Significance Of Current Of Injury In Active Fixation Pacing Lead Implantation:Experimental And Clinical Study

PART I Prevalence and Relevant Factors of Pacing Lead Displacement:A Single Center ExperienceOBJECTIVES:To investigate the 5-year prevalence of pacing lead displacement at our center; compare the incidence of displacement in differnet lead types; summerize the clinical features and optimal management protocls in theses cases; and to seek the relevant risk factors of active fixation pacing lead dislodgement.METHODS:This part included a spectrum of studies with different designs:general investigation, clinical analysis, and case-control study in each section, respectively. Section one included total of 2992 patients who underwent pacemaker lead implantation in our hospital, the accurate prevalence of pacing lead displacement was estimated in total and annual, comparisons were made among different lead types; learning curves were drawed to display the process of procedure optimization. Section two was focused to analyze the clinical manifestations, diagnosic options and management strategies of pacing lead dislodgement, retrosepectively. The definite adverse effects of lead related complication were furthur evaluated. In section three, a retrospective case-control study was designed to investigate the relevant risk factors of active-fixation pacing lead dislodgement via a multivariate logistic regression model.RESULTS:1. Section one included 5409 leads in total, the prevalence of pacing lead dislodgement in the recent 5 years was 1.88%, which was acceptable. Pacing lead displacement was more frequent in active fixation leads than in passive fixation leads (3.00% vs.1.47%, P=0.002), and in coronary sinus leads than in endocardial pacing leads(P=0.004). The same was true in patients with CRT/CRT-D than those with dual or single chamber pacemakers (P=0.000). Difference was found neither among the different manufacturers and lead brands, nor between defibrillator leads and pacing leads. The learning curve demonstrated the significance of surgeon’s experience which was quantifyed by the cumulative procedure volume.2. A total of 95 patients suffered pacing lead dislocation; mean age of this population was 66.9±12.9 years; male to female ratio was 1.2:1. The medium time to event was 69 days post procedure (range:lday to 499 days), and 53.57% of cases were occurred within the first three month. Fifty-four patients presented with symptoms. The presence of pacing dependency is associated with 9.93-fold increase risk of significant symptoms. X-ray and electrocardiogram were of limited value in detection of pacing lead displacement, whereas pacing system interrogation was more useful especially in the case of micro-dislodgement. Repositioning and replacement of pacing leads were conducted in 46 and 7 cases respectively; while 34 patients underwent pacing system interrogation, and in eight patients, the malfunctioned leads were closed. Generally, patients with pacing dependency, macro-dislodgement and with symptoms were prone to invasive managements (P=0.000). Pacing lead displacement prolonged the hospital stays to 3-5days, increased the risks of re-hospitalization and re-operation by more than 50%, which further caused additional medical cost of 6000-yuan RMB.3. Total of 548 patients with 584 active-fixation pacing leads were included in the case-control cohort. In the final logistic regression model, female (OR 2.53,95%CI 1.38-4.47), severe tricuspid regurgitation (OR 10.48,95%CI 4.36-25.21), the presence of current of injury (COI) (OR 0.74,95%CI 0.03-0.21), and cumulative procedure volume (OR 0.8895%, CI 0.38-0.97) were independently associated with active-fixation pacing lead displacement.CONCLUSIONS:The prevalence of pacing lead displacement at our center in the past 5 years was 1.88%, which was within an acceptable range. Dislodgement in active-fixation leads was much more frequent compared to that in passive-fixation pacing leads. There was a general trend towards decrease in the risk of lead dislocation with increasing procedure volume. The medium time to event was 69 days, slightly longer than previous reports. Patients with pacing dependency were in the high odds to present symptoms. The management option was patient dependent. As a consequence of lead dislodgement, hospital stays were significantly prolonged, and the risk of re-hospitalization and re-operation increased at the cost of extra 6000-yuan RMB. Female patients with severe tricuspid regurgitation, absence of current of injury and surgeons with low procedure volume were independent risk factors for pacing lead displacement.PART II Experimental Study on the Association of Current of Injury with Active-fixation Lead Performance in Animal Models.OBJECTIVES:To investigate the association of COI magnitude and time course with active-fixation pacing lead performance; compare characteristics of COI derived from leads placed with different depths and angles; demonstrate the acute myocardial injury caused by different lead positioning manners in animal models; and to explore the implication of negative COI.METHODS:This part was involved with four kinds of animal models with cardiac pacing lead implantation. Three sections were conducted as follows:(1) a rabbit cardiac model of pacing lead implantation was established in 24 adult New Zealand rabbits both in vivo and in vitro, applying three different approaches of lead engagement(contacting the helix to the endocardium with no rotation, half rotation and giving full rotation). Langdendorff perfusion and open-chest observation were conducted respectively in vitro and in vivo. Comparisons on COI magnitude and time properties were made among these three groups with different lead placing approaches; the correlation between COI and lead stability was tested using Spearman correlation analysis.(2) The correlation of COI magnitude and time persistency with pacing threshold was investigated using a canine heart model in 8 adult beagles. Multivariate analysis was conducted in the seek of potential indicators for good pacing threshold. Receiver operating characteristic curve (ROC) was introduced to evaluate the accuracy and reliance of each independent factor. (3) Six adult beagles were used to establish a canine heart model of pacing leads placed with different angles and depths. The COI parameters, lead stability, and pacing threshold were compared between groups, respectively. The acute myocardial injury caused by different lead placing manners was demonstrated by the means of TUNNEL test and immunofiuorescent assay; another five New Zeeland rabbit hearts underwent Langendorff perfusion to establish the animal model representing pacing leads with extreme depths as lead perforation. Morphological behavior of COI was then observed dynamically. RESULTS: 1. All animal models were satisfactorily established both in vitro and in vivo. Seventy-two pacing leads were implanted, and 70 of them presented notable COI in intracardiac electrogram (IECG) observation. The COI time course in fully rotated leads were longer than in half rotated leads, and longer in half rotation leads than in contacted leads in vitro (26.5±2.8min vs.5.6±2.0min vs.1.5±1.1min, P<0.05). There was no significant difference in ST, ST/R and ICEG duration (IED) at initial measurements (P>0.05), but their differences were clear with time. Time course of COI was significantly correlated with lead stability (r=0.72, n=46, P<0.001). The same observation was true for in vivo study.2. Sixty-four leads were implanted in 8 canine models, and 63 of them demonstrated good COI features. There was a general trend toward decline in COI magnitude with different timings. The time persistency at 5min and 10min was significantly higher in fully rotated leads than in half rotated leads (P=0.000). Within the range of 0-80%, a positive correlation existed between COI persistency and good pacing threshold, whereas the opposite was true when COI persistency was beyond 80%. Although ST5min<16 mV, ST10min<8 mV, ST/R5min<0.5, as well as ST/R10min<0.3 were associated with poor pacing threshold showing area under the ROC curve (AUC) as 0.776-0.832, COI persistency at 50-80% was the only independent indicator of pacing threshold (OR=0.02,95%CI=0.02-0.165, P=0.000) confirmed in multivariate regression analysis.3. Seventy-two pacing leads with different depths and angles were implanted in 6 canine heart models, and all leads produced COI. Compared to the control group, over-torqued leads were associated with longer COI persistency, and better lead stability but poor pacing threshold (P=0.000). The apoptotic cells were more abundant (P=0.041), but Cx43 expression (P=0.009) was dramatically reduced in the myocardium around the tip of lead; whereas the opposite was observed in angled leads. However, the initial measurements of COI magnitude did not differ among three groups. Another four Langendorff perfused rabbit hearts demonstrated 7 negative COI, which occured exclusively in the case of either lead perforation or lead displacement.CONCLUSIONS:There was a distinct association between COI magnitude and time course with active-pacing lead performance in animal models both in vivo and in vitro. An initial COI measurement may overestimate lead performance, whereas the dynamic lead behaviors would confer additional benefit in the prediction of lead performance. Significant differences in COI magnitude, time properties and morphology were presented in leads with different depths and angles. A small COI with quick recovery indicated the insufficiency of lead stability, whereas a prominent COI with no meaningful recovery with time predicted the risk of lead perforation. A negative COI may associate either with lead dislodgement or perforation.PART III Predictive Value of Current of Injury on Active-fixation Lead Stability and Pacing Threshold: Clinical studyOBJECTIVES:To compare the ICEG characteristics of different lead types; validate the predictive significance of COI magnitude and time persistency on acute and short-to-mid-term pacing lead performance in a real-clinical setting; establish the optimal COI standards and observation intervals; and to methodologically analyze the two different protocols of COI acquisition.METHODS:The present part was a clinical investigation with combined designs, including acute observational study, prospective follow-up, and methodological analysis, and consisted of four sections as follows:(1) patients who required permanent pacing were included, the ICEG was simultaneously recorded via both pacing analyzer and surface electrocardiogram (ECG) during lead implantation. Comparisons of ICEG between different lead types were made. (2) Patients who required active-fixation pacing leads during 2011 and 2012 were included. COI was simultaneously acquired up to 1 Omins after lead positioning using before-mentioned two protocols. Pacing lead displacement or high pacing threshold more than 1.5V was defined as an adverse event. Comparisons were then made among a spectrum of potentially relevant factors, including COI parameters, according to different lead outcomes, and then a logistic regression model was introduced to confirm their predictive values. ROC curve analysis was used to establish the optimal COI standards that yield both good lead stability and pacing threshold. (6) A 6-months follow-up was carried out. The primary endpoint was any kind of lead displacement, and the secondary endpoint was high pacing threshold without evidence of lead displacement. Baseline demographics and clinical factors were compared between patients with endpoint and patients without. Multivariate models were generated to validate their predictive values.(4) Seventy-four patients were included from the before-mentioned cohort in section two; correlation analysis was conducted between COI parameters simultaneously obtained from two protocols. A ROC curve analysis was introduced to compare the validity and reliance of each COI parameters in terms of lead stability, and a cut-point was generated for each of them. AUC was calculated utilizing Hanley-McNeil nonparametric method. A kappa value was also estimated in order to evaluate the agreement of two protocols.RESULTS:1. Eighty-one patients were enrolled in section one; a total of 48 active-fixation leads, 21 passive-fixation leads,6 coronary sinus leads, and 6 previously implanted leads were studied. The COI magnitude in active-fixation leads was higher, and presented more strong time persistency than in passive-fixation leads. Neither Coronary sinus lead nor old pacing lead produced COI.2. Section two included 92 patients, with a mean age of 63.8±12.7 years, and a slight male predominance. A total of 92 active-fixation leads were implanted with 121 attempts. The prevalence of acute lead dislodgement was 17.2%, and of high pacing threshold was 6.56%. There were three cases of negative COI and five of absent COI, all of whom were associated with poor lead stability. Binary analysis demonstrated that female and right ventricular enlargement was associated with poor lead performance. The result of hierarchical logistic regression model showed the presence of COI, ST/R5min, ST/R10min, COI5min and COI persistency measured from pacing analyzer could independently predict good lead performance. ROC curve analysis revealed that ST/R5min>1.0, ST/R10min>0.6, COI5minpersistency>50% and COI10min persistency>35% were the standards for optimum COI concerning excellent lead performance. COI obtained from surface ECG is of limited value in predicting pacing lead threshold.3. One primary endpoint event and 4 secondary end point events have occured during 6-month follow-up duration. There was no variant independently associated with 6-month-lead performance according to the multivariate regression analysis.4. ST/R from two different protocols showed a strongest correlation (r=0.633, P=0.008 for 5min, and r=0.675, P=0.005 for lOmin). ROC curve analysis generated a series of optimal COI standards concerning good lead stability:ST10min>4 mV, ST/R5min>1.0, ST/R10min>O.6, COI5min persistency>50% nd COI10min persistency>35% for pacing analyzer and ST10min>6 mV and COI10min persistency>65% for surface ECG. The AUC for the former is bigger than the latter (P<0.05). There was a medium degree of agreement between ST10min>4 mV by pacing analyzer and ST10min>12 mV by surface ECG, and between ST/R10min>0.6 by pacing analyzer and ST/R10min>0.8 by surface ECG. There was a complete agreement between the two protocols in identification of COI (Kappa=1).CONCLUSIONS:Active-fixation leads were associated to higher amplitude and longer time persistency of COI compared to passive-fixation leads, whereas coronary sinus leads and pervious leads produced ICEG without COI; absence of COI or presence of negative COI indicated poor lead performance, and repositioning should be concerned. The optimal COI standard for pacing analyzer observation in terms of good pacing threshold and lead stability were ST10min>4mV, ST/R5min>1.0, ST/R10min>0.6, COI5min persistency>50% and COI10min persistency>35%. The predictive value was high in COI time properties compared to that in magnitude. Pacing analyzer is superior to surface ECG in COI measurement. This study recommended the minimum COI observation time interval was 5min for pacing analyzer and 10min for ECG.