【作者】 张宜春；

【导师】 徐岩；

【作者基本信息】 安徽医科大学 ， 内科学， 2010， 硕士

【摘要】 背景与目的慢性心力衰竭(chronic heart failure,CHF)患者是发生心脏性猝死(sudden cardiac death,SCD)的高危人群,如何早期发现SCD的高危老年患者,并制定相应的干预模式一直是临床上的研究热点。窦性心率震荡(heart rate turbulance,HRT)是评价自主神经系统(autonomic Nervous System,ANS)功能的指标,在预测SCD风险方面有重要的临床意义。HRT是指单个室性期前收缩(ventricular premature complex,VPC)后窦性周期的生理性变化,当人体自主神经功能完好时表现为短暂的初期心率加速和紧随其后的心率减慢,而自主神经功能受损时VPC后HRT现象减弱或消失。本研究以老年慢性心力衰竭患者为研究对象,分析其HRT指标的变化特点以及不同病因、不同危险分层CHF患者HRT指标的差异,明确HRT在CHF患者危险分层中的作用;进一步分析与心率变异性(heart rate variability,HRV)、左室射血分数(left ventricular ejection fraction,LVEF)、左室舒张末内径(left ventricular end dilatation diameter ,LVEDD )、6分钟步行试验(6-minute walk test,6-MWT)、B型利钠肽(B-type natriuretic peptide,BNP)及QRS时限(QRS duration,QRSD)等多个临床因素的相关性及预后影响,以探讨老年慢性心衰自身发展机制,评估慢性心衰的进程,以期及时筛选出高危猝死心衰患者,为心脏再同步治疗(cardiac resynchronization therapy,CRT)或CRT联合心脏除颤器治疗(CRT-D)提供理论依据。以利于临床医师早期采取积极有效的干预措施,制定个体化的治疗方案,降低患者心脏事件的发生率并改善其预后,从而达到治疗进展性慢性心力衰竭的目的。方法选择确诊为CHF的患者66例,且动态心电图(dynamic electrocardiogram,DCG)符合HRT测定要求,以及年龄、性别相匹配的健康体检者40例,作为研究对象。入选者经24hDCG获取HRT的以下参数:震荡初始(turbulence onset,TO)、震荡斜率(turbulence slope,TS)和时域指标(SDNN)。接受血生化指标测定、常规心电图、超声心动图检查及6分钟步行试验测试。CHF组根据不同的病因、CHF严重程度及危险分层分别分成若干亚组:根据不同病因分缺血性心肌病组、高血压心脏病组、扩张型心肌病组;根据美国纽约心脏病协会(NYHA)分级为轻度CHF组(NYHAⅠ-Ⅱ级)、重度CHF组(NYHAⅢ-Ⅳ级);根据HRT组成不同将患者分为3个亚组: HRT0组(TO<0且TS>2.5 ms/RRI)、HRT1组(TO≥0或TS≤2.5 ms/RRI)、HRT2组(TO≥0且TS≤2.5ms/RRI)。其中HRT0为HRT正常组;HRT1和HRT2为异常组。比较CHF组和健康对照组及CHF各亚组间HRT指标差异,进一步分析HRT与HRV,6-MWT,QRSD,LVEF,LVEDD及BNP等临床因素的相关性并通过随访观察6-24月心血管事件(包括心脏性死亡、恶性室性心律失常、心源性休克、反复心力衰竭发作再住院等)的发生率及HRT对其预后的影响。凡发生上述终点事件者均归为CHF高危组(35例:随访中发生恶性室性心律失常者13例,心力衰竭发作再住院14,心源性休克3例,猝死5例),无上述终点事件者均归为CHF低危组(29例),失访2例。结果1. CHF组TO,BNP,LVEDD,QRSD明显高于对照组(P < 0.05);TS,SDNN,6-MWT,LVEF明显低于对照组(P <0.05)。慢性心衰患者HRT现象明显减弱〔TO:( 0.04±0.029)%,TS:( 10.63±5.34)ms/RRI,P <0.05〕。差异有统计学意义。2.缺血性心肌病组、高血压心脏病组、扩张型心肌病组各组间指标差异无统计学意义。3.重度CHF组中TO,BNP,LVEDD,QRSD明显高于轻度CHF组(P <0.01);TS,SDNN,LVEF,6-MWT明显低于轻度CHF组(P <0.01)。重度心衰患者HRT [TO:(0.05±0.045)%,TS:(8.36±7.42)ms/RRI]明显比轻度心衰患者[TO:( 0.03±0.028)%,TS:( 13.71±8.41) ms/RRI]减弱。差异有统计学意义。4. CHF组HRT与其他指标相关性分析,在CHF组TO与BNP,LVEF,LVEDD,QRSD,6-MWT,SDNN无明显相关性(P>0.05);TS与QRSD ,LVEDD,BNP水平呈负相关(r分别为-0.342,-0.563,-0.579,P<0.05),与LVEF,6-MWT,SDNN呈正相关(r分别0.473,0.394, 0.315, P<0.05)。CHF患者TS越低,SDNN越低,血浆BNP水平越高,则LVEF越低,LVEDD越大。5.心衰组中HRT2组心血管事件明显高于HRT1组和HRT0组,HRT2组即TO和TS均异常时患者预后较差:再住院人数增多,恶性心律失常发生率增加,死亡率高。(x2=5.9514, P =0.0147)。差异有统计学意义。6.单变量生存分析结果表明,在多个指标预测价值的比较中,TO TS相结合(RR=2.176)与TS(RR=0.726)都是对发生终点事件患者有预测价值的指标;多变量生存分析结果表明,当TO和TS作为单独变量进入Cox风险回归模型时,其预测强度略次于LVEF,而将TO,TS相结合作为一个变量进入模型时,则TO,TS相结合的预测价值(RR=2.894)远远高于LVEF(RR=0.201)及其他指标。结论1. CHF患者HRT现象减弱。2.缺血性心肌病、高血压心脏病、扩张型心肌病CHF患者HRT无显著差异。3. HRT现象在轻度CHF患者中减弱,在重度CHF患者则显著减弱甚至消失。在高危组中HRT现象亦比低危组明显减弱。HRT可以作为CHF患者病情严重程度的指标。4.组间比较和相关分析均证明HRT是一个独立于其他传统指标的预测指标。5. HRT可以作为CHF危险分层的一个有价值的心电指标,其预测价值优于众多传统指标。更多还原

【Abstract】 Background and Objective There is a high risk of sudden cardiac death (SCD) in elderly patients with chronic heart failure (CHF). Recently some scholars proposed a phenomenon, which the heart rate turbulence weakens even vanishes, was observed in patients with CHF .Heart rate turbulence (HRT), defined as a biphasic acceleration–deceleration response of a sinus node triggered by a ventricular premature complex, has proved to be a predictor of mortality in post infarction patients. The predictive value of HRT for mortality in patients with CHF remains controversial. There are limited data regarding the association between HRT parameters and the comprehensive evaluation of left ventricular (LV) dysfunction and CHF indexes in patients with CHF. HRT is considered a vagally dependent effective measure of barore?ex sensitivity, and as such is expected to be related to the advancement of CHF. The aim of this study was to evaluate the association between HRT parameters and clinical, biochemical, echocardiographic, and electrocardiographic measures of CHF in a large, prospectively enrolled population of patients with CHF to determine whether HRT could be considered a marker of CHF advancement and progression, giving insight into hemodynamic changes as well as changes of the autonomic nervous system.Patients and Methods 66 CHF patients and 40 health person were enrolled (mean age 68 years) in the study. The following tests were performed: 12-lead surface electrocardiography, 24-hour Holter, echocardiography, chest x-rays, B-type natriuretic peptide levels, Heart rate variability (HRV), mean heart rate Turbulence onset (TO) and turbulence slope (TS) were calculated from 24-hour Holter records. Left ventricular ejection fraction(LVEF)and were measured by Ultrasonic Cardiography. Three groups were diviled, ischemic heart disease, and hypertension with heart failure and dilated cardiomyopathy according to etiopathogenisis. CHF patients were classified into mild group (NYHAⅠ-Ⅱ级) and severe group(NYHAⅢ-Ⅳ级)according to NewYork Heart Association class; Patients were classified into the following HRT categories: HRT0 if both TO and TS were normal;HRT1 if either TO or TS was abnormal; HRT2 if both TO and TS were abnormal. Then patients were followed up 6-24 mouths. The primary end point was cardiac mortality or malignancy.According to the results,the patients were divided into the low-risk group and the high-risk group.Results CHF patients group showed significantly lower turbulence slopes and greater turbulence onset values compare with health group(P<0.05). The same trend is excist in severe and mild heart failure, which the heart rate turbulence more weaken even vanish in severe group(P<0.05). Both HRT parameters, especially turbulence slope, were significantly correlated with clinical indexes of CHF(P<0.05), were not correlated with etiopathogenisis of heart failure(P>0.05). Significant correlations were found betweenTS and the LVEF as well as with LV diameters.TS was significantly correlated with B-type natriuretic peptide (BNP) levels (r=-0.579, p<0.001 for turbulence slope).TS was associated with longer QRS duration, and progressively decreasing parameters of heart rate variability.There was no significant correlated with TO and TS. (r=-0.184, P>0.05).Abnormal HRT parameters were independent predictors of CHF severity measured by SDNN and LVEF <30%. There was significant difference in survival status among HRT0 group,HRT1 group and HRT2 group(all P<0.05).HRT2 was the strongest predictor and showed prognostic value to the primary end point in elderly patients with CHF(x2=5.9514, P =0.0147). Survival analysis indicated that TS and combination of TO and TS contributed to the end-point accident in patients with CHF. The combination of abnormal TO and abnormal TS (RR=2.894) was more powerful in multivate risk stratifier than LVEF(RR=0. 201) and others.Conclusion The findings indicate that in elderly patients with CHF, TS re?ects well the severity of CHF and is associated with LV dysfunction, SDNN, QRSD and BNP, but is not associated with etiopathogenisis of heart failure. It suggests that HRT is not only an index to decide the degree of CHF but also a new predictor of prognosis. HRT is a predictor better than other traditional factors.HRT may become a new and independent predictor of high-risk patients with CHF. HRT could be considered a well-accepted method for assessing risk stratifies in elderly patients with CHF.更多还原