Apixaban for Stroke Prevention in Subclinical Atrial Fibrillation.

BACKGROUND: Subclinical atrial fibrillation is short-lasting and asymptomatic and can usually be detected only by long-term continuous monitoring with pacemakers or defibrillators. Subclinical atrial fibrillation is associated with an increased risk of stroke by a factor of 2.5; however, treatment with oral anticoagulation is of uncertain benefit. METHODS: We conducted a trial involving patients with subclinical atrial fibrillation lasting 6 minutes to 24 hours. Patients were randomly assigned in a double-blind, double-dummy design to receive apixaban at a dose of 5 mg twice daily (2.5 mg twice daily when indicated) or aspirin at a dose of 81 mg daily. The trial medication was discontinued and anticoagulation started if subclinical atrial fibrillation lasting more than 24 hours or clinical atrial fibrillation developed. The primary efficacy outcome, stroke or systemic embolism, was assessed in the intention-to-treat population (all the patients who had undergone randomization); the primary safety outcome, major bleeding, was assessed in the on-treatment population (all the patients who had undergone randomization and received at least one dose of the assigned trial drug, with follow-up censored 5 days after permanent discontinuation of trial medication for any reason). RESULTS: We included 4012 patients with a mean (±SD) age of 76.8±7.6 years and a mean CHA2DS2-VASc score of 3.9±1.1 (scores range from 0 to 9, with higher scores indicating a higher risk of stroke); 36.1% of the patients were women. After a mean follow-up of 3.5±1.8 years, stroke or systemic embolism occurred in 55 patients in the apixaban group (0.78% per patient-year) and in 86 patients in the aspirin group (1.24% per patient-year) (hazard ratio, 0.63; 95% confidence interval [CI], 0.45 to 0.88; P = 0.007). In the on-treatment population, the rate of major bleeding was 1.71% per patient-year in the apixaban group and 0.94% per patient-year in the aspirin group (hazard ratio, 1.80; 95% CI, 1.26 to 2.57; P = 0.001). Fatal bleeding occurred in 5 patients in the apixaban group and 8 patients in the aspirin group. CONCLUSIONS: Among patients with subclinical atrial fibrillation, apixaban resulted in a lower risk of stroke or systemic embolism than aspirin but a higher risk of major bleeding. (Funded by the Canadian Institutes of Health Research and others; ARTESIA ClinicalTrials.gov number, NCT01938248.).

Diagnosis and Management of Cardiac Sarcoidosis: A Scientific Statement From the American Heart Association.

Cardiac sarcoidosis is an infiltrative cardiomyopathy that results from granulomatous inflammation of the myocardium and may present with high-grade conduction disease, ventricular arrhythmias, and right or left ventricular dysfunction. Over the past several decades, the prevalence of cardiac sarcoidosis has increased. Definitive histological confirmation is often not possible, so clinicians frequently face uncertainty about the accuracy of diagnosis. Hence, the likelihood of cardiac sarcoidosis should be thought of as a continuum (definite, highly probable, probable, possible, low probability, unlikely) rather than in a binary fashion. Treatment should be initiated in individuals with clinical manifestations and active inflammation in a tiered approach, with corticosteroids as first-line treatment. The lack of randomized clinical trials in cardiac sarcoidosis has led to treatment decisions based on cohort studies and consensus opinions, with substantial variation observed across centers. This scientific statement is intended to guide clinical practice and to facilitate management conformity by providing a framework for the diagnosis and management of cardiac sarcoidosis.

Adaptive versus conventional cardiac resynchronisation therapy in patients with heart failure (AdaptResponse): a global, prospective, randomised controlled trial.

BACKGROUND: Continuous automatic optimisation of cardiac resynchronisation therapy (CRT), stimulating only the left ventricle to fuse with intrinsic right bundle conduction (synchronised left ventricular stimulation), might offer better outcomes than conventional CRT in patients with heart failure, left bundle branch block, and normal atrioventricular conduction. This study aimed to compare clinical outcomes of adaptive CRT versus conventional CRT in patients with heart failure with intact atrioventricular conduction and left bundle branch block. METHODS: This global, prospective, randomised controlled trial was done in 227 hospitals in 27 countries across Asia, Australia, Europe, and North America. Eligible patients were aged 18 years or older with class 2-4 heart failure, an ejection fraction of 35% or less, left bundle branch block with QRS duration of 140 ms or more (male patients) or 130 ms or more (female patients), and a baseline PR interval 200 ms or less. Patients were randomly assigned (1:1) via block permutation to adaptive CRT (an algorithm providing synchronised left ventricular stimulation) or conventional biventricular CRT using a device programmer. All patients received device programming but were masked until procedures were completed. Site staff were not masked to group assignment. The primary outcome was a composite of all-cause death or intervention for heart failure decompensation and was assessed in the intention-to-treat population. Safety events were collected and reported in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT02205359, and is closed to accrual. FINDINGS: Between Aug 5, 2014, and Jan 31, 2019, of 3797 patients enrolled, 3617 (95·3%) were randomly assigned (1810 to adaptive CRT and 1807 to conventional CRT). The futility boundary was crossed at the third interim analysis on June 23, 2022, when the decision was made to stop the trial early. 1568 (43·4%) of 3617 patients were female and 2049 (56·6%) were male. Median follow-up was 59·0 months (IQR 45-72). A primary outcome event occurred in 430 of 1810 patients (Kaplan-Meier occurrence rate 23·5% [95% CI 21·3-25·5] at 60 months) in the adaptive CRT group and in 470 of 1807 patients (25·7% [23·5-27·8] at 60 months) in the conventional CRT group (hazard ratio 0·89, 95% CI 0·78-1·01; p=0·077). System-related adverse events were reported in 452 (25·0%) of 1810 patients in the adaptive CRT group and 440 (24·3%) of 1807 patients in the conventional CRT group. INTERPRETATION: Compared with conventional CRT, adaptive CRT did not significantly reduce the incidence of all-cause death or intervention for heart failure decompensation in the included population of patients with heart failure, left bundle branch block, and intact AV conduction. Death and heart failure decompensation rates were low with both CRT therapies, suggesting a greater response to CRT occurred in this population than in patients in previous trials. FUNDING: Medtronic.

High-power short-duration versus low-power long-duration ablation for pulmonary vein isolation: A substudy of the AWARE randomized controlled trial.

INTRODUCTION: Pulmonary vein isolations (PVI) are being performed using a high-power, short-duration (HPSD) strategy. The purpose of this study was to compare the clinical efficacy and safety outcomes of an HPSD versus low-power, long-duration (LPLD) approach to PVI in patients with paroxysmal atrial fibrillation (AF). METHODS: Patients were grouped according to a HPSD (≥40 W) or LPLD (≤35 W) strategy. The primary endpoint was the 1-year recurrence of any atrial arrhythmia lasting ≥30 s, detected using three 14-day ambulatory continuous ECG monitoring. Procedural and safety endpoints were also evaluated. The primary analysis were regression models incorporating propensity scores yielding adjusted relative risk (RRa ) and mean difference (MDa ) estimates. RESULTS: Of the 398 patients included in the AWARE Trial, 173 (43%) underwent HPSD and 225 (57%) LPLD ablation. The distribution of power was 50 W in 75%, 45 W in 20%, and 40 W in 5% in the HPSD group, and 35 W with 25 W on the posterior wall in the LPLD group. The primary outcome was not statistically significant at 30.1% versus 22.2% in HPSD and LPLD groups with RRa 0.77 (95% confidence interval [CI]) 0.55-1.10; p = .165). The secondary outcome of repeat catheter ablation was not statistically significant at 6.9% and 9.8% (RRa 1.59 [95% CI 0.77-3.30]; p = .208) respectively, nor was the incidence of any ECG documented AF during the blanking period: 1.7% versus 8.0% (RRa 3.95 [95% CI 1.00-15.61; p = .049) in the HPSD versus LPLD group respectively. The total procedure time was significantly shorter in the HPSD group (MDa 97.5 min [95% CI 84.8-110.4)]; p < .0001) with no difference in adjudicated serious adverse events. CONCLUSIONS: An HPSD strategy was associated with significantly shorter procedural times with similar efficacy in terms of clinical arrhythmia recurrence. Importantly, there was no signal for increased harm with a HPSD strategy.

Cardiac sarcoidosis with extensive and heterogeneous left ventricular FDG uptake in absence of guidelines indication for an implantable defibrillator: Ventricular tachycardia precipitated by immunosuppressive therapy, should we have done differently?

A 40-year-old man, newly diagnosed with cardiac sarcoidosis (CS) presented with symptomatic ventricular tachycardia three days after starting steroid-based immunosuppressive therapy (IT). There was no clear guideline indication for implantable cardioverter-defibrillator (ICD) before the initiation of IT. Shortly after ICD implantation and the initiation of anti-arrhythmic drugs, recurring ventricular arrhythmias required titration of the anti-arrhythmic drug therapy. One-year follow-up assessment showed no significant arrhythmias and complete PET scan FDG uptake suppression. This case, along with recent publications, suggests transient pro-arrhythmic effects of steroids in patients with CS, which are not appropriately addressed in the current guidelines. We believe ICD implantation should be considered in clinically manifest CS before initiating IT, particularly in cases with heterogeneous and/or extensive FDG uptake on PET scans.

The role of the host-microbiome and metabolomics in sarcoidosis.

Sarcoidosis is a complex inflammatory fibrotic disease that affects multiple organ systems. It is characterized by the infiltration of lymphocytes and mononuclear phagocytes, which form non-caseating granulomas in affected organs. The lungs and intrathoracic lymph nodes are the most commonly affected organs. The underlying cause of sarcoidosis is unknown, but it is believed to occur in genetically predisposed individuals who are exposed to pathogenic organisms, environmental contaminants, or self and non-self-antigens. Recent research has suggested that the microbiome may play a role in the development of respiratory conditions, including sarcoidosis. Additionally, metabolomic studies have identified potential biomarkers for monitoring sarcoidosis progression. This review will focus on recent microbiome and metabolomic findings in sarcoidosis, with the goal of shedding light on the pathogenesis and possible diagnostic and therapeutic approaches.

A Randomized Trial of Lenient Versus Strict Arm Instruction Post Cardiac Device Surgery (LENIENT).

BACKGROUND: Arm restriction after cardiac implantable electronic device (CIED) placement is common practice despite minimal supporting evidence. Patients receive a range of restriction recommendations of variable durations with the goal of reducing complications such as wound dehiscence, infection, lead dislodgement, or hematoma formation. These movement limitations can lead to emotional stress and anxiety, complications such as frozen shoulder, and upper extremity venous thrombosis due to immobilization. There are no published clinical trials assessing the benefits and risks of arm restrictions post-CIED implant. OBJECTIVES: The randomized trial of lenient vs strict arm and activity instruction post-CIED surgery (LENIENT trial; NCT04915261) is a single center nonblinded randomized prospective study designed to evaluate lenient compared to restrictive post-CIED care instructions. We hypothesize that there will be no significant difference in complications between the arms. METHODS/DESIGN: All patients receiving a de novo CIED or those with upgrades and revisions requiring a new lead implant will be enrolled. Subjects are enrolled in a nonblinded randomized prospective trial with 6 randomly assigned 8-month periods, during which either a lenient or restrictive postoperative activity instructions will be given to all patients. Postoperative instructions are given at the time of discharge and further reinforced by recurrent interactive voice recognition (IVR) phone calls, text messages and emails. The requirement for individual consent has been waived. The primary end point is a composite of (1) lead dislodgement, (2) frozen shoulder, (3) upper extremity venous thrombosis, (4) clinically significant hematoma, and (5) infection occurring within 52 weeks of index surgery. The study is a noninferiority trial with a sample size of 1,250 per group. DISCUSSION: This is the first large randomized clinical trial designed to establish an evidence-based postoperative standard of care for patients undergoing CIED implantation. This will improve the quality of care provided to patients and help guide implanting physicians providing postoperative care instructions. TRIAL REGISTRATION: ClinicalTrials.gov NCT04915261.

Diagnosis and Treatment of Cardiac Sarcoidosis.

About 5% of sarcoidosis patients develop clinically manifest cardiac features. Cardiac sarcoidosis (CS) typically presents with conduction abnormalities, ventricular arrhythmias and heart failure. Its diagnosis is challenging and requires a substantial degree of clinical suspicion as well as expertise in advanced cardiac imaging. Adverse events, particularly malignant arrhythmias and development of heart failure, are common among CS patients. A timely diagnosis is paramount to ameliorating outcomes for these patients. Despite weak evidence, immunosuppression (primarily with corticosteroids) is generally recommended in the presence of active inflammation in the myocardium. The burden of malignant arrhythmias remains important regardless of treatment, thus leading to the recommended use of an implantable cardioverter defibrillator in most patients with clinically manifest CS.

Perioperative Safety and Early Patient and Device Outcomes Among Subcutaneous Versus Transvenous Implantable Cardioverter Defibrillator Implantations : A Randomized, Multicenter Trial.

BACKGROUND: Implantable cardioverter defibrillators (ICDs) improve survival in patients at risk for cardiac arrest, but are associated with intravascular lead-related complications. The subcutaneous ICD (S-ICD), with no intravascular components, was developed to minimize lead-related complications. OBJECTIVE: To assess key ICD performance measures related to delivery of ICD therapy, including inappropriate ICD shocks (delivered in absence of life-threatening arrhythmia) and failed ICD shocks (which did not terminate ventricular arrhythmia). DESIGN: Randomized, multicenter trial. (ClinicalTrials.gov: NCT02881255). SETTING: The ATLAS trial. PATIENTS: 544 eligible patients (141 female) with a primary or secondary prevention indication for an ICD who were younger than age 60 years, had a cardiogenetic phenotype, or had prespecified risk factors for lead complications were electrocardiographically screened and 503 randomly assigned to S-ICD (251 patients) or transvenous ICD (TV-ICD) (252 patients). Mean follow-up was 2.5 years (SD, 1.1). Mean age was 49.0 years (SD, 11.5). MEASUREMENTS: The primary outcome was perioperative major lead-related complications. RESULTS: There was a statistically significant reduction in perioperative, lead-related complications, which occurred in 1 patient (0.4%) with an S-ICD and in 12 patients (4.8%) with TV-ICD (-4.4%; 95% CI, -6.9 to -1.9; P = 0.001). There was a trend for more inappropriate shocks with the S-ICD (hazard ratio [HR], 2.37; 95% CI, 0.98 to 5.77), but no increase in failed appropriate ICD shocks (HR, 0.61 (0.15 to 2.57). Patients in the S-ICD group had more ICD site pain, measured on a 10-point numeric rating scale, on the day of implant (4.2 ± 2.8 vs. 2.9 ± 2.2; P < 0.001) and 1 month later (1.3 ± 1.8 vs. 0.9 ± 1.5; P = 0.035). LIMITATION: At present, the ATLAS trial is underpowered to detect differences in clinical shock outcomes; however, extended follow-up is ongoing. CONCLUSION: The S-ICD reduces perioperative, lead-related complications without significantly compromising the effectiveness of ICD shocks, but with more early postoperative pain and a trend for more inappropriate shocks. PRIMARY FUNDING SOURCE: Boston Scientific.

Augmented wide area circumferential catheter ablation for reduction of atrial fibrillation recurrence (AWARE) trial: Design and rationale.

BACKGROUND: Recurrence of atrial fibrillation (AF) after a pulmonary vein isolation procedure is often due to electrical reconnection of the pulmonary veins. Repeat ablation procedures may improve freedom from AF but are associated with increased risks and health care costs. A novel ablation strategy in which patients receive "augmented" ablation lesions has the potential to reduce the risk of AF recurrence. OBJECTIVE: The Augmented Wide Area Circumferential Catheter Ablation for Reduction of Atrial Fibrillation Recurrence (AWARE) Trial was designed to evaluate whether an augmented wide-area circumferential antral (WACA) ablation strategy will result in fewer atrial arrhythmia recurrences in patients with symptomatic paroxysmal AF, compared with a conventional WACA strategy. METHODS/DESIGN: The AWARE trial was a multicenter, prospective, randomized, open, blinded endpoint trial that has completed recruitment (ClinicalTrials.gov NCT02150902). Patients were randomly assigned (1:1) to either the control arm (single WACAlesion set) or the interventional arm (augmented- double WACA lesion set performed after the initial WACA). The primary outcome was atrial tachyarrhythmia (AA; atrial tachycardia [AT], atrial flutter [AFl] or AF) recurrence between days 91 and 365 post catheter ablation. Patient follow-up included 14-day continuous ambulatory ECG monitoring at 3, 6, and 12 months after catheter ablation. Three questionnaires were administered during the trial- the EuroQuol-5D (EQ-5D) quality of life scale, the Canadian Cardiovascular Society Severity of Atrial Fibrillation scale, and a patient satisfaction scale. DISCUSSION: The AWARE trial was designed to evaluate whether a novel approach to catheter ablation reduced the risk of AA recurrence in patients with symptomatic paroxysmal AF.

Characterization of arrhythmia substrate to ablate persistent atrial fibrillation (COAST-AF): Randomized controlled trial design and rationale.

BACKGROUND: Atrial low voltage area (LVA) catheter ablation has emerged as a promising strategy for ablation of persistent atrial fibrillation (AF). It is unclear if catheter ablation of atrial LVA increases treatment success rates in patients with persistent AF. OBJECTIVE: The primary aim of this trial is to assess the potential benefit of adjunctive catheter ablation of atrial LVA in addition to pulmonary vein isolation (PVI) in patients with persistent AF, when compared to PVI alone. The secondary aims are to evaluate safety outcomes, the quality of life and the healthcare resource utilization. METHODS/DESIGN: A multicenter, prospective, parallel-group, 2-arm, single-blinded randomized controlled trial is under way (NCT03347227). Patients who are candidates for catheter ablation for persistent AF will be randomly assigned (1:1) to either PVI alone or PVI + atrial LVA ablation. The primary outcome is 18-month documented event rate of atrial arrhythmia (AF, atrial tachycardia or atrial flutter) post catheter ablation. Secondary outcomes include procedure-related complications, freedom from atrial arrhythmia at 12 months, AF burden, need for emergency department visits/hospitalization, need for repeat ablation for atrial arrhythmia, quality of life at 12 and 18 months, ablation time, and procedure duration. DISCUSSION: Characterization of Arrhythmia Mechanism to Ablate Atrial Fibrillation (COAST-AF) is a multicenter randomized trial evaluating ablation strategies for catheter ablation. We hypothesize that catheter ablation of atrial LVA in addition to PVI will result in higher procedural success rates when compared to PVI alone in patients with persistent AF.

Metabolic activity of the left and right atria are differentially altered in patients with atrial fibrillation and LV dysfunction.

BACKGROUND: Alterations in atrial metabolism may play a role in the perpetuation of atrial fibrillation (AF). This study sought to compare 18F-fluorodeoxyglucose (FDG) uptake on PET, in patients with LV dysfunction versus those without AF. METHODS: Seventy-two patients who underwent myocardial viability assessment were evaluated. AF patients (36) had persistent or permanent AF based on history and ECG. Patients without AF (36) were matched to AF patients based on sex, diabetes, age, and LVEF. Maximum and mean FDG Standard Uptake Values (SUV) in the left atrial (LA) wall and right atrial (RA) wall were measured. Tissue-to-blood ratios (TBR) were calculated as atrial wall to blood-pool activity. Atrial volumes were measured by echocardiography. RESULTS: Maximum and mean FDG SUV and TBRs were significantly increased in the RA (but not the LA) of patients with AF compared to those without (P < 0.01). When accounting for changes in atrial volume, the presence of AF remained a significant predictor of higher RAMAX, but not RAMEAN FDG uptake. CONCLUSION: In patients with LV dysfunction from ischemic cardiomyopathy, LA and RA glucose metabolism are differentially altered in those with persistent atrial fibrillation. Further investigations should elucidate the temporal relationship between AF and glucose metabolic changes, as a potential target for therapy.

The consequences of living with a severe malocclusion: A review of the literature.

AIM: To facilitate the orthognathic shared decision-making process by identifying and applying existing research evidence to establish the potential consequences of living with a severe malocclusion. METHODS: A comprehensive narrative literature review was conducted to explore the potential complications of severe malocclusion. A systematic electronic literature search of four databases combined with supplementary hand searching identified 1024 articles of interest. A total of 799 articles were included in the narrative literature review, which was divided into 10 themes: Oral Health Related Quality Of Life; Temporomandibular Joint Dysfunction; Masticatory Limitation; Sleep Apnoea; Traumatic Dental Injury; Tooth Surface Loss; Change Over Time; Periodontal Injury; Restorative Difficulty; and Functional Shift and Dual Bite. A deductive approach was used to draw conclusions from the evidence available within each theme. RESULTS: The narrative literature review established 27 conclusions, indicating that those living with a severe malocclusion may be predisposed to a range of potential consequences. With the exception of Oral Health Related Quality Of Life, which is poorer in adults with severe malocclusion than those with normal occlusions, and the risk of Traumatic Dental Injury, which increases when the overjet is >5 mm in the permanent and 3 mm in the primary dentition, the evidence supporting the remaining conclusions was found to be of low to moderate quality and at high risk of bias. CONCLUSION: This article summarises the findings of a comprehensive narrative literature review in which all of the relevant research evidence within a substantive investigative area is established and evaluated. Notwithstanding limitations regarding the quality of the available evidence; when combined with clinical expertise and an awareness of individual patient preferences, the conclusions presented may facilitate the orthognathic shared decision-making process and furthermore, may guide the development of the high-quality longitudinal research required to validate them.

Electrical versus pharmacological cardioversion for emergency department patients with acute atrial fibrillation (RAFF2): a partial factorial randomised trial.

BACKGROUND: Acute atrial fibrillation is the most common arrythmia treated in the emergency department. Our primary aim was to compare conversion to sinus rhythm between pharmacological cardioversion followed by electrical cardioversion (drug-shock), and electrical cardioversion alone (shock-only). Our secondary aim was to compare the effectiveness of two pad positions for electrical cardioversion. METHODS: We did a partial factorial trial of two protocols for patients with acute atrial fibrillation at 11 academic hospital emergency departments in Canada. We enrolled adult patients with acute atrial fibrillation. Protocol 1 was a randomised, blinded, placebo-controlled comparison of attempted pharmacological cardioversion with intravenous procainamide (15 mg/kg over 30 min) followed by electrical cardioversion if necessary (up to three shocks, each of ≥200 J), and placebo infusion followed by electrical cardioversion. For patients having electrical cardioversion, we used Protocol 2, a randomised, open-label, nested comparison of anteroposterior versus anterolateral pad positions. Patients were randomly assigned (1:1, stratified by study site) for Protocol 1 by on-site research personnel using an online electronic data capture system. Randomisation for Protocol 2 occurred 30 min after drug infusion for patients who had not converted and was stratified by site and Protocol 1 allocation. Patients and all research and emergency department staff were masked to treatment allocation for Protocol 1. The primary outcome was conversion to normal sinus rhythm for at least 30 min at any time after randomisation and up to a point immediately after three shocks. Protocol 1 was analysed by intention to treat and Protocol 2 excluded patients who did not receive electrical cardioversion. This study is registered at ClinicalTrials.gov, number NCT01891058. FINDINGS: Between July 18, 2013, and Oct 17, 2018, we enrolled 396 patients, and none were lost to follow-up. In the drug-shock group (n=204), conversion to sinus rhythm occurred in 196 (96%) patients and in the shock-only group (n=192), conversion occurred in 176 (92%) patients (absolute difference 4%; 95% CI 0-9; p=0·07). The proportion of patients discharged home was 97% (n=198) versus 95% (n=183; p=0·60). 106 (52%) patients in the drug-shock group converted after drug infusion only. No patients had serious adverse events in follow-up. The different pad positions in Protocol 2 (n=244), had similar conversions to sinus rhythm (119 [94%] of 127 in anterolateral group vs 108 [92%] of 117 in anteroposterior group; p=0·68). INTERPRETATION: Both the drug-shock and shock-only strategies were highly effective, rapid, and safe in restoring sinus rhythm for patients in the emergency department with acute atrial fibrillation, avoiding the need for return to hospital. The drug infusion worked for about half of patients and avoided the resource intensive procedural sedation required for electrical cardioversion. We also found no significant difference between the anterolateral and anteroposterior pad positions for electrical cardioversion. Immediate rhythm control for patients in the emergency department with acute atrial fibrillation leads to excellent outcomes. FUNDING: Heart and Stroke Foundation of Canada and the Canadian Institutes of Health Research.

Interleukin-1 blockade in cardiac sarcoidosis: study design of the multimodality assessment of granulomas in cardiac sarcoidosis: Anakinra Randomized Trial (MAGiC-ART).

BACKGROUND: Sarcoidosis is an inflammatory disease characterized by the formation of granulomas, which involve the heart in up to 25% of patients. Cardiac sarcoidosis can lead to life threatening arrhythmias and heart failure. While corticosteroids have been used as a treatment for over 50 years, they are associated with hypertension, diabetes, and weight gain, further increasing cardiovascular risk. Interleukin-1 (IL-1) is the prototypical proinflammatory cytokine that works to activate the nuclear transcription factor NF-kB, one of the targets of glucocorticoids. IL-1 also plays an important role also in the pathophysiology of heart disease including atherosclerosis, myocardial infarction, and myocarditis. METHODS: Building on a network of research collaborators developed in the Cardiac Sarcoidosis Consortium, we will investigate the feasibility and tolerability of treatment of CS with anakinra at two National Institute of Health Clinical and Translational Science Award (CTSA) hubs with expertise in cardiac sarcoidosis. In this pilot study, up to 28 patients with cardiac sarcoidosis will be recruited to compare the administration of an IL-1 blocker, anakinra, 100 mg daily on top of standard of care versus standard of care only for 28 days and followed for 180 days. Utilizing surrogate endpoints of changes in systemic inflammatory biomarkers and cardiac imaging, we aim to determine whether IL-1 blockade with anakinra can combat systemic and cardiac inflammation in patients with cardiac sarcoidosis. DISCUSSION: The current trial demonstrates an innovative collaborative approach to clinical trial development in a rare, understudied disease that disproportionately affects females and minorities. Trial Registration The trial was registered prospectively with ClinicalTrials.gov on July 12, 2019, identifier NCT04017936.

High-power, short-duration atrial fibrillation ablation compared with a conventional approach: Outcomes and reconnection patterns.

BACKGROUND: The effectiveness, safety, and pulmonary vein (PV) reconnection patterns of point-by-point high-power, short-duration (HPSD) ablation relative to conventional force-time integral (FTI)-guided strategies for atrial fibrillation (AF) ablation are unknown. OBJECTIVES: To compare 1-year freedom from atrial arrhythmia (AA), complication rates, procedural times, and PV reconnection patterns with HPSD AF AF ablation versus an FTI-guided low-power, long-duration (LPLD) strategy. METHODS: We compared consecutive patients undergoing a first ablation procedure for paroxysmal or persistent AF. The HPSD protocol utilized a power of 50 W and durations of 6-8 s posteriorly and 8-10 s anteriorly. The LPLD protocol was FTI-guided with a power of ≤25 W posteriorly (FTI ≥ 300g·s) and ≤35 W anteriorly (FTI ≥ 400g·s). RESULTS: In total, 214 patients were prospectively included (107 HPSD, 107 LPLD). Freedom from AA at 1 year was achieved in 79% in the HPSD group versus 73% in the LPLD group (p = .339; adjusted hazard ratio with HPSD, 0.67; 95% confidence interval, 0.36-1.23; p < .004 for non-inferiority). Procedure duration was shorter in the HPSD group (229 ± 60 vs. 309 ± 77 min; p < .005). Patients undergoing repeat ablation had a higher propensity for reconnection at the right PV carina in the HPSD group compared with the LPLD group (14/30 = 46.7% vs. 7/34 = 20.6%; p = .035). There were no differences in complication rates. CONCLUSION: HPSD AF ablation resulted in similar freedom from AAs at 1 year, shorter procedure times, and a similar safety profile when compared with an LPLD ablation strategy. Patients undergoing HPSD ablation required more applications at the right carina to achieve isolation, and had a significantly higher rate of right carinal reconnections at redo procedures.

Epidemiology of cardiac implantable electronic device infections: incidence and risk factors.

Cardiac implantable electronic device (CIED) infection is a potentially devastating complication of CIED procedures, causing significant morbidity and mortality for patients. Of all CIED complications, infection has the greatest impact on mortality, requirement for re-intervention and additional hospital treatment days. Based on large prospective studies, the infection rate at 12-months after a CIED procedure is approximately 1%. The risk of CIED infection may be related to several factors which should be considered with regards to risk minimization. These include technical factors, patient factors, and periprocedural factors. Technical factors include the number of leads and size of generator, the absolute number of interventions which have been performed for the patient, and the operative approach. Patient factors include various non-modifiable underlying comorbidities and potentially modifiable transient conditions. Procedural factors include both peri-operative and post-operative factors. The contemporary PADIT score, derived from a large cohort of CIED patients, is useful for the prediction of infection risk. In this review, we summarize the key information regarding epidemiology, incidence and risk factors for CIED infection.

Post-operative pain following cardiac implantable electronic device implantation: insights from the BRUISE CONTROL trials.

AIMS: Post-operative pain following cardiac implantable electronic device (CIED) insertion is associated with patient dissatisfaction, emotional distress, and emergency department visits. We sought to identify factors associated with post-operative pain and develop a prediction score for post-operative pain. METHODS AND RESULTS: All patients from the BRUISE CONTROL-1 and 2 trials were included in this analysis. A validated Visual Analogue Scale (VAS) was used to assess the severity of pain related to CIED implant procedures. Patients were asked to grade the most severe post-operative pain, average post-operative pain, and pain on the day of the first post-operative clinic. Multivariable regression analyses were performed to identify predictors of significant post-operative pain and to develop a pain-prediction score. A total of 1308 patients were included. Multivariable regression analysis found that the presence of post-operative clinically significant haematoma {CSH; P value < 0.001; odds ratio (OR) 3.82 [95% confidence interval (CI): 2.37-6.16]}, de novo CIED implantation [P value < 0.001; OR 1.90 (95% CI: 1.47-2.46)], female sex [P value < 0.001; OR 1.61 (95% CI: 1.22-2.12)], younger age [<65 years; P value < 0.001; OR 1.54 (95% CI: 1.14-2.10)], and lower body mass index [<20 kg/m2; P value < 0.05; OR 2.05 (95% CI: 0.98-4.28)] demonstrated strong and independent associations with increased post-operative pain. An 11-point post-operative pain prediction score was developed using the data. CONCLUSION: Our study has identified multiple predictors of post-operative pain after CIED insertion. We have developed a prediction score for post-operative pain that can be used to identify individuals at risk of experiencing significant post-operative pain.

Decision Support for Implantable Cardioverter-Defibrillator Replacement: A Pilot Feasibility Randomized Controlled Trial.

BACKGROUND: Decision support can help patients facing implantable cardioverter-defibrillator (ICD) replacement understand their options and reach an informed decision reflective of their preferences. OBJECTIVE: The aim of this study was to evaluate the feasibility of a decision support intervention for patients faced with the decision to replace their ICD. METHODS: A pilot feasibility randomized trial was conducted. Patients approaching ICD battery depletion were randomized to decision support intervention or usual care. Feasibility outcomes included recruitment rates, intervention use, and completeness of data; secondary outcomes were knowledge, values-choice concordance, decisional conflict, involvement in decision making, and choice. RESULTS: A total of 30 patients were randomized to intervention (n = 15) or usual care (n = 15). The intervention was used as intended, with 2% missing data. Patients in the intervention arm had better knowledge (77.4% vs 51.1%; P = .002). By 12 months, 8 of 13 (61.5%) in the intervention arm and 10 of 14 (71.4%) in the usual care arm accepted ICD replacement; 1 per arm declined (7.7% vs 7.1%, respectively). CONCLUSION: It was feasible to deliver the intervention, collect data, despite slow recruitment. The decision support intervention has the potential to improve ICD replacement decision quality.