Comparison of intravascular ultrasound-guided with angiography-guided double kissing crush stenting for patients with complex coronary bifurcation lesions: Rationale and design of a prospective, randomized, and multicenter DKCRUSH VIII trial.

BACKGROUND: Double kissing (DK) crush approach for patients with coronary bifurcation lesions, particularly localized at distal left main or lesions with increased complexity, is associated with significant reduction in clinical events when compared with provisional stenting. Recently, randomized clinical trial has demonstrated the net clinical benefits by intravascular ultrasound (IVUS)-guided implantation of drug-eluting stent in all-comers. However, the improvement in clinical outcome after DK crush treatment guided by IVUS over angiography guidance for patients with complex bifurcation lesions have never been studied in a randomized fashion. TRIAL DESIGN: DKCRUSH VIII study is a prospective, multicenter, randomized controlled trial designed to assess superiority of IVUS-guided vs angiography-guided DK crush stenting in patients with complex bifurcation lesions according to DEFINITION criteria. A total of 556 patients with complex bifurcation lesions will be randomly (1:1 of ratio) assigned to IVUS-guided or angiography-guided DK crush stenting group. The primary end point is the rate of 12-month target vessel failure, including cardiac death, target vessel myocardial infarction, or clinically driven target vessel revascularization. The secondary end points consist of the individual component of primary end point, all-cause death, myocardial infarction, and in-stent restenosis. The safety end point is the incidence of definite or probable stent thrombosis. An angiographic follow-up will be performed for all patients at 13 months and clinical follow-up will be continued annually until 3 years after the index procedure. CONCLUSIONS: DKCRUSH VIII trial is the first study designed to evaluate the differences in efficacy and safety between IVUS-guided and angiography-guided DK crush stenting in patients with complex true bifurcation lesions. This study will also provide IVUS-derived criteria to define optimal DK crush stenting for bifurcation lesions at higher complexity.

Association of long-term inhalation of caffeine-sodium benzoate with coronary heart disease in men.

OBJECTIVE: A possible correlation between caffeine and coronary heart disease (CHD) is controversial. The objective of this study was to explore the effect of long-term inhalation of caffeine-sodium benzoate (CSB) on the development of CHD in men, the severity of coronary artery lesions and the possible contributing effects of smoking. MATERIALS: A retrospective analysis was performed on 2,001 consecutive men who underwent selective coronary angiography. These men were assigned to a CSB inhalation group (CSB; 1 - 6 times/d, 274 - 1,644 mg/d, > 10 years; n = 326) or a non-inhalation group (non-CSB; n = 1,675). METHODS: The two groups were compared for the prevalence, onset age, and risk factors of CHD. The men were also stratified as CSB-only, smoking-only, combined CSB+ smoking, and the control (non-CSB+non-smoking). The prevalence, onset age, risk factors of CHD, and severity of coronary artery lesions and major adverse cardiovascular events (MACE) were compared among these groups. RESULTS: The prevalence of CHD in the CSB group was higher compared with the non-CSB group (91.72 vs. 86.09%, p < 0.01). In the CSB+smoking group, the percentages of men with CHD (93.11%) or > 70% stenosis of the coronary artery lesion (64.92%) were significantly higher than that of the smoking-only group (88.19 and 54.29%, respectively) or control (83.20 and 52.90%), while the percentage with stenosis involving the anterior descending branch was lower (62.30 vs. 72.29% and 74.17%, p < 0.01). CONCLUSION: Men who inhaled CSB long-term had a higher rate of CHD compared with those who did not take CSB. The combination of CSB inhalation and smoking appears to increase synergistically the risk and severity of CHD.

Periprocedural myocardial infarction is associated with increased mortality in patients with coronary artery bifurcation lesions after implantation of a drug-eluting stent.

OBJECTIVES: The present study aimed to investigate the association between periprocedural myocardial infarction (PMI), defined by creatine kinase (CK)-MB or troponin I (TNI) level elevations >5 times the 99 th percentile of the upper reference limit (URL) within 48 hr after implantation of a drug-eluting stent (DES), and one-year mortality in patients with coronary bifurcation. BACKGROUND: PMI is reported to be associated with increased one-year mortality after DES implantation. However, the prevalence and association of PMI with mortality after stenting bifurcation lesions remains unclear. METHODS: We prospectively followed 1,971 patients with true coronary bifurcations who underwent DES implantation as part of the multicenter DEFINITION study. These patients were grouped into categories based on PMI outcome: Non-PMI, CKMB-PMI, TNI-PMI, and CKMB/TNI-PMI. The primary endpoint was the rate of all-cause mortality at one year. RESULTS: PMI occurred in 11.4% of patients by CKMB criteria and 41.3% of patients by TNI criteria. At one-year follow-up, the mortality rate was 2.3% in the entire patient population. However, mortality was significantly higher in the CKMB-PMI (6.4%) and CKMB/TNI-PMI (6.1%) groups compared to the Non-PMI (1.7%) and TNI-PMI (2.1%) groups (all P < 0.05). A 10-fold increase in TNI levels resulted in similar PMI rate (5.2%) and mortality risk (adjusted HR 2.7, 95% CI 3.0-5.2) as a fivefold increase in CKMB levels. CONCLUSIONS: PMI, as defined by CKMB elevations following coronary bifurcation lesion stenting, was associated with increased one-year mortality. Additionally, to attain an equal frequency of PMI, the elevation in TNI levels needed to be twice as high as the elevation in CKMB levels.

[The expression and clinical implication of plasma miR-328 in patients with atrial fibrillation].

OBJECTIVE: To observe the expression and clinical implication of plasma miR-328 in patients with atrial fibrillation (AF). METHODS: Fifty-eight patients with AF (AF group: 17 paroxysmal AF, 21 persistent AF, and 20 permanent AF) and 15 healthy volunteers (Control group) were included. General clinical data and related biochemical parameters were collected. Plasma miR-328 levels were detected with quantitative real-time polymerase chain reaction (qRT-PCR) analysis. The correlation between plasma miR-328 and AF risk factors was analyzed. RESULTS: (1) Compared with the control group, the expression level of plasma miR-328 was significantly elevated in AF group (fold 7.72 ± 9.32) (P < 0.05). (2) In AF group, the expression of plasma miR-328 was significantly different in different type of AF[paroxysmal AF with (1.98 ± 0.81), persistent AF with (6.57 ± 5.82) and permanent AF with (13.47 ± 12.29)] (P < 0.05), and which was increased in proportion to the duration of AF. (3) There was a positive correlation between plasma miR-328 level and left atrial diameter in the AF group (r = 0.310, P < 0.05). CONCLUSION: miR-328 expression is significantly increased in patients with AF, which may be involved in the atrial remodeling process of AF.

Incidence, risk factors, and clinical sequelae of incomplete stent apposition after sirolimus-eluting stent.

Incomplete stent apposition has been documented after sirolimus-eluting stent implantation. However, its clinical sequelae remain controversial. To identify the incidence and its clinical consequences of ISA, IVUS was performed on 78 patients. In spite of well apposition immediately after the deployment, late stent malapposition occurred after 6-months follow-up. A total of 7 patients who received SES showed ISA. There were no significant differences in IVUS measurements between patients with or without ISA. However, there was an increase in external elastic membrane area in ISA group than non-ISA group (19.69 ± 3.50 vs. 15.05 ± 2.56 mm2, P<0.05). There were positive clinical events for ISA cases at 6-months clinical follow-up. Univariate and multivariable analyses indicated that hs-CRP, miR-21, and MMP-2 were risk factor for ISA. ISA was observed in 9% of patients after SES implantation, which was related to vessel positive remodeling. The incidence of MACEs in patients with ISA was higher than those without ISA. However, careful long-term follow-up remains to be clarified.

Drug-coated balloons for the treatment of ostial left anterior descending or ostial left circumflex artery lesions: a patient-level propensity score-matched analysis.

BACKGROUND: Controversy exists as to the optimal treatment approach for ostial left anterior descending (LAD) or ostial left circumflex artery (LCx) lesions. Drug-coated balloons (DCB) may overcome some of the limitations of drug-eluting stents (DES). Therefore, we investigated the security and feasibility of the DCB policy in patients with ostial LAD or ostial LCx lesions, and compared it with the conventional DES-only strategy. METHODS: We retrospectively enrolled patients with de novo ostial lesions in the LAD or LCx who underwent interventional treatment. They were categorized into two groups based on their treatment approach: the DCB group and the DES group. The treatment strategies in the DCB group involved the use of either DCB-only or hybrid strategies, whereas the DES group utilized crossover or precise stenting techniques. Two-year target lesion revascularization was the primary endpoint, while the rates of major adverse cardiovascular events, cardiac death, target vessel myocardial infarction, and vessel thrombosis were the secondary endpoints. Using propensity score matching, we assembled a cohort with comparable baseline characteristics. To ensure result analysis reliability, we conducted sensitivity analyses, including interaction, and stratified analyses. RESULTS: Among the 397 eligible patients, 6.25% of patients who were planned to undergo DCB underwent DES. A total of 108 patients in each group had comparable propensity scores and were included in the analysis. Two-year target lesion revascularization occurred in 5 patients (4.90%) and 16 patients (16.33%) in the DCB group and the DES group, respectively (odds ratio = 0.264, 95% CI: 0.093-0.752, P = 0.008). Compared with the DES group, the DCB group demonstrated a lower major adverse cardiovascular events rate (7.84% vs. 19.39%, P = 0.017). However, differences with regard to cardiac death, non-periprocedural target vessel myocardial infarction, and definite or probable vessel thrombosis between the groups were non-significant. CONCLUSIONS: The utilization of the DCB approach signifies an innovative and discretionary strategy for managing isolated ostial lesions in the LAD or LCx. Nevertheless, a future randomized trial investigating the feasibility and safety of DCB compared to the DES-only strategy specifically for de novo ostial lesions in the LAD or LCx is highly warranted.

Stentless at ostium: a novel approach for treating ostial left anterior descending or left circumflex coronary artery lesions with drug-coated balloons.

BACKGROUND: Currently, there is no optimal treatment strategy for ostial left anterior descending (LAD) or ostial left circumflex artery (LCx) lesions. This study explored effectiveness and safety of drug-coated balloons (DCB) in individuals presenting with ostial LAD or LCx lesions. METHODS: A total of 137 patients with de novo ostial LAD or LCx lesions scheduled for DCB treatment were prospectively recruited into the study. After mandatory lesion preparation, DCB-only or hybrid strategy [DCB + drug-eluting stent (DES)] were performed on 120 patients (87.59%). The primary endpoint was the rate of 2-year target lesion revascularization (TLR). Rates of major adverse cardiovascular events (MACE), cardiac death, target vessel myocardial infarction (TVMI), and vessel thrombosis were explored as the secondary outcomes. Quantitative coronary angiography software was used to analyze coronary angiograms. RESULTS: Of the participants, 58 were treated with DCB-only and 62 with hybrid strategy. Relative to the DCB-only group, patients in the hybrid group had longer target lesions (15.47 ± 10.08 vs. 36.85 ± 9.46 mm, P<0.001) and higher Synergy between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery (SYNTAX) scores (23.47 ± 5.22 vs. 29.98 ± 3.18, P<0.001). During follow-up (731 ± 64 days), neither the primary endpoint (TLR) nor the secondary endpoints (including MACE, cardiac death, TVMI, and vessel thrombosis) differed statistically between the two groups (all P > 0.05). Treatment strategy (DCB-only or hybrid) was not a significant risk factor for TLR. Patients who underwent DCB-only exhibited less late lumen loss compared with the patients who underwent hybrid strategy (-0.26 ± 0.59 vs. 0.42 ± 0.47 mm, P<0.001) at 1-year angiographic follow-up. CONCLUSIONS: With regards to safety and efficacy, the strategy of DCB as a standalone therapy was similar in comparison with the hybrid strategy of DCB + DES for ostial LAD and ostial LCx lesions. This approach might be effective and technically easy in treating ostial LAD and LCx diseases.

Rationale and design for comparison of non-compliant balloon with drug-coating balloon angioplasty for side branch after provisional stenting for patients with true coronary bifurcation lesions: a prospective, multicentre and randomised DCB-BIF trial.

INTRODUCTION: Provisional stenting using drug-eluting stent is effective for simple coronary bifurcation lesions. Kissing balloon inflation using conventional non-compliant balloon is the primary treatment of side branch (SB) after main vessel (MV) stenting. Drug-coating balloon (DCB) is reported to be associated with less frequent clinical events in in-stent restenosis and small vessel disease. The importance of DCB in bifurcation treatment is understudied. Accordingly, this trial is designed to investigate the superiority of DCB to non-compliant balloon angioplasty for SB after provisional stenting in patients with true coronary bifurcation lesions. METHODS AND ANALYSIS: The DCB-BIF trial is a prospective, multicentre, randomised, superiority trial including 784 patients with true coronary bifurcation lesions. Patients will be randomised in a 1:1 fashion to receive either DCB or non-compliant balloon angioplasty if SB diameter stenosis >70% after MV stenting. The primary endpoint is the composite of major adverse cardiac event at the 1-year follow-up, including cardiac death, myocardial infarction (MI) or clinically driven target lesion revascularisation. The major secondary endpoints include all-cause death, periprocedural MI, spontaneous MI, clinically driven target vessel revascularisation, in-stent restenosis, stroke and individual component of the primary endpoint. The safety endpoint is the risk of stent thrombosis. ETHICS AND DISSEMINATION: The study protocol and informed consent have been reviewed and approved by the Institutional Review Board of all participating centres. The written informed consent for participation in the trial will be obtained from all participants. The results of this study will be published in a peer-reviewed journal and disseminated at conferences. TRIAL REGISTRATION NUMBER: NCT04242134.

[Assessment of left ventricular systolic synchronicity by quantitative tissue velocity imaging in patients with left ventricular noncompaction].

OBJECTIVE: To assess left ventricular systolic synchronicity by quantitative tissue velocity imaging (QTVI) in patients with left ventricular noncompaction (LVNC). METHODS: Eighteen LVNC patients and 30 healthy controls were included. Two-dimensional echocardiography, QTVI was applied on parasternal long axis view, apical two-chamber and four-chamber view. Tissue velocity curve was obtained from the middle and basal segments of left ventricular posterior, lateral, septal, anterior, inferior and anteroseptal walls. Time interval from the beginning of QRS complex to the peak systolic velocity (Q-Ts) and the maximal difference in Ts among all 12 LV segments (Max-DeltaTs) was calculated. RESULTS: Q-Ts from basal and middle segments of left ventricular inferior, lateral and posterior walls was significantly prolonged in LVNC patients compared to controls (P < 0.001). Max-DeltaTs was also significantly increased in LVNC patients [(161.9 +/- 93.2) ms] than that in controls [(61.2 +/- 27.4) ms, P < 0.001]. CONCLUSIONS: There was significant left ventricular asynchronies in patients with LVNC and delayed systolic contraction occurred mostly in the basal and middle segments of left ventricular inferior, posterior and lateral walls.

Bailcalin Protects against Diabetic Cardiomyopathy through Keap1/Nrf2/AMPK-Mediated Antioxidative and Lipid-Lowering Effects.

Previous studies demonstrated that Bailcalin (BAI) prevented cardiac injuries under different disease models. Whether BAI protected against type 2 diabetes mellitus- (T2DM-) associated cardiomyopathy was investigated in this study. T2DM was established by the combination of streptozotocin injection and high-fat diet in mice. BAI was administered daily for 6 months. After evaluating cardiac functions, mice hearts were removed and processed for morphological, biochemical, and molecular mechanism analyses. Neonatal rat cardiomyocytes (NRCM) were isolated and treated with high glucose and palmitate (HG/Pal) for in vitro investigation. BAI significantly ameliorated T2DM-induced cardiomyocyte hypertrophy, interstitial fibrosis, and lipid accumulation accompanied by markedly improved cardiac functions in diabetic mice. Mechanically, BAI restored decreased phosphorylation of AMPK and enhanced expression and nuclei translocation of Nrf2. In in vitro experiments, BAI also prevented NRCM from HG/Pal-induced apoptosis and oxidative stress injuries by increasing p-AMPK and Nrf2 accumulation. The means by which BAI restored p-AMPK seemed to be related to the antioxidative effects of Nrf2 after silencing AMPK or Nrf2 in NRCM. Furthermore, BAI regulated Nrf2 by inhibiting Nrf2 ubiquitination and consequent degradation mediated by Keap1. This study showed that BAI alleviated diabetes-associated cardiac dysfunction and cardiomyocyte injuries in vivo and in vitro via Keap1/Nrf2/AMPK-mediated antioxidation and lipid-lowering effects. BAI might be a potential adjuvant drug for diabetes cardiomyopathy treatment.

Ginkgo biloba extract-761 protects myocardium by regulating Akt/Nrf2 signal pathway.

OBJECTIVE: The aim of this study was to investigate the protective effect and mechanism of Ginkgo biloba extract-761 (EGb 761) in the rat with myocardial ischemia-reperfusion injury (MIRI). MATERIALS AND METHODS: Forty Sprague Dawley rats were randomly divided into following four groups: sham group, I/R group and EGb 761 groups (20 and 40 mg/kg). MIRI model was established after 14 days of administration. The myocardial infarct size and myocardial histology were measured and compared. Meanwhile, the levels of creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), troponin T (TnT), TNF-α, IL-6, IL-1ß, superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) were evaluated. Western blot was used to detect the expression of Caspase-3, Bax, Bcl-2, HO-1, Nrf2, Akt, p-Akt and nuclear protein Nrf2. RESULTS: The levels of infarct size, CK-MB, LDH, TnT, TNF-α, IL-6 and IL-1ß in the EGb 761 groups were significantly lower than those in the ischemia/reperfusion (I/R) group. The content of MDA was lower in the myocardium, whereas the activities of SOD and GSH-Px were higher than those in the I/R group. The expressions of Caspase-3 and Bax in the EGb 761 groups were significantly lower than those in the I/R group, whereas the expressions of Bcl-2, p-Akt and HO-1 and nuclear protein Nrf2 in the EGb 761 groups were higher than those in the I/R group. CONCLUSION: EGb 761 might inhibit the apoptosis of myocardial cells and protect the myocardium by activating the Akt/Nrf2 pathway, increasing the expression of HO-1, decreasing oxidative stress and repressing inflammatory reaction.

Valsartan regulates TGF-ß/Smads and TGF-ß/p38 pathways through lncRNA CHRF to improve doxorubicin-induced heart failure.

This study investigated the interaction among valsartan (VAL), TGF-ß pathways, and long non-coding RNA (lncRNA) cardiac hypertrophy-related factor (CHRF) in doxorubicin (DOX)-induced heart failure (HF), and explored their roles in DOX-induced HF progression. HF mice models in vivo were constructed by DOX induction. The expression of CHRF and TGF-ß1 in hearts was detected, along with cardiac function, caspase-3 activity, and cell apoptosis. Primary myocardial cells were pretreated with VAL, followed by DOX induction in vitro for functional studies, including the detection of cell apoptosis with terminal deoxynucleotidyl transferase dUTP nick-end labeling and the expression of proteins associated with TGF-ß1 pathways. HF models were established in vivo and in vitro. Expression of CHRF and TGF-ß1 was up-regulated, and cell apoptosis and caspase-3 activity were increased in the hearts and cells of the HF models. VAL supplementation alleviated the cardiac dysfunction and injury in the HF process. Moreover, overexpressed CHRF up-regulated TGF-ß1, promoted myocardial cell apoptosis, and reversed VAL's cardiac protective effect, while interference of CHRF (si-CHRF) did the opposite. Down-regulation of CHRF reversed the increased expression of TGF-ß1 and the downstream proteins induced by pcDNA-TGF-ß1 in HL-1 cells, while overexpression of CHRF reversed the VAL's cardiac protective effect in vivo. In conclusion, VAL regulates TGF-ß pathways through lncRNA CHRF to improve DOX-induced HF.

The association between an endothelial nitric oxide synthase gene polymorphism and coronary heart disease in young people and the underlying mechanism.

With the development of molecular biological technology, the association between genes and diseases has drawn increasing attention of researchers; the endothelial nitric oxide synthase (eNOS) gene has been reported to be a candidate gene for cardiovascular disease (CHD). The present study aimed to investigate the association between a polymorphism of eNOS and the risk of CHD in young people (≤40 years old), in addition to the underlying mechanism. A total of 234 cases of CHD in young individuals were collected as the CHD group and 228 cases of healthy individuals as the control group. Peripheral blood was collected and the genotype of the eNOS G894T polymorphism was identified by polymerase chain reaction-restriction fragment length polymorphism, the gene frequency was calculated and the distributions of genotype and allele frequency between the two groups were compared. Bioinformatics tools were employed to analyze the differences in the local protein structures of the eNOS G894T polymorphism and the biological mechanism was preliminary discussed. The results demonstrated that there were significant differences in the distribution of genotype frequency and allele frequency of the eNOS G894T gene polymorphism between the CHD group and control group (P<0.05). The risk of CHD in GT and TT genotypes were higher compared with the GG genotype (P<0.05). The G894T polymorphism led to Glu298Asp mutation of encoded protein, which is within the active site of eNOS, and partial structures of the protein were converted from random coil to α­helix. In conclusion, the eNOS G894T gene polymorphism was associated with the occurrence and development of CHD in young people. The potential mechanism is that the G894T polymorphism leads to altered protein structure, which affects the function of eNOS in generating nitric oxide and cardiovascular diastole. The results of the present study suggested a potential target gene for the prevention and treatment of CHD in young people (≤40 years old).

Combined value of red blood cell distribution width and global registry of acute coronary events risk score on predicting long-term major adverse cardiac events in STEMI patients undergoing primary PCI.

The combined value of RDW and GRACE risk score for cardiovascular prognosis in ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) has not been fully investigated. This study was designed to explore the combined value of RDW and GRACE risk score on predicting long-term major adverse cardiac event (Mace) in STEMI patients undergoing primary PCI. This study included 390 STEMI patients. The primary endpoint at the (33.5 ± 7.1) months follow-up was composed of cardiac death and nonfatal myocardial infarction. The relationship between clinical parameters and clinical outcomes was evaluated using Cox regression model and receiver operating characteristic (ROC) analysis. Mace occurred in 126 (32.3%) patients including 54 (13.8%) cardiac deaths and 72 (18.5%) nonfatal myocardial infarctions. Patients in Mace group had significantly higher RDW and GRACE score than the patients in non-Mace group. According to the Cox model, RDW and GRACE score were the most important independent predictors of Mace and cardiac death. The best cut-off value for RDW to predict the occurrence of primary events was 13.25% (AUC = 0.694, 95% CI:0.639-0.750, P < 0.001) and that for GRACE score was 119.5 (AUC = 0.721, 95% CI:0.666-0.777, P < 0.001). The combination of RDW and GRACE score were more valuable (AUC = 0.775, 95% CI: 0.727-0.824, P < 0.001). Kaplan-Meier analysis provided significant prognostic information with the highest risk for cardiac death (Log-Rank χ2 = 24.684, P < 0.001) in group with both high RDW (> 13.25%) and high GRACE score (> 119.5). The combination of RDW level and GRACE score may be valuable and simple independent predictors of Mace and cardiac death in STEMI patients undergoing primary PCI. They may be useful tools for risk stratification and may indicate long-term clinical outcomes.

Association of dietary vitamin E intake with risk of lung cancer: a dose-response meta-analysis.

BACKGROUND AND OBJECTIVES: Several epidemiological studies investigating the association between dietary vitamin E intake and the risk of lung cancer have demonstrated inconsistent results. Hence, a meta-analysis was conducted to summarise evidence of the association of dietary vitamin E intake with the risk of lung cancer. METHODS AND STUDY DESIGN: In this meta-analysis, a systematic literature search of PubMed and Web of Science was conducted to identify relevant studies published from 1955 to April 2015. If p<0.05 or I2 >50%, a random effect model was used to estimate overall relative risks (RRs) and 95% confidence intervals (CIs). Otherwise, a fixed effect model was applied. Publication bias was estimated using the funnel plot and Egger's test. The doseresponse relationship was assessed using the method of restricted cubic splines with 4 knots at percentiles 5, 35, 65, and 95 of the distribution. RESULTS: The pooled RR of lung cancer for the highest versus lowest categories of dietary vitamin E intake was 0.84 (95% CI=0.76-0.93). With every 2 mg/d increase in dietary vitamin E intake, the risk of lung cancer statistically decreased by 5% (RR=0.95, 95% CI =0.91-0.99, plinearity=0.0237). CONCLUSIONS: Our analysis suggests that higher dietary vitamin E intake exerts a protective effect against lung cancer.

[Mutation screening of RET proto-oncogene in Chinese sporadic patients with pheochromocytoma].

OBJECTIVE: To screen the mutations of RET proto-oncogene in sporadic patients with pheochromocytoma. METHODS: Forty-two cases of sporadic pheochromocytoma were tested for mutations of RET gene. Of these 42 DNA samples, 12 were extracted from peripheral blood cells and 30 from paraffin-embedded pheochromocytoma specimens. The PCR product of exon 10 and exon 11 was used to molecular analysis of the RET proto-oncogene. RESULTS: Among 42 patients, 2 were found to have RET gene mutations. One of mutations located at codon 634 (TGC>TAC) in exon 11 of RET proto-oncogene. Another one located at codon 632 (GAG>AAG). CONCLUSION: Some patients with apparently sporadic pheochromacytoma were carrier of mutations, a routine genetic analysis for mutations of RET gene is indicated for these patients.

Correlating blood levels of 8-hydroxydeoxyguanosine to hOGG1 genotypes and the incidence of ischemic cardiomyopathy.

We measured the serum levels of 8-hydroxydeoxyguanosine (8-OHdG) and investigated whether these levels correlate with incidence of ischemic cardiomyopathy (ICM), and whether these levels correlate with underlying oxidative stress in patients with ICM. Polymerase chain reaction-restriction fragment length polymorphism analysis was performed to assess the prevalence of the Ser/Cys polymorphism in the human 8-oxoguanine glycosylase (hOGG1) gene. We analyzed the samples from 246 ICM cases (the ICM group) and another 246 age- and sex-matched volunteers with normal coronary artery function (the control group). Levels of 8-OHdG in participants' blood samples were 6.7 ± 1.7 and 3.0 ± 0.8 in the ICM and control groups, respectively (p < 0.05). Although there were no differences in allele frequency (p = 0.140), significant differences were present in the genotype distributions (p = 0.002). The Cys/Cys genotype correlated strongly with the risk of developing ICM (odds ratio, 2.2; 95% confidence interval, 1.4-3.3). Treating the Ser/Ser and Ser/Cys genotypes as members of the same group increased the predicted ICM risk for patients carrying the Cys/Cys genotype (odds ratio, 1.9; 95% confidence interval, 1.2-2.9). The serum level of 8-OHdG in the ICM group was higher than that in the control group (p < 0.05) and significantly increased in those carrying the Cys/Cys genotype (8.7 ± 1.7 for the Cys/Cys group, and 4.5 ± 0.8 for the Ser/Ser+Ser/Cys group; p < 0.05). Patients carrying the Cys/Cys genotype had a significantly increased risk of developing ICM. Serum levels of 8-OHdG were significantly increased in patients with ICM.

Assessment of mitochondrial DNA mutations in Chinese family with essential hypertension.

Mitochondrial DNA (MtDNA) mutations played an important role in the development of essential hypertension. Mitochondrial tRNA point mutations, caused the failure in tRNA metabolism, responsible for the pathogenesis of this complex disease. In this study, we evaluated the possible role of the 4329C >G mutation in the clinical expression of hypertension in a Chinese family. Analysis of the complete mtDNA sequence variants showed that other mutations may play synergic roles in the phenotypic manifestation of hypertension. In addition, other potential pitfalls were also discussed in this context.

Impact of the complexity of bifurcation lesions treated with drug-eluting stents: the DEFINITION study (Definitions and impact of complEx biFurcation lesIons on clinical outcomes after percutaNeous coronary IntervenTIOn using drug-eluting steNts).

OBJECTIVES: The present study established criteria to differentiate simple from complex bifurcation lesions and compared 1-year outcomes stratified by lesion complexity after provisional stenting (PS) and 2-stent techniques using drug-eluting stents. BACKGROUND: Currently, no criterion can distinguish between simple and complex coronary bifurcation lesions. Comparisons of PS and 2-stent strategies stratified by lesion complexity have also not been reported previously. METHODS: Criteria of bifurcation complexity in 1,500 patients were externally tested in another 3,660 true bifurcation lesions after placement of drug-eluting stents. The primary endpoint was the occurrence of a major adverse cardiac event (MACE) at 12 months. The secondary endpoint was the rate of stent thrombosis (ST). RESULTS: Complex (n = 1,108) bifurcation lesions were associated with a higher 1-year rate of MACE (16.8%) compared with simple (n = 2,552) bifurcation lesions (8.9%) (p < 0.001). The in-hospital ST and 1-year target lesion revascularization rates after 2-stent techniques in the simple group (1.0% and 5.6%, respectively) were significantly different from those after PS (0.2% [p = 0.007] and 3.2% [p = 0.009], respectively); however, 1-year MACE rates were not significantly different between the 2 groups. For complex bifurcation lesions, 2-stent techniques had lower rates of 1-year cardiac death (2.8%) and in-hospital MACE (5.0%) compared with PS (5.3%, p = 0.047; 8.4%, p = 0.031). CONCLUSIONS: Complex bifurcation lesions had higher rates of 1-year MACE and ST. The 2-stent and PS techniques were overall equivalent in 1-year MACE. However, 2-stent techniques for complex lesions elicited a lower rate of cardiac death and in-hospital MACE but higher rates of in-hospital ST and revascularization at 1 year for simple lesions.