Impact of Triple Therapy in Elderly Patients with Atrial Fibrillation Undergoing Percutaneous Coronary Intervention

Background and Purpose

Selecting an ideal antithrombotic therapy for elderly patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) can be challenging since they have a higher thromboembolic and bleeding risk than younger patients. The current study aimed to assess the efficacy and safety of triple therapy (TT: oral anticoagulation plus dual antiplatelet therapy: aspirin plus clopidogrel) in patients ≥75 years of age with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI).

Methods

A prospective multicenter study was conducted from 2003 to 2012 at 6 Spanish teaching hospitals. A cohort study of consecutive patients with AF undergoing PCI and treated with TT or dual antiplatelet therapy (DAPT) was analyzed. All outcomes were evaluated at 1-year of follow-up.

Results

Five hundred and eighty-five patients, 289 (49%) of whom were ≥75 years of age (79.6±3.4 years; 33% women) were identified. TT was prescribed in 55.9% of patients at discharge who had a higher thromboembolic risk (CHA₂DS₂VASc score: 4.23±1.51 vs 3.76±1.40, p = 0.007 and a higher bleeding risk (HAS-BLED ≥3: 88.6% vs 79.2%, p = 0.02) than those on DAPT. Therefore, patients on TT had a lower rate of thromboembolism than those on DAPT (0.6% vs 6.9%, p = 0.004; HR 0.08, 95% CI: 0.01–0.70, p = 0.004). Major bleeding events occurred more frequently in patients on TT than in those on DAPT (11.7% vs 2.4%, p = 0.002; HR 5.2, 95% CI: 1.53–17.57, p = 0.008). The overall mortality rate was similar in both treatment groups (11.9% vs 13.9%, p = 0.38); however, after adjustment for confounding variables, TT was associated with a reduced mortality rate (HR 0.33, 95% CI: 0.12–0.86, p = 0.02).

Conclusions

In elderly patients with AF undergoing PCI, the use of TT compared to DAPT was associated with reduced thromboembolism and mortality rates, although a higher rate of major bleeding.     

冠状动脉介入术中对比剂应用对肾功能影响的研究

目的:观察冠状动脉介入术后患者肾功能变化情况、CIN发生率及其相关危险因素。方法:选择从2009年12月至2010年3月在新疆维吾尔自治区人民医院心内科接受冠状动脉介入术的患者131人,测定介入术前5天内任何一天和术后48小时的Scr,分析CIN危险因素。结果:131例患者中有8例发生CIN,发病率为6.1%,Logistic多因素回归分析均显示糖尿病、年龄大于70岁、LVEF小于45%是CIN发生的独立危险因素。结论:糖尿病、LVEF<45%、年龄>70岁是CIN的独立危险因素。     

冠状动脉介入术中对比剂应用对肾功能影响的研究

目的：观察冠状动脉介入术后患者肾功能变化情况、CIN发生率及其相关危险因素。方法：选择从2009年12月至2010年3月在新疆维吾尔自治区人民医院心内科接受冠状动脉介入术的患者131人,测定介入术前5天内任何一天和术后48小时的Scr,分析CIN危险因素。结果：131例患者中有8例发生CIN,发病率为6.1%,Logistic多因素回归分析均显示糖尿病、年龄大于70岁、LVEF小于45%是CIN发生的独立危险因素。结论：糖尿病、LVEF〈45%、年龄〉70岁是CIN的独立危险因素。     

Renal Denervation Suppresses Atrial Fibrillation in a Model of Renal Impairment

BackgroundA close association exists between renal impairment (RI) and atrial fibrillation (AF) occurrence. Increased activity of the sympathetic nervous system (SNS) may contribute to the development of AF associated with RI. Renal denervation (RDN) decreases central sympathetic activity.ObjectiveThe main objective of the study was to explore the effects of RDN on AF occurrence and its possible mechanisms in beagles with RI.MethodsUnilateral RI was induced in beagles by embolization of small branches of the renal artery in the right kidney using gelatin sponge granules in Model (n = 6) and RDN group (n = 6). The Sham group (n = 6) underwent the same procedure, except for embolization. Then animals in RDN group underwent radiofrequency ablation of the renal sympathetic nerve. Cardiac electrophysiological parameters, blood pressure, left ventricular end-diastolic pressure, and AF inducibility were investigated. The activity of the SNS, renin-angiotensin-aldosterone system (RAAS), inflammation and atrial interstitial fibrosis were measured.ResultsEmbolization of small branches of the renal artery in the right kidney led to ischemic RI. Heart rate, P wave duration and BP were increased by RI, which were prevented or attenuated by RDN. Atrial effective refractory period was shortened and AF inducibility was increased by RI, which were prevented by RDN. Antegrade Wenckebach point was shortened, atrial and ventricular rates during AF were increased by RI, which were attenuated or prevented by RDN. Levels of norepinephrine, renin and aldosterone in plasma, norepinephrine, angiotensin II, aldosterone, interleukin-6 and high sensitivity C-reactive protein in atrial tissue were elevated, and atrial interstitial fibrosis was enhanced by RI, which were attenuated by RDN.ConclusionsRDN significantly reduced AF inducibility, prevented the atrial electrophysiological changes in a model of RI by combined reduction of sympathetic drive and RAAS activity, and inhibition of inflammation activity and fibrotic pathway in atrial tissue.     

Galectin-3 in Patients with Atrial Fibrillation Undergoing Radiofrequency Catheter Ablation

Background

Galectin-3 (Gal-3) is an emerging biomarker in heart failure that is involved in fibrosis and inflammation. However, its potential value as a prognostic marker in atrial fibrillation (AF) is unknown. The aim of this study was to assess the impact of AF catheter ablation on Gal-3 and evaluate its prognostic impact for predicting rhythm outcome after catheter ablation.

Methods

Gal-3 was measured at baseline and after 6 months using specific ELISA. AF recurrences were defined as any atrial arrhythmia lasting longer than 30 sec within 6 months after ablation.

Results

In 105 AF patients (65% males, age 62±9 years, 52% paroxysmal AF) undergoing catheter ablation, Gal-3 was measured at baseline and after 6 months and compared with an AF-free control cohort (n=14, 50 % males, age 58±11 years). Gal-3 was higher in AF patients compared with AF-free controls (7.8±2.9 vs. 5.8±1.8, ng/mL, p=0.013). However, on multivariable analysis, BMI (p=0.007) but not AF (p=0.068) was associated with Gal-3. In the AF cohort, on univariable analysis higher Gal-3 levels were associated with female gender (p=0.028), higher BMI (p=0.005) and both CHADS2 (p=0.008) and CHA2DS2-VASC (p=0.016) scores, however, on multivariable analysis only BMI remained significantly associated with baseline Gal-3 (p=0.016). Gal-3 was similar 6 months after AF catheter ablation and was not associated with sinus rhythm maintenance.

Conclusions

Although galectin-3 levels are higher in AF patients, this is driven by cardiometabolic co-morbidities and not heart rhythm. Gal-3 is not useful for predicting rhythm outcome of catheter ablation.     

Establishment of a Model of Renal Impairment with Mild Renal Insufficiency Associated with Atrial Fibrillation in Canines

Background

Chronic kidney disease and occurrence of atrial fibrillation (AF) are closely related. No studies have examined whether renal impairment (RI) without severe renal dysfunction is associated with the occurrence of AF.

Methods

Unilateral RI with mild renal insufficiency was induced in beagles by embolization of small branches of the renal artery in the left kidney for 2 weeks using gelatin sponge granules in the model group (n = 5). The sham group (n = 5) underwent the same procedure, except for embolization. Parameters associated with RI and renal function were tested, cardiac electrophysiological parameters, blood pressure, left ventricular pressure, and AF vulnerability were investigated. The activity of the sympathetic nervous system, renin-angiotensin-aldosterone system, inflammation, and oxidative stress were measured. Histological studies associated with atrial interstitial fibrosis were performed.

Results

Embolization of small branches of the renal artery in the left kidney led to ischemic RI with mild renal insufficiency. The following changes occurred after embolization. Heart rate and P wave duration were increased. Blood pressure and left ventricular systolic pressure were elevated. The atrial effective refractory period and antegrade Wenckebach point were shortened. Episodes and duration of AF, as well as atrial and ventricular rate during AF were increased in the model group. Plasma levels of norepinephrine, renin, and aldosterone were increased, angiotensin II and aldosterone levels in atrial tissue were elevated, and atrial interstitial fibrosis was enhanced after 2 weeks of embolization in the model group.

Conclusions

We successfully established a model of RI with mild renal insufficiency in a large animal. We found that RI with mild renal insufficiency was associated with AF in this model.     

急性心肌梗死行PCI患者炎症因子的检测及其与预后的关系

目的:探讨急性心肌梗死行经皮冠状动脉介入治疗(PCI)血清炎症因子的改变及其与预后的关系。方法:选择126例拟行PCI治疗的急性心肌梗死患者为研究对象,比较PCI手术前后血清超敏C反应蛋白(hs-CRP)及肿瘤坏死因子α(TNF-α)的改变。同时比较PCI术后3月发生心血管事件患者与未发生心血管事件患者术后12h血清hs-CRP及TNF-α的差别。结果:患者PCI术后血清hs-CRP及TNF-α水平均显著升高,与术前相比差别具有统计学意义(P<0.05);PCI术后3月发生心血管事件患者PCI术后12h血清hs-CRP及TNF-α水平显著高于未发生心血管事件患者(P<0.05);Logistic回归结果显示:hs-CRP及TNF-α与心血管事件发生率显著相关。结论:急性心肌梗死行PCI患者术后发生急性炎症反应,hs-CRP及TNF-α水平升高与患者心血管事件发生密切相关,可作为评估预后的血清学指标。     

High Platelet Reactivity in Patients with Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention: Randomised Controlled Trial Comparing Prasugrel and Clopidogrel

Background

Prasugrel is more effective than clopidogrel in reducing platelet aggregation in acute coronary syndromes. Data available on prasugrel reloading in clopidogrel treated patients with high residual platelet reactivity (HRPR) i.e. poor responders, is limited.

Objectives

To determine the effects of prasugrel loading on platelet function in patients on clopidogrel and high platelet reactivity undergoing percutaneous coronary intervention for acute coronary syndrome (ACS).

Patients

Patients with ACS on clopidogrel who were scheduled for PCI found to have a platelet reactivity ≥40 AUC with the Multiplate Analyzer, i.e. “poor responders” were randomised to prasugrel (60 mg loading and 10 mg maintenance dose) or clopidogrel (600 mg reloading and 150 mg maintenance dose). The primary outcome measure was proportion of patients with platelet reactivity <40 AUC 4 hours after loading with study medication, and also at one hour (secondary outcome). 44 patients were enrolled and the study was terminated early as clopidogrel use decreased sharply due to introduction of newer P2Y12 inhibitors.

Results

At 4 hours after study medication 100% of patients treated with prasugrel compared to 91% of those treated with clopidogrel had platelet reactivity <40 AUC (p = 0.49), while at 1 hour the proportions were 95% and 64% respectively (p = 0.02). Mean platelet reactivity at 4 and 1 hours after study medication in prasugrel and clopidogrel groups respectively were 12 versus 22 (p = 0.005) and 19 versus 34 (p = 0.01) respectively.

Conclusions

Routine platelet function testing identifies patients with high residual platelet reactivity (“poor responders”) on clopidogrel. A strategy of prasugrel rather than clopidogrel reloading results in earlier and more sustained suppression of platelet reactivity. Future trials need to identify if this translates into clinical benefit.

Trial Registration

ClinicalTrials.gov NCT01339026     

医患通平台在经皮冠状动脉介入治疗术后患者中的应用

目的:探讨医患通平台对经皮冠状动脉介入治疗(PCI)术后患者进行护理的临床效应。方法:选取54例冠心病行PCI治疗术后患者,随机分为对照组和试验组,各27例。对照组采用常规护理,试验组在对照组的基础上采用医患通平台进行护理干预,比较两组患者血压、血脂、血糖的控制情况,主要不良心脏事件(MACE)的发生情况,并采用汉密尔顿焦虑量表(HAMA)及汉密尔顿抑郁量表(HAMD)对两组患者进行心理状况调查。结果:实施干预后,试验组血压、血脂、血糖的控制率优于对照组(P0.05),MACE的发生率低于对照组(P0.05);两组患者两组干预前HAMA、HAMD评分比较无明显差异(P0.05),干预后试验组患者HAMA评分、HAMD评分有所下降,与干预前及对照组比较差异显著(P0.01),对照组干预前后无变化(P0.05)。结论:医患通平台能有效地让PCI术后患者对危险因素进行控制,降低MACE的发生,改善患者的负性情绪,是较好的健康教育方式。     

Plasma Asymmetric Dimethylarginine and Adverse Events in Patients with Atrial Fibrillation Referred for Coronary Angiogram

Objectives

Elevated plasma levels of asymmetric dimethylarginine (ADMA) have been reported to be associated with endothelial dysfunction, inflammation, and oxidative stress in multiple cardiovascular diseases. This study aimed to investigate whether ADMA was a predictor of clinical outcomes in atrial fibrillation (AF).

Methods and Results

From 2006-2009, 990 individuals were referred to our institution for coronary angiography. Among these patients, 141 subjects with a diagnosis of AF, including 52 paroxysmal AF (PAF) and 89 non-paroxysmal AF (non-PAF) patients, were identified as the study population. Plasma ADMA levels were measured. An adverse event was defined as the occurrence of ischemic stroke or cardiovascular death. The ADMA levels were higher in AF than non-AF patients (0.50±0.13 versus 0.45±0.07 µmol/L; p<0.001). Besides, non-PAF patients had higher ADMA levels than PAF patients (0.52±0.15 versus 0.48±0.08 µmol/L; p<0.001). During the follow-up of 30.7±14.4 months, 21 patients (14.9%) experienced adverse events, including cardiovascular death in 7 patients and ischemic stroke in 14. ADMA level, CHA₂DS₂-VASc score, and left atrial diameter were independent predictors of adverse events in the multivariate analysis. At a cutoff-value of 0.55 µmol/L, the Kaplan-Meier survival analysis showed that patients with a high ADMA level had a higher event rate during the follow-up period.

Conclusions

A higher level of ADMA was a risk factor of adverse events in AF patients, which was independent from the CHA₂DS₂-VASc score. It deserves to further study whether ADMA could potentially refine the clinical risk stratification in AF.     

饮食提示卡在经皮冠状动脉介入治疗术后患者中的应用

目的：探讨饮食提示卡在经皮冠状动脉介入治疗（PCI）术后患者护理中的临床效应。方法：选取62例冠心病行PCI治疗术后患者,随机分为对照组和试验组,各31例。对照组采用常规护理,试验组在对照组的基础上采用饮食提示卡进行护理干预,比较两组患者血压、血脂、血糖的控制情况,饮食知识的知晓率,治疗的依从性以及护理的满意度。结果：实施干预后．试验组血压、血脂、血糖的控制率优于对照组（P〈0．05）,饮食知识知晓率高于对照组（P〈0．01）,治疗的依从性与护理的满意度优于对照组（P〈0．01）。结论：饮食提示卡能使PCI术后患者对危险因素进行有效地控制,提高对知识的掌握,增加治疗的依从性,提高护理质量。     

饮食提示卡在经皮冠状动脉介入治疗术后患者中的应用

目的:探讨饮食提示卡在经皮冠状动脉介入治疗(PCI)术后患者护理中的临床效应。方法:选取62例冠心病行PCI治疗术后患者,随机分为对照组和试验组,各31例。对照组采用常规护理,试验组在对照组的基础上采用饮食提示卡进行护理干预,比较两组患者血压、血脂、血糖的控制情况,饮食知识的知晓率,治疗的依从性以及护理的满意度。结果:实施干预后,试验组血压、血脂、血糖的控制率优于对照组(P0.05),饮食知识知晓率高于对照组(P0.01),治疗的依从性与护理的满意度优于对照组(P0.01)。结论:饮食提示卡能使PCI术后患者对危险因素进行有效地控制,提高对知识的掌握,增加治疗的依从性,提高护理质量。     

Additive Effect of Anemia and Renal Impairment on Long-Term Outcome after Percutaneous Coronary Intervention

Introduction

Anemia and renal impairment are important co-morbidities among patients with coronary artery disease undergoing Percutaneous Coronary Intervention (PCI). Disease progression to eventual death can be understood as the combined effect of baseline characteristics and intermediate outcomes.

Methods

Using data from a prospective cohort study, we investigated clinical pathways reflecting the transitions from PCI through intermediate ischemic or hemorrhagic events to all-cause mortality in a multi-state analysis as a function of anemia (hemoglobin concentration <120 g/l and <130 g/l, for women and men, respectively) and renal impairment (creatinine clearance <60 ml/min) at baseline.

Results

Among 6029 patients undergoing PCI, anemia and renal impairment were observed isolated or in combination in 990 (16.4%), 384 (6.4%), and 309 (5.1%) patients, respectively. The most frequent transition was from PCI to death (6.7%, 95% CI 6.1–7.3), followed by ischemic events (4.8%, 95 CI 4.3–5.4) and bleeding (3.4%, 95% CI 3.0–3.9). Among patients with both anemia and renal impairment, the risk of death was increased 4-fold as compared to the reference group (HR 3.9, 95% CI 2.9–5.4) and roughly doubled as compared to patients with either anemia (HR 1.7, 95% CI 1.3–2.2) or renal impairment (HR 2.1, 95% CI 1.5–2.9) alone. Hazard ratios indicated an increased risk of bleeding in all three groups compared to patients with neither anemia nor renal impairment.

Conclusions

Applying a multi-state model we found evidence for a gradient of risk for the composite of bleeding, ischemic events, or death as a function of hemoglobin value and estimated glomerular filtration rate at baseline.     

房颤患者心房肌细胞的原代培养与应用

探索成功培养房颤(atrial fibrillation,AF)患者原代心房肌细胞的方法,能够为房颤发病机制的研究奠定实验基础。取心胸外科行迷宫手术患者的左心耳,利用I型胶原蛋白酶消化法培养房颤患者的原代心房肌细胞,通过免疫组化进行鉴定,同时对培养的心房肌细胞进行初步研究。与动物实验相反,房颤患者心房肌细胞缝隙连接蛋白40(connexin40,Cx40)及Kv1.5钾离子通道蛋白的表达量均降低。由此可见直接研究成人房颤患者的心房肌细胞具有更高的可靠性,同时也证明了房颤患者心房肌细胞的培养是研究其发病机制的基础。     

医患通平台在经皮冠状动脉介入治疗术后患者中的应用

目的：探讨医患通平台对经皮冠状动脉介入治疗（PCI）术后患者进行护理的临床效应。方法：选取54例冠心痛行PCI治疗术后患者,随机分为对照组和试验组,各27例。对照组采用常规护理,试验组在对照组的基础上采用医患通平台进行护理干预,比较两组患者血压、血脂、血糖的控制情况,主要不良心脏事件（MACE）的发生情况,并采用汉密尔顿焦虑量表（HAMA）及汉密尔顿抑郁量表（HAMD）对两组患者进行心理状况调查。结果：实施干预后,试验组血压、血脂、血糖的控制率优于对照组（P〈0．05）,MACE的发生率低于对照组（P〈0．05）;两组患者两组干预前HAMA、HAMD评分比较无明显差异（P〉0．05）,干预后试验组患者HAMA评分、HAMD评分有所下降,与干预前及对照组比较差异显著（P〈O．01）,对照组干预前后无变化（P〉0．05）。结论：医患通平台能有效地让PCI术后患者对危险因素进行控制,降低MACE的发生,改善患者的负性情绪,是较好的健康教育方式．     

术前参观对冠状动脉介入治疗患者焦虑的影响

目的:探讨术前参观对择期进行心脏介入术患者心理焦虑的影响。方法:将400例择期行心脏介入手术的患者分为参观组和对照组,对照组术前采用常规护理干预,参观组患者在此基础上进行术前参观,熟悉环境,了解手术过程。调查比较两组患者术前2日及术前1小时的焦虑值。结果:参观组与对照组术前2日焦虑值无明显差异,术前1小时参观组焦虑值明显低于对照组,差异具有统计学意义(P0.05)。结论:通过术前参观能够减轻患者的焦虑程度。     

Effect of Trimetazidine in Patients Undergoing Percutaneous Coronary Intervention: A Meta-Analysis

Optimizing the metabolism of the myocardium is a new strategy for patients with ischemic heart disease. Many studies have reported beneficial effects of trimetazidine (TMZ) on the clinical prognosis of patients with ischemic heart disease, but whether these beneficial effects are extended to patients undergoing percutaneous coronary intervention (PCI) remains uncertain. A meta-analysis was performed to evaluate the effect of TMZ on patients undergoing PCI. We conducted an electronic search of PubMed, Cochrane databases, the China National Knowledge Infrastructure, and Chinese Biological Medicine Database to identify randomized controlled trials. Methodological quality was assessed according to the Jadad scale score, and the meta-analysis was performed using Cochrane Collaboration RevMan 5.2 and Comprehensive Meta-Analysis. Dichotomous data were analyzed using relative risk (RR) or odds ratio (OR) with effect size indicated by the 95% confidence interval (CI), and continuous variables were analyzed using weighted mean differences (WMD) with effect size indicated by the 95% CI. Sensitivity analysis was performed by changing the statistical methods and effect model. Nine studies involving a total of 778 patients were included in this meta-analysis. Additional use of TMZ significantly improved the left ventricular ejection fraction (WMD: 3.11, 95% CI: [2.26, 3.96]) and reduced elevated cardiac troponin Ic level (RR: 0.69, 95% CI: [0.48, 0.99]), angina attacks during PCI (OR: 0.16, 95% CI: [0.07, 0.38]), and ischemic ST-T changes on the echocardiogram during PCI (RR: 0.76, 95% CI: [0.59, 0.98]). However, no significant difference was observed in serum BNP level 30 days after PCI between the experimental and control group. Additional use of TMZ for patients undergoing PCI may reduce myocardial injury during the procedure and improve cardiac function.     

胺碘酮联合厄贝沙坦治疗阵发性心房颤动的疗效观察

目的:探讨胺碘酮与厄贝沙坦联合治疗阵发性心房颤动的临床疗效。方法:将我院收治的97例阵发性心房颤动患者,随机分为观察组(N=49)和对照组(N=48)。对照组单纯服用胺碘酮,治疗组在此基础上加用厄贝沙坦。治疗随访12个月,一级观测终点为房颤复发。结果:治疗后12个月,观察组左心房内径显著小于对照组(P>0.05);治疗后6、12个月,观察组窦性维持率分别为89.8%、81.6%,对照组分别为72.9%、62.5%,两组均有统计学差异(P<0.05);治疗期间,观察组房颤复发率24.5%,显著低于对照组47.9%(P<0.05)。结论:胺碘酮联合厄贝沙坦治疗阵发性心房颤动于窦性心律的维持优于单用胺碘酮,且减少房颤复发,抑制左心房扩大。     

Plasma Digoxin Concentrations in Patients with Atrial Fibrillation

Plasma digoxin concentrations were measured by radioimmunoassay in 116 patients with atrial fibrillation on long-term oral treatment with the drug, and in 23 patients with digoxin toxicity. The mean concentrations were 1·4 ng./ml. and 3·1 ng./ml., respectively. Though an overlap occurred between the therapeutic and toxic ranges, toxicity is unlikely to occur below a level of 2 ng./ml. Plasma concentration showed a poor correlation with resting heart rate during atrial fibrillation. In patients with good renal function, however, a significant correlation was found between oral dose and plasma concentration. No evidence was obtained for increased sensitivity to therapeutic concentrations of the drug in elderly subjects, but the doses required to achieve these concentrations tended to be less than in younger patients.