| Part I Prognostic Sig-nificance of Frequent Premature Ventricular Complex Early After Implantation Among Patients with Implantable Cardioverter DefibrillatorBackground:Premature ventricular complex(PVC)facilitates imminent ventricular arrhythmia events(VAEs),shocks and cardiac death,which was mainly studied by 24-hour Holter.However,the value of long-term monitoring of PVC burden early after ICD implantation is unknown.Methods:The data of 309 patients implanted with ICD were analyzed.The number of days with frequent PVC(>10/hour)in 60-day was monitored and was calculated as the continuous frequent PVC(CfPVC)percentage.ROC curves of CfPVC percentage were plotted,Kaplan-Meier survival and Cox regression were used to assess the cumulative risks.Subgroup analysis was also performed.Results:Based on ROC curves,the cut-off value for the CfPVC percentage was 40%.In Kaplan-Meier analysis,CfPVC percentage≥40%indicated higher incidences of VAEs(HR=3.143;95%CI=2.324-4.250;p<0.0001),shocks(HR=2.609;95%CI=1.797-3.787;p<0.001),and cardiac death(HR=3.288;95%CI=1.720-6.283;p<0.001).Multivariate Cox regression analysis showed CfPVC percentage≥40%remained as an independent predictor for these outcomes.Conclusion:A long-term continuous burden of frequent PVC with CfPVC percentage>40%can be a predictor of future VAEs,shocks and cardiac death in ICD recipients.Part II The Prognostic Effects of Different β-Blockers on Heart Failure Patients with Implantable Cardioverter Defibrillator(ICD)or Cardiac Resynchronization Therapy-Defibrillator(CRT-D)1.Metoprolol with insufficient dose causes increased risks of Ventricular Arrhythmia and Appropriate Shocks in Patients with Non-Ischemic Heart Failure Implanted with ICD/CRT-DBackground:It is controversial whether one type of β-blocker is superior to another.In addition,the usage of P-blockers in real-world condition is different from clinical trials.There is a paucity in evidence concerning β-blockers in non-ischemic heart failure patients with ICD or CRT-D.Methods:The data of 309 non-ischemic heart failure patients implanted with ICD or CRT-D was analyzed.The dosage of different types of β-blockers was recorded during the in-office interrogation on the device,and the events of arrhythmia was transferred and analyzed by Home Monitoring.Kaplan-Meier analysis and Multivariate Cox regression were performed to investigate the cumulative risks of ventricular arrhythmia,appropriate shocks,cardiac death and all-cause mortalities.Time-dependent multi-covariate Cox regression was performed to adjust the influence of different onset of β-blocker therapy.Logistics regression was used in subgroup analysis.Results:Median follow up time was 40 months.Except for Bisoprolol,patients were on insufficient dose of β-blockers.Kaplan-Meier indicated that patients with β-blockers had a significantly high risk of ventricular and appropriate shocks,whereas no benefit was shown in cardiac death and all-cause mortality.The same trend was shown when patients were divided into≥50%GDMD and<50%GDMD.Time-dependent multivariate Cox regression showed the same trend.Multivariate Cox analysis showed that the effect was probably caused by Metoprolol.Conclusion:Beta-blockers with insufficient dose does not show benefit in survival in patients with non-ischemic heart failure implanted with ICD/CRT-D.However,it may increase the risk of ventricular arrhythmia and appropriate shocks.2.Metoprolol Succinate Reduces the Risks of Ventricular Arrhythmia,Appropriate Shocks and All-cause Mortality in Patients with Ischemic Heart Failure Implanted with ICD/CRT-DBackground:It is controversial whether one type of β-blocker is superior to another.There is a paucity in evidence concerning β-blockers in ischemic heart failure patients with ICD or CRT-D.The present study investigates the effect of different(3-blockers on patients with ischemic heart failure implanted with ICD/CRT-D.Methods:The data of 164 ischemic heart failure patients implanted with ICD or CRT-D was analyzed.The dosage of different types of β-blockers was recorded during the in-office interrogation,and the events of arrhythmia was transferred and analyzed by Home Monitoring.Kaplan-Meier analysis and Multivariate Cox regression were performed to investigate the cumulative risks of ventricular arrhythmia,appropriate shocks,cardiac death and all-cause mortalities.Time-dependent multi-covariate Cox regression was performed to adjust the influence of different onset of P-blocker therapy.Results:Median follow up time was 44.5 months.Kaplan-Meier indicated that patients with β-blockers had a significantly low risk of ventricular,appropriate shocks,and all-cause mortality,whereas no benefit was shown in appropriate anti-tachyarrhythmic pacing.Time-dependent multivariate Cox regression showed the same trend.Multivariate Cox analysis showed that the effect was probably contributed by Metoprolol succinate.Conclusion:Beta-blockers significantly reduces risk of ventricular,appropriate shocks,and all-cause mortality in patients with ischemic heart failure and ICD/CRT-D.Metoprolol succinate is the main contributor.Part III The Effect of Low-level Left Vagus Nerve Stimulation on Rat Gene Expression in Newly Onset Heart Failure after Myocardial InfarctionBackground:There are controversies on effect of vagus nerve stimulation in heart failure.The present study investigates the effect of low-level left vagus nerve stimulation on rat gene expression in newly onset heart failure after myocardial infarction.Methods:Fourteen models of post myocardial infarction heart failure were induced by ligation of the left anterior descending coronary artery and the randomly grouped into control group(N=7)and low-level vagus nerve stimulation group(N=7).Gene expression profile was analyzed by using Illumina RNA-seq array.Results:Compared with control group,there was a significant improvement of LVEF in low-level vagus nerve stimulation group.According to Ensembl gene database,in the differentially expressed genes(DEGs),Irxl,Myo 5b and Hsp90aal was associated with cardiovascular diseases,involved in Wnt signaling pathway.Conclusion:Low-level vagus nerve stimulation improves the LVEF in rats,but does not improve the cardiac remodeling parameters,such as LVEDD and LVESD.According to Ensembl gene database,in the differentially expressed genes(DEGs),Irxl,Myo 5b and Hsp90aal was associated with cardiovascular diseases,involved in Wnt signaling pathway. |