A systematic review of ICD complications in randomised controlled trials versus registries: is our 'real-world' data an underestimation?

Implantable cardioverter defibrillator (ICD) implantation carries a significant risk of complications, however published estimates appear inconsistent. We aimed to present a contemporary systematic review using meta-analysis methods of ICD complications in randomised controlled trials (RCTs) and compare it to recent data from the largest international ICD registry, the US National Cardiovascular Data Registry (NCDR). PubMed was searched for any RCTs involving ICD implantation published 1999-2013; 18 were identified for analysis including 6433 patients, mean follow-up 3 months-5.6 years. Exclusion criteria were studies of children, hypertrophic cardiomyopathy, congenital heart disease, resynchronisation therapy and generator changes. Total pooled complication rate from the RCTs (excluding inappropriate shocks) was 9.1%, including displacement 3.1%, pneumothorax 1.1% and haematoma 1.2%. Infection rate was 1.5%.There were no predictors of complications but longer follow-up showed a trend to higher complication rates (p=0.07). In contrast, data from the NCDR ICD, reporting on 356 515 implants (2006-2010) showed a statistically significant threefold lower total major complication rate of 3.08% with lead displacement 1.02%, haematoma 0.86% and pneumothorax 0.44%. The overall ICD complication rate in our meta-analysis is 9.1% over 16 months. The ICD complication reported in the NCDR ICD registry is significantly lower despite a similar population. This may reflect under-reporting of complications in registries. Reporting of ICD complications in RCTs and registries is very variable and there is a need to standardise classification of complications internationally

Ultrastructure and complex polar architecture of the human pathogen Campylobacter jejuni

Campylobacter jejuni is one of the most successful food-borne human pathogens. Here we use electron cryotomography to explore the ultrastructure of C. jejuni cells in logarithmically growing cultures. This provides the first look at this pathogen in a near-native state at macromolecular resolution (∼5 nm). We find a surprisingly complex polar architecture that includes ribosome exclusion zones, polyphosphate storage granules, extensive collar-shaped chemoreceptor arrays, and elaborate flagellar motors

Dynamic spatial dispersion of repolarization is present in regions critical for ischemic ventricular tachycardia ablation

Background: The presence of dynamic substrate changes may facilitate functional block and reentry in ventricular tachycardia (VT). Objective: We aimed to study dynamic ventricular repolarization changes in critical regions of the VT circuit during sensed single extrastimulus pacing known as the Sense Protocol (SP). Methods: Twenty patients (aged 67 ± 9 years, 17 male) underwent VT ablation. A bipolar voltage map was obtained during sinus rhythm (SR) and right ventricular SP pacing at 20 ms above ventricular effective refractory period. Ventricular repolarization maps were constructed. Ventricular repolarization time (RT) was calculated from unipolar electrogram T waves, using the Wyatt method, as the dV/dtmax of the unipolar T wave. Entrainment or pace mapping confirmed critical sites for ablation. Results: The median global repolarization range (max-min RT per patient) was 166 ms (interquartile range [IQR] 143-181 ms) during SR mapping vs 208 ms (IQR 182-234) during SP mapping (P = .0003 vs intrinsic rhythm). Regions of late potentials (LP) had a longer RT during SP mapping compared to regions without LP (mean 394 ± 40 ms vs 342 ± 25 ms, P < .001). In paired regions of normal myocardium there was no significant spatial dispersion of repolarization (SDR)/10 mm2 during SP mapping vs SR mapping (SDR 11 ± 6 ms vs 10 ± 6 ms, P = .54). SDR/10 mm2 was greater in critical areas of the VT circuit during SP mapping 63 ± 29 ms vs SR mapping 16 ± 9 ms (P < .001). Conclusion: Ventricular repolarization is prolonged in regions of LP and increases dynamically, resulting in dynamic SDR in critical areas of the VT circuit. These dynamic substrate changes may be an important factor that facilitates VT circuits

Body size and the risk of biliary tract cancer: a population-based study in China

Though obesity is an established risk factor for gall bladder cancer, its role in cancers of the extrahepatic bile ducts and ampulla of Vater is less clear, as also is the role of abdominal obesity. In a population-based case–control study of biliary tract cancer in Shanghai, China, odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for biliary tract cancer in relation to anthropometric measures, including body mass index (BMI) at various ages and waist-to-hip ratio (WHR), adjusting for age, sex, and education. The study included 627 patients with biliary tract cancer (368 gall bladder, 191 bile duct, 68 ampulla of Vater) and 959 healthy subjects randomly selected from the population. A higher BMI at all ages, including early adulthood (ages 20–29 years), and a greater WHR were associated with an increased risk of gall bladder cancer. A high usual adult BMI (⩾25) was associated with a 1.6-fold risk of gall bladder cancer (95% CI 1.2–2.1, P for trend <0.001). Among subjects without gallstones, BMI was also positively associated with gall bladder cancer risk. Regardless of BMI levels, increasing WHR was associated with an excess risk of gall bladder cancer risk, with those having a high BMI (⩾25) and a high WHR (>0.90) having the highest risk of gall bladder cancer (OR=12.6, 95% CI 4.8–33.2), relative to those with a low BMI and WHR. We found no clear risk patterns for cancers of the bile duct and ampulla of Vater. These results suggest that both overall and abdominal obesity, including obesity in early adulthood, are associated with an increased risk of gall bladder cancer. The increasing prevalence of obesity and cholesterol stones in Shanghai seems at least partly responsible for the rising incidence of gall bladder cancer in Shanghai

Cost-effectiveness of ablation of ventricular tachycardia in ischaemic cardiomyopathy: Limitations in the trial evidence base

Objective: Catheter ablation is an important treatment for ventricular tachycardia (VT) that reduces the frequency of episodes of VT. We sought to evaluate the cost-effectiveness of catheter ablation versus antiarrhythmic drug (AAD) therapy. / Methods: A decision-analytic Markov model was used to calculate the costs and health outcomes of catheter ablation or AAD treatment of VT for a hypothetical cohort of patients with ischaemic cardiomyopathy and an implantable cardioverter-defibrillator. The health states and input parameters of the model were informed by patient-reported health-related quality of life (HRQL) data using randomised clinical trial (RCT)-level evidence wherever possible. Costs were calculated from a 2018 UK perspective. / Results: Catheter ablation versus AAD therapy had an incremental cost-effectiveness ratio (ICER) of £144 150 (€161 448) per quality-adjusted life-year gained, over a 5-year time horizon. This ICER was driven by small differences in patient-reported HRQL between AAD therapy and catheter ablation. However, only three of six RCTs had measured patient-reported HRQL, and when this was done, it was assessed infrequently. Using probabilistic sensitivity analyses, the likelihood of catheter ablation being cost-effective was only 11%, assuming a willingness-to-pay threshold of £30 000 used by the UK’s National Institute for Health and Care Excellence. / Conclusion: Catheter ablation of VT is unlikely to be cost-effective compared with AAD therapy based on the current randomised trial evidence. However, better designed studies incorporating detailed and more frequent quality of life assessments are needed to provide more robust and informed cost-effectiveness analyses

Predictive role of BNP/NT-proBNP in non-heart failure patients undergoing catheter ablation for atrial fibrillation: An updated systematic review

Atrial fibrillation (AF) is a growing public health issue, associated with significant morbidity and mortality. In addition to pharmacological therapy, catheter ablation is an effective strategy in restoring and maintaining sinus rhythm. However, ablation is not without risk, and AF recurs in a significant proportion of patients. Non-invasive, easily accessible markers or indices that could stratify patients depending on the likelihood of a successful outcome following ablation would allow us to select the most appropriate patients for the procedure, reducing the AF recurrence rate and exposure to potentially life-threatening risks. There has been much attention paid to brain natriuretic peptide (BNP) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) as possible predictive markers of successful ablation. Several studies have demonstrated an association between higher pre-ablation levels of these peptides, and a greater likelihood of AF recurrence. Therefore, there may be a role for measuring brain natriuretic peptides levels when selecting patients for catheter ablation

Epicardial catheter ablation for ventricular tachycardia on uninterrupted warfarin: A safe approach for those with a strong indication for peri-procedural anticoagulation?

BACKGROUND: Current guidelines for epicardial catheter ablation for ventricular tachycardia (VT) advocate that epicardial access is avoided in anticoagulated patients and should be performed prior to heparinisation. Recent studies have shown that epicardial access may be safe in heparinised patients. However, no data exist for patients on oral anticoagulants. We investigated the safety of obtaining epicardial access on uninterrupted warfarin. METHODS: A prospective registry of patients undergoing epicardial VT ablation over two years was analysed. Consecutive patients in whom epicardial access was attempted were included. All patients were heparinised prior to epicardial access with a target activated clotting time (ACT) of 300-350s. Patients who had procedures performed on uninterrupted warfarin (in addition to heparin) were compared to those not taking an oral anticoagulant. RESULTS: 46 patients were included of which 13 were taking warfarin. There was no significant difference in clinical and procedural characteristics (except INR and AF) between the two groups. Epicardial access was achieved in all patients. There were no deaths and no patients required surgery. A higher proportion of patients in the warfarin group had a drop in haemoglobin of >2g/dL compared to the no-warfarin group (38.5% versus 27.3%, p=0.74) and delayed pericardial drain removal (7.8% versus 3.03%, p=0.47). There was no difference in overall procedural complication rate. No patients required warfarin reversal or blood transfusion. CONCLUSION: Epicardial access can be achieved safely and effectively in patients' anticoagulated with warfarin and heparinised with therapeutic ACT. This may be an attractive option for patients with a high stroke risk

Assessment of a conduction-repolarisation metric to predict Arrhythmogenesis in right ventricular disorders

Background: The re-entry vulnerability index (RVI) is a recently proposed activation-repolarization metric designed to quantify tissue susceptibility to re-entry. This study aimed to test feasibility of an RVI-based algorithm to predict the earliest endocardial activation site of ventricular tachycardia (VT) during electrophysiological studies and occurrence of haemodynamically significant ventricular arrhythmias in follow-up. Methods: Patients with Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) (n = 11), Brugada Syndrome (BrS) (n = 13) and focal RV outflow tract VT (n = 9) underwent programmed stimulation with unipolar electrograms recorded from a non-contact array in the RV. Results: Lowest values of RVI co-localised with VT earliest activation site in ARVC/BrS but not in focal VT. The distance between region of lowest RVI and site of VT earliest site (D min ) was lower in ARVC/BrS than in focal VT (6.8 ± 6.7 mm vs 26.9 ± 13.3 mm, p = 0.005). ARVC/BrS patients with inducible VT had lower Global-RVI (RVI G ) than those who were non-inducible (−54.9 ± 13.0 ms vs −35.9 ± 8.6 ms, p = 0.005) or those with focal VT (−30.6 ± 11.5 ms, p = 0.001). Patients were followed up for 112 ± 19 months. Those with clinical VT events had lower Global-RVI than both ARVC and BrS patients without VT (−54.5 ± 13.5 ms vs −36.2 ± 8.8 ms, p = 0.007) and focal VT patients (−30.6 ± 11.5 ms, p = 0.002). Conclusions: RVI reliably identifies the earliest RV endocardial activation site of VT in BrS and ARVC but not focal ventricular arrhythmias and predicts the incidence of haemodynamically significant arrhythmias. Therefore, RVI may be of value in predicting VT exit sites and hence targeting of re-entrant arrhythmias

Ventricular Stimulus Site Influences Dynamic Dispersion of Repolarization In The Intact Human Heart

The spatial variation in restitution properties in relation to varying stimulus site is poorly defined. This study aimed to investigate the effect of varying stimulus site on apico-basal and transmural activation time (AT), action potential duration (APD) and repolarization time (RT) during restitution studies in the intact human heart. Ten patients with structurally normal hearts, undergoing clinical electrophysiology studies were enrolled. Decapolar catheters were placed apex to base in the endocardial right ventricle (RVendo) and left ventricle (LVendo), and an LV branch of the coronary sinus (LVepi) for transmural recording. S1-S2 restitution protocols were performed pacing RVendo apex, LVendo base and LVepi base. Overall 725 restitution curves were analyzed, 74% of slopes had an Smax>1 (p < 0.001), mean Smax=1.76. APD was shorter in the LVepi compared to LVendo regardless of pacing site (30ms difference during RVendo pacing, 25ms during LVendo and 48ms during LVepi; 50(th) quantile, p<0.01). Basal LVepi pacing resulted in a significant transmural gradient of RT (77ms, 50(th) quantile: p<0.01), due to loss of negative transmural AT-APD coupling (mean slope 0.63±0.3). No significant transmural gradient in RT was demonstrated during endocardial RV or LV pacing, with preserved negative transmural AT-APD coupling (mean slope -1.36 ±1.9 and -0.71 ±0.4, respectively). Steep ARI restitution slopes predominate in the normal ventricle and dynamic ARI, RT gradients exist which are modulated by the site of activation. Epicardial stimulation to initiate ventricular activation promotes significant transmural gradients of repolarization that could be pro-arrhythmic

Early Results on the Utilisation of ECG-Imaging during Catheter Ablation Procedures for Prediction of Sites of Earliest Activation during Re-entrant Ventricular Tachycardia

Success rate of ventricular tachycardia (VT) ablation remains sub-optimal. Current technology does not allow fast and accurate delineation of the ablation target. Noninvasive panoramic ECG-imaging (ECGI) offers the possibility of studying the interaction between arrhythmogenic substrate and earliest sites of activation during VT to improve ablation strategies. ECGI mapping (CardioInsight, Medtronic) was performed in 5 patients undergoing VT ablation. Ventricular pacing was delivered from the RV and three indices were measured at each ventricular site to map susceptibility to arrhythmia initiation: Re-entry vulnerability index (RVI), local dispersion of AT (∆AT) and local dispersion of repolarization (∆ARI). Regions of high susceptibility were defined as those corresponding to the bottom 5% of RV I and the upper 5% of ∆AT and ∆ARI. Morphologically distinct VTs were analyzed to measure the AT sequence and localize the region of earliest epicardial activation (AT < 5 ms). In total, 20 VTs were analyzed (4.0 ± 1.2 per patient). The minimum distance between the region of high vulnerability and the region of earliest AT during VT was 5.6 ± 8.6 mm for RV I, 6.1 ± 10.8 mm for ∆AT and 12.8 ± 22.4 mm for ∆ARI (P > 0.13 for all pair-wise comparison). The vulnerable region presented at least partial overlap with the region of earliest activation during VT in 50%, 55% and 50% of all VTs for RV I, ∆AT and ∆ARI, respectively. These early data confirm the mechanistic link between markers of arrhythmogenic risk and VT initiation and suggest that ECGI could be potentially used for targeting ablation in non-inducible or hemodynamically non-tolerated VTs