| BackgroundSick sinus syndrome(SSS) is manifestation of sinus node dysfunction(SND), and it consists of various arrhythmia because of abnormal pacing of sino-atrial node (SAN) or sinoatrial conduction obstacle resulted from lesions of SAN and surrounding tissue. Brady-tachy arrhythmia syndrome is a common type of SSS, and it often represents paroxysmal atrial fibrillation(PAF) on basis of sinus bradycardia. The tendency of patients with SSS to suffer from paroxysmal atrial tachycardia including PAF is one part of the natural development of the disease, and PAF not only can cause continuous atrial fibrillation, increase incidence of embolism complications, still can cause left atrium expansion and left ventricular disfunction.Patients with SSS usually suffer from brady-tachy arrhythmia syndrome. Because treatment of these patients involves the use of a pacemaker to reduce the occurrence of bradycardia, these patients are typically treated with drugs to prevent or reduce the occurrence AF. Amiodarone is one of the most commonly used drugs with proven therapeutic value in reducing AF. Patients with SSS who have a history of PAF after dual-chamber pacemaker implantation still have a high incidence of PAF, even though the patients were treated with amiodarone to eliminate arrhythmia. Reasonable application of the non-antiarrhythmic drugs to reduce and prevent the recurrence of AF is one of the research direction of today. This study was focused on determining how to further reduce the occurrence of PAF. In recent years, with the announcement of a series of large-scale multicenter randomized clinical trials such as 4S, LIPID, CARE, WOSCOPS and so on, people realized that statins had more benefical function other than lipid-lowering, these beneficial effects independent of cholesterol-lowering role was called statins pleiotropic effects.One of these effects is the prevention of the occurrence and recurrence of AF. Statins have been shown to play a role in maintaining the sinus rhythm in patients who developed PAF along with coronary disease, hypertension and cardiac insufficiency. Gillis et al concluded that patients with sinus node disease and paroxysmal AF after dual-chamber pacemaker implantation treated with statins had a much smaller incidence of AF recurrence and reduced AF load compared to patients in a control group. Research by Tsai et al showed that atorvastatin can suppress the occurrence of PAF after implantation of an atrial-based or dual-chamber pacemaker. However, whether statins can further inhibit the occurrence of PAF in amiodarone treated patients with SSS has not yet been reported.This research is aimed at this problem.Objectives1. To determine the effectiveness of atorvastatin treatment combined with amiodarone on reducing the occurrence of PAF and apoplexia in patients with SSS.2. To determine the effectiveness of atorvastatin on the prevention of PAF after dual-chamber pacemaker implantation.3. To determine the clinical application value of AHREs recorded by the pacemaker.Research Methods1. Clinical dataIn this study,94 patients who had undergone implantation of a dual-chamber pacemaker (Medtronic Kappa700, Adapt or EnPulse series) due to SSS and PFA between January 2007 to August 2009 were enrolled and were devided into treatment and control groups for the follow-up of 12 months. Following standard therapy practices, patients in the control group (n=46) were treated with amiodarone after dual-chamber pacemaker implantation. Patients in the treatment group (n=48) took amiodarone combined with atorvastatin at a dosage of 20 mg/day until the end of the study.2. Methods2.1 General data collectionPatients were visited 1,3, and 6 months after surgery and then every 6 months. If visited patients suffered from precordium unfitness symptoms, they were asked to take an electrocardiogram examination in a nearby hospital to verify the occurrence of PFA. The date and duration of every PFA occurrence were recorded.2.2 MeasurementThe detection of high sensitive C-reactive protein (hsCRP) was conducted using a CX7 automatic biochemistry analyzer produced by American Beckman Coulter. The normal reference range was 0.01～3 mg/L. The kit was provided by Beijing Leadman Biochemical Technology Co., Ltd.Biochemical indicators such as blood lipid, Blood fat, and Liver function, were detected by HITACHI 7060 automatic biochemistry analyzer detection. TSH was detected by American Roche's production of electrochemical luminescence immune analyzer.2.3 Criteria for judging clinical effectivenessSignificantly effective:PAF disappeared,or occurred less once a month, or the duration of PAF was less than 5% of the time experienced before surgery; effective: the frequency or duration of PFA occurrence was less than 50% of that before surgery; ineffective:did not reach the previous standards; relapse:the frequency and duration of PFA was the same as before treatment.2.4 Pacemaker-associated settingsAHREs are high frequency events recorded in the internal memory of the pacemaker. The minimum detectable frequency of AHREs was 175-180 times/minute (generally. AHREs were recorded automatically if they occur continually during more than 3 cardiac cycles). During the visits, the pacemaker memories were recorded. The frequency of AHRE occurrence (time/year, those that were longer than 5 minutes were recorded), the duration of the AHREs (hours/year), the percentage of atrial pace-making (AP%) and the percentage of ventricular pace-making (VP%) were recorded.2.5 Methods of follow-upAll patients were observed and follow-up for 12 months and the frequency of AF, the duration of AF, visit data of pacemaker as well as occurrence of cerebral apoplexy were all recorded.3 Statistical analysisThe SPSS 16.0 software package was used for statistical analysis. The measurement data follow a normal distribution represented by means±SD.t tests andχ2 tests were used to analyze the data differences between the 2 groups. Correlation analysis of single influence factors of stroke was made by Spearman rank correlation analysis, indexes with statistically significance were introduced into logistic multivariate linear regression analysis. ROC curves were used to judge the prognostic value of variables.Results1. Comparisons of clinical data of two groups92 cases completed the study. The index variables at baseline did not have any statistical significance between two groups.2. Comparison of AF therapeutic effectiveness between two groupsFollowing treatment, the frequency and duration of AF in two groups showed significant reduction compared to the frequency and duration observed before treatment (P<0.05). The total effectiveness of reducing AF in both groups was over 90%. Compared to the control group, there was a significant (P<0.01) reduction in the frequency and the duration of PAF in the treatment group along with an additional increase in total treatment effectiveness and a decrease in apoplexia incidence. 3. Comparison of hsCRP levels, LAD and blood lipid level between two groupsThe hsCRP levels following treatment in both two groups showed a significant reduction when compared to levels observed prior to treatment (P<0.05). After treatment, treatment group hsCRP levels showed a marked decrease compared to the control group. LAD between treatment group and control group did not attain significance. After treatment, the level of TC, TG, and LDL-C decreased significantly in the treatment group, and HDL-C increased significantly. These changes were also significant when compared with lipid values in the control group after treatment.4. Comparison of drug safety indexes between two groupsAfter treatment, the level of cereal third transaminase, creatine kinase and TSH did not show any statistical significance between two groups. And again the difference did not attain significance when compared with the indexes before treatment.5. Comparison of visit pacemaker data between two groupsThe times and duration of AHREs in the treatment group was significantly smaller than what was observed in the control group (P<0.05). Comparisons of AP% and VP% between groups did not show significant difference.6. Correlation analysis of hsCRP with clinical and pacemaker dataHsCRP level during follow-up respectively correlated well with the frequency and duration of AF, AHREs times, AHREs duration as well as apoplexia.7. Correlation analysis of statins application with AF dataStatins application negatively correlated with the duration of AF and with AHREs duration.8. Comparisons of clinical data of stroke group and non-stroke groupDuring the follow-up,17 patients suffered from cerebral apoplexy,5 in the treatment group and 12 in the control group. Statins application, VP%, hsCRP during follow-up, the frequency of AF during follow-up, the duration of AF during follow-up, AHREs times, AHREs duration all had statistical significance between stroke group and non-stroke group. 9. Correlation analysis of Research factors with apoplexiaAmong all the research factors,8 factors (age, statins application, VP%, hsCRP level during follow-up, the frequency of AF during follow-up, the duration of AF during follow-up, AHREs times and AHREs duration) respectively correlated well with apoplexia.10. Multi-factor analysis of factors that influerce apoplexiaIntroduced the above 8 factors into logistic multivariate linear regression analysis and got the results as follows:statins application, age>60, AHREs durations 12.5 h entered the regression model, were all independent risk factors for forecasting apoplexia. Patients applied with statins had 35% of the risk to suffer from apoplexia (OR=0.352, p=0.089), thus statin application was a protect factor for prevent apoplexia. Patients older than 60 years had 6-fold the risk to suffer from apoplexia(OR=6.043, p=0.014). Patients with AHREs>12.5h had 30-fold the risk to suffer from apoplexia(OR=30.363, p=0.047).11. ROCcurveROC curve show that, among all the 8 correlative factors,5 factors(age, the frequency of AF during follow-up, the duration of AF during follow-up, AHREs times and AHREs duration) respectively had a p value smaller than 0.05, while the area under the curve of hsCRP levels during follow-up and of the duration of AF during follow-up was>0.7. Thus these factors had certain predict value for apoplexia, but the predict value was moderate.12. Correlation analysis of AHREs recorded by pacemaker and clinical dataThe frequency and duration of AF respectively correlated well with AHREs times and AHREs duration recorded by pacemaker.Conclusions1. Aatorvastatin, when combined with amiodarone, can further decrease the frequency and duration of AF after dual-chamber pacemaker implantation, it is possible that the mechanism may have a relationship to the anti-inflammatory actions of statins.2. Atorvastatin, when combined with amiodarone, can further decrease the incidence of apoplexia after dual-chamber pacemaker implantation, it is possible that the mechanism may have a relationship to the anti-AF and anti-inflammatory actions of statins.3. AHREs recorded by pacemaker correlate well with frequency and duration of AF recorded by patients and can be applied in clinical studies to forecast apoplexia4. HsCRP levels during follow-up correlate well with occurrence of AF and with apoplexia.. BackgroundSick sinus syndrome(SSS) is manifestation of sinus node dysfunction(SND), and it consists of various arrhythmia including sinus bradycardia, sinus arrest, sinoatrial block and brady-tachy arrhythmia syndrome. Brady-tachy arrhythmia syndrome is a common type of SSS, and it often represents paroxysmal atrial fibrillation (PAF) on basis of sinus bradycardia. The tendency of patients with SSS to suffer from paroxysmal atrial tachycardia including PAF is one part of the natural development of the disease, and PAF not only can cause continuous atrial fibrillation, increase incidence of embolism complications, still can cause left atrium expansion and left ventricular disfunction.Patients with brady-tachy arrhythmia syndrome are typically treated with drugs to prevent or reduce the occurrence AF on basis of the use of a pacemaker to reduce the occurrence of bradycardia. SSS Patients with a history of PAF and related symptoms, no bradycardia-related symptoms, donot need the treatment of implantation of a permanent pacemaker, but these patients could not tolerate therapy with antiarrhythmic drugs, such as amiodarone or P-blockers. Thus these patients often have high incidence of PAF, often suffer from obvious palpitations, declined exercise tolerance, deteriorating cardiac function, even serious complications of artery embolization, such as cerebral embolism and peripheral artery embolization, which may make mortality increased to 2-3 times and the morbidity had further increase. For these patients, the rational use of non-antiarrhythmic drugs to inhibit or prevent the recurrence of PAF is of clinical significance.In recent years, Statins have been shown to play a role in maintaining the sinus rhythm in patients who developed PAF along with coronary disease, hypertension and cardiac insufficiency. Foreign researchers found that statins can suppress the occurrence of PAF after implantation of an atrial-based or dual-chamber pacemaker. However, the application of statins in SSS patients who do not have implanted pacemakers has not been reported. Objectives1. To determine the effectiveness of atorvastatin treatment on reducing the occurrence of PAF and apoplexia in patients with SSS.2. To determine the clinical application value of atorvastatin on the prevention of PAF in SSS patients who do not have implanted pacemakers.Research Methods1. Clinical dataIn this study, 62 SSS Patients with a history of PAF and did not reach the indication of pacemaker implantation between January 2007 to September 2009 were enrolled and were devided into treatment and control groups for the follow-up of 12 months. During follow-up, the control group (n = 32) was given conventional therapy while patients in the treatment group (n=32) took atorvastatin at a dosage of 20 mg/day in addition to their other medications until the end of the study.2. Methods2.1 General data collectionIf hospitalized patients had palpitations and other symptoms, they were examined by electrocardiogram (ECG) or monitored by dynamic electrocardiogram (DCG). Follow-up visits were conducted by means of our outpatient clinic service12 months after disrharcre from hospital.During this period, patients with symptoms such as palpitations were seen by a doctor in their local hospital for ECG examination to confirm the PAF. Patients were asked to record the date and duration of the PAF event at every occurrence.2.2 MeasurementThe detection of high-sensicitive c-reactive protein (hsCRP) was conducted using a CX7 automatic biochemistry analyzer produced by American Beckman Coulter. The normal reference range was 0.01 ~3 mg/L. The kit was provided by Beijing Leadman Biochemical Technology Co., Ltd.Biochemical indicators such as blood lipid, Blood fat, and Liver function, are detected by HITACHI 7060 automatic biochemistry analyzer detection.2.3 Methods of follow-upAll patients were observed and follow-up for 12 months and the frequency of AF, the duration of AF as well as occurrence of cerebral apoplexy were all recorded.3. Statistical analysisThe SPSS 16.0 software package was used for statistical analysis, t tests and x2 tests were used to analyze the data differences between the 2 groups. Correlation analysis of single influence factors of stroke was made by Spearman rank correlation analysis, indexes with statistically significance were introduced into logistic multivariate linear regression analysis. ROC curves were used to judge the prognostic value of variables.Results1. Comparison of clinical features before treatment between groupsOne patient in control group withdrew from the study because of severe renal insufficiency. 3 patients in the treatment group and 5 in the control group withdrew from the study because of increasingly serious symptoms and acceptance of permanent cardiac pacemakers. Thus, the actual number of analyzed cases in the treatment group is 27, and 26 in the control group. There was no significance between the groups in clinical features before treatment.2.Comparison of PAF times and duration between groups The frequency and duration of AF in the treatment group was significantly reduced (P = 0.0026 and P = 0.019, respectively) compared with that in the control group after treatment. The duration of AF in the control group was significantly increased (P = 0.027) compared with that before treatment. The incidence of apoplexia in the treatment group(14.8%) had a tendency to decrease than that in the control group(30.8%), but this trend did not attain significance (P =0.165).3. Comparison of hsCRP levels, LAD and blood lipid level between two groupsAfter treatment, treatment group hsCRP levels showed a marked decrease compared to the control group(.P<0. 001). LAD between treatment group and control group did not attain significance. After treatment, the level of TC, TG, and LDL-C decreased significantly in the treatment group, and HDL-C increased significantly. These changes were also significant when compared with lipid values in the control group after treatment.4. Comparison of drug safety indexes between two groupsAfter treatment, the level of cereal third transaminase, creatine kinase and TSH did not show any statistical significance between two groups. And again the difference did not attain significance when compared with the indexes before treatment.5. Correlation analysis of hsCRP with clinical dataHsCRP level during follow-up respectively correlated well with the frequency and duration of AF as well as with apoplexia.6. Correlation analysis of statins application with AF dataStatins application negatively correlated with the frequency and duration of AF.7. Comparisons of clinical data of stroke group and non-stroke groupDuring the follow-up, 12 patients suffered from cerebral apoplexy, 4 in the treatment group and 8 in the control group. HsCRP during follow-up, the frequency of AF during follow-up, the duration of AF during follow-up all had statistical significance between stroke group and non-stroke group.8. Correlation analysis of Research factors with apoplexia Among all the research factors, 3 factors (hsCRP level during follow-up, the frequency of AF during follow-up, the duration of AF during follow-up) respectively correlated well with apoplexia.9. Multi-factor analysis of factors that influerce apoplexiaIntroduced the above 3 factors into logistic multivariate linear regression analysis and got the results as follows: the frequency of AF during follow-up>13 entered the regression model, which was an independent risk factor for forecasting apoplexia. Patients with the frequency of AF during follow-up>13 had 7-fold the risk to suffer from apoplexia(OR=7.059, P=0.020).10. ROC curveROC curve show that, all the 3 correlative factors respectively had a p value smaller than 0.05, while the area under the curve of the frequency of AF and of the duration of AF during follow-up was >0.7. Thus these factors had certain predict value for apoplexia.Conclusions1. Atorvastatin can reduce the occurrence of PAF in SSS patients who do not have implanted pacemakers. The mechanism may be related to the role of statins in lipid lowering and antiinflammatory effects.2. The frequency and the duration of AF during follow-up respectively correlated well with apoplexia.3. HsCRP levels during follow-up correlate well with occurrence of AF and with apoplexia.
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