndrome, hemodynamic depression, stroke, myocardial infarction and death were assessed. RESULTS: The patients were 43 - 78 (65.9 ± 8.5) years old, and there were 25 (64.1%) male. Carotid stenting procedure success rate was 100%. Distal embolic protection devices were used in all patients, and 20 (51.3%) out of 39 patients underwent coronary artery bypass surgery after carotid stenting. The angiographic diameter stenosis reduced from (87.0 ± 5.8)% to (10.2 ± 5.6)% after stenting (P < 0.01). Up to 30 days after carotid artery stenting, the incidence of hyperperfusion syndrome, hemodynamic depression, minor stroke, major stroke, myocardial infarction and death was 2.6% (1/39), 28.2% (11/39), 5.1% (2/29), 0, 2.6% (1/39), 2.6% (1/39), respectively. CONCLUSION: The data show that simultaneous bilateral carotid stenting is a technically feasible and safe alternative for patients with severe bilateral atherosclerotic carotid stenosis.

[Readthrough of nonsense mutation W822X in the SCN5A gene can effectively restore expression of cardiac Na+ channels W822X].

OBJECTIVE: In this study we investigated the functional restoration of nonsense mutations in the SCN5A gene. METHODS: The readthrough-enhancing reagents were introduced to HEK293 cells to suppress one nonsense mutation W822X in the SCN5A gene. Patch-clamp was used to record the whole-cell current and dynamics. Western blot and immunofluorescence staining were used to certify the expression and the location of the sodium channel. RESULTS: In transfected HEK293 cells, the nonsense mutation in SCN5A inhibited the expression level of full-length protein, and the sodium currents from the mutant channels were less than 3% of the wild-type level. Readthrough enhancement by decreasing translation termination efficiency with a siRNA targeting eukaryotic release factor eRF3a (a GTPase that binds eRF1), the sodium current from the mutant cDNAs was restored to as much as 30% of the wild-type. After the treatment by the readthrough-enhancing reagents, the channels from cDNA carrying W822X remained the features of wild-type phenotype, and Western blot and immunochemical staining also showed the expression of full-length channel proteins. CONCLUSION: Readthrough-enhancing reagents could effectively suppress nonsense mutations in SCN5A and partially restore the function of sodium channel and the expression of full-length channels.

Novel compound heterozygous mutations T2C and 1149insT in the KCNQ1 gene cause Jervell and Lange-Nielsen syndrome.

Mutations in the KCNQ1 gene account for more than 90% of the individuals with Jervell and Lange-Nielsen syndrome (JLNS). In this study, we identified and characterized two novel KCNQ1 mutations that caused JLNS. A 6-year-old deaf girl suffering from recurrent syncope had a documented electrocardiogram with polymorphic ventricular fibrillation since the age of 4 years. The baseline electrocardiogram showed a significantly prolonged corrected QT interval (524 msec). Genetic analysis revealed that the proband carried two heterozygous mutations of T2C and 1149insT in the KCNQ1 gene on separate alleles. Patch-clamp analysis demonstrated that the T2C mutation resulted in significant reduction in the slowly activated delayed rectifier current (IKs). Furthermore, western blot analysis and confocal imaging revealed that the T2C mutation produced a truncated protein with trafficking defects. In contrast, the 1149insT mutation failed to generate any measurable current, consistent with no protein expression in both the cell membrane and cytoplasm. Moreover, co-expression of the T2C and 1149insT mutations significantly reduced the peak tail current density to 8.27% of the wild-type (WT) current value, while co-transfected WT channels with either T2C or 1149insT mutant channels produced comparable current and channel kinetics to that of WT channels. Our study demonstrates that the compound heterozygous mutations T2C and 1149insT cause the 'loss-of-function' of the IKs that may account for the clinical phenotype of the proband. Multiple mechanisms have been involved in the pathogenesis of 'loss-of-function' of IKs.

[The Val606Met mutation of human beta myosin heavy chain in a Chinese familial hypertrophic cardiomyopathy family].

OBJECTIVE: To explore the disease-causing gene mutation in Chinese families with hypertrophic cardiomyopathy (HCM) and to analyze the correlation between the genotype and phenotype. METHODS: Samples of peripheral blood were collected from three Chinese families with HCM (at least two HCM patients existed/family). The exons in the functional regions of the beta myosin heavy chain gene (MYH7) were amplified with PCR and the products were sequenced. RESULTS: A Val606Met missen mutation was identified in the exon 16 of MYH7 gene in a Chinese family and this mutation was identified in all HCM patients (n = 4) and there was also a 15-years-old young mutation carrier who was not HCM patient now (penetrance of 80%). This mutation was not identified in other healthy family members in this family, in other 2 Chinese familiar HCM families and in 120 non-HCM control patients. CONCLUSION: The Val606Met missen mutation is closely associated with familiar HCM in a Chinese family which is associated with clinical phenotype with a penetrance of 80%.

Modulation of KCNQ1 current by atrial fibrillation-associated KCNE4 (145E/D) gene polymorphism.

BACKGROUND: Atrial fibrillation is a common arrhythmia with multi-factorial pathogenesis. Recently, a single nucleotide polymorphism (G/T) at position 1057 in the KCNE4 gene, resulting in a glutamic acid (Glu, E)/aspartic acid (Asp, D) substitution at position 145 of the KCNE4 peptide, was found in our laboratory to be associated with idiopathic atrial fibrillation (atrial fibrillation more frequent with KCNE4 145D). However, the functional effect of the KCNE4 145E/D polymorphism is still unknown. METHODS: We constructed KCNE4 (145E/D) expression plasmids and transiently co-transfected them with the KCNQ1 gene into Chinese hamster ovary-K1 cells and performed whole-cell patch-clamping recording to identify the possible functional consequences of the single nucleotide polymorphism. Quantitative data were analyzed by Student;s t test. Probability values less than 0.05 were considered statistically significant. RESULTS: A slowly activating, non-inactivating voltage-dependent current ((24.0 +/- 2.9) pA/pF, at +60 mV)) could be recorded in the cells transfected with KCNQ1 alone. Co-expression of wild type KCNE4 inhibited the KCNQ1 current ((7.3 +/- 1.1) pA/pF)). By contrast, co-expression of KCNE4 (145D) augment the KCNQ1 current ((42.9 +/- 7) pA/pF)). The V(1/2) of activation for the KCNQ1/KCNE4 (145D) current was shifted significantly towards the depolarizing potential compared to that for the KCNQ1 current ((-2.3 +/- 0.2) mv vs (-13.0 +/- 1.5) mv, P < 0.01)) without changing the slope factorkappa. Furthermore, KCNE4 (145D) also affected the activation and deactivation kinetics of KCNQ1 channels. CONCLUSION: We provide experimental evidence that the KCNE4 (145E/D) polymorphism exerts the effect of "gain of function" on the KCNQ1 channel. It may underlie the genetic mechanism of atrial fibrillation. Further studies on the functional association between I(Ks) and KCNE4 (145D) polymorphism in cardiac myocytes are suggested.

[Electrocardiogram analysis in high risk population of unexplained sudden death in Yunnan province].

OBJECTIVE: The purpose of this study was to analyze the electrocardiographic features of the people living in the area with high incidence of unexplained sudden deaths in Yunnan province. METHOD: The electrocardiograms of 338 residents from three villages (Dayao, Ninglang, Heqing) with high incidence of unexplained sudden deaths and one control village (Dali) were analyzed [averaged age was (33.4 +/- 11.7) years, 175 men and 163 women]. RESULTS: The incidence of cardiac arrhythmias was similar low in all groups. The left ventricular hypertrophy was observed in 34.6% of residents from Dayao. QTc significantly prolonged in the residents from all 3 high incidence areas compare the control area of Dali [control (386.8 +/- 27.22) ms, Ninglang (428.92 +/- 25.71) ms, Heqing (440.67 +/- 28.03) ms, Dayao (417.7 +/- 24.00) ms, P < 0.05 vs. control]. Incidence of U wave was significantly higher in Heqing village than that in control village (P < 0.05). The QUc of these 3 villages was: (613.67 +/- 37.34) ms, (597.19 +/- 46.47) ms, (608.59 +/- 39.59) ms respectively, and also significantly longer than the control village of Dali (589.33 +/- 41.27) ms (P < 0.05). The typical pattern of U wave presents as enlarged U wave and apparent T-U complex. In the 7 residents who have the family history of unexplained sudden death, 6 residents have U wave, and 4 of them present typical U wave pattern. CONCLUSION: The significant ECG changes in villages with high incidence of unexplained sudden death in Yunnan province were prolonged QTc, enlarged U wave and apparent T-U complex and these ECG features suggested the repolarization abnormalities of the heart in these subjects.

[Electrophysiological characterization of long QT syndrome associated mutations V630A and N633S].

OBJECTIVE: To identify the electrophysiological properties of long-QT syndrome (LQTS) associated missense mutations in the outer mouth of the HERG potassium channel in vitro. METHODS: Mutations V630A and N633S were constructed by Megaprimer PCR method and cRNA were produced by T7 RNA polymerase. The electrophysiological properties of the mutation were investigated in the Xenopus oocyte heterologous expression system. RESULTS: Coexpression of mutant and wild-type HERG subunits caused a dominant-negative effect, and the currents were significantly decreased. Compared with wild-type HERG channels, V630A and N633S mutations were related to decreased time constants for inactivation for V630A/WT and N633S/WT at all potentials, reduced slope conductance and the voltage dependence of steady-state inactivation was shifted to negative potentials for V630A/WT and N633S/WT. CONCLUSION: Present study shows that LQTS associated missense mutations located in the outer mouth of HERG cause a dominant-negative effect and alterations in steady-state voltage dependence of channel gating of heteromultimeric channels suggesting a reduction in expressional current might be one of the pathophysiologic mechanisms of LQTS.

[Observation of functional remodeling of Ca2+-activated Cl- channel in pacing-induced canine failing heart].

OBJECTIVE: To study whether Ca(2+)-activated Cl(-) current (I(to2)) contributes to the functional remodeling of the failing heart. METHODS: The cardiac myocytes were isolated enzymatically from rapidly pacing-induced failing canine hearts (HF) at room temperature. Patch-Clamp whole cell recording technique was employed to record the I(to2). The Cl(-) transport blocker 4, 4'-diisothiocyanostilbene-2, 2'-disulfonic acid (DIDS, 200 micromol) was used to isolated the I(to2). The relations of I(to2) to L-type Ca(2+) current (I(Ca-L)) and to the membrane voltage under the constant intracellular [Ca(2+)]i were evaluated in HF and the normal hearts. RESULTS: We found that the current density of I(to2) was significantly decreased in HF cells compared with the controls. At membrane voltage of 20 mV, for example, the I(to2) density was (3.02 +/- 0.54) pA/pF in control cells (n = 7) vs. (1.31 +/- 0.25) pA/pF in HF (n = 8) cells, P < 0.05. While the averaged I(Ca-L) density did not show difference between two groups. The time constant of current decay of I(to2) was similar in both types of cells. However, in intracellular Ca(2+) clamped mode with 100 micromol [Ca(2+)]i, I(to2) density was increased significantly in HF cells at membrane voltage of +30 mV or higher. CONCLUSIONS: Our results suggest that the decrease of I(to2) density may contribute to the prolongation of the action potential in failing heart. I(to2) density abnormality may cause cardiac arrhythmia and a delayed after-depolarization. Impaired Ca(2+) handing in HF cells rather than reduced CLCA function itself may result in this abnormality.

[The association of single nucleotide polymorphism of slow delayed rectifier K+ channel genes with atrial fibrillation in Han nationality Chinese].

OBJECTIVE: To investigate the association between atrial fibrillation and the single nucleotide polymorphism (SNP) of slow delayed rectifier K(+) channel (I(Ks)) genes in Han nationality Chinese. METHODS: Three hundred and eighty of Han nationality Chinese (142 atrial fibrillation, 120 in-hospital and 118 out-hospital control) were enrolled in this study. Asian specific non-synonymous SNPs of KCNQ1 P448R, KCNQ1 R519H, KCNQ1 G643S, KCNE1 G38S and KCNE1 D85N were genotyped by restriction fragment length polymorphism analysis. A newly cloned KCNE4 gene was also screened for any possible SNP. RESULTS: The minor allele frequency of KCNQ1 P448R, KCNQ1 R519H, KCNQ1 G643S, KCNE1 G38S and KCNE1 D85N in out-hospital subjects was 0.079, 0, 0.042, 0.317 and 0.004, respectively. None of these SNPs was relationed with any atrial fibrillation phenotype. A KCNE4 E145D was discovered and proven statistically to relation significantly to atrial fibrillation by logistic regression analysis (OR = 1.66, P = 0.044). The minor allele frequency of KCNE4 E145D was as high as 0.271 in out-hospital subjects. CONCLUSIONS: None of the SNPs of KCNQ1 P448R, KCNQ1 R519H, KCNQ1 G643S, KCNE1 G38S and KCNE1 D85N was associated with atrial fibrillation phenotype, but KCNE4 E145D may relation to atrial fibrillation. The effect of KCNE4 E145D variation on the function of I(Ks) channel is to be determined.