Antibacterial Envelope to Prevent Cardiac Implantable Device Infection.

BACKGROUND: Infections after placement of cardiac implantable electronic devices (CIEDs) are associated with substantial morbidity and mortality. There is limited evidence on prophylactic strategies, other than the use of preoperative antibiotics, to prevent such infections. METHODS: We conducted a randomized, controlled clinical trial to assess the safety and efficacy of an absorbable, antibiotic-eluting envelope in reducing the incidence of infection associated with CIED implantations. Patients who were undergoing a CIED pocket revision, generator replacement, or system upgrade or an initial implantation of a cardiac resynchronization therapy defibrillator were randomly assigned, in a 1:1 ratio, to receive the envelope or not. Standard-of-care strategies to prevent infection were used in all patients. The primary end point was infection resulting in system extraction or revision, long-term antibiotic therapy with infection recurrence, or death, within 12 months after the CIED implantation procedure. The secondary end point for safety was procedure-related or system-related complications within 12 months. RESULTS: A total of 6983 patients underwent randomization: 3495 to the envelope group and 3488 to the control group. The primary end point occurred in 25 patients in the envelope group and 42 patients in the control group (12-month Kaplan-Meier estimated event rate, 0.7% and 1.2%, respectively; hazard ratio, 0.60; 95% confidence interval [CI], 0.36 to 0.98; P = 0.04). The safety end point occurred in 201 patients in the envelope group and 236 patients in the control group (12-month Kaplan-Meier estimated event rate, 6.0% and 6.9%, respectively; hazard ratio, 0.87; 95% CI, 0.72 to 1.06; P<0.001 for noninferiority). The mean (±SD) duration of follow-up was 20.7±8.5 months. Major CIED-related infections through the entire follow-up period occurred in 32 patients in the envelope group and 51 patients in the control group (hazard ratio, 0.63; 95% CI, 0.40 to 0.98). CONCLUSIONS: Adjunctive use of an antibacterial envelope resulted in a significantly lower incidence of major CIED infections than standard-of-care infection-prevention strategies alone, without a higher incidence of complications. (Funded by Medtronic; WRAP-IT ClinicalTrials.gov number, NCT02277990.).

A retrospective evaluation of catheter ablation in atrial flutter post cardiac transplantation.

BACKGROUND: Atrial flutter is the most common arrhythmia post cardiac transplantation. Observational studies in the non-transplant population have shown prognostic benefit with catheter ablation; however, there are no data in the heart transplant population. OBJECTIVES: This study evaluated the experience of catheter ablation in atrial flutter post cardiac transplantation. METHODS: A retrospective review of experience of late onset atrial flutter at the Freeman Hospital, Newcastle-upon-Tyne, UK, between 1985 and January 2020. RESULTS: Sixty eight of the 722 patients who survived 6 months post cardiac transplantation developed late atrial flutter giving an incidence of 9.4%. Thirty-two patients were managed with ablation with treatment largely determined by time of flutter onset. Kaplan Meier estimates for arrhythmia free survival post first ablation for organized atrial arrhythmias was 83.3% at 1 year. Kaplan-Meier estimates for median survival post onset of atrial arrhythmias treated with ablation was 11.34 years (95% CI 8.00-14.57), compared to 5.79 years in patients managed medically (95%CI 2.26-9.32) (P = .026). CONCLUSIONS: Atrial flutter is an important late complication of cardiac transplantation. Patients treated with ablation in the modern era had increased survival compared to a historical cohort.

Cost-Effectiveness Analyses of an Absorbable Antibacterial Envelope for Use in Patients at Increased Risk of Cardiac Implantable Electronic Device Infection in Germany, Italy, and England.

OBJECTIVES: To model the cost-effectiveness of the TYRX Absorbable Antibacterial Envelope when used in patients at increased risk of cardiac implantable electronic device (CIED) infection in the context of 3 European healthcare systems: Germany, Italy, and England. METHODS: A decision tree model with a lifetime horizon was populated using data from the Worldwide Randomized Antibiotic Envelope Infection Prevention Trial, a large multicenter randomized controlled trial. Use of the antibacterial envelope adjunctive to standard of care was compared to standard of care infection prevention alone. Patients in the model were divided into subgroups based on presence of factors known to increase infection risk. RESULTS: The antibacterial envelope had the most favorable cost-effectiveness profile when patients had previously experienced CIED infection, had a history of immunosuppressive therapy, or had a Prevention of Arrhythmia Device Infection Trial (PADIT) score indicating high risk of infection (scores ≥6) at cost-effectiveness thresholds of €50 000 in Germany (assumed in the absence of an official threshold), €40 000 in Italy, and £30 000 in England. Probabilistic sensitivity analysis indicated that the antibacterial envelope was likely to be cost-effective in patients with other risk factors (including replacement of high power CIEDs, generator replacement with lead modification, and PADIT scores indicating intermediate risk of infection) when used with some device types and in some countries. CONCLUSIONS: The absorbable antibacterial envelope was associated with cost-effectiveness ratios below European benchmarks in selected patients at increased risk of infection, suggesting the envelope provides value for European healthcare systems by reducing CIED infections.

Remote management of heart failure using implantable electronic devices.

AIMS: Remote management of heart failure using implantable electronic devices (REM-HF) aimed to assess the clinical and cost-effectiveness of remote monitoring (RM) of heart failure in patients with cardiac implanted electronic devices (CIEDs). METHODS AND RESULTS: Between 29 September 2011 and 31 March 2014, we randomly assigned 1650 patients with heart failure and a CIED to active RM or usual care (UC). The active RM pathway included formalized remote follow-up protocols, and UC was standard practice in nine recruiting centres in England. The primary endpoint in the time to event analysis was the 1st event of death from any cause or unplanned hospitalization for cardiovascular reasons. Secondary endpoints included death from any cause, death from cardiovascular reasons, death from cardiovascular reasons and unplanned cardiovascular hospitalization, unplanned cardiovascular hospitalization, and unplanned hospitalization. REM-HF is registered with ISRCTN (96536028). The mean age of the population was 70 years (range 23-98); 86% were male. Patients were followed for a median of 2.8 years (range 0-4.3 years) completing on 31 January 2016. Patient adherence was high with a drop out of 4.3% over the course of the study. The incidence of the primary endpoint did not differ significantly between active RM and UC groups, which occurred in 42.4 and 40.8% of patients, respectively [hazard ratio 1.01; 95% confidence interval (CI) 0.87-1.18; P = 0.87]. There were no significant differences between the two groups with respect to any of the secondary endpoints or the time to the primary endpoint components. CONCLUSION: Among patients with heart failure and a CIED, RM using weekly downloads and a formalized follow up approach does not improve outcomes.

Sympathetic reinnervation in cardiac transplant recipients: Prevalence, time course and association with long-term survival.

BACKGROUND: Partial cardiac sympathetic reinnervation after cardiac transplant has been extensively investigated and evidenced. However, there have been no large-scale, long-term studies evaluating the prevalence, time-course, and association with long-term survival of sympathetic reinnervation of the heart. METHODS: Cardiac transplant recipients (n=232) were recruited from outpatient clinic at a single transplant centre in the United Kingdom. Participants were each tested once for the presence of sympathetic reinnervation of the sinus node using the low frequency component of power spectral analysis of heart rate variability, with a cut-off defined as 2 standard deviations above the mean for denervated participants (those tested <56 days post-transplant). Time-course was calculated based on the timing of testing post-transplant. Patients were then followed-up over a period of up to 27 years after transplant for survival analysis. RESULTS: The overall prevalence of cardiac sympathetic reinnervation in the 225 patients tested >56 days post-transplant was 64.9%. Sympathetic reinnervation primarily occurred in the first 18 months after transplant, with a plateau thereafter. The prevalence in participants tested >18 months post-transplant was 69.6%. In Kaplan-Meier survival analysis, sympathetic reinnervation was associated with significantly improved survival (Log-rank P=0.019), with a median survival time for reinnervated patients of 19.9 years compared to 14.4 years for the denervated group. CONCLUSIONS: Sympathetic reinnervation of the sinus node occurs mostly within 18 months of transplant, is found in 70% of cardiac transplant recipients tested >18 months post-transplant, and is associated with significantly improved long-term survival.

'You can't start a car when there's no petrol left': a qualitative study of patient, family and clinician perspectives on implantable cardioverter defibrillator deactivation.

OBJECTIVE: To explore the attitudes towards implantable cardioverter defibrillator (ICD) deactivation and initiation of deactivation discussions among patients, relatives and clinicians. DESIGN: A multiphase qualitative study consisting of in situ hospital ICD clinic observations, and semistructured interviews of clinicians, patients and relatives. Data were analysed using a constant comparative approach. SETTING: One tertiary and two district general hospitals in England. PARTICIPANTS: We completed 38 observations of hospital consultations prior to ICD implantation, and 80 interviews with patients, family members and clinicians between 2013 and 2015. Patients were recruited from preimplantation to postdeactivation. Clinicians included cardiologists, cardiac physiologists, heart failure nurses and palliative care professionals. RESULTS: Four key themes were identified from the data: the current status of deactivation discussions; patients' perceptions of deactivation; who should take responsibility for deactivation discussions and decisions; and timing of deactivation discussions. We found that although patients and doctors recognised the importance of advance care planning, including ICD deactivation at an early stage in the patient journey, this was often not reflected in practice. The most appropriate clinician to take the lead was thought to be dependent on the context, but could include any appropriately trained member of the healthcare team. It was suggested that deactivation should be raised preimplantation and regularly reviewed. Identification of trigger points postimplantation for deactivation discussions may help ensure that these are timely and inappropriate shocks are avoided. CONCLUSIONS: There is a need for early, ongoing and evolving discussion between ICD recipients and clinicians regarding the eventual need for ICD deactivation. The most appropriate clinician to instigate deactivation discussions is likely to vary between patients and models of care. Reminders at key trigger points, and routine discussion of deactivation at implantation and during advance care planning could prevent distressing experiences for both the patient and their family at the end of life.

A multicenter prospective randomized controlled trial of cardiac resynchronization therapy guided by invasive dP/dt.

BACKGROUND: No periprocedural metric has demonstrated improved cardiac resynchronization therapy (CRT) outcomes in a multicenter setting. OBJECTIVE: We sought to determine if left ventricular (LV) lead placement targeted to the coronary sinus (CS) branch generating the best acute hemodynamic response (AHR) results in improved outcomes at 6 months. METHODS: In this multicenter randomized controlled trial, patients were randomized to guided CRT or conventional CRT. Patients in the guided arm had LV dP/dtmax measured during biventricular (BIV) pacing. Target CS branches were identified and the final LV lead position was the branch with the best AHR and acceptable threshold values. The primary endpoint was the proportion of patients with a reduction in LV end-systolic volume (LVESV) of ≥15% at 6 months. RESULTS: A total of 281 patients were recruited across 12 centers. Mean age was 70.8 ± 10.9 years and 54% had ischemic etiology. Seventy-three percent of patients in the guided arm demonstrated a reduction in LVESV of ≥15% at 6 months vs 60% in the conventional arm (P = .02). Patients with AHR ≥ 10% were more likely to demonstrate a reduction of ESV ≥ 15% (84% of patients with an AHR ≥10% vs 28% with an AHR <10%; P < 0.001). Procedure duration and fluoroscopy times were longer in the pressure wire-guided arm (104 ± 39 minutes vs 142 ± 39 minutes; P < .001 and 20 ±16 minutes vs 28 ± 15 minutes; P = .002). CONCLUSIONS: AHR determined by invasively measuring LV dP/dtmax during BIV pacing predicts reverse remodeling 6 months after CRT. Patients in whom LV dP/dtmax was used to guide LV lead placement demonstrated better rates of reverse remodeling.

Prevalence and prognostic significance of device-detected subclinical atrial fibrillation in patients with heart failure and reduced ejection fraction.

BACKGROUND: Cardiac implanted electronic devices (CIEDs) can detect short durations of previously unrecognised atrial fibrillation (AF). The prognostic significance of device-detected subclinical AF, in the context of contemporary heart failure (HF) therapy, is unclear. METHODS: Amongst patients enrolled in the Remote Monitoring in HF with implanted devices (REM-HF) trial, three categories were defined based on total AF duration in the first year of follow-up: no AF, subclinical AF (≥6 min to ≤24 h), and AF >24 h. All-cause mortality, stroke, and cardiovascular hospitalisation were assessed. RESULTS: 1561 patients (94.6%) had rhythm data: 71 (4.6%) had subclinical AF (median of 4 episodes, total duration 3.1 h) and 279 (17.9%) had AF >24 h. During 2.8 ± 0.8 years' follow-up, 39 (2.5%) patients had a stroke. Stroke rate was highest amongst patients with subclinical AF (2.0 per 100-person years) versus no AF or AF >24 h (0.8 and 1.0 per 100-person years, respectively). In the overall cohort, AF >24 h was not an independent predictor of stroke. However, amongst patients with no history of AF (n = 932), new-onset subclinical AF conferred a three-fold higher stroke risk (adjusted HR 3.35, 95%CI 1.15-9.77, p = 0.027). AF >24 h was associated with more frequent emergency cardiovascular hospitalisation (adjusted HR 1.46, 95%CI 1.19-1.79, p < 0.0005). Neither AF classification was associated with mortality. CONCLUSIONS: In patients with HF and a CIED, subclinical AF was infrequent but, as a new finding, was associated with an increased risk of stroke. Anticoagulation remains an important consideration in this population, particularly when the clinical profile indicates a high stroke risk.

Impact of remote monitoring on clinical outcomes for patients with heart failure and atrial fibrillation: results from the REM-HF trial.

AIMS: Studies of remote monitoring (RM) in heart failure (HF) speculate that patients with atrial fibrillation (AF) derive the greatest benefit. We compared the impact of RM vs. usual care on clinical outcomes for patients with and without AF enrolled in the Remote Management of Heart Failure Using Implanted Electronic Devices (REM-HF) trial. METHODS AND RESULTS: Rhythm status was available for 1561 patients (94.6%). Three categories were defined based on total AF duration during the first year of follow-up: (i) no AF (n = 1211, 77.6%), (ii) paroxysmal AF (≥6 min to ≤7 days; n = 92, 5.9%), and (iii) persistent/permanent AF (>7 days; n = 258, 16.5%). Clinical activity, mortality, and hospitalisation rates were compared between treatment strategies for each group. RM resulted in a greater volume of clinical activity in patients with any AF, vs. no AF, with the highest per-patient intervention required for patients with persistent/permanent AF. During 2.8 ± 0.8 years of follow-up, RM was not associated with a reduction in all-cause or cardiovascular mortality for patients with AF. However, in patients with persistent/permanent AF, RM conferred an increased risk of recurrent cardiovascular [hazard ratio (HR) 1.40, 95% confidence interval (CI) 1.06-1.85, P = 0.018] and HF-related (HR 2.05, 95% CI 1.14-3.69, P = 0.016) hospitalisations. CONCLUSION: In patients with HF and a cardiac implanted electronic device, RM generated greater clinical activity for patients with AF, with no associated reduction in mortality, and conversely, greater risk of cardiovascular hospitalisation amongst patients with persistent/permanent AF. RM strategies may vary in their capability to guide HF management; modified approaches may be needed to improve outcomes for HF patients with AF.

Inequity of access to implantable cardioverter defibrillator therapy in England: possible causes of geographical variation in implantation rates.

AIMS: There is marked geographical variation in implantable cardioverter defibrillator (ICD) implantation rates in England. This study examined factors which might explain this variation. METHODS AND RESULTS: Detailed data relating to 1510 patients who received an implanted defibrillator and who were reported to a national pacemaker and implantable defibrillator registry in 2002 were examined and correlated with factors which have been suggested as affecting ICD implantation. None of the factors examined, which included factors related both to the need for ICD implantation and service provision, in addition to socio-economic deprivation, was found to correlate with regional ICD implantation rates. CONCLUSION: There appears to have been no systematic planning of ICD services. Whether this has led to the marked regional variation and in inequity of service provision is not clear.

Blackout? Cause: misdiagnosis of cardiac arrest.

Patients with syncope or epilepsy commonly present to primary or secondary care physicians. This lesson presents two patients, both known to have cardiac disease, with implanted cardiac devices, who presented with loss of consciousness, who were initially investigated for epilepsy, but were subsequently shown to have had a cardiac arrhythmia, diagnosed following device interrogation.

The use of a single chamber leadless pacemaker for the treatment of cardioinhibitory vasovagal syncope.

BACKGROUND: The use of pacemakers in the treatment of cardioinhibitory vasovagal syncope is controversial with a mixed message from the limited evidence base. Single chamber leadless pacemakers have been shown to be an effective alternative option to conventional pacemakers. OBJECTIVE: This study examines the use of leadless pacemakers in a cardioinhibitory vasovagal population in the United Kingdom. METHODS: Observational data on 32 patients implanted with the Micra Transcatheter Pacemaker System for vasovagal syncope are presented. Data was collected on implant indications, implant procedure and follow up data from 12 centres across the United Kingdom that had elected to use a Micra leadless pacemaker in this patient population. RESULTS: 32 patients aged 37 ±â€¯14 years (range 18 to 64 years) with 62% of the patients being female were recruited to the study. Vasovagal syncope was diagnosed clinically and with the support of Holter monitoring, tilt table testing and implantable loop recorders. The duration of symptoms was 8 ±â€¯8 yrs. with an average frequency of syncope being 4 ±â€¯6 times/year. The Micra pacemaker was successfully implanted in all patients with a major complication rate of 3.1%. Patients were followed up for 404 ±â€¯237 days (range 63-928 days). At follow up 28 (87%) patients were free from symptoms. CONCLUSIONS: This observational study suggests that the use of a single chamber leadless pacemaker in the treatment of cardioinhibitory vasovagal syncope might be a reasonable clinical option.

Significance of silent ischemia and microalbuminuria in predicting coronary events in asymptomatic patients with type 2 diabetes.

OBJECTIVES: The aim of this study was to investigate the relationships between future coronary heart disease (CHD) events and baseline silent myocardial ischemia (SMI) and microalbuminuria (MA) in subjects with type 2 diabetes (T2D) free from known CHD. BACKGROUND: Coronary heart disease is often asymptomatic in subjects with diabetes. There is limited information on the prognostic value of SMI and MA in this group. METHODS: Eighty-six patients with T2D and no history of CHD were studied (43 with MA individually matched with 43 normoalbuminuric patients; mean [SD] age 62 [+/-7] years, 62 men). Metabolic assessment, three timed overnight urine collections for albumin excretion rate, a treadmill exercise test and ankle brachial index (ABI) were performed at baseline. Patients were followed for 2.8 years. RESULTS: Forty-five (52%) patients had SMI during treadmill testing. At review, there had been 23 coronary (CHD) events in 15 patients. Univariate Cox regression analysis showed that CHD events were significantly related to baseline ABI (p = 0.014), SMI (p = 0.020), MA (p = 0.046), 10-year Framingham CHD risk >30% (p = 0.035) and fibrinogen (p = 0.026). In multivariate analysis, SMI was the strongest independent predictor of CHD events (p = 0.008); risk ratio (95% confidence interval) for SMI: 21 (2 to 204). In the prediction of CHD events, SMI showed higher sensitivity and positive predictive value than MA or Framingham calculated CHD risk. CONCLUSIONS: The presence of baseline SMI and MA are associated with future CHD events in asymptomatic patients with T2D and may be of practical use in risk stratification.

Temporary left ventricular pacing improves haemodynamic performance in patients requiring epicardial pacing post cardiac surgery.

OBJECTIVE: In the 1990s, sequential atrio-ventricular pacing demonstrated haemodynamic benefit relative to right ventricular pacing in patients with sinus rhythm requiring pacing post cardiopulmonary bypass. The benefit of biventricular pacing has been demonstrated in non-surgical patients with severe left ventricular dysfunction. It was hypothesised that left ventricular pacing would increase cardiac output in surgical patients. We report the findings of a prospective trial of left ventricular pacing with active lead placement on the anterior or posterior left ventricular surface, compared to standard practice of active lead placement on the right ventricular surface. METHODS: Twenty five patients with left ventricular dysfunction underwent pacing with active lead placement on the right ventricle (control), the anterior left ventricle and the posterior left ventricle in random order, with each pacing mode of 10 min duration, following cardiopulmonary bypass. Haemodynamic parameters were measured with a thermodilution pulmonary artery catheter. Patients provided their control values. RESULTS: In the 25 patients studied, pacing with the active lead posteriorly on the left ventricle increased cardiac index from 2.74 to 3.08 l/min per m2 (P=0.019). Significant increases in mean arterial pressure with the use of this pacing mode were observed. There were no complications relating to application or removal of the left ventricle pacing leads. CONCLUSIONS: Left ventricular pacing with active lead placed on the postero-lateral left ventricular wall affords haemodynamic benefit to cardiac surgical patients.

Rationale and study design of the REM-HF study: remote management of heart failure using implanted devices and formalized follow-up procedures.

AIMS: We wish to assess the clinical and cost-effectiveness of remote monitoring of heart failure patients with cardiac implanted electronic devices. METHODS: REM-HF is a multicentre, randomized, non-blinded, parallel trial designed to compare weekly remote monitoring-driven management with usual care for patients with cardiac implanted electronic devices (ICD, CRT-D, or CRT-P). The trial is event driven, and the final analysis will be performed when 546 events have been observed or the study is terminated at the interim analysis. We have randomized 1650 patients to be followed up for a minimum of 2 years. Patients will remain in the trial up to study termination. The first patient was randomized in September 2011 and the study is expected to complete in early 2016. The primary combined endpoint is time to first event of all-cause death or unplanned hospitalization for cardiovascular reasons. An economic evaluation will be performed, estimating the cost per quality-adjusted life year, with direct costs estimated from the National Health Service perspective and quality of life assessed by the EQ-5D, Short-Form 12, and Kansas City Cardiomyopathy Questionnaires. The study design has been informed by a feasibility study. CONCLUSION: REM-HF is a multicentre randomized study that will provide important data on the effect of remote monitoring-driven management of implanted cardiac devices on morbidity and mortality, as well as the cost-effectiveness of this approach.

Incorporating the patient perspective: a critical review of clinical practice guidelines for implantable cardioverter defibrillator therapy.

PURPOSE: Implantable cardioverter defibrillators (ICDs) are recommended for patients with heart failure and/or ventricular arrhythmias at risk of sudden cardiac death. Guidelines for ICD implantation are derived from robust clinical data. However, critical factors which might influence treatment decisions include patient preferences. We set out to determine how clinical practice guidelines (CPGs) incorporate the patient perspective into supporting decision making about ICDs. METHODS: CPGs on ICD implantation were purposively selected from national and professional bodies in Europe, North America and Australasia. CPGs were then appraised according to three key domains of shared decision making: (a) informing patients about the risks, benefits and consequences known to be important to patients; (b) personalising risks and benefits and (c) involvement of patient (plus family/significant others if desired) in decision making. RESULTS: Appraisal of six current CPGs found major deficiencies or inconsistencies in guidance. CPGs tended to focus on evidence of device effectiveness, with sparse consideration of other outcomes important to patients such as impacts on quality of life and psychosocial well-being. Little reference was made to involvement of the patient in decision making. CONCLUSIONS: This suggests that embedding shared decision in CPGs will improve the patient-centeredness of ICD treatment by enabling patients to make informed, value-based decisions. Specific recommendations for CPG development include the need for signposting to preference sensitive decision points as well as inclusion of a broader range of outcomes which are known to be important to patients when deciding whether or not to have a device fitted.

Comparison of Sprint Fidelis and Riata defibrillator lead failure rates.

BACKGROUND/OBJECTIVES: Sprint Fidelis and Riata defibrillator leads are prone to early failure. Few data exist on the comparative failure rates and mortality related to lead failure. The aims of this study were to determine the failure rate of Sprint Fidelis and Riata leads, and to compare failure rates and mortality rates in both groups. METHODS: Patients implanted with Sprint Fidelis leads and Riata leads at a single centre were identified and in July 2012, records were reviewed to ascertain lead failures, deaths, and relationship to device/lead problems. RESULTS: 113 patients had Sprint Fidelis leads implanted between June 2005 and September 2007; Riata leads were implanted in 106 patients between January 2003 and February 2008. During 53.0 ± 22.3 months of follow-up there were 13 Sprint Fidelis lead failures (11.5%, 2.60% per year) and 25 deaths. Mean time to failure was 45.1 ± 15.5 months. In the Riata lead cohort there were 32 deaths, and 13 lead failures (11.3%, 2.71% per year) over 54.8 ± 26.3 months follow-up with a mean time to failure of 53.5 ± 24.5 months. There were no significant differences in the lead failure-free Kaplan-Meier survival curve (p=0.77), deaths overall (p=0.17), or deaths categorised as sudden/cause unknown (p=0.54). CONCLUSIONS: Sprint Fidelis and Riata leads have a significant but comparable failure rate at 2.60% per year and 2.71% per year of follow-up respectively. The number of deaths in both groups is similar and no deaths have been identified as being related to lead failure in either cohort.