Association of the Timing and Extent of Cardiac Implantable Electronic Device Infections With Mortality.

Importance: Cardiac implantable electronic device (CIED) infection is a potentially devastating complication with an estimated 12-month mortality of 15% to 30%. The association of the extent (localized or systemic) and timing of infection with all-cause mortality has not been established. Objective: To evaluate the association of the extent and timing of CIED infection with all-cause mortality. Design, Setting, and Participants: This prospective observational cohort study was conducted between December 1, 2012, and September 30, 2016, in 28 centers across Canada and the Netherlands. The study included 19 559 patients undergoing CIED procedures, 177 of whom developed an infection. Data were analyzed from April 5, 2021, to January 14, 2023. Exposures: Prospectively identified CIED infections. Main Outcomes and Measures: Time-dependent analysis of the timing (early [≤3 months] or delayed [3-12 months]) and extent (localized or systemic) of infection was performed to determine the risk of all-cause mortality associated with CIED infections. Results: Of 19 559 patients undergoing CIED procedures, 177 developed a CIED infection. The mean (SD) age was 68.7 (12.7) years, and 132 patients were male (74.6%). The cumulative incidence of infection was 0.6%, 0.7%, and 0.9% within 3, 6, and 12 months, respectively. Infection rates were highest in the first 3 months (0.21% per month), reducing significantly thereafter. Compared with patients who did not develop CIED infection, those with early localized infections were not at higher risk for all-cause mortality (no deaths at 30 days [0 of 74 patients]: adjusted hazard ratio [aHR], 0.64 [95% CI, 0.20-1.98]; P = .43). However, patients with early systemic and delayed localized infections had an approximately 3-fold increase in mortality (8.9% 30-day mortality [4 of 45 patients]: aHR, 2.88 [95% CI, 1.48-5.61]; P = .002; 8.8% 30-day mortality [3 of 34 patients]: aHR, 3.57 [95% CI, 1.33-9.57]; P = .01), increasing to a 9.3-fold risk of death for those with delayed systemic infections (21.7% 30-day mortality [5 of 23 patients]: aHR, 9.30 [95% CI, 3.82-22.65]; P < .001). Conclusions and Relevance: Findings suggest that CIED infections are most common within 3 months after the procedure. Early systemic infections and delayed localized infections are associated with increased mortality, with the highest risk for patients with delayed systemic infections. Early detection and treatment of CIED infections may be important in reducing mortality associated with this complication.

Impact of Choice of Prophylaxis on the Microbiology of Cardiac Implantable Electronic Device Infections: Insights From the Prevention of Arrhythmia Device Infection Trial (PADIT).

BACKGROUND: The Prevention of Arrhythmia Device Infection Trial (PADIT) investigated whether intensification of perioperative prophylaxis could prevent cardiac implantable electronic device (CIED) infections. Compared with a single dose of cefazolin, the perioperative administration of cefazolin, vancomycin, bacitracin, and cephalexin did not significantly decrease the risk of infection. Our objective was to compare the microbiology of infections between study arms in PADIT. METHODS: This was a post hoc analysis. Differences between study arms in the microbiology of infections were assessed at the level of individual patients and at the level of microorganisms using the Fisher exact test. RESULTS: Overall, 209 microorganisms were reported from 177 patients. The most common microorganisms were coagulase-negative staphylococci (CoNS; 82/209 [39.2%]) and S. aureus (75/209 [35.9%]). There was a significantly lower proportion of CoNS in the incremental arm compared with the standard arm (30.1% vs 46.6%; P = .04). However, there was no significant difference between study arms in the frequency of recovery of other microorganisms. In terms of antimicrobial susceptibility, 26.5% of microorganisms were resistant to cefazolin. CoNS were more likely to be cefazolin-resistant in the incremental arm (52.2% vs 26.8%, respectively; P = .05). However, there was no difference between study arms in terms of infections in which the main pathogen was sensitive to cefazolin (77.8% vs 64.3%; P = .10) or vancomycin (90.8% vs 90.2%; P = .90). CONCLUSIONS: Intensification of the prophylaxis led to significant changes in the microbiology of infections, despite the absence of a decrease in the overall risk of infections. These findings provide important insight on the physiopathology of CIED infections. TRIAL REGISTRATION: NCT01002911.

Risk Factors for Infections Involving Cardiac Implanted Electronic Devices.

BACKGROUND: Cardiac implantable electronic device infection is a major complication that usually requires device removal. PADIT (Prevention of Arrhythmia Device Infection Trial) was a large cluster crossover trial of conventional versus incremental antibiotics. OBJECTIVES: This study sought to investigate independent predictors of device infection in PADIT and develop a novel infection risk score. METHODS: In brief, over 4 6-month periods, 28 centers used either conventional or incremental prophylactic antibiotic treatment in all patients. The primary outcome was hospitalization for device infection within 1 year (blinded endpoint adjudication). Multivariable logistic prediction modeling was used to identify the independent predictors and develop a risk score for device infection. The prediction models were internally validated with bootstrap methods. RESULTS: Device procedures were performed in 19,603 patients, and hospitalization for infection occurred in 177 (0.90%) within 1 year of follow-up. The final prediction model identified 5 independent predictors of device infection (prior procedures [P], age [A], depressed renal function [D], immunocompromised [I], and procedure type [T]) with an optimism-corrected C-statistic of 0.704 (95% confidence interval: 0.660 to 0.744). A PADIT risk score ranging from 0 to 15 points classified patients into low (0 to 4), intermediate (5 to 6) and high (≥7) risk groups with rates of hospitalization for infection of 0.51%, 1.42%, and 3.41%, respectively. CONCLUSIONS: This study identified 5 independent predictors of device infection and developed a novel infection risk score in the largest cardiac implantable electronic device trial to date, warranting validation in an independent cohort. The 5 independent predictors in the PADIT score are readily adopted into clinical practice. (Prevention of Arrhythmia Device Infection Trial [PADIT Pilot]; NCT01002911).

Prevention of Arrhythmia Device Infection Trial: The PADIT Trial.

BACKGROUND: Infection of implanted medical devices has catastrophic consequences. For cardiac rhythm devices, pre-procedural cefazolin is standard prophylaxis but does not protect against methicillin-resistant gram-positive organisms, which are common pathogens in device infections. OBJECTIVE: This study tested the clinical effectiveness of incremental perioperative antibiotics to reduce device infection. METHODS: The authors performed a cluster randomized crossover trial with 4 randomly assigned 6-month periods, during which centers used either conventional or incremental periprocedural antibiotics for all cardiac implantable electronic device procedures as standard procedure. Conventional treatment was pre-procedural cefazolin infusion. Incremental treatment was pre-procedural cefazolin plus vancomycin, intraprocedural bacitracin pocket wash, and 2-day post-procedural oral cephalexin. The primary outcome was 1-year hospitalization for device infection in the high-risk group, analyzed by hierarchical logistic regression modeling, adjusting for random cluster and cluster-period effects. RESULTS: Device procedures were performed in 28 centers in 19,603 patients, of whom 12,842 were high risk. Infection occurred in 99 patients (1.03%) receiving conventional treatment, and in 78 (0.78%) receiving incremental treatment (odds ratio: 0.77; 95% confidence interval: 0.56 to 1.05; p = 0.10). In high-risk patients, hospitalization for infection occurred in 77 patients (1.23%) receiving conventional antibiotics and in 66 (1.01%) receiving incremental antibiotics (odds ratio: 0.82; 95% confidence interval: 0.59 to 1.15; p = 0.26). Subgroup analysis did not identify relevant patient or site characteristics with significant benefit from incremental therapy. CONCLUSIONS: The cluster crossover design efficiently tested clinical effectiveness of incremental antibiotics to reduce device infection. Device infection rates were low. The observed difference in infection rates was not statistically significant. (Prevention of Arrhythmia Device Infection Trial [PADIT Pilot] [PADIT]; NCT01002911).

Using left-ventricular-only pacing to eliminate T-wave oversensing in a biventricular implantable cardiac defibrillator.

A man aged 75 years and with nonischemic cardiomyopathy had implantation of a biventricular implantable cardiac defibrillator (ICD). Consistent biventricular pacing was limited by intermittent T-wave oversensing (TWOS). A strategy of left-ventricular-only pacing was used to eliminate TWOS. This strategy obviates the need to reduce ventricular sensitivity and thus may be an effective alternative to biventricular pacing complicated by TWOS.

Maximum oxygen uptake corrected for skeletal muscle mass accurately predicts functional improvements following exercise training in chronic heart failure.

BACKGROUND: Skeletal muscle mass and peak oxygen uptake are important predictors of functional status and outcome in patients with stable chronic heart failure. AIMS: To assess changes in skeletal muscle mass and peak oxygen uptake following an exercise training program. METHODS: Thirty-six patients with moderate stable chronic heart failure were randomly allocated to either a bicycle ergometer (bike) or functional electrical muscle stimulators (FES) applied to quadriceps and gastrocnemius muscles to be used daily for six weeks. Dual-energy X-ray absorptionometry (DEXA) scanning was performed before and after training along with symptom limited cardiopulmonary exercise test, quadriceps strength and fatigue resistance, and 6-min walk test. RESULTS: Both exercise modalities resulted in improvements in treadmill exercise time, leg strength, 6-min walk test and peak oxygen uptake per kilogram of skeletal muscle. Despite significant improvements in functional capacity, there were no significant changes in body composition for total skeletal muscle mass, leg muscle mass or total body fat content. Skeletal muscle mass was strongly predictive of maximum oxygen uptake at baseline (r=0.61, p<0.001) and after exercise training (r=0.68, p<0.001). CONCLUSIONS: In moderate stable chronic heart failure, exercise training using bicycle ergometer or FES results in favourable qualitative rather than quantitative changes in skeletal muscle. Correction of maximum oxygen uptake for skeletal muscle mass rather than total body mass is a more sensitive measure of changes associated with exercise training.

Change in circulating cytokines after 2 forms of exercise training in chronic stable heart failure.

BACKGROUND: A proinflammatory state is recognized in chronic heart failure and the degree of immune activation corresponds to disease severity and prognosis. Training is known to improve symptoms in heart failure but less is known about the effects of specific forms of training on the proinflammatory state. METHODS: Forty-six patients with stable chronic heart failure underwent a home-based program of exercise training for 30 minutes a day, 5 days per week over a 6-week period. Twenty-four used a bicycle ergometer and 22 used an electrical muscle stimulator applied to quadriceps and gastrocnemius muscles. Tumour necrosis factor-alpha (TNF-alpha), TNF-alpha soluble receptors 1 and 2, interleukin 6, and C-reactive protein were measured before and after the training period. RESULTS: Significant improvements in markers of exercise performance were seen in both training groups. Soluble TNF-alpha receptor 2 levels decreased after training in the bike group only (2900 +/- 1069 pg/mL to 2625 +/- 821 pg/mL, P =.013). Trends towards a decrease in levels of TNF-alpha and soluble receptor 1 were also seen in the bike group only. No change in circulating inflammatory markers was observed after stimulator training. CONCLUSIONS: Physical training improves exercise capacity for patients with chronic heart failure but degree of attenuation of the proinflammatory response may depend on the mode of training despite similar improvements in exercise capacity.

Management of chronic heart failure due to systolic left ventricular dysfunction by cardiologist and non-cardiologist physicians.

There are now a number of guidelines outlining the diagnosis and management of patients with chronic heart failure (CHF). The extent to which these guidelines are used and the effects on patient outcomes are not well known. The aim of this study was to examine the implementation of a heart failure guideline among cardiologist and non-cardiologist physicians in a university hospital setting. Case record data were examined from 400 patients with a primary diagnosis of CHF. Management of these patients was assessed using a systolic heart failure guideline (Scottish Intercollegiate Guideline Network, number 35) as a benchmark. Hospital admission data were examined contemporaneously over a 17-month period to assess associations between adherence to drug therapies and number of admissions. Overall, there was poor adherence to the guideline, with relatively high use of angiotensin-converting enzyme (ACE) inhibitors/angiotensin II receptor blockers (ARBs) (80%), low use of beta-blockers (32%) and digoxin (36%), and very low use of spironolactone (13%). Cardiologists used more beta-blockers (37 vs. 21%, P=0.003) and digoxin in sinus rhythm (18 vs. 5%, P<0.001) than non-cardiologists. Hospital admission rate was individually associated with increasing age, NYHA status, beta-blocker, diuretic and spironolactone prescription (all P<0.001). At multivariable analysis, only age, NYHA status and increased diuretic prescription were associated with more frequent admission (P<0.001, R(2)=0.15). Despite carefully designed guidelines, the implementation of evidence-based therapies for CHF remains inadequate, even in a university hospital environment. This may reflect a lack of organisational developments to facilitate the increasingly complex management of patients with CHF.

A randomised study of home-based electrical stimulation of the legs and conventional bicycle exercise training for patients with chronic heart failure.

AIMS: Recent guidelines recommend regular exercise in the management of patients with chronic heart failure (CHF). This study was designed to compare the safety and efficacy of conventional bicycle exercise and functional electrical stimulation (FES) of the legs as forms of home-based exercise training for patients with stable CHF. METHODS AND RESULTS: Forty-six patients (38 male) with stable NYHA Class II/III heart failure underwent a 6-week training programme using either a bicycle ergometer or electrical stimulation of the quadriceps and gastrocnemius muscles. In the bike group, significant increases were seen in 6-min walk (44.6m, 95% confidence interval (CI) 29.3-60.9 m), treadmill exercise time (110 s, 95% CI 72.2-148.0 s), maximum leg strength (5.32 kg, 95% CI 3.18-7.45 kg), and quadriceps fatigue index (0.08, 95% CI 0.04-0.12) following training. In the stimulator group, similar significant increases were seen following training for 6-min walk (40.6m, 95% CI 28.2-53.0m), treadmill exercise time (67 s, 95% CI 11.8-121.8s), maximum leg strength (5.35 kg, 95% CI 1.53-9.17 kg), and quadriceps fatigue index (0.10, 95% CI 0.04-0.17). Peak VO(2)did not change in either group following training, indicating a low-intensity regime. Quality of life scores improved following training when the bicycle and stimulator groups were considered together, but not when considered separately (-0.43, 95% CI -8.13 to -0.56). CONCLUSIONS: FES produces beneficial changes in muscle performance and exercise capacity in patients with CHF. Within this study, the benefits were similar to those observed following bicycle training. FES could be offered to patients with heart failure as an alternative to bicycle training as part of a home-based rehabilitation programme.