Ablation of Complex Fractionated Electrograms Improves Outcome in Persistent Atrial Fibrillation of Over 2 Year's Duration.

AIM: There is controversy and sparse data on whether substrate based techniques in addition to pulmonary vein isolation (PVI) confer benefit in the catheter ablation of persistent atrial fibrillation (AF), especially if long standing. We performed an observational study to assess whether substrate based ablation improved freedom from atrial arrhythmia. METHODS: A total of 286 patients undergoing first ablation procedures for persistent AF with PVI only(n = 79), PVI plus linear ablation(n = 85), or PVI plus complex fractionated electrogram (CFAE) and linear ablation(n = 107) were followed. Primary end point was freedom from atrial arrhythmia at one year. RESULTS: Mean duration of pre-procedure time in AF was 28+/-27 months.There were no differences in baseline characteristics between groups except a higher proportion of patients with a severely dilated LA in those receiving PVI+CFAEs+lines. Freedom from atrial arrhythmia was higher with a PVI+CFAE+lines strategy then for PVI alone (HR 1.56, 95% CI: 1.04-2.34, p=0.032) but was not higher with PVI+lines. Benefit of substrate modification was conferred for preprocedure times in AF of over 30 months. The occurrence of atrial tachycardia was higher when lines were added to the ablation strategy (HR 0.08, 95% CI: 0.01-0.59, p=0.014). Freedom from atrial arrhythmia at 1 year was higher with lower patient age, use of general anaesthetic (GA), normal or mildly dilated left atrium and decreasing time in AF. CONCLUSIONS: In patients with long standing persistent AF of over 30 months duration,CFAE ablation resulted in improved freedom from atrial arrhythmia. Increased freedom from atrial arrhythmia occurs in patients who are younger and have smaller atria, and with GA procedures. Linear ablation did not improve outcome and resulted in a higher incidence of atrial tachycardia.

Improved outcome and cost effectiveness in ablation of persistent atrial fibrillation under general anaesthetic.

Aims: Outcome of persistent atrial fibrillation (AF) ablation remains suboptimal. Techniques employed to reduce arrhythmia recurrence rate are more likely to be embraced if cost-effectiveness can be demonstrated. A single-centre observational study assessed whether use of general anaesthesia (GA) in persistent AF ablation improved outcome and was cost-effective. Methods and results: Two hundred and ninety two patients undergoing first ablation procedures for persistent AF under conscious sedation or GA were followed. End points were freedom from listing for repeat ablation at 18 months and freedom from recurrence of atrial arrhythmia at 1 year. Freedom from atrial arrhythmia was higher in patients who underwent ablation under GA rather than sedation (63.9% vs. 42.3%, hazard ratio (HR) 1.87, 95% confidence interval (CI): 1.23-2.86, P = 0.002). Significantly fewer GA patients were listed for repeat procedures (29.2% vs. 42.7%, HR 1.62, 95% CI: 1.01-2.60, P = 0.044). Despite GA procedures costing slightly more, a saving of £177 can be made per patient in our centre for a maximum of two procedures if all persistent AF ablations are performed under GA. Conclusions: In patients with persistent AF, it is both clinical and economically more effective to perform ablation under GA rather than sedation.

Diagnostic yield of molecular autopsy in patients with sudden arrhythmic death syndrome using targeted exome sequencing.

AIMS: The targeted genetic screening of Sudden Arrhythmic Death Syndrome (SADS) probands in a molecular autopsy has a diagnostic yield of up to 35%. Exome sequencing has the potential to improve this yield. The primary aim of this study is to examine the feasibility and diagnostic utility of targeted exome screening in SADS victims, utilizing familial clinical screening whenever possible. METHODS AND RESULTS: To determine the feasibility and diagnostic yield of targeted exome sequencing deoxyribonucleic acid (DNA) was isolated from 59 SADS victims (mean age 25 years, range 1-51 years). Targeted exome sequencing of 135 genes associated with cardiomyopathies and ion channelopathies was performed on the Illumina HiSeq2000 platform. Non-synonymous, loss-of-function, and splice-site variants with a minor allele frequency <0.02% in the NHLBI exome sequencing project and an internal set of control exomes were prioritized for analysis followed by <0.5% frequency threshold secondary analysis. First-degree relatives were offered clinical screening for inherited cardiac conditions. Seven probands (12%) carried very rare (<0.02%) or novel non-sense candidate mutations and 10 probands (17%) had previously published rare (0.02-0.5%) candidate mutations-a total yield of 29%. Co-segregation fully confirmed two private SCN5A Na channel mutations. Variants of unknown significance were detected in a further 34% of probands. CONCLUSION: Molecular autopsy using targeted exome sequencing has a relatively low diagnostic yield of very rare potentially disease causing mutations. Candidate pathogenic variants with a higher frequency in control populations are relatively common and should be interpreted with caution.

A minimal or maximal ablation strategy to achieve pulmonary vein isolation for paroxysmal atrial fibrillation: a prospective multi-centre randomized controlled trial (the Minimax study).

AIMS: Pulmonary vein isolation (PVI) is the cornerstone of catheter ablation of atrial fibrillation (AF). The intervenous ridge (IVR) may be incorporated into ablation strategies to achieve PVI; however, randomized trials are lacking. We performed a randomized multi-centre international study to compare the outcomes of (i) circumferential antral PVI (CPVI) alone (minimal) vs. (ii) CPVI with IVR ablation to achieve individual PVI (maximal). METHODS AND RESULTS: Two hundred and thirty-four patients with paroxysmal AF underwent CPVI and were randomized to a minimal or maximal ablation strategy. The primary outcome of recurrent atrial arrhythmia was assessed with 7-day Holter monitoring at 6 and 12 months. PVI was achieved in all patients. Radiofrequency ablation time was longer in the maximal group (46.6 ± 14.6 vs. 41.5 ± 13.1 min; P < 0.01), with no significant differences in procedural or fluoroscopy times. At mean follow-up of 17 ± 8 months, there was no difference in freedom from AF after a single procedure between a minimal (70%) and maximal ablation strategy (62%; P = 0.25). In the minimal group, ablation was required on the IVR to achieve electrical isolation in 44%, and was associated with a significant reduction in freedom from AF (57%) compared with the minimal group without IVR ablation (80%; P < 0.01). CONCLUSION: There was no statistically significant difference in freedom from AF between a minimal and maximal ablation strategy. Despite attempts to achieve PVI with antral ablation, IVR ablation is commonly required. Patients in whom antral isolation can be achieved without IVR ablation have higher long-term freedom from AF (the Minimax study; ACTRN12610000863033).

P wave morphology in guiding the ablation strategy of focal atrial tachycardias and atrial flutter.

Focal atrial tachycardias arise preferentially from specific locations within the atria. Careful analysis of the P wave can provide useful information about the chamber and likely site of origin within that chamber. Macro-reentrant atrial flutter also tends to occur over a limited number of potential circuits. In this case, the ECG usually gives a guide to the chamber of origin, but unless it shows a specific morphology it is less useful in delineating the circuit involved. Nonetheless, prior knowledge of the likely chamber of origin helps to plan the ablation strategy.

Cardiac resynchronisation therapy: pacemaker versus internal cardioverter-defibrillator in patients with impaired left ventricular function.

OBJECTIVE: Studies have shown beneficial effects of cardiac resynchronisation therapy (CRT) on mortality among patients with heart failure. However the incremental benefits in survival from CRT with a defibrillator (CRT-D) are unclear. The choice of appropriate device remains unanswered. METHOD: This is a single-centre observational study in a tertiary cardiac centre. Patients (n=500) implanted with a CRT device with pacing alone (CRT-P) (n=354) and CRT-D (n=146) were followed for at least 2 years (mean 29 months, SD 14 months). The primary end point was all-cause mortality. RESULTS: A total of 116 deaths (23.2%) were recorded: 88 (24.8%) and 28 (19.2%), in the CRT-P and CRT-D groups, respectively. At 1 year there was a trend favouring CRT-D (HR 0.54, 95% CI 0.27 to 1.07, p=0.08) but this was attenuated by the 2nd year and became insignificant at the end of follow-up (HR 0.76, 95% CI 0.50 to 1.170, p=0.21). There was no survival benefit from having an internal cardioverter-defibrillator if patients were deemed non-responders to CRT. 27% of the CRT-P patients with ischaemic cardiomyopathy met indications for potential internal cardioverter-defibrillator implantation for primary prevention. These were older patients with poorer baseline function in comparison with CRT-D patients with devices for primary prevention. Once these differences were adjusted for, there was no difference in outcome between the groups. CONCLUSIONS: CRT-D did not offer additional survival advantage over CRT-P at longer-term follow-up, as the clinical benefit of a defibrillator attenuated with time. Further work is needed to define which subset of patients benefit from CRT-D.

Mechanisms of atrial mitral regurgitation: insights using 3D transoesophageal echo.

AIMS: Functional mitral regurgitation (FMR) is a consequence of mitral annular enlargement, leaflet tethering and reduced co-aptation. The importance of the left atrium (LA) as a cause of mitral regurgitation (MR) is less clear. We applied a co-aptation index using three-dimensional (3D) transoesophageal echocardiography to FMR and MR secondary to LA dilatation (atrial mitral regurgitation, AMR). METHODS AND RESULTS: Seventy-two patients underwent comprehensive 3D echo studies: FMR (n = 19); AMR (n = 33); and 20 controls. We recorded: LV size and function; LA dimensions; mitral annular area (MVA); and leaflet area in early and late systole. MVA fractional change was defined: (MVA late systole - MVA early systole)/MVA late systole × 100%; the co-aptation index was defined: (leaflet area early systole - leaflet area late systole)/leaflet area early systole × 100%. Despite normal LV size and function in AMR, MVA was increased similarly to FMR (AMR 12.86 cm(2) vs. FMR 12.33 cm(2), P = ns; both P < 0.01 vs. controls 8.83 cm(2)), and MVA fractional change similarly reduced (AMR 5.1% vs. FMR 6.3%; P = ns; both P < 0.001 vs. controls 14.6%). The co-aptation index was reduced in both MR groups (FMR 6.6% vs. AMR 7.0%, P = ns; both P < 0.001 vs. controls 19.6%). After multivariate analysis, the co-aptation index (χ(2) = 41.2) and MVA fractional change (χ(2) = 22.1) remained the strongest predictors of MR (both P < 0.001 for the model). A co-aptation index of ≤13% was 96% sensitive and 90% specific for the presence of MR. CONCLUSION: LA dilatation leads to MVA enlargement, reduced leaflet co-aptation and MR even without LV dilatation. A co-aptation index describes this in vivo. This work provides insights into the mechanism of AMR.

Supraventricular arrhythmias late after orthotopic cardiac transplantation: electrocardiographic and electrophysiological characterization and radiofrequency ablation.

AIMS: Cardiac transplantation (CTX) is an effective treatment for end-stage heart disease. Cardiac arrhythmias are increasingly recognized and associated with significant morbidity and mortality. We aim to describe the clinical and electrophysiological characteristics of patients with atrial arrhythmias occurring late after CTX. METHODS AND RESULTS: Sixteen patients with prior CTX who presented with late atrial arrhythmias for electrophysiological studies (EPS) were identified at two cardiac transplant centres. Among 859 patients, 16 (mean age 52 ± 14 years, 11 of 16 were men) patients underwent EPS for atrial arrhythmias presenting 8.6 ± 5.7 years following CTX. Among 16 patients, 14 underwent cardiac alone and 2 included lung transplantation. There were no cases of cardiac rejection. Arrhythmias were due to counterclockwise cavotricuspid-dependent atrial flutter (AFL) in 10 of 16, atrial tachycardia (AT) in 6 (1 patient had AFL and AT), and 1 due to atrioventricular nodal re-entrant tachycardia. Recipient-donor atrial electrical connection was seen in two of six AT and in no cases of AFL. In two cases, a focal AT was mapped to the remnant atrium conducting 2 : 1 or at variable block to the donor atrium. In four cases a focal/micro re-entrant AT originated within the vicinity of the interatrial suture scar. All cases were successfully ablated with radiofrequency energy; however, one case of AFL required a repeat ablation. Patients remained free of arrhythmia at 34 ± 15 months post-ablation. CONCLUSION: Typical AFL and AT are the most frequent supraventricular arrhythmias occurring late following CTX. Focal ATs may originate in low-voltage or border zones immediately adjacent to the atrio-atrial anastomosis. Radiofrequency ablation is an effective treatment strategy with high long-term success.

Targeted left ventricular lead placement to guide cardiac resynchronization therapy: the TARGET study: a randomized, controlled trial.

OBJECTIVES: This study sought to assess the impact of targeted left ventricular (LV) lead placement on outcomes of cardiac resynchronization therapy (CRT). BACKGROUND: Placement of the LV lead to the latest sites of contraction and away from the scar confers the best response to CRT. We conducted a randomized, controlled trial to compare a targeted approach to LV lead placement with usual care. METHODS: A total of 220 patients scheduled for CRT underwent baseline echocardiographic speckle-tracking 2-dimensional radial strain imaging and were then randomized 1:1 into 2 groups. In group 1 (TARGET [Targeted Left Ventricular Lead Placement to Guide Cardiac Resynchronization Therapy]), the LV lead was positioned at the latest site of peak contraction with an amplitude of >10% to signify freedom from scar. In group 2 (control) patients underwent standard unguided CRT. Patients were classified by the relationship of the LV lead to the optimal site as concordant (at optimal site), adjacent (within 1 segment), or remote (≥2 segments away). The primary endpoint was a ≥15% reduction in LV end-systolic volume at 6 months. Secondary endpoints were clinical response (≥1 improvement in New York Heart Association functional class), all-cause mortality, and combined all-cause mortality and heart failure-related hospitalization. RESULTS: The groups were balanced at randomization. In the TARGET group, there was a greater proportion of responders at 6 months (70% vs. 55%, p = 0.031), giving an absolute difference in the primary endpoint of 15% (95% confidence interval: 2% to 28%). Compared with controls, TARGET patients had a higher clinical response (83% vs. 65%, p = 0.003) and lower rates of the combined endpoint (log-rank test, p = 0.031). CONCLUSIONS: Compared with standard CRT treatment, the use of speckle-tracking echocardiography to the target LV lead placement yields significantly improved response and clinical status and lower rates of combined death and heart failure-related hospitalization. (Targeted Left Ventricular Lead Placement to Guide Cardiac Resynchronization Therapy [TARGET] study); ISRCTN19717943).

Cardiac resynchronization therapy optimization using noninvasive cardiac output measurement.

AIMS: Noninvasive cardiac output (CO) measurement (NICOM) is a novel method to assess ventricular function and offers a potential alternative for optimization of cardiac resynchronization therapy (CRT) devices. We compared the effect of NICOM-based optimization to no optimization (empiric settings) on CRT outcomes. METHODS: Two hundred and three patients undergoing CRT were assessed in two consecutive nonrandomized groups; an empiric group (n = 54) was programmed to "out of the box" settings with a fixed AV delay of 120 ms and a VV delay of 0 ms; and the optimization group (n = 149) underwent adjustments of both the AV and VV delays according to the greatest improvement in resting CO. The primary endpoints were improvements in left ventricular (LV) volumes and function from baseline at 6 months. Secondary endpoints were change in New York Heart Association (NYHA) class, quality of life score, and 6-minute walk test (6 MWT) performance. RESULTS: After 6 months of CRT, the optimization group had a better clinical response with lower NYHA class (2.1 ± 0.8 vs 2.4 ± 0.8, P = 0.048) and quality of life scores (35 ± 18 vs 42 ± 20, P = 0.045) but no differences in 6-MWT performance (269 ± 110 vs 277 ± 114 m, P = 0.81). Echocardiographic response was also better in the optimization group with lower LV end systolic volume (108 ± 51 vs 126 ± 60 mL, P = 0.048) and higher ejection fraction (30 ± 7 vs 27 ± 8, P = 0.01) compared to empiric settings. CONCLUSION: Device optimization using noninvasive measures of CO is associated with better clinical and echocardiographic response compared to empiric settings.

An unusual atrial tachycardia in a patient with Friedreich ataxia.

We present the unusual association of an atrial tachycardia with Friedreich ataxia. The arrhythmia was initially suspected to be focal in origin; however, use of a three-dimensional mapping system demonstrated that the tachycardia was macro-reentrant. This was subsequently treated successfully by linear ablation.

Impact of VV optimization in relation to left ventricular lead position: an acute haemodynamic study.

AIMS: Left ventricular (LV) lead placement to the most delayed segment offers the greatest potential benefit to cardiac resynchronization therapy (CRT). We assessed the impact of interventricular (VV) optimization on acute changes in cardiac output (CO) in patients with and without LV pacing of the most delayed segment. METHODS AND RESULTS: In 124 patients, the most delayed segment was defined by speckle tracking radial strain and the LV lead position by biplane fluoroscopy. Patients were classified as either a concordant (LV lead at latest site), adjacent (within one segment), or remote (two or more segments away) LV lead. Atrioventricular (AV) and VV delays were optimized by echocardiography. Cardiac output was measured non-invasively and a >20% increase in CO from baseline (intrinsic) defined acute response. Changes in CO in patients with concordant, adjacent, or remote LV leads were recorded following atrioventricular optimization alone (AV OPT) and after combined AV and VV optimization (AV/VV OPT). Compared with AV OPT pacing, AV/VV OPT produced a greater rise in CO (5.45 ± 1.1 vs. 5.76 ± 1.2 L/min, P< 0.001) and higher acute response rates (48.4 vs. 61.3%, P= 0.041). In adjacent patients, compared with AV OPT pacing, AV/VV OPT settings increased the response rate from 36.4 to 63.6% (P= 0.037). VV optimization had no effect on acute response rates in patients with remote (26.7 vs. 33.3%, P = 0.581) or concordant LV leads (65.6 vs. 72.1%, P = 0.438). CONCLUSION: VV optimization overcomes some but not all of the deleterious effects of a suboptimal LV lead position.

The impact of the right ventricular lead position on response to cardiac resynchronization therapy.

INTRODUCTION: Left ventricular (LV) lead placement to the latest contracting area (concordant LV lead) is associated with better response to cardiac resynchronization therapy (CRT) compared to a discordant LV lead. However, the effect of the right ventricular (RV) lead site on CRT response is unclear. We investigated the relationship of the RV and LV lead positions on CRT response. METHODS: In 131 CRT patients, the LV lead was positioned preferentially in a lateral or posterolateral vein and the RV lead to either the RV septum (RVS, n = 55) or RV apex (RVA, n = 76). The latest site of contraction was determined with two-dimensional speckle tracking radial strain imaging and patients had a concordant LV lead position if pacing the latest segment, and discordant if not. Response was defined as ≥15% reduction in LV end systolic volume (LVESV) at 6-month follow-up. RESULTS: There were no significant differences in mean reduction of LVESV at follow-up (RVS vs RVA: -23.3 ± 16% vs 22.1 ± 18%, P = 0.70) or rate of responders (58.2% vs 57.9%, P = 0.97) between the two groups. In patients with a concordant LV lead (n = 71), the response rate was significantly higher than those with a discordant lead (76.1% vs 36.7%, P < 0.001). There were no differences in outcomes in patients with a concordant or discordant LV lead according to the RV lead location. CONCLUSION: The extent of LV reverse remodeling following CRT is not related to the RV lead position, but is significantly higher in patients with a concordant LV lead.

An entirely subcutaneous implantable cardioverter-defibrillator.

BACKGROUND: Implantable cardioverter-defibrillators (ICDs) prevent sudden death from cardiac causes in selected patients but require the use of transvenous lead systems. To eliminate the need for venous access, we designed and tested an entirely subcutaneous ICD system. METHODS: First, we conducted two short-term clinical trials to identify a suitable device configuration and assess energy requirements. We evaluated four subcutaneous ICD configurations in 78 patients who were candidates for ICD implantation and subsequently tested the best configuration in 49 additional patients to determine the subcutaneous defibrillation threshold in comparison with that of the standard transvenous ICD. Then we evaluated the long-term use of subcutaneous ICDs in a pilot study, involving 6 patients, which was followed by a trial involving 55 patients. RESULTS: The best device configuration consisted of a parasternal electrode and a left lateral thoracic pulse generator. This configuration was as effective as a transvenous ICD for terminating induced ventricular fibrillation, albeit with a significantly higher mean (+/-SD) energy requirement (36.6+/-19.8 J vs. 11.1+/-8.5 J). Among patients who received a permanent subcutaneous ICD, ventricular fibrillation was successfully detected in 100% of 137 induced episodes. Induced ventricular fibrillation was converted twice in 58 of 59 patients (98%) with the delivery of 65-J shocks in two consecutive tests. Clinically significant adverse events included two pocket infections and four lead revisions. After a mean of 10+/-1 months, the device had successfully detected and treated all 12 episodes of spontaneous, sustained ventricular tachyarrhythmia. CONCLUSIONS: In small, nonrandomized studies, an entirely subcutaneous ICD consistently detected and converted ventricular fibrillation induced during electrophysiological testing. The device also successfully detected and treated all 12 episodes of spontaneous, sustained ventricular tachyarrhythmia. (ClinicalTrials.gov numbers, NCT00399217 and NCT00853645.)

Non-invasive cardiac output measurements based on bioreactance for optimization of atrio- and interventricular delays.

AIMS: Non-invasive cardiac output monitoring (NICOM) based on bio-reactance offers a portable method to assess ventricular function. Optimization of cardiac resynchronization therapy (CRT) by echocardiography is labour-intensive. We compared the ability of NICOM and echocardiography to facilitate optimum CRT device programming. METHODS AND RESULTS: Forty-seven patients in sinus rhythm were evaluated within 14 days of CRT implantation. The atrio- (AV) and interventricular (VV) delay intervals were incrementally adjusted and at each setting, NICOM and echocardiographic data were recorded. Left ventricular (LV) volumes and function were assessed by echocardiography at baseline and 3 months. Response to CRT was defined as a reduction in LV end-systolic volume (LVESV) by >15%. In all patients, cardiac output (CO) increased significantly at optimized settings compared with baseline (5.66 +/- 1.4 vs. 4.35 +/- 1.1 L/min, P < 0.001). A 20% increase in acute CO following CRT predicted LVESV reduction of >15% with a sensitivity of 81% and specificity of 92% (AUC 0.86). The optimum AV delay determined by NICOM was confirmed by echocardiography in 40 of 47 patients (85%, r = 0.89, P < 0.01) and for VV delay in 39 of 47 patients (83%, r = 0.89, P < 0.01). CONCLUSION: Non-invasive cardiac output monitoring is a simple, reliable, and portable alternative to echocardiography to program CRT devices.

P-wave morphology in focal atrial tachycardia: development of an algorithm to predict the anatomic site of origin.

OBJECTIVES: The purpose of this study was to perform a detailed analysis of the P-wave morphology (PWM) in focal atrial tachycardia (AT) and construct and prospectively evaluate an algorithm for identification of the anatomic site of origin. BACKGROUND: Although smaller studies have described the PWM from particular anatomic locations, a detailed algorithm characterizing the likely location of a tachycardia associated with a P-wave of unknown origin has been lacking. METHODS: The PWMs for 126 consecutive patients undergoing successful radiofrequency ablation of 130 ATs are reported. P waves were included only when the onset was preceded by a discernible isoelectric segment. P waves were classified as positive (+), negative (-), isoelectric, or biphasic. Sensitivity, specificity, and predictive values were calculated. On the basis of these results, an algorithm was constructed and prospectively evaluated in 30 new consecutive ATs. RESULTS: The distribution of ATs was right atrial (RA) in 82 of 130 (63%) and left atrial (LA) in 48 of 130 (37%). Right atrial sites included crista (n = 28), tricuspid annulus (n = 29), coronary sinus (CS) ostium (n = 14), perinodal (n = 7), right septum (n = 1), and RA appendage (n= 3). Left atrial sites included pulmonary veins (n = 32), mitral annulus (n = 8), CS body (n= 3), left septum (n = 3), and LA appendage (n = 2). In electrocardiographic lead V1, a negative or +/- P-wave demonstrated a specificity of 100% for a RA focus, and a + or -/+ P-wave demonstrated a sensitivity of 100% for a LA focus. A characteristic PWM was associated with high sensitivity and specificity at common atrial sites for tachycardia foci. A P-wave algorithm correctly identified the focus in 93%. CONCLUSIONS: Characteristic PWMs corresponding to known anatomic sites for focal AT are associated with high specificity and sensitivity. A P-wave algorithm correctly identified the site of tachycardia origin in 93%.

Rapid decline in acute stimulation thresholds with steroid-eluting active-fixation pacing leads.

BACKGROUND AND AIM: There is an increasing use of active-fixation leads for cardiac pacing, yet concerns remain regarding initial high stimulation thresholds. The aim was to perform a detailed analysis of pacing parameters at the time of implantation to determine when lead repositioning should be considered. METHODS: We performed a prospective observational study of consecutive new pacemaker implants. Detailed analysis of pacing parameters was collected at 2-minute intervals for 10 minutes, and at day 1 and week 8 following implant. RESULTS: Ninety-four patients underwent implantation of 79 dual-chamber and 15 single-chamber pacemakers using active-fixation leads in both chambers. An initial threshold of >1 V was demonstrated in 45/94 (48%) ventricular leads (mean threshold 1.5 +/- 0.3 V). This declined rapidly to 0.9 +/- 0.3 V at 4 minutes (P < 0.01), 0.7 +/- 0.3 V at 10 minutes (P < 0.01), and 0.6 +/- 0.3 V at day 1 (P < 0.01). At day 1, 43/45 leads were <1 V. There were 79 atrial leads. An initial threshold of >1 V (mean 1.7 +/- 0.6 V) was demonstrated in 41/79 (52%) leads falling significantly to 1.1 +/- 0.5 V at 4 minutes (P < 0.01), 0.9 +/- 0.4 V at 10 minutes (P < 0.01), and 0.6 +/- 0.2 V at day 1 (P < 0.01). At 10 minutes, 32 of 41 leads demonstrated a threshold of <1 V with all leads <1 V at day 1. Thresholds were maintained medium term. CONCLUSIONS: Active-fixation leads are commonly associated with initially high thresholds that fall rapidly. An initial threshold of 2 V should be provisionally accepted and retested at 4 minutes. The majority will have a threshold of <1 V the following day. A failure of a high threshold to decline at 4 minutes requires lead repositioning.