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.).

Long-Term Changes in Atrial Arrhythmia Burden After Renal Denervation Combined With Pulmonary Vein Isolation: SYMPLICITY-AF.

BACKGROUND: The autonomic nervous system plays an important role in atrial fibrillation (AF) and hypertension. Renal denervation (RDN) lowers blood pressure (BP), but its role in AF is poorly understood. OBJECTIVES: The purpose of this study was to investigate whether RDN reduces AF recurrence after pulmonary vein isolation (PVI). METHODS: This study randomized patients from 8 centers (United States, Germany) with drug-refractory AF for treatment with PVI+RDN vs PVI alone. A multielectrode radiofrequency Spyral catheter system was used for RDN. Insertable cardiac monitors were used for continuous rhythm monitoring. The primary efficacy endpoint was ≥2 minutes of AF recurrence or repeat ablation during all follow-up. The secondary endpoints included atrial arrhythmia (AA) burden, discontinuation of class I/III antiarrhythmic drugs, and BP changes from baseline. RESULTS: A total of 70 patients with AF (52 paroxysmal, 18 persistent) and uncontrolled hypertension were randomized (RDN+PVI, n = 34; PVI, n = 36). At 3.5 years, 26.2% and 21.4% of patients in RDN+PVI and PVI groups, respectively, were free from the primary efficacy endpoint (log rank P = 0.73). Patients with mean ≥1 h/d AA had less daily AA burden after RDN+PVI vs PVI (4.1 hours vs 9.2 hours; P = 0.016). More patients discontinued class I/III antiarrhythmic drugs after RDN+PVI vs PVI (45% vs 14%; P = 0.040). At 1 year, systolic BP changed by -17.8 ± 12.8 mm Hg and -13.7 ± 18.8 mm Hg after RDN+PVI and PVI, respectively (P = 0.43). The composite safety endpoint was not significantly different between groups. CONCLUSIONS: In patients with AF and uncontrolled BP, RDN+PVI did not prevent AF recurrence more than PVI alone. However, RDN+PVI may reduce AF burden and antiarrhythmic drug usage, but this needs further prospective validation.

Cost-Effectiveness of an Antibacterial Envelope for Cardiac Implantable Electronic Device Infection Prevention in the US Healthcare System From the WRAP-IT Trial.

BACKGROUND: In the WRAP-IT trial (Worldwide Randomized Antibiotic Envelope Infection Prevention), adjunctive use of an absorbable antibacterial envelope resulted in a 40% reduction of major cardiac implantable electronic device infection without increased risk of complication in 6983 patients undergoing cardiac implantable electronic device revision, replacement, upgrade, or initial cardiac resynchronization therapy defibrillator implant. There is limited information on the cost-effectiveness of this strategy. As a prespecified objective, we evaluated antibacterial envelope cost-effectiveness compared with standard-of-care infection prevention strategies in the US healthcare system. METHODS: A decision tree model was used to compare costs and outcomes of antibacterial envelope (TYRX) use adjunctive to standard-of-care infection prevention versus standard-of-care alone over a lifelong time horizon. The analysis was performed from an integrated payer-provider network perspective. Infection rates, antibacterial envelope effectiveness, infection treatment costs and patterns, infection-related mortality, and utility estimates were obtained from the WRAP-IT trial. Life expectancy and long-term costs associated with device replacement, follow-up, and healthcare utilization were sourced from the literature. Costs and quality-adjusted life years were discounted at 3%. An upper willingness-to-pay threshold of $150 000 per quality-adjusted life year was used to determine cost-effectiveness, in alignment with the American College of Cardiology/American Heart Association practice guidelines and as supported by the World Health Organization and contemporary literature. RESULTS: The base case incremental cost-effectiveness ratio of the antibacterial envelope compared with standard-of-care was $112 603/quality-adjusted life year. The incremental cost-effectiveness ratio remained lower than the willingness-to-pay threshold in 74% of iterations in the probabilistic sensitivity analysis and was most sensitive to the following model inputs: infection-related mortality, life expectancy, and infection cost. CONCLUSIONS: The absorbable antibacterial envelope was associated with a cost-effectiveness ratio below contemporary benchmarks in the WRAP-IT patient population, suggesting that the envelope provides value for the US healthcare system by reducing the incidence of cardiac implantable electronic device infection. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02277990.

A randomized trial comparing effects of radiofrequency and cryoablation on the structural integrity of esophageal tissue.

BACKGROUND: Esophageal injury is a rare, but catastrophic complication of radiofrequency (RF) pulmonary vein isolation. It is not known if cryoablation is less likely to injure esophageal tissue. The purpose of this study is to compare the effects of RF and cryoablation on the structural integrity of esophageal tissue. METHODS AND RESULTS: Porcine esophageal tissue was sectioned into 396 strips measuring 3 mm in width by 30 mm in length. Samples were randomly assigned to receive no ablation (149 specimens in the control group), RF ablation (126 specimens) or cryoablation (121 specimens). A single ablation was administered in the center of the tissue sample. A force gauge was used to measure the tensile strength of the tissue sample in Newtons. Groups were compared using ANOVA and a Bonferroni post-test. The mean tensile strength in the control group was 2.19 N (SD, 2.17), 1.66 N (SD, 0.88) for RF ablated tissue and 1.96 N (SD, 1.68) for cryo. RF ablation resulted in a significant reduction in esophageal tensile strength when compared to control (t = 2.59), however cryo did not (t = 1.11). On microscopic evaluation RF ablation disrupted elastic fiber architecture whereas cryoablation did not. CONCLUSIONS: Cryoablation has no significant adverse impact on the structural integrity of esophageal tissue. Cryoablation may be a safer alternative to RF for left atrial ablation and reduce the risk of esophageal injury and atrial-esophageal fistula formation.

Short and long-term outcomes of percutaneous left atrial appendage suture ligation: Results from a US multicenter evaluation.

BACKGROUND: Published studies of epicardial ligation of left atrial appendage (LAA) have reported discordant results. OBJECTIVE: The purpose of this study was to delineate the safety and efficacy of LAA closure with the LARIAT device. METHODS: This is a multicenter registry of 712 consecutive patients undergoing LAA ligation with LARIAT at 18 US hospitals. The primary end point was successful suture deployment, no leak by intraprocedural transesophageal echocardiography (TEE), and no major complication (death, stroke, cardiac perforation, and bleeding requiring transfusion) at discharge. A leak of 2-5 mm on follow-up TEE was the secondary end point. RESULTS: LARIAT was successfully deployed in 682 patients (95.5%). A complete closure was achieved in 669 patients (98%), while 13 patients (1.8%) had a trace leak (<2 mm). There was 1 death related to the procedure. Ten patients (1.44%) had cardiac perforation necessitating open heart surgery, while another 14 (2.01%) did not need surgery. The risk of cardiac perforation decreased significantly after the introduction of a micropuncture (MP) needle for pericardial access. Delayed complications (pericarditis requiring >2 weeks of treatment with nonsteroidal anti-inflammatory drugs/colchicine and pericardial and pleural effusion after discharge) occurred in 34 (4.78%) patients, and the risk decreased significantly with the periprocedural use of colchicine. Follow-up TEE (n = 480) showed a leak of 2-5 mm in 6.5% and a thrombus in 2.5%. One patient had a leak of >5 mm. CONCLUSION: LARIAT effectively closes the LAA and has acceptable procedural risks with the evolution of the use of the micropuncture needle for pericardial access and the use of colchicine for mitigating the postinflammatory response associated with LAA ligation and pericardial access.

Implantable cardioverter defibrillator therapy in patients with ischemic or non-ischemic cardiomyopathy and nonsustained ventricular tachycardia.

BACKGROUND: Mortality benefit from implantable cardioverter defibrillator (ICD) therapy in ischemic cardiomyopathy (ICM) with non-sustained ventricular tachycardia (NS-VT) and inducible VT is well defined. Although NS-VT may suggest an increased risk of sudden cardiac death (SCD) in non-ischemic cardiomyopathy (NICM), the role of ICD therapy is unclear. This retrospective study compares follow-up data in these two groups after ICD implantation. METHODS: 153 consecutive patients with ICD implantation for NS-VT were analyzed. ICM patients received an ICD if they had inducible VT at electrophysiology study (EPS). NICM patients did not routinely undergo EPS before ICD implantation. RESULTS: There were 48 patients (33 males) in NICM group and 105 patients (89 males) in the ICM group. Baseline characteristics including mean ejection fraction (EF), distribution in various New York Heart Association (NYHA) classes, and the mean duration of follow up in the two groups were similar. 50% of the patients in the NICM group and 36% in the ICM group received appropriate therapies (p = 0.106). The mean number of appropriate therapies in the two groups were similar (23.3 +/- 56.7 and 22.5 +/- 59.5 respectively, p = NS). The percentage of patients with inappropriate therapies in the two groups were 27% and 23% respectively (p = NS). Patients in the NICM group received appropriate ICD discharges at a greater rate (p = 0.02). CONCLUSION: Patients undergoing ICD implantation for NICM and NS-VT receive appropriate ICD therapy at a greater rate than those implanted for ICM, NS-VT, and a positive EPS. Although these data do not prove survival benefit in NICM, they suggest a beneficial effect.

The prevalence of methicillin resistant organisms among pacemaker and defibrillator implant recipients.

INTRODUCTION: Pacemaker and defibrillator infections are an uncommon, but catastrophic complication of device implantation. The present study examined the prevalence of device-related infections, the patterns of antibiotic resistance, and the presence of methicillin resistant staphylococcus aureus (MRSA) nares colonization in device implant recipients. METHODS: Two protocols were employed using a retrospective and a prospective analysis. A retrospective chart review of 218 patients with suspected device infection from 1/2000 to 1/2011 was performed. Demographics, infection rates, and patterns of antibiotic resistance were compared. The prospective analysis enrolled one hundred eighty two patients undergoing device implantations or generator replacements. The nares were swabbed and analyzed for the presence of staphylococcus aureus, and tested for methicillin sensitivity. RESULTS: Over a period of ten years, 12,771 device implants/generator changes/system revisions were performed, with an infection rate of 1.2%. Methicillin resistance (MR) was identified in 98/218 (44.9%) of patients. Those with MR infection had more diabetes and cardiomyopathy. There was no significant increase in methicillin resistance over time (p=0.30). Our prospective analysis included 110 men. A total of 32 patients (17.6%) had positive cultures for SA: 6.6% with MRSA. Patients positive for MRSA nares colonization had a statistically significant greater length of hospital stay 8.5 days (mean) versus 4.4 days (P=0.049). CONCLUSIONS: Methicillin resistant organisms appear to be emerging and persistent pathogens in device implants. The screening of MRSA colonization may identify new populations at risk. Further studies and analysis are needed to determine the cost effectiveness of a screening protocol.

Efficacy of pulmonary vein isolation with a novel hot balloon ablation catheter.

BACKGROUND: Due to the variable anatomy of the human pulmonary vein (PV), PV isolation for atrial fibrillation ablation is challenging. A novel hot balloon ablation catheter has been developed to improve ablation outcomes. The efficacy, histopathologic lesion characteristics, and thermodynamics of this technology were examined. METHODS: Swine underwent left atrial (n = 24) and superior vena cava (SVC, n = 7) catheterization with a compliant balloon catheter filled with saline and contrast. After PV mapping and angiography, ablation was performed with radiofrequency energy heating of the balloon contents. Central balloon temperatures were varied from 60°C to 90°C, and durations of energy delivery were varied from 60 to 300 s. Endocardial and epicardial temperatures were recorded contiguous to the balloon during SVC ablations. Pathology was examined. RESULTS: With a mean of 1.4 ± 0.9 ablations per PV at 70°C, 93% were electrically isolated. Necropsy exam revealed extraostial lesions without charring. PVs ablated at temperatures ≥80°C and durations ≥180 s were associated with a high rate of successful isolation with a single ablation. Higher-temperature lesions displayed greater histopathologic uniformity, but more marked fibrin deposition. Chronic lesions revealed granulation tissue and fibrosis. No thromboembolic events were observed and histopathology of the phrenic nerve and esophagus was normal in all specimens. CONCLUSIONS: The hot balloon ablation catheter appears to be a safe and effective tool for PV isolation. Higher temperatures and longer ablation durations are associated with a higher single ablation success rate.

Analysis of limited resuscitations in patients suffering in-hospital cardiac arrest.

BACKGROUND: Although clinicians are expected to help patients make decisions about end-of-life care, there is insufficient data to help guide patient preferences. The objective of this study was to determine the frequency of patients who undergo 'limited code' and compare survival to discharge with those who undergo maximum resuscitative efforts ('full code'). METHODS: We performed a retrospective analysis of all adult in-hospital cardiac arrests (IHCA) at a tertiary care teaching hospital from January 1999 to December 2003 to compare survival in patients with limited code to survival in patients with a full code. We collected data on demographic and clinical variables known to influence survival in IHCA. Logistic regression was used to assess the association of code status with subsequent survival through the code and to hospital discharge after adjusting for potential confounding factors. RESULTS: Of the 309 patients having IHCA, there were 17 (5.5%) patients with limited code status and 292 (94.5%) with full code status. Among full code patients, 171 (58.6%) survived the code compared to five patients (29.4%) who had a limited code (p=0.023). After adjusting for demographic variables and pre-arrest co-morbidities, patients with full code status compared to limited code status had an odds ratio for return of spontaneous circulation of 3.69 (95% CI: 1.13-14.34). CONCLUSIONS: Patients who opt for limited code have a significantly lower probability of survival compared to patients who choose full code. Patients who choose limited code should be informed of the likely negative outcome as compared to full resuscitation.

The role of temporary biventricular pacing in the cardiac surgical patient with severely reduced left ventricular systolic function.

OBJECTIVE: The objective was to evaluate the effects of atrial synchronous biventricular pacing in postoperative patients with severe cardiomyopathy. METHODS: Atrial synchronous biventricular pacing epicardial leads were placed during cardiac surgery in patients with an ejection fraction of 30% or less. Patients were randomized to usual care pacing, the mode determined by the surgeon (excluding atrial synchronous biventricular pacing) with a preference for no pacing or atrial pacing (atrial inhibited pacing); atrial synchronous right ventricular pacing; or atrial synchronous biventricular pacing. Pacing was continued until cessation of hemodynamic support. At 12 hours postoperatively, patients were randomly tested in each mode (atrial inhibited, atrial synchronous right ventricular, and atrial synchronous biventricular pacing), and thermodilution outputs were measured. RESULTS: Forty subjects were randomized. Groups were similar in age (66 +/- 11 years), gender (85% were male), ejection fraction (23% +/- 6%), QRS duration (111 +/- 30 ms), and surgical indication. There was no difference in stroke index or cardiac index at 12 hours, duration of inotropic or intra-aortic balloon pump support, intensive care unit, or hospital length of stay. On comparative crossover testing, stroke volume was similar with atrial inhibited pacing and atrial synchronous biventricular pacing (59.3 +/- 13.4 vs 57 +/- 12.1, respectively, P = not significant); however, atrial synchronous right ventricular pacing was inferior (56 +/- 12.9, P < .05 for comparison with atrial inhibited pacing). When compared with atrial inhibited pacing, atrial synchronous biventricular pacing showed a positive response in 17% of subjects (increase in stroke volume >or= 5%), whereas 41% had a 5% or greater decrease in stroke volume. CONCLUSION: Pacing mode affects stroke volume in patients with severe cardiomyopathy. Atrial synchronous biventricular pacing was helpful in a minority, but in 41% it compromised stroke volume.