The Clinical Investigation Of Paced QRS Duration And Plasma Levles Of N-terminal Pro-brain Natriuretic Peptide In Paced Patients

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.