【作者】 潘文志；

【导师】 舒先红； 宿燕岗；

【作者基本信息】 复旦大学 ， 内科， 2009， 博士

【摘要】 第一部分起搏QRS波时限与左心结构和功能的关系目的:评价起搏QRS波时限(pQRSd)与左心结构和功能的关系及其对左室收缩功能不全的诊断价值。方法:入选272例右心室心尖部起搏患者,包括99例有左室收缩功能不全(LVEF＜0.55)的患者及173例心功能正常(LVEF≥0.55)的患者。通过常规体表心电图测得pQRSd。对患者心功能行纽约心功能(NYHA)分级,同时检测患者血浆的NT-proBNP水平并将之对数转化后以log(NT-proBNP)表示;通过超声心动图(心超)检查获取左心房内径(LAD)、左心室收缩末期内径(LVDs)、左心室舒张末期内径(LVDd)、室间隔厚度(IVST)、左室后壁厚度(LVPWT)及左心室射血分数(LVEF)。分析pQRSd与以上各指标的关系。结果:1.pQRSd与LVDd(r=0.572,p＜0.001)、LVDs(r=0.625,p＜0.001)、LAD(r=0.278,p＜0.001)、IVST(r=0.216,p＜0.001)、LVPWT(r=0.208,p＜0.001)正相关,与LVEF负相关(r=—0.585,P＜0.001)。随着NYHA心功能分级的增加,pQRSd时限也逐渐延长,即NYHAⅠ级＜NYHAⅡ级＜NYHAⅢ级＜NYHAⅣ级(pQRSd分别为177.33±17.88,195.29±23.48,210.70±22.40和228.4.6±23.04 ms,p值均＜0.05)正相关,pQRSd与log(NT-proBNP)水平正相关(r=0.342,P＜0.001)。2.pQRSd诊断左室收缩功能不全受试者工作特征(ROC)曲线下面积为0.849±0.024(p＜0.001);以pQRSd≥200ms诊断左室收缩功能不全,敏感度及特异度均较佳,分别为71.72%和86.71%。如患者的pQRSd≥240 ms,那么左室收缩功能不全的阳性预测值可达100%;如pQRSd＜180 ms,那么97.3%以上的患者无左室收缩功能不全。结论:对于右室心尖部起搏的患者,pQRSd是一个简便而实用的初步判断心脏结构和功能的指标。以pQRSd≥200ms来诊断左室收缩功能不全有较高的灵敏度和特异度。第二部分右室心尖部起搏患者起搏QRS波时限与心室同步性的关系目的:探讨长期右室心尖部起搏患者起搏QRS波时限(pQRSd)与心室同步性的关系。方法:入选长期右室心尖部起搏患者,通过常规体表心电图测得pQRSd,应用常规心超测得患者的左心室射血分数(LVEF),组织多普勒技术测得12节段的达峰时间的标准差(TS—SD)、心室间机械延迟时间(IVMD),分析pQRSd与心室同步性指标的关系。结果:共入选79例患者,平均年龄68.24±13.69岁,其中LVEF＜0.55(左室收缩功能不全组)15例,LVEF≥0.55(左室收缩功能正常组)64例。相关分析显示pQRSd与TS—SD、IVMD无关(P＞0.05)。亚组分析显示,左室收缩功能不全组及左室收缩功能正常组的pQRSd均与TS—SD及IVMD无相关性(P＞0.05),但左室收缩功能不全组的TS—SD(39.80±9.00 ms vs28.74±15.38 ms,P＜0.05)及IVMD(30.55±21.12 ms vs 17.05±21.04 ms,P＜0.05)均大于左室收缩功能正常组。结论:对于长期右室心尖部起搏患者,pQRSd不能反应心室的同步性,左室收缩功能不全患者的心室同步性差于左室收缩功能正常者。第三部分QRS波时限对心脏再同步化治疗疗效的预测价值目的:探讨QRS波时限(QRSd)对心脏再同步化治疗(CRT)疗效的预测价值。方法:入选NYHA心功能Ⅲ～Ⅳ级、左心室射血分数≤0.35、心超提示心室不同步患者行CRT治疗。术前、术后当天及术后6月行心电图和心超检查。以治疗6个月后左室收缩末容积较术前减小的百分数(△LVESV%)≥15%作为治疗有效的标准,分析术前QRSd、术后QRSd及QRS波时限缩短值(△QRSd=术前QRSd-术后QRSd)对CRT疗效的预测价值。结果:(1)共入选40例患者,随访期间1例死亡,2例失访,余37例进入分析。其中,7例为窄QRS波(＜120 ms)者,30例为宽QRS波(≥120 ms)者。窄QRS波者CRT的有效率较宽QRS波者有降低的趋势(28.57%vs66.67%,P=0.079);(2)宽QRS波组中,治疗有效者与无效者比,术前的左室容积、左心室射血分数、QRSd、男/女比例、心律、室内阻滞情况及△QRSd均无差异(P＞0.05);(3)宽QRS波组中:治疗有效者术后QRSd缩短(151.00±23.15 vs 167.00±25.15 ms,P＜0.05),而无效者的QRSd无变化(166.00±18.97 vs 168.00±42.11 ms,P＞0.05);受试者工作特征(ROC)曲线显示术前QRSd和△QRSd均不能预测CRT的疗效(P＞0.05);△QRSd与△LVESV%无相关性(P＞0.05)。结论:窄QRS波者的CRT疗效可能较宽QRS波者差。虽然QRSd缩短仅见于CRT有效者,但术前ORSd和△QRSd均不能预测宽QRS波者的CRT疗效。第四部分缓慢心律失常对血浆氨基末端脑钠素前体水平的影响目的:探讨缓慢心律失常对血浆氨基末端脑钠素前体(NT-proBNP)影响。方法:将100例无明确结构性心脏疾病患者按缓慢心律失常情况分为三组:B组为病窦综合征组(43例),C组为Ⅱ度房室传导阻滞(AVB)组(22例),D组为Ⅲ度AVB组(35例)。另选42例无明确结构性心脏疾病、无心律失常者为A组,35例无明确结构性心脏疾病的持续性心房颤动(房颤)患者为E组。测定各组血浆NT-proBNP水平,分析血浆NT-proBNP水平与房室同步性、年龄、性别、体重指数、QRS波时限、左心房内径(LAD)、左心室射血分数(LVEF)、高血压和糖尿病的关系。结果:A组、B组、C组、D组及E组血浆log(NT-proBNP)水平分别为1.869±0.333,2.174±0.394,2.596±0.464,3.023±0.551和2.924±0.391 ng/L。这5组分别有0.00%,0.00%,18.18%,54.29%和54.29%患者血浆的NT-proBNP水平达到心衰诊断标准。血浆NT-proBNP水平:A、B组＜C组＜D组、E组(P＜0.01)。A与B组、D组与E组血浆间的NT-proBNP水平无明显差异(p＞0.05)。多元逐步回归分析显示房室同步性和年龄是血浆NT-proBNP水平的独立影响因素(P＜0.001),而性别、心率、体重指数、高血压、糖尿病、QRS波时限、LAD及LVEF与血浆NT-proBNP水平无关(P＞0.10)。结论:缓慢心律失常可导致血浆NT-proBNP水平的升高;缓慢心律失常患者的NT-proBNP水平随着房室失同步加重而逐渐升高。第五部分右室起搏对心功能正常者血浆氨基末端脑钠素前体水平的影响目的:探讨心脏起搏治疗对心功能正常、无明确结构性心脏病患者血浆氨基末端脑钠素前体(NT-proBNP)水平的影响。方法:入选缓因慢性心律失常在我院行起搏器植入术的心功能正常、无明结构性心脏病患者104例。患者的起搏模式为DDD或ⅤⅥ,心室电极置于右室心尖部(RVA)或右室流出道(RVOT)。测定患者术前及术后第三天血浆NT-proBNP水平,并比较不同起搏模式及起搏部位对血浆NT-proBNP水平的影响。NT-proBNP水平对数转化后以log(NT-proBNP)表示,术前术后log(NT-proBNP)的变化值以△log(NT-0roBNP)表示。结果:1.DDD起搏患者血浆NT-proBNP水平比ⅤⅥ起搏患者低(2.32±0.44ng/L vs 2.87±0.62ng/L,p＜0.0001)。房室同步性(AVS)恶化组术后的NT-proBNP水平较术前升高(2.43±0.55ng/L vs 2.67±0.56ng/L,P＜0.01);AVS不变组无明显改变(2.54±0.64ng/L vs 2.52±0.66ng/L,p＞0.05);AVS改善组降低(2.67±0.58ng/L vs 2.41±0.48ng/L,P＜0.01)。2.RVA起搏患者QRS波时限(QRSd)比RVOT起搏者宽(179.81±25.17ms vs 161.92±14.97ms,p＜0.001),但两组术后NT-proBNP水平无差异(2.59±0.56ng/L vs 2.69±0.66ng/L,P＞0.05),在校正了术前的NT-proBNP水平及房室同步性的变化值(AAVS)后仍无差异。3.术前为病窦综合征、术后植入DDD起搏器患者术前、房室顺序起搏、AAI模式下的NToro-BNP水平无差异(2.25±0.35ng/L vs 2.21±0.34ng/L vs 2.17±0.33ng/L,P＞0.05)。4.多元回归分析,结果显示只有△AVS是△log(NT-proBNP)的独立影响因素(P＜0.0001),而心率变化值(△HR)及QRSd的变化值(△QRSd)不是△log(NT-proBNP)的独立影响因素(P＞0.10)。结论:对于心功能正常、无明确结构性心脏病患者,右室起搏并不增加血浆NT-proBNP水平,RVA与RVOT起搏对血浆NT-proBNP水平无差别,提示右室起搏对这类患者心功能损害可能较小。更多还原

【Abstract】 Part One:Relationships between Paced QRS Duration and Left Cardiac Structures and FunctionsBackground:The value for paced QRS duration(pQRSd) to detect left ventricular (LV) dysfunction in right ventricular apical(RVA) paced patients has not been evaluated.Methods:A total of 272 RVA paced patients including 99 with LV systolic dysfunction(LVSD,def’med as LV ejection fraction(LVEF)＜0.55) and 173 without LVSD(LVEF≥0.55) were enrolled in this study.The pQRSd,N-terminal pro-brain natriuretic peptide(NT-proBNP) levels and some echocardiographic variables,including left atrial diameter(LAD),LV end-systolic diameter(LVDS), LV end-diastolic diameter(LVDD),interventricular septum thickness(IVST),LV posterior wall thickness(LVPWT) and LVEF were measured.Relationships between pQRSd and echocardiographic variables,NT-proBNP levels as well as New York Heart Association(NYHA) cardiac functions class were analyzed.Results:1.pQRSd was positively correlated with LVDD(r=0.572,P＜0.001), LVDS(r=0.625,P＜0.001),LAD(r=0.278,P＜0.001),IVST(r=0.216,P＜0.001) and LVPWT(r=0.208,P＜0.001).pQRSd in patients with NYHA classⅠ,Ⅱ,ⅢandⅣwas 177.33±17.88,195.29±23.48,210.70±22.40 and 228.46±23.04 ms,respectively.There was a step-wise increase in pQRSd corresponding to increase in NYHA class(all P＜0.05).pQRSd was negatively correlated with LVEF(r=-0.585,P＜0.001).Multi-variables linear regression demonstrated that LVEF,NYHA class,LVDD,IVST were independently associated with pQRSd(all P＜0.01).In addition,pQRSd was positively correlated with log(NT-proBNP)(r=0.342,P＜0.001),even after adjusting for pacing mode,atrial fibrillation and age(P＜0.001).2.To evaluate the value for pQRSd to detect LVSD,receiver operating characteristic (ROC) curve was drawn and the area under curve(AUC) was calculated as 0.849±0.024(P＜0.001).The pQRSd cut-off value derived from the Youden index, giving equal weighting to sensitivity and specificity,was 200 ms.It had sensitivity of 71.72%(67.19%～76.25%) and specificity of 86.71(84.13%～89.29%) to detect LVSD.pQRSd≥240ms gave a positive predictive value 100%while＜180 ms excluded＞97.3%(96.4%～98.2%) of patients with LVSD.Conclusions:In RVA paced patients,pQRSd is correlated with left cardiac structures and function and a cut-off value for pQRSd of 200 ms provides a satisfactory balance of sensitivity and specificity for detecting LVSD.Part Two:Relationships between Paced QRS Duration and Ventricular Dyssynchrony in Patients with Chronic Right Ventricular Apical PacingObjective:To investigate the relationships between paced QRS duration(pQRSd) and ventricular dyssynchrony in patients with chronic right ventricular apical(RVA) pacing.Methods:Patients with chronic right ventricular apical(RVA) pacing were enrolled.The pQRSd was obtained from the standard 12-leads electrocardiography. Left ventricular(LV) ejection fraction(LVEF),interventricular mechanical delay (IVMD) and systolic asynchrony index(TS—SD) were measured through routine echocardiography or Doppler tissue imaging(DTI).The relationships between pQRSd and such echocardiographical variables were examined.Results:A total of 79 patients(mean age:68.24±13.69 yeasrs) were enrolled in this study,including 15 with LVEF＜0.55 as LV systolic dysfunction(LVSD) group, and 64 patients with LVEF≥0.55 as normal LV systolic function group.There were no correlations between pQRSd and IVMD and TS—SD(P＞0.05).Subgroup analysis demonstrated that no correlations were found between pQRSd and IVMD and TS—SD both in LVSD group and normal LV systolic function group(P＞0.05).However,IVMD(30.55±21.12 ms vs 17.05±21.04 ms,P＜0.05) and TS—SD(39.80±9.00 ms vs 28.74±5.38 ms,P＜0.05 ) were greater in LVSD group than in normal LV systolic function group.Cunelusions:In patients with chronic right ventricular apical(RVA) pacing: pQRSd can not exactly predict ventricular dyssynchrony,and the ventricular dyssynchrony is more severe in patients with LVSD than in those with normal LV systolic function.Part Three:Value of QRS Duration in Predicting Response to Cardiac Resynchronization Therapy in Patients With End-Stage Heart FailureObjective:To evaluate the predictive value of QRS duration(QRSd) for response to cardiac resynchronization therapy(CRT) in patients with end-stage heart failure.Methods:Patients with heart failure scheduled for implantation ofa CRT device were studied.Selection criteria for CRT included moderate to severe heart failure(New York Heart Association classesⅢtoⅣ),left ventricular ejection fraction(LVEF)＜35%,and ventricular asynchrony detected by echocardiography.Before CRT implantation,QRSd and 2-dimensional echocardiographical valuables(LV volumes and LVEF) was measured.QRSd,LVEF and LV volumes were reassessed immediately after CRT implantation and at 6-month follow-up.CRT response were defined as decreasing＞15%in LV end-systolic volume(LVESV).The value for QRS duration to predict response to CRT was assessed.Results:A total of 40 patients were enrolled in the study.During the follow-up,one died and 2 lost to follow-up.The rest stepped into the analysis,including 7 with wide QRSd(≥120 ms) and 7 with narrow QRSd(＜120 ms).After 6 months of CRT, there was a trend that the rate of response to CRT in narrow QRSd group was lower than that in wide QRSd group(28.57%vs 66.67%,P=0.079).In wide QRSd group,no significant differences were observed in baseline QRSd,LV volumes and LVEF between responders and non-responders(P＞0.05).The QRSd was shortened in responders(151.00±23.15 vs 167.00±25.15 ms,P＜0.05) and remained unchanged(166.00±18.97 vs 168.00±42.11 ms,P＞0.05) immediately after CRT in wide QRSd group.However,receiver operating characteristic(ROC) curve showed that both baseline QRSd and change of QRSd(ΔQRSd) could not predict response to CRT(P＞0.05).No significant relation was demonstrated betweenΔQRSd andΔLVESV%(ΔLVESV%was the percent decrease in LVESV after 6 months CRT) at 6-month follow-up(P＞0.05). Conclusion:Patients with narrow QRSd might have lower rate of response to CRT than wide QRSd patients.In wide QRSd patients,although shortening of QRSd after CRT was observed only in responders,but individual response varied highly,not allowing adequate selection of responders.Part Four:Effect of Brady-arrhythmia on the Plasma Levels of Nterminal Pro-brain Natriuretic PeptideObjective:To investigate the effect of Brady-arrhythmia on the plasma levels of Nterminal pro-brain natriuretic peptide(NT-proBNP).Methods:A total of 100 consecutive patients with sick sinus syndrome(SSS) or non-intermittentⅡ°orⅢ°atrioventricular block(AVB) were enrolled in the study. Patients were divided into 3 groups:group B,43 patients with sick sinus syndrome; group C,22 patients withⅡ°AVB;group D,35 patients withⅢ°AVB.Moreover,42 patients without arrhythmia were enrolled as group A and 35 patients with persistent atrial fibrillation as group E.The plasma levels of NT-proBNP were assayed.The logarithm of NT-proBNP level was presented as log(NT-proBNP),and differences of them among groups were evaluated.Stepwise multivariate linear regression analysis was performed to search independent determinants of log(NT-proBNP) from valuables including severity of atrioventricular asynchrony(group B=1, group C=2,group D=3),heart rate,gender,age,body mass index(BMI), hypertension,diabetes,QRS duration,left artial diameter and left ventricular ejection fraction.Results:The log(NT-proBNP) in group A,B,C,D and E were 1.869±0.333,2.174±0.394,2.596±0.464,3.023±0.551 and 2.924±0.391 ng/L,respectively.0.00%, 0.00%,18.18%,54.29%and 54.29%of patients in group A,B,C,D and E were above the cut-off points for diagnosing heart failure,respectively.Multiple comparisons adjusting for age and heart rate demonstrated that the NT-proBNP levels were lower in group A and B than in group C,D and E(P＜0.01),and lower in group C than in group D and E(P＜0.001),with no differences found between group A and B(P=1.000),between group D and E(P=1.000).Multivariate analysis revealed that age and the severity of atrioventricular asynchrony rather than heart rate were independent determinants of NT-proBNP levels(P＜0.001).Conclusions:Patients with Brady-arrhythmia without heart failure may have high NT-proBNP levels.The plasma NT-proBNP levels in patients with Brady-arrhythmia increased in proportion to aggravation of atrioventricular asynchrony.Part five:Effect of Right Ventricular Pacing on Plasma N-terminal pro-brain Natrinretic Peptide Levels in Patients with Normal Cardiac FunctionObjective:To investigate the effect of right ventricular pacing on plasma N-terminal pro-brain natriuretic peptide(NT-proBNP) levels in patients with normal cardiac function without defined structural heart disease.Methods:A total of 104 patients with normal cardiac function without defined structural heart disease who referred to our department for pacemaker implantation due to Brady-arrhythmia were enrolled in this study.The pacing modes were DDD or VVI and ventricular pacing leads were placed in right ventricular apical(RVA) or right ventricular outflow tract(RVOT).The plasma levels of NT-proBNP before and 3 days after pacemaker implantation were assayed and the logarithm of NT-proBNP level was presented as log(NT-proBNP).The effect of pacing mode and ventricular pacing sites on plasma NT-proBNP levels were analyzed.Results:1.Patients with DDD pacing had lower NT-proBNP levels than those with VVI pacing(2.32±0.44 ng/L vs 2.87±0.62 ng/L,P＜0.0001).2.The paced QRS duration in RVA paced patients was wider than in RVOT paced patients(179.81±25.17 ms vs 161.92±14.97 ms,P＜0.001).However,the difference of NT-proBNP levels between the two groups was not significant(2.59±0.56 ng/L vs 2.69±0.66 ng/L,P＞0.05 ),even after adjusting for the baseline NT-proBNP levels and the change of atrioventricular asynchrony(ΔAVS).3.The NT-proBNP levels of SSS patients implanted with DDD pacemaker were not different between baseline,atrialventricular sequence pacing and AAI pacing(2.25±0.35 ng/L vs 2.21±0.34 ng/L vs 2.17±0.33ng/L,P＞0.05).4.Multivariate analysis revealed thatΔAVS(P＜0.001) rather than change of heart rate or change of QRS duration(P＞0.10) was the independent determinant of the change of NT-proBNP levels.Conclusions:In patients with normal cardiac function without defined structural heart disease,right ventricular pacing doesn’t increase NT-proBNP levels,and the NT-proBNP levels in RVA pacing are not different from those in RVOT pacing. These results suggest that RVA pacing may do little harm to these patients.更多还原