Automated Bioanalytical Workflow for Ligand Binding-Based Pharmacokinetic Assay Development.

The growth of therapeutic monoclonal antibodies (mAbs) continues to accelerate due to their success as treatments for many diseases. As new therapeutics are developed, it is increasingly important to have robust bioanalytical methods to measure the pharmacokinetics (PK) of circulating therapeutic mAbs in serum. Ligand-binding assays such as enzyme-linked immunosorbent assays (ELISAs) with anti-idiotypic antibodies (anti-IDs) targeting the variable regions of the therapeutic antibody are sensitive and specific bioanalytical methods to measure levels of therapeutic antibodies in a biological matrix. However, soluble circulating drug mAb targets can interfere with the anti-IDs binding to the therapeutic mAb, thereby resulting in an underestimation of total drug concentration. Therefore, in addition to a high binding affinity for the mAb, the selection of anti-IDs and the assay format that are not impacted by soluble antigens and have low matrix interference is essential for developing a robust PK assay. Standardized automated approaches to screen and select optimal reagents and assay formats are critical to increase efficiency, quality, and PK assay robustness. However, there does not exist an integrated screening and analysis platform to develop robust PK assays across multiple formats. We have developed an automated workflow and scoring platform with multiple bioanalytical assay parameters that allow for ranking of candidate anti-IDs. A primary automated indirect electrochemiluminescence (ECL) was utilized to shortlist the anti-IDs that were selected for labeling and screening in pairs. A secondary screen using an ECL sandwich assay with labeled-anti-ID pairings was used to test multiple PK assay formats to identify the best anti-ID pairing/PK assay format. We developed an automated assay using fixed plate maps combined with a human-guided graphical user interface-based scoring system and compared it to a data-dependent scoring system using Gaussian mixture models for automated scoring and selection. Our approach allowed for screening of anti-IDs and identification of the most robust PK assay format with significantly reduced time and resources compared with traditional approaches. We believe that such standardized, automated, and integrated platforms that accelerate the development of PK assays will become increasingly important for supporting future human clinical trials.

DREAM-ICD-II Study.

BACKGROUND: Regulatory authorities of most industrialized countries recommend 6 months of private driving restriction after implantation of a secondary prevention implantable cardioverter-defibrillator (ICD). These driving restrictions result in significant inconvenience and social implications. This study aimed to assess the incidence rate of appropriate device therapies in contemporary recipients of a secondary prevention ICD. METHODS: This retrospective study at 3 Canadian tertiary care centers enrolled consecutive patients with new secondary prevention ICD implants between 2016 and 2020. RESULTS: For a median of 760 days (324, 1190 days), 721 patients were followed up. The risk of recurrent ventricular arrhythmia was highest during the first 3 months after device insertion (34.4%) and decreased over time (10.6% between 3 and 6 months, 11.7% between 6 and 12 months). The corresponding incidence rate per 100 patient-days was 0.48 (95% CI, 0.35-0.64) at 90 days, 0.28 (95% CI, 0.17-0.45) at 180 days, and 0.21 (95% CI, 0.13-0.33) between 181 and 365 days after ICD insertion (P<0.001). The cumulative incidence of arrhythmic syncope resulting in sudden cardiac incapacitation was 1.8% within the first 90 days and subsequently dropped to 0.4% between 91 and 180 days (P<0.001) after ICD insertion. CONCLUSIONS: The incidence rate of appropriate therapies resulting in sudden cardiac incapacitation in contemporary recipients of a secondary prevention ICD is much lower than previously reported and declines significantly after the first 3 months. Lowering driving restrictions to 3 months after the index cardiac event seems safe, and revision of existing guidelines should be considered in countries still adhering to a 6-month period. Existing restrictions for private driving after implantation of a secondary prevention ICD should be reconsidered.

Same-day discharge for atrial fibrillation ablation: outcomes and impact of ablation modality.

AIMS: Same-day discharge is increasingly common after catheter ablation for atrial fibrillation (AF). However, the impact of same-day discharge on healthcare utilization after ablation and whether this differs by ablation modality remains uncertain. We examined the safety, efficacy, and subsequent healthcare utilization of a same-day discharge protocol for AF ablation, including radiofrequency (RF) and cryoballoon ablation, in a contemporary cohort. METHODS AND RESULTS: All consecutive patients for whom full healthcare utilization data were available at two centres and who underwent AF ablation from 2018 to 2019 were included. Same-day discharge was the default strategy for all patients. The efficacy and safety outcomes were proportions of same-day discharge and readmission/emergency room (ER) visits, and post-discharge complications, respectively. Of the 421 patients who underwent AF ablation (mean 63.3 ± 10.2 years, 33% female), 90.5% (381/421) achieved same-day discharge with no difference between RF and cryoballoon ablation (89.8 vs. 95.1%, adjusted P = 0.327). Readmission ≤30 days occurred in 4.8%, with ER visits ≤30 days seen in 26.1% with no difference between ablation modalities (P = 0.634). Patients admitted overnight were more likely to present to the ER (40.0 vs. 24.7% with same-day discharge, P = 0.036). The overall post-discharge complication rate was low at 4/421 (1.0%), with no difference between ablation modality (P = 0.324) and admission/same-day discharge (P = 0.485). CONCLUSION: Same-day discharge can be achieved in a majority of patients undergoing RF or cryoballoon ablation for AF. Healthcare utilization, particularly ER visits, remains high after AF ablation, regardless of ablation modality or same-day discharge.

Correlation of unipolar electrogram modification with ablation index during pulmonary vein isolation: A pilot study.

BACKGROUND: Pulmonary vein isolation (PVI) using radiofrequency catheter ablation is a widely accepted therapy for drug-refractory atrial fibrillation patients. Elimination of the negative component of the local unipolar electrogram (UEGM) during PVI is a marker of transmural lesion formation. The ablation index (AI) can predict the quality of ablation lesion. Combining these two parameters could make PVI safer and efficient. The purpose of this pilot study was to examine the correlation between UEGM modification characteristics of the different target areas of left atrium and the associated AI values during PVI. METHODS: We analyzed 10 patients who underwent PVI using radiofrequency energy. The local electrophysiological properties and ablation parameters of 15 designated areas of interest in the left atria targeted by radiofrequency catheter ablation were collected. RESULTS: Out of the 10 patients, six were men (mean age 66 years) and 80% had paroxysmal AF. The mean time to achieve the UEGM modification in the posterior wall was shorter than that of the anterior wall (8.9 seconds vs. 11.1 s, respectively). The UEGM modification for every lesion was achieved at significantly lower AI values than conventional AIs (p < .001). CONCLUSION: During PVI, the AIs deduced according to the local UEGM modification are markedly shorter than those generally recommended AIs in contemporary practice. This indicates that conventionally recommended AIs could be safely reduced while ensuring the efficacy and quality of radiofrequency ablation during PVI. This approach would probably reduce to risk of collateral thermal injuries.

Fascia Iliaca Block in Hip and Femur Fractures to Reduce Opioid Use.

BACKGROUND: Fascia iliaca compartment block (FICB) has become a keystone technique for acute pain management in patients with hip and proximal femur fractures. OBJECTIVES: To demonstrate that administering FICB preoperatively to patients with hip or proximal femur fractures in the emergency department (ED) is likely to reduce opioid use and related complications, and to decrease hospital length of stay (LOS). METHODS: An unblinded study of adult patients with hip and proximal femur fractures who consented to receive an FICB with 30 cc of bupivacaine with epinephrine administered in the ED. We compared this group with a contemporaneous group of controls who only received systemic opioids. Over the course of approximately 6 months, main outcome measured between the two groups was amount of morphine equivalents given from block administration until 8 h after. We also compared complications such as delirium, constipation, and bleeding rates (oozing from injection site or hematoma formation). RESULTS: A total of 166 patients with hip and proximal femur fractures from August 12, 2018 to April 25, 2021; 81 received FICB plus systemic opioids, and 85 received only systemic opioids. Among the FICB group, morphine equivalents were reduced by 0.6 mg/h with no significant difference in LOS. A statistically significant difference in opioid-related adverse outcomes was found between the anticoagulated group vs. the no anticoagulation group. CONCLUSIONS: FICB is a safe and effective preoperative technique for initial pain management in patients with hip and proximal femur fractures, as it can also be used with additional systemic opioids. FICB administration may reduce systemic opioid use preoperatively, thus reducing opioid-related adverse effects with no significant impact on hospital LOS.

Effectiveness of medical therapy for treatment of idiopathic frequent premature ventricular complexes.

INTRODUCTION: The relative effectiveness of medical therapy compared with a conservative approach of monitoring in patients with idiopathic frequent premature ventricular complexes (PVCs) is uncertain. We evaluated the effectiveness of medical versus conservative therapy for frequent PVCs. METHODS: Patients with frequent PVCs (≥5%) were prospectively enrolled in this cohort study between 2016 and 2020. In patients with normal cardiac function and no structural heart disease, those receiving medical therapy were compared with controls without therapy. Patients were followed longitudinally for change in PVC burden and with serial echocardiography. RESULTS: Overall, 120 patients met inclusion criteria (mean: 56.5 ± 14.6 years, 54.2% female) with 53 on beta-blockers or calcium channel blockers (BBs/CCBs), 27 on Class I or III antiarrhythmic drugs (AADs), and 40 patients treated conservatively. Median initial PVC burden ranged from 15.5% to 20.6%. The median relative reduction of PVCs was 32.7%, 30.5%, and 81.3%, in the conservative therapy, BBs/CCBs, and AADs cohorts, respectively. AADs had greater PVC reduction compared with BBs/CCBs (p = 0.017) and conservative therapy (p = 0.045). PVC reduction to <1% was comparable across groups at 35.0%, 17.0%, 33.3%, respectively. Four patients (4/120, 3.3%) developed left ventricular dysfunction. Rates of adverse drug reactions and medication discontinuation were similar between groups, with no serious adverse events noted. CONCLUSION: In patients with idiopathic frequent PVCs, BB, and CCB have limited effectiveness in PVC reduction. Class I and III AADs have superior effectiveness for medical therapy in symptomatic patients, but only achieved complete PVC resolution suppression in one-third of patients.

Three-Year Survival after Transcatheter Aortic Valve Replacement: Findings from the Marshfield Aortic Valve Experience (MAVE) Study.

Background: Transcatheter aortic valve replacement (TAVR) is a rapidly evolving treatment for severe aortic stenosis. However, uncertainties exist for optimal valve selection as there are few long-term studies comparing patient survival by valve type.Objective: We hypothesized that self-expandable valves (SEV) would provide a survival advantage over balloon expandable valves (BEV), as SEV continue to expand and might better accommodate to the anatomy of the aortic valve over time.Methods: We examined outcomes according to valve type from a rural tertiary referral center between 2012 and 2017.Results: Out of 269 patients, 77 deaths (28.6%) occurred over the study period with 6 deaths by 1 month post-TAVR and 37 deaths by 1 year post-TAVR. The median observation time for survivors was 21.5 months. The probability of survival at 3 years was 60.7% and 61.9% for patients who underwent treatment with SEV and BEV, respectively. There was no statistically significant difference in overall patient survival with or without adjustment for factors such as age, sex, race, and aortic valve area. Additionally, in a secondary analysis restricted to those patients treated in later years (2015-2017) survival among patients with BEV appeared superior (HR=0.456, P=0.015).Conclusion: Patients who underwent TAVR at a rural medical center with SEV showed similar survival compared to those who received a BEV. Superior survival was observed among those who received BEV versus SEV between 2015 and 2017.

Lead Integrity Alert Is Useful for Assessment of Performance of Biotronik Linox Leads.

INTRODUCTION: Medtronic's Lead Integrity Alert (LIA) software algorithm is useful for detecting abnormal parameters across various ICD-lead families. However, its utility in the assessment of the Biotronik Linox™ family of high-voltage (HV) leads is unknown. METHODS: We conducted a retrospective cohort study to assess the performance of the LIA algorithm to detect abnormalities and lead failure in Linox ICD-leads. All LIA-enabled Medtronic devices connected to an active Linox lead were included. The alerts were adjudicated by 2 blinded electrophysiologists and correlated with clinical data. RESULTS: Between 2008 and 2012, data from 208 patients with 564 patient-years of follow-up were available for analysis. The median follow-up duration was 32 (IQR 21-41 months). Twenty-one LIA triggers were noted in 20 different patients. The median delay until a positive LIA was 32 months (IQR 21-41 months) postimplant with a 5-year lead survival free from LIA of 76%. Ninety-five percent (19/20) LIA alerts were true lead failures. The most common LIA triggers were short V-V intervals (85%) and nonsustained ventricular tachycardia (85%). Abrupt changes of the ICD-lead impedance occurred in 5/20 triggers. Inappropriate ICD-shocks were strongly associated with a positive LIA (30% vs. 7.4%; P = 0.006). Of the explanted Linox leads 53% had visible abnormalities. The sensitivity, specificity, and positive predictive value for lead failure in the presence of a LIA trigger were 87%, 99.5%, and 95.2%, respectively. CONCLUSIONS: A positive LIA trigger in Biotronik Linox ICD-leads is highly predictive of lead failure. LIA is useful in ongoing surveillance of lead performance.

Cryoablation versus RF ablation for AVNRT: A meta-analysis and systematic review.

INTRODUCTION: Atrioventricular nodal reentrant tachycardia (AVNRT) is the most common supraventricular tachycardia referred for ablation. High success rates have been accompanied with a small risk of atrioventricular (AV) block. Cryoablation has been used as an alternative to radiofrequency (RF) ablation, but studies have been underpowered in comparing the 2 techniques. METHODS AND RESULTS: An electronic search and hand-search of reference lists for published and unpublished data was carried out. Comparative studies (cohort and randomized controlled trials) of RF versus cryoablation for AVNRT were identified independently by 2 reviewers. Searches were limited to English language human studies. The primary metameter was long-term AVNRT recurrence (>2 months postprocedure and ECG/electrophysiology study [EPS]-documented) and secondary metameters included acute procedural failure and AV block requiring pacing. A total of 5,617 patients in 14 trials were included in this systematic review. Acute procedural failure with cryoablation was slightly higher than with RF ablation, but the difference was not statistically significant (risk ratio [RR] 1.44 [95% confidence interval; CI 0.91-2.28], P = 0.12). Long-term recurrence was higher with cryoablation (RR 3.66 [95% CI 1.84-7.28], P = 0.0002) even after adjusting for larger (6 mm) cryocatheter tips, "insurance lesions" and longer (>6 months) follow-up duration. RF ablation for AVNRT was associated with permanent AV block in 0.75% of patients, but was not reported in any patients treated with cryoablation (n = 1066, P = 0.01). CONCLUSIONS: Cryoablation is a safe and effective treatment for AVNRT. Although late-recurrence is more common with cryoablation than with RF ablation, avoidance of permanent AVN block makes it an attractive option in patients where the avoidance of AV block assumes higher priority (such as children and young adults).

MK-4815, a potential new oral agent for treatment of malaria.

Malaria continues to have a significant impact on the health of the developing world. Efforts to combat this disease now focus on combination therapy in order to stem the emergence of resistant parasites. Continued efforts are needed to discover and develop new agents for use in combination antimalarial regimens. MK-4815 is a small molecule with antimalarial activity that was identified from a large pharmaceutical compound collection using a semiautomated version of a well-established in vitro assay for the erythrocytic stages of Plasmodium falciparum. In vitro studies indicate that the compound selectively accumulates in infected red blood cells and is most effective against the metabolically active late trophozoite/early schizont stages. A variety of drug-resistant field isolates of P. falciparum were found to be as sensitive to MK-4815 as the wild-type lines. MK-4815 is orally active in a P. berghei mouse model of acute malaria. In this model, where untreated animals succumb to infection 10 to 12 days postinfection, MK-4815 was completely curative when given as a single dose of 50 mg/kg, 2 doses of 25 mg/kg, or 4.5 doses of 12.5 mg/kg. In pharmacokinetic studies with mice and rhesus monkeys, MK-4815 demonstrated oral bioavailability and low clearance. In addition, MK-4815 is inexpensive to synthesize, an important characteristic for providing affordable antimalaria therapy to the developing world. The attractive biological and pharmaceutical profile of MK-4815 demonstrates its potential for use in combination with other agents in the fight against malaria.

Translation and validation of the Hong Kong Chinese version of the breastfeeding self-efficacy scale-short form.

Healthcare providers do not have a validated instrument to measure breastfeeding self-efficacy among Hong Kong Chinese. In this study, we sought to translate the breastfeeding self-efficacy scale-short form (BSES-SF) into Hong Kong Chinese and to examine the psychometric properties in a sample of 185 breastfeeding mothers. The construct validity of the translated scale was supported by confirmatory factor analysis and known group analysis. The receiver operating characteristics analysis indicated that the total score of the translated scale at 48-72 hours after delivery could be a useful diagnostic tool for identifying mothers likely to discontinue breastfeeding prematurely, before 6 months postpartum. Further research to cross-validate the suggested cut-off value of the scale is recommended.

Cardiac Magnetic Resonance in the Evaluation of Patients With Frequent Premature Ventricular Complexes.

BACKGROUND: The role of cardiac magnetic resonance (CMR) in the evaluation and management of patients with frequent premature ventricular complexes (PVCs) of unknown etiology remains unclear. OBJECTIVES: This study evaluated the prevalence and prognostic significance of myocardial abnormalities detected with CMR among patients with frequent PVCs and no known structural heart disease. METHODS: This prospective cohort study included consecutive patients with frequent PVCs and a negative initial diagnostic work-up who underwent CMR with late gadolinium enhancement imaging. The clinical outcome was a composite of mortality, ventricular fibrillation, sustained ventricular tachycardia, or reduction in left ventricular ejection fraction of ≥10%. RESULTS: A total of 255 patients were included, of whom 35 (13.7%) had evidence of myocardial abnormality on CMR. Age ≥60 years (odds ratio [OR]: 6.96; 95% CI: 1.30-37.18), multifocal PVCs (OR: 10.90; 95% CI: 3.21-36.97), and non-outflow tract left ventricular PVC origin (OR: 3.00; 95% CI: 1.00-8.95) were independently associated with the presence of a myocardial abnormality on CMR. After a median follow-up of 36 months, the composite outcome occurred in 15 (5.9%) patients. The presence of a myocardial abnormality on CMR was independently associated with the composite outcome (HR: 4.35; 95% CI: 1.34-14.15; P = 0.014). CONCLUSIONS: One in 7 patients with frequent PVCs with no known structural heart disease had myocardial abnormality detected on CMR, and these abnormalities were associated with adverse clinical outcomes. These findings highlight the important role of CMR in the evaluation of patients with frequent PVCs.

Effectiveness of a simple medication adjustment protocol for optimizing peri-cardioversion rate control: A derivation and validation cohort study.

BACKGROUND: Rate control medications are foundational in the management of persistent atrial fibrillation (AF). There are no guidelines for adjusting these medications prior to elective direct-current cardioversion (DCCV). OBJECTIVE: To derive and validate a preprocedural medication adjustment protocol that maintains peri-DCCV rate control and minimizes risk of postconversion bradycardia, pauses, need for pacing, and cardiopulmonary resuscitation (CPR). METHODS: Consecutive patients with persistent AF awaiting elective DCCV across 2 hospitals were screened for inclusion into derivation, validation, and control cohorts. In the derivation cohort, each patient taking an atrioventricular (AV) nodal blocker had medications adjusted based on heart rate (HR) 2 days before DCCV, and the magnitude of dose adjustment was compared with peri-DCCV HR. The adjustment protocol that achieved the highest percentage of optimal peri-DCCV rate control was tested prospectively in the validation cohort and compared to a standard-of-care control group. RESULTS: The optimal protocol from the derivation cohort (n = 71), based on the 2-day pre-DCCV HR, was to (1) CONTINUE AV nodal blocker for HR ≥ 100 beats per minute (bpm), (2) reduce dose by ONE increment when 80-99 bpm, (3) reduce dose by TWO increments when 60-79 bpm, and (4) HOLD when <60 bpm. In the prospective validation cohort (n = 106), this protocol improved peri-DCCV rate control (82% vs 62%, P < .001) compared to current standard of care (n = 107). There were no conversion pauses ≥5 seconds, need for pacing, or CPR post-DCCV. CONCLUSION: This simple preprocedural medication adjustment protocol provides an effective strategy of optimizing peri-DCCV rate control in patients with AF.

Anticoagulation for Patients With Atrial Fibrillation and End-Stage Renal Disease on Dialysis: A National Survey.

Patients with atrial fibrillation (AF) have a significant increased risk of embolic stroke. Patients with end-stage renal disease who are on dialysis have an increased risk of both embolic stroke and bleeding. Stroke-prevention studies with the use of anticoagulation for AF patients have excluded patients on dialysis, so there remains no consensus on their management. We developed and implemented a pan-Canadian multidisciplinary survey to explore the current beliefs and practices concerning patients with AF on dialysis. We developed an online investigator-designed survey with both quantitative and qualitative responses with the use of a secure university-affiliated electronic service. The survey was distributed to physicians via the QxMD platform and directly to internal medicine, cardiology, and nephrology residency program directors for distribution to faculty members. 130 participants responded, including 46 cardiologists, 45 nephrologists, 30 general internists, and 9 other physicians. The preferred anticoagulant was warfarin. The CHADS2 score used to initiate anticoagulation was highly variable, with specialties differing in use of a CHADS2 threshold of ≥ 1 (P < 0.001) and the impact of previous transient ischemic attack/stroke (P = 0.02). Calciphylaxis history affected the decision to prescribe anticoagulation. Specialties differed in thresholds used to consider direct oral anticoagulants for dialysis patients, with nephrologists more likely to prescribe anticoagulation at higher CHADS2 scores. Our survey demonstrated significant heterogeneity of anticoagulation use for stroke prevention in patients with AF on dialysis. Physician specialty and patient risk profiles contributed to the observed variability. This study reemphasises the need for clinical trials, large observational studies, and consensus guidelines to address evident equipoise.

A Tiered Approach for Characterization to Ensure Quality, Reproducibility, and Long-Term Stability of Critical Reagents in Regulated Bioanalysis to Support PK/ADA/NAb Assays for Biologics and Vaccines Programs.

The robustness of good laboratory practice and clinical data is reliant upon a clear understanding of the bioanalytical assays. One of the most important components of ligand-binding based assays is critical reagents used to directly or indirectly measure biologic markers or signals. High quality, reproducible, sustainable critical reagents through the development lifecycle could avoid unnecessary rework, multiple validations, cross-validations, and ensure consistency of the data. Numerous analytical methods (UPLC-size exclusion chromatography, cation exchange chromatography, biacore/octet, and high-resolution mass spectrometry) have been evaluated by using current critical reagents. A comprehensive analytical toolbox of biochemical and biophysical methods has been employed to evaluate the quality of critical reagents and explore potential issues if there are any. Moving forward, this "tiered approach" of critical reagents characterization will be used not only to establish critical quality attributes for new reagents but also to evaluate stability in support of reagents recertification.

Establishing reference ranges for ambulatory electrocardiography parameters: meta-analysis.

OBJECTIVE: Despite the widespread and increasing use of ambulatory electrocardiography (ECG), there is no consensus on reference ranges for ambulatory electrocardiogram parameters to guide interpretation. We sought to determine population distribution-based reference ranges for parameters measured during ambulatory electrocardiogram in healthy adults, based on existing literature. METHODS: We searched multiple databases from 1950 to 2020. Articles reporting original data from ≥24-hour ambulatory electrocardiogram monitoring in healthy adults were included. Data extraction and synthesis were performed according to Meta-analysis of Observational Studies in Epidemiology guidelines. The prevalence/mean and SD for common parameters (sinus pauses, conduction abnormalities and ectopy) were extracted by age group (18-39, 40-59, 60-79 and 80+ years). RESULTS: We identified 33 studies involving 6466 patients. Sinus pauses of >3 s were rare (pooled prevalence <1%) across all ages. Supraventricular ectopy of >1000/24 hours increased with age, from 0% (95% CI 0% to 0%) in those aged 18-39 years to 6% (95% CI 0% to 17%) in those aged 60-79 years. Episodes of supraventricular tachycardia increased from 3% (95% CI 1% to 6%) in those aged 18-39 years to 28% (95% CI 9% to 52%) in those aged 60-79 years. Ventricular ectopy of >1000/24 hours also increased with age, from 1% (95% CI 0% to 2%) in those aged 18-39 years to 5% (95% CI 1% to 10%) in those aged 60-79 years. Episodes of non-sustained ventricular tachycardia ranged from 0% (95% CI 0% to 1%) in those aged 18-39 years to 2% (95% CI 0% to 5%) in those aged 60-79 years. CONCLUSION: Despite the limitations of existing published data, this meta-analysis provides evidence-based reference ranges for ambulatory electrocardiogram parameters and highlights significant age-dependent differences that should be taken into account during interpretation.

The impact of steerable sheaths on unblinded contact force during catheter ablation for atrial fibrillation.

PURPOSE: The purpose of this study was to evaluate the impact of steerable sheaths on multiple contact force parameters during atrial fibrillation (AF) ablation. Steerable sheaths are commonly used during AF ablation, at an additional cost to standard fixed-curve sheaths. However, there is little data on their incremental value in the era of contact force-guided radiofrequency ablation. METHODS: This multi-center cohort study included consecutive patients undergoing index pulmonary vein (PV) isolation with a force-sensing catheter. Operators employed either only steerable or only fixed-curve sheaths. Operators targeted a force of 10-40 g for each ablation lesion. Automated ablation lesion assessment software with standardized settings was employed. RESULTS: Of 85 subjects, 52 and 33 underwent ablation with steerable and fixed-curve sheaths, respectively. The steerable sheath group showed significantly higher average and maximum forces, but predominantly for the right PVs. The proportion of lesions with ≥ 10% of time with less than 10 g of force was lower in the steerable sheath group (adjusted odds ratio 0.56, steerable vs. fixed; 95% confidence interval 0.35, 0.89, p = 0.01). Improved stability was seen in the posterior aspect of both PV pairs. The proportion of RF time-in-target (the proportion of RF time meeting lesion criteria) was not different between the two groups (p = 0.176). CONCLUSIONS: Even with contemporary contact force targets, steerable sheath use in AF ablation is associated with better average and maximum contact force and increased stability in comparison to fixed-curve sheaths.

Efficacy and Safety of Same-Day Discharge for Atrial Fibrillation Ablation.

OBJECTIVES: The purpose of this study was to evaluate the efficacy, health care utilization, and safety of a same-day discharge protocol. BACKGROUND: Catheter ablation of atrial fibrillation (AF) is the most common ablation performed. Increasing volumes of AF ablation are placing demands on hospital resources. In response, our institutions developed a same-day discharge protocol for AF ablation. METHODS: This was a multicenter cohort study of all patients undergoing AF ablation from 2010 to 2014 at 2 major centers. The primary efficacy outcome was the proportion of successful same-day discharges. The primary health care utilization outcome was 30-day hospital readmission for any reason. The primary safety outcome was a composite of 30-day death, stroke/transient ischemic attack or embolism, or bleeding requiring hospitalization. RESULTS: A total of 3,054 patients underwent AF ablation from 2010 to 2014 and met inclusion criteria. Same-day discharge was achieved in 79.2% (2,418 of 3,054). Hospital readmission at 30 days was 7.7% for the same-day discharge group, 10.2% for those who remained in the hospital overnight without complications (p = 0.055 for comparison with same-day discharge), and 19.5% (p < 0.001) for those who remained in the hospital with procedural complications (7.7%). Complication rates from discharge to 30 days (excluding immediate procedural complications) were 0.37% for the same-day discharge group, 0.36% (p = 0.999) for those kept overnight without complications, and 2.5% (p = 0.044) for those with initial procedural complications. CONCLUSIONS: Same-day discharge after AF ablation is feasible in the majority of patients with use of a standardized protocol. This approach was not associated with higher hospital readmission or complication rates after discharge.

Driving Restrictions and Early Arrhythmias in Patients Receiving a Primary-Prevention Implantable Cardioverter-Defibrillator (DREAM-ICD) Study.

BACKGROUND: Current guidelines recommend 4 weeks of private driving restriction after implantation of a primary-prevention implantable cardioverter-defibrillator (ICD). These driving restrictions result in significant inconvenience and social implications. Advances in medical treatment and ICD programming have lowered the overall rate of device therapies. The objective of this study was to assess the incidence of ICD therapies at 30, 60, and 180 days after implantation. METHODS: Driving Restrictions and Early Arrhythmias in Patients Receiving a Primary-Prevention Implantable Cardioverter-Defibrillator (DREAM-ICD) was a retrospective cohort study conducted at 2 Canadian university centres enrolling patients with new implantation of a primary-prevention ICD. Device programming was standardised according to current guidelines. A total of 803 patients were enrolled. RESULTS: The cumulative rates of appropriate ICD therapies at 30, 60, and 180 days were 0.12%, 0.50%, and 0.75%, respectively. There was no syncope during the first 6 months. The median duration to the first appropriate ICD therapy was 208 (range 23-1109) days after implantation. The rate of inappropriate ICD therapies at 30 days was only 0.2%. Overall, < 13.6% of all appropriate ICD therapies occurred within the first 6 months after implantation. CONCLUSIONS: The rate of appropriate ICD therapies within the first 30 days after device insertion is extremely low in contemporary primary prevention cohorts with guideline-concordant device programming. There was no increased risk for ventricular arrhythmia early after ICD insertion. The results of DREAM-ICD suggest the need for a revision of the existing driving restrictions for primary-prevention ICD recipients.