Long-Term Outcomes of Resynchronization-Defibrillation for Heart Failure.

BACKGROUND: The Resynchronization-Defibrillation for Ambulatory Heart Failure Trial (RAFT) showed a greater benefit with respect to mortality at 5 years among patients who received cardiac-resynchronization therapy (CRT) than among those who received implantable cardioverter-defibrillators (ICDs). However, the effect of CRT on long-term survival is not known. METHODS: We randomly assigned patients with New York Heart Association (NYHA) class II or III heart failure, a left ventricular ejection fraction of 30% or less, and an intrinsic QRS duration of 120 msec or more (or a paced QRS duration of 200 msec or more) to receive either an ICD alone or a CRT defibrillator (CRT-D). We assessed long-term outcomes among patients at the eight highest-enrolling participating sites. The primary outcome was death from any cause; the secondary outcome was a composite of death from any cause, heart transplantation, or implantation of a ventricular assist device. RESULTS: The trial enrolled 1798 patients, of whom 1050 were included in the long-term survival trial; the median duration of follow-up for the 1050 patients was 7.7 years (interquartile range, 3.9 to 12.8), and the median duration of follow-up for those who survived was 13.9 years (interquartile range, 12.8 to 15.7). Death occurred in 405 of 530 patients (76.4%) assigned to the ICD group and in 370 of 520 patients (71.2%) assigned to the CRT-D group. The time until death appeared to be longer for those assigned to receive a CRT-D than for those assigned to receive an ICD (acceleration factor, 0.80; 95% confidence interval, 0.69 to 0.92; P = 0.002). A secondary-outcome event occurred in 412 patients (77.7%) in the ICD group and in 392 (75.4%) in the CRT-D group. CONCLUSIONS: Among patients with a reduced ejection fraction, a widened QRS complex, and NYHA class II or III heart failure, the survival benefit associated with receipt of a CRT-D as compared with ICD appeared to be sustained during a median of nearly 14 years of follow-up. (RAFT ClinicalTrials.gov number, NCT00251251.).

A Dual-Chamber Leadless Pacemaker.

BACKGROUND: Single-chamber ventricular leadless pacemakers do not support atrial pacing or consistent atrioventricular synchrony. A dual-chamber leadless pacemaker system consisting of two devices implanted percutaneously, one in the right atrium and one in the right ventricle, would make leadless pacemaker therapy a treatment option for a wider range of indications. METHODS: We conducted a prospective, multicenter, single-group study to evaluate the safety and performance of a dual-chamber leadless pacemaker system. Patients with a conventional indication for dual-chamber pacing were eligible for participation. The primary safety end point was freedom from complications (i.e., device- or procedure-related serious adverse events) at 90 days. The first primary performance end point was a combination of adequate atrial capture threshold and sensing amplitude at 3 months. The second primary performance end point was at least 70% atrioventricular synchrony at 3 months while the patient was sitting. RESULTS: Among the 300 patients enrolled, 190 (63.3%) had sinus-node dysfunction and 100 (33.3%) had atrioventricular block as the primary pacing indication. The implantation procedure was successful (i.e., two functioning leadless pacemakers were implanted and had established implant-to-implant communication) in 295 patients (98.3%). A total of 35 device- or procedure-related serious adverse events occurred in 29 patients. The primary safety end point was met in 271 patients (90.3%; 95% confidence interval [CI], 87.0 to 93.7), which exceeded the performance goal of 78% (P<0.001). The first primary performance end point was met in 90.2% of the patients (95% CI, 86.8 to 93.6), which exceeded the performance goal of 82.5% (P<0.001). The mean (±SD) atrial capture threshold was 0.82±0.70 V, and the mean P-wave amplitude was 3.58±1.88 mV. Of the 21 patients (7%) with a P-wave amplitude of less than 1.0 mV, none required device revision for inadequate sensing. At least 70% atrioventricular synchrony was achieved in 97.3% of the patients (95% CI, 95.4 to 99.3), which exceeded the performance goal of 83% (P<0.001). CONCLUSIONS: The dual-chamber leadless pacemaker system met the primary safety end point and provided atrial pacing and reliable atrioventricular synchrony for 3 months after implantation. (Funded by Abbott Medical; Aveir DR i2i ClinicalTrials.gov number, NCT05252702.).

Atrioventricular Synchrony Delivered by a Dual-Chamber Leadless Pacemaker System.

BACKGROUND: A dual-chamber leadless pacemaker system has been designed for AV synchronous pacing using wireless, beat-to-beat, implant-to-implant (i2i) communication between distinct atrial and ventricular leadless pacemakers. The AV synchrony achieved across various ambulatory scenarios has yet to be systematically evaluated. METHODS: A prospective, single-arm, unblinded, multicenter, international clinical trial of the leadless pacemaker system was conducted in patients with a conventional dual-chamber pacing indication enrolled from February 2022 to March 2023. Leadless pacemaker systems were implanted, and 12-lead Holter electrocardiographic recordings were collected 3 months after implantation over various postures/activities: sitting, supine, left lateral recumbent, right lateral recumbent, standing, normal walk, and fast walk. An independent Holter core laboratory performed a manual adjudication of the percent of AV synchronous beats using the standard 300-millisecond PR interval limit. Atrium-to-ventricle and ventricle-to-atrium i2i communication success rates were also assessed. Post hoc summary statistics describing the relationships between AV synchrony and i2i success, posture/activity, implantation indication, AV event, and heart rate were calculated. RESULTS: In the evaluable population (n=384 of 464 enrolled [83%]; 61% male; age, 70 years; weight, 82 kg; 60% ejection fraction; 95% of beats evaluable), the mean AV synchrony of 98% of beats observed across all postures using the standard 300-millisecond limit was greater than both atrium-to-ventricle i2i (94%) and ventricle-to-atrium i2i (94%; P<0.001), exceeding both i2i values in 95% of patients. AV synchrony was achieved in >95% of evaluable beats across all postures/activities, implantation indications, AV paced/sensed event combinations, and heart rate ranges (including >100 bpm). CONCLUSIONS: This dual-chamber leadless pacemaker system demonstrated AV synchrony in 98% of evaluable beats at 3 months after implantation. AV synchrony was maintained across postures/activities and remained robust for heart rates >100 bpm.

Self-Management Support Using Advertising Principles for Older Adults With Low Income at High Cardiovascular Risk: A Randomized Controlled Trial.

BACKGROUND: Self-management education and support (SMES) interventions have modest effects on intermediate outcomes for those at risk of cardiovascular disease, but few studies have measured or demonstrated an effect on clinical end points. Advertising for commercial products is known to influence behavior, but advertising principles are not typically incorporated into SMES design. METHODS: This randomized trial studied the effect of a novel tailored SMES program designed by an advertising firm among a population of older adults with low income at high cardiovascular risk in Alberta, Canada. The intervention included health promotion messaging from a fictitious "peer" and facilitated relay of clinical information to patients' primary care provider and pharmacist. The primary outcome was the composite of death, myocardial infarction, stroke, coronary revascularization, and hospitalizations for cardiovascular-related ambulatory care-sensitive conditions. Rates of the primary outcome and its components were compared using negative binomial regression. Secondary outcomes included quality of life (EQ-5D [EuroQoL 5-dimension] index score), medication adherence, and overall health care costs. RESULTS: We randomized 4761 individuals, with a mean age of 74.4 years, of whom 46.8% were female. There was no evidence of statistical interaction (P=0.99) or of a synergistic effect between the 2 interventions in the factorial trial with respect to the primary outcome, which allowed us to evaluate the effect of each intervention separately. Over a median follow-up time of 36 months, the rate of the primary outcome was lower in the group that received SMES compared with the control group (incidence rate ratio, 0.78 [95% CI, 0.61 to 1.00]; P=0.047). No significant between-group changes in quality of life over time were observed (mean difference, 0.0001 [95% CI, -0.018 to 0.018]; P=0.99). The proportion of participants who were adherent to medications was not different between the 2 groups (P=0.199 for statins and P=0.754 for angiotensin-converting enzyme inhibitors/angiotensin receptor blockers). Overall adjusted health care costs did not differ between those receiving SMES and the control group ($2015 [95% CI, -$1953 to $5985]; P=0.320). CONCLUSIONS: For older adults with low income, a tailored SMES program using advertising principles reduced the rate of clinical outcomes compared with usual care. The mechanisms of improvement are unclear and further studies are required. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02579655.

Eliminating Medication Copayments for Low-Income Older Adults at High Cardiovascular Risk: A Randomized Controlled Trial.

BACKGROUND: One in eight people with heart disease has poor medication adherence that, in part, is related to copayment costs. This study tested whether eliminating copayments for high-value medications among low-income older adults at high cardiovascular risk would improve clinical outcomes. METHODS: This randomized 2×2 factorial trial studied 2 distinct interventions in Alberta, Canada: eliminating copayments for high-value preventive medications and a self-management education and support program (reported separately). The findings for the first intervention, which waived the usual 30% copayment on 15 medication classes commonly used to reduce cardiovascular events, compared with usual copayment, is reported here. The primary outcome was the composite of death, myocardial infarction, stroke, coronary revascularization, and cardiovascular-related hospitalizations over a 3-year follow-up. Rates of the primary outcome and its components were compared using negative binomial regression. Secondary outcomes included quality of life (Euroqol 5-dimension index score), medication adherence, and overall health care costs. RESULTS: A total of 4761 individuals were randomized and followed for a median of 36 months. There was no evidence of statistical interaction (P=0.99) or of a synergistic effect between the 2 interventions in the factorial trial with respect to the primary outcome, which allowed us to evaluate the effect of each intervention separately. The rate of the primary outcome was not reduced by copayment elimination, (521 versus 533 events, incidence rate ratio 0.84 [95% CI, 0.66-1.07], P=0.162). The incidence rate ratio for nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death (0.97 [95% CI, 0.67-1.39]), death (0.94 [95% CI, 0.80 to 1.11]), and cardiovascular-related hospitalizations (0.78 [95% CI, 0.57 to 1.06]) did not differ between groups. No significant between-group changes in quality of life over time were observed (mean difference, 0.012 [95% CI, -0.006 to 0.030], P=0.19). The proportion of participants who were adherent to statins was 0.72 versus 0.69 for the copayment elimination versus usual copayment groups, respectively (mean difference, 0.03 [95% CI, 0.006-0.06], P=0.016). Overall adjusted health care costs did not differ ($3575 [95% CI, -605 to 7168], P=0.098). CONCLUSIONS: In low-income adults at high cardiovascular risk, eliminating copayments (average, $35/mo) did not improve clinical outcomes or reduce health care costs, despite a modest improvement in adherence to medications. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02579655.

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.

Economic evaluation of an absorbable antibiotic envelope for prevention of cardiac implantable electronic device infection.

AIMS: Recent evidence suggests that an antibiotic impregnated envelope inserted at time of cardiac implantable electronic device (CIED) implantation may reduce risk of subsequent CIED infection compared with standard of care (SoC). The objective of the current work was to perform a cost-effectiveness analysis comparing an antibiotic impregnated envelope with SoC at time of CIED insertion. METHODS AND RESULTS: Decision analytic models were used to project healthcare costs and benefits of two strategies, an antibiotic impregnated envelope plus SoC (Env+SoC) vs. SoC alone, in a cohort of patients undergoing CIED implantation over a 1-year time horizon. Evidence from published literature informed the model inputs. Probabilistic and deterministic sensitivity analyses were performed. The primary outcome was the incremental cost per infection prevented, assessed from the Canadian healthcare system perspective. Envelope plus SoC was associated with fewer CIED infection (7 CIED infections/1000 patients) at higher total costs ($29 033 000/1000 patients) compared with SoC (11 CIED infections and $27 926 000/1000 patients). The incremental cost per infection prevented over 1 year was $274 416. Use of Env+SoC was cost saving only when baseline CIED infection risk was increased to 6% (vs. base case of 1.2%). CONCLUSIONS: A strategy of Env+SoC was not economically favourable compared with SoC alone, and the opportunity cost of widescale implementation should be considered. Future work is required to develop validated risk stratification tools to identify patients at greatest risk of CIED infection. The value proposition of Env+SoC improves when applying this intervention to patients at greatest infection risk.

Canadian Registry of Electronic Device Outcomes: remote monitoring outcomes in the Abbott battery performance alert-a multicentre cohort.

AIMS: Cardiac implantable electronic devices with device advisories have the potential of device malfunction. Remote monitoring (RM) of devices has been suggested to allow the identification of abnormal device performance and permit early intervention. We sought to describe the outcomes of patients with and without RM in devices subject to the Abbott Premature Battery Depletion (PBD) advisory with data from a Canadian registry. METHODS AND RESULTS: Patients with an Abbott device subject to the PBD advisory from nine implantable cardioverter defibrillator (ICD) implanting centres in Canada were included in the registry. The use of RM was identified from baseline and follow-up data in the registry. The primary outcome was detection of PBD and all-cause mortality. A total of 2666 patients were identified with a device subject to the advisory. In all, 1687 patients (63.2%) had RM at baseline. There were 487 deaths during follow-up. At a mean follow-up of 5.7 ± 0.7 years, mortality was higher in those without a remote monitor compared with RM at baseline (24.7% vs. 14.5%; P < 0.001). Pre-mature battery depletion was identified in 36 patients (2.1%) with RM vs. 7 (0.7%) without RM (P = 0.004). Time to battery replacement was significantly reduced in patients on RM (median 5 vs. 13 days, P = 0.001). CONCLUSION: The use of RM in patients with ICD and cardiac resynchronization therapy under advisory improved detection of PBD, time to device replacement, and was associated with a reduction in all-cause mortality. The factors influencing the association with mortality are unknown and deserve further study.

Predictors of appropriate shock after generator replacement in patients with an implantable cardioverter defibrillator.

BACKGROUND: Implantable cardioverter defibrillators (ICDs) are indicated for the primary prevention of sudden cardiac death in patients with reduced left ventricular ejection fraction (LVEF). The ongoing risk/benefit profile of an ICD at generator replacement is unknown. This study aimed to identify predictors of appropriate ICD shocks and therapies after first ICD generator replacement, and its procedure-related complications. METHODS: We conducted a multicenter, retrospective cohort study including patients with primary prevention ICDs who underwent generator replacement between April 2005 and July 2015 at three Canadian centers. The primary and secondary outcomes were appropriate ICD shock and any appropriate ICD therapy, respectively. Procedure-related complication rates were also reported. RESULTS: Of the 219 patients in the cohort, 61 (28%) experienced an appropriate shock while 40 (18%) experienced appropriate antitachycardia pacing over a median follow up of 2.2 years. Independent predictors of appropriate ICD shocks included: LVEF at time of replacement (adjusted odds ratio [OR] 0.4 per 10% increase in LVEF, P < .001), a history of appropriate ICD shocks prior to replacement (OR 4.9, P < .001), and a history of inappropriate ICD shocks (OR 4.2, 95%, P < .002). Similar predictors were identified for the secondary outcome of any appropriate ICD therapy. Device-related complications were reported in 25 (11%) patients, with 1 (0.5%) resulting in death, 14 (6.3%) requiring site re-operation, and 6 (2.7%) requiring cardiac surgical management. CONCLUSION: Not all primary prevention ICD patients undergoing generator replacement will require appropriate device therapies afterwards. Generator replacement is associated with several risks that should be weighed against its anticipated benefit. A comprehensive assessment of the risk-benefit profile of patients undergoing generator replacement is warranted.

Canadian national electrophysiology ablation registry report 2011-2016.

BACKGROUND/PURPOSE: Interventional cardiac electrophysiology (EP) is a rapidly evolving field in Canada; a nationwide registry was established in 2011 to conduct a periodic review of resource allocation. METHODS: The registry collects annual data on EP lab infrastructure, imaging, tools, human resources, procedural volumes, success rates, and wait times. Leading physicians from each EP lab were contacted electronically; participation was voluntary. RESULTS: All Canadian EP centres were identified (n = 30); 50 and 45 % of active centres participated in the last 2 instalments of the registry. A mean of 508 ± 270 standard and complex catheter ablation procedures were reported annually for 2015-2016 by all responding centres. The most frequently performed ablation targets atrial fibrillation (PVI) arrhythmia accounting for 36 % of all procedures (mean = 164 ± 85). The number of full time physicians ranges between 1 and 7 per centre, (mean = 4). The mean wait time to see an electrophysiologist for an initial non-urgent consult is 23 weeks. The wait time between an EP consult and ablation date is 17.8 weeks for simple ablation, and 30.1 weeks for AF ablation. On average centres have 2 (range: 1-4) rooms equipped for ablations; each centre uses the EP lab an average of 7 shifts per week. While diagnostic studies and radiofrequency ablations are performed in all centres, point-by-point cryoablation is available in 85 % centres; 38 % of the respondents use circular ablation techniques. CONCLUSIONS: This initiative provides contemporary data on invasive electrophysiology lab practices. The EP registry provides activity benchmarks on national trends and practices.

Effect of Implantable vs Prolonged External Electrocardiographic Monitoring on Atrial Fibrillation Detection in Patients With Ischemic Stroke: The PER DIEM Randomized Clinical Trial.

Importance: The relative rates of detection of atrial fibrillation (AF) or atrial flutter from evaluating patients with prolonged electrocardiographic monitoring with an external loop recorder or implantable loop recorder after an ischemic stroke are unknown. Objective: To determine, in patients with a recent ischemic stroke, whether 12 months of implantable loop recorder monitoring detects more occurrences of AF compared with conventional external loop recorder monitoring for 30 days. Design, Setting, and Participants: Investigator-initiated, open-label, randomized clinical trial conducted at 2 university hospitals and 1 community hospital in Alberta, Canada, including 300 patients within 6 months of ischemic stroke and without known AF from May 2015 through November 2017; final follow-up was in December 2018. Interventions: Participants were randomly assigned 1:1 to prolonged electrocardiographic monitoring with either an implantable loop recorder (n = 150) or an external loop recorder (n = 150) with follow-up visits at 30 days, 6 months, and 12 months. Main Outcomes and Measures: The primary outcome was the development of definite AF or highly probable AF (adjudicated new AF lasting ≥2 minutes within 12 months of randomization). There were 8 prespecified secondary outcomes including time to event analysis of new AF, recurrent ischemic stroke, intracerebral hemorrhage, death, and device-related serious adverse events within 12 months. Results: Among the 300 patients who were randomized (median age, 64.1 years [interquartile range, 56.1 to 73.7 years]; 121 were women [40.3%]; and 66.3% had a stroke of undetermined etiology with a median CHA2DS2-VASc [congestive heart failure, hypertension, age ≥75 years, diabetes, stroke or transient ischemic attack, vascular disease, age 65 to 74 years, sex category] score of 4 [interquartile range, 3 to 5]), 273 (91.0%) completed cardiac monitoring lasting 24 hours or longer and 259 (86.3%) completed both the assigned monitoring and 12-month follow-up visit. The primary outcome was observed in 15.3% (23/150) of patients in the implantable loop recorder group and 4.7% (7/150) of patients in the external loop recorder group (between-group difference, 10.7% [95% CI, 4.0% to 17.3%]; risk ratio, 3.29 [95% CI, 1.45 to 7.42]; P = .003). Of the 8 specified secondary outcomes, 6 were not significantly different. There were 5 patients (3.3%) in the implantable loop recorder group who had recurrent ischemic stroke vs 8 patients (5.3%) in the external loop recorder group (between-group difference, -2.0% [95% CI, -6.6% to 2.6%]), 1 (0.7%) vs 1 (0.7%), respectively, who had intracerebral hemorrhage (between-group difference, 0% [95% CI, -1.8% to 1.8%]), 3 (2.0%) vs 3 (2.0%) who died (between-group difference, 0% [95% CI, -3.2% to 3.2%]), and 1 (0.7%) vs 0 (0%) who had device-related serious adverse events. Conclusions and Relevance: Among patients with ischemic stroke and no prior evidence of AF, implantable electrocardiographic monitoring for 12 months, compared with prolonged external monitoring for 30 days, resulted in a significantly greater proportion of patients with AF detected over 12 months. Further research is needed to compare clinical outcomes associated with these monitoring strategies and relative cost-effectiveness. Trial Registration: ClinicalTrials.gov Identifier: NCT02428140.

Cost-Effectiveness of Extended Electrocardiogram Monitoring for Atrial Fibrillation After Stroke: A Systematic Review.

BACKGROUND AND PURPOSE: Management of cryptogenic stroke involves the identification of modifiable risk factors, such as atrial fibrillation (AF). Extended rhythm monitoring increases AF detection rates but at an increased device cost compared with conventional Holter monitoring. The objective of the study was to identify and synthesize the existing literature on the cost-effectiveness of prolonged rhythm monitoring devices for AF detection in cryptogenic stroke. METHODS: We conducted a systematic review of available economic evaluations of prolonged ECG monitoring for AF detection following cryptogenic stroke compared with standard care. RESULTS: Of the 530 unique citations, 8 studies assessed the cost-utility of prolonged ECG monitoring compared with standard care following cryptogenic stroke. The prolonged ECG monitoring strategies included 7-day ambulatory monitoring, 30-day external loop recorders or intermittent ECG monitoring, and implantable loop recorders. The majority of cost-utility analyses reported incremental cost-effectiveness ratios below $50 000 per QALY gained; and two studies reported a cost-savings. CONCLUSIONS: There is limited economic literature on the cost-effectiveness of extended ECG monitoring devices for detection of atrial fibrillation in cryptogenic stroke. In patients with cryptogenic stroke, extended ECG monitoring for AF detection may be economically attractive when traditional willingness-to-pay thresholds are adopted. However, there was substantial variation in the reported ICERs. The direct comparison of cost-effectiveness across technologies is limited by heterogeneity in modeling assumptions.

Rationale and design of the randomized prospective ATLAS study: Avoid Transvenous Leads in Appropriate Subjects.

BACKGROUND: The defibrillator lead is the weakest part of the transvenous (TV) implantable cardioverter defibrillation (ICD) system and a frequent cause of morbidity. Lead dislodgement, cardiac perforation, insertion-related trauma including pneumothorax and vascular injury, are common early complications of TV-ICD implantation. Venous occlusion, tricuspid valve dysfunction, lead fracture and lead insulation failure are additional, later complications. The introduction of a totally sub-cutaneous ICD (S-ICD) may reduce these lead-related issues, patient morbidity, hospitalizations and costs. However, such benefits compared to the TV-ICD have not been demonstrated in a randomized trial. DESIGN: ATLAS (Avoid Transvenous Leads in Appropriate Subjects) is a multi-centered, randomized, open-label, parallel group trial. Patients younger than 60 years are eligible. If older than 60 years, patients are eligible if they have an inherited heart rhythm disease, or risk factors for ICD-related complication, such as hemodialysis, a history of ICD or pacemaker infection, heart valve replacement, or severe pulmonary disease. This study will determine if using an S-ICD compared to a TV-ICD reduces a primary composite outcome of perioperative complications including pulmonary or pericardial perforation, lead dislodgement or dysfunction, tricuspid regurgitation and ipsilateral venous thrombosis. Five hundred patients will be enrolled from 14 Canadian hospitals, and data collected to both early- (at 6 months) and mid-term complications (at 24 months) as well as mortality and ICD shock efficacy. SUMMARY: The ATLAS randomized trial is comparing early- and mid-term vascular and lead-related complications among S-ICD versus TV-ICD recipients who are younger or at higher risk of ICD-related complications.

Percutaneous Implantation of an Entirely Intracardiac Leadless Pacemaker.

BACKGROUND: Cardiac pacemakers are limited by device-related complications, notably infection and problems related to pacemaker leads. We studied a miniaturized, fully self-contained leadless pacemaker that is nonsurgically implanted in the right ventricle with the use of a catheter. METHODS: In this multicenter study, we implanted an active-fixation leadless cardiac pacemaker in patients who required permanent single-chamber ventricular pacing. The primary efficacy end point was both an acceptable pacing threshold (≤2.0 V at 0.4 msec) and an acceptable sensing amplitude (R wave ≥5.0 mV, or a value equal to or greater than the value at implantation) through 6 months. The primary safety end point was freedom from device-related serious adverse events through 6 months. In this ongoing study, the prespecified analysis of the primary end points was performed on data from the first 300 patients who completed 6 months of follow-up (primary cohort). The rates of the efficacy end point and safety end point were compared with performance goals (based on historical data) of 85% and 86%, respectively. Additional outcomes were assessed in all 526 patients who were enrolled as of June 2015 (the total cohort). RESULTS: The leadless pacemaker was successfully implanted in 504 of the 526 patients in the total cohort (95.8%). The intention-to-treat primary efficacy end point was met in 270 of the 300 patients in the primary cohort (90.0%; 95% confidence interval [CI], 86.0 to 93.2, P=0.007), and the primary safety end point was met in 280 of the 300 patients (93.3%; 95% CI, 89.9 to 95.9; P<0.001). At 6 months, device-related serious adverse events were observed in 6.7% of the patients; events included device dislodgement with percutaneous retrieval (in 1.7%), cardiac perforation (in 1.3%), and pacing-threshold elevation requiring percutaneous retrieval and device replacement (in 1.3%). CONCLUSIONS: The leadless cardiac pacemaker met prespecified pacing and sensing requirements in the large majority of patients. Device-related serious adverse events occurred in approximately 1 in 15 patients. (Funded by St. Jude Medical; LEADLESS II ClinicalTrials.gov number, NCT02030418.).

Left ventricular ejection fraction reassessment post-myocardial infarction: Current clinical practice and determinants of adverse remodeling.

BACKGROUND: Left ventricular (LV) dysfunction may be sustained or aggravated during the convalescent months following an acute myocardial infarction (MI) and is difficult to predict. We sought to determine current practice patterns of LV ejection fraction (LVEF) reassessment during the months following MI and evaluate the predictors and clinical significance of LVEF change in a prospective post-MI patient cohort. METHODS: Patients with an acute MI between June 2010 and August 2014 were identified using the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease registry. Patients with initial LV dysfunction (LVEF <40% with first MI or <45% with multiple MI events) underwent a protocol-driven repeat LVEF assessment in follow-up if routine LVEF reassessment was not performed. RESULTS: Of 5,964 MI patients, follow-up LVEF assessments were attained for 442 of the 695 patients who had significant LV dysfunction. A sizable proportion (25%) had either no increase or a decline in LVEF. Adverse remodeling was associated with an anterior MI location, a greater peak serum troponin T, and a higher baseline LVEF at time of MI. Adverse LV remodeling conferred a 3-fold risk of death (hazard ratio 3.0, 95% CI 1.6-5.7, P=.001) adjusted for baseline LVEF, anterior MI location, and medication use. CONCLUSIONS: Current practice of LVEF reassessment during the convalescent months post-MI is suboptimal despite a sizeable proportion of patients that undergo adverse LV remodeling. Targeting processes affecting low rates of LVEF reassessment may reduce missed care opportunities and ensure that patients consistently receive appropriate evidence-based and guideline-recommended care.

Long-term electrical performance of Attain Performa quadripolar left ventricular leads with all steroid-eluting electrodes: Results from a large worldwide clinical trial.

BACKGROUND: Steroid-eluting (SE) electrodes suppress local inflammation and lower pacing capture thresholds (PCT); however, their effectiveness on quadripolar left ventricular (LV) leads in the cardiac vein is not fully studied. We evaluated the effectiveness of SE on all four LV pacing electrodes in human subjects enrolled in the Medtronic Attain® Performa™ quadripolar LV lead study. METHODS: A total of 1,097 subjects were included in this evaluation. At each follow-up visit (1, 3, 6, and 12 months), LV PCT and pacing impedance were measured using either manual or automated testing methods. Summary statistics for PCT and impedance values were obtained for implant and each scheduled follow-up visit for all lead models. RESULTS: Average extended bipolar (LV electrode to right ventricular Coil) PCTs for the four LV SE pacing electrodes (LV1, LV2, LV3, and LV4) on the three shapes of the quadripolar LV leads were 1.06 ± 0.97 V, 1.38 ± 1.26 V, 1.51 ± 1.33 V, and 2.25 ± 1.63 V, respectively, at 0.5-ms pulse width. PCTs remained low and stable throughout the 12-month follow-up period. CONCLUSION: This clinical trial demonstrated that SE on all LV pacing electrodes is associated with low and stable PCTs for all quadripolar LV lead electrodes, resulting in multiple viable vectors for LV pacing. The large number of available vectors facilitates basal pacing, avoidance of PNS, and potentially prolongs generator longevity due to lower PCTs.

Fragmented QRS complexes after acute myocardial infarction are independently associated with unfavorable left ventricular remodeling.

BACKGROUND: Recovery of left ventricular ejection fraction (LVEF) after acute myocardial infarction (MI) is not universal and is difficult to predict. Fragmented QRS (fQRS) complexes are thought to be markers of myocardial scar. We hypothesized that fQRS complexes on 12­lead surface ECGs during the initial post-MI period would be associated with adverse LV remodeling over the following year. METHODS: Change in LVEF between the early (0-2 month) and later (2-12 month) post-MI periods was assessed in two independent cohorts of post-MI patients with initial LV dysfunction. A decline or no recovery in LVEF (ΔLVEF ≤0%) was used as a primary outcome. fQRS complexes were measured on 12­lead ECGs within a week of acute MI. A subset of patients underwent cardiac magnetic resonance imaging (CMR) for scar quantification. RESULTS: Of 705 patients in the combined cohort, 27% experienced the primary outcome (average ΔLVEF of -4%). fQRS complexes were associated with a two-fold higher risk of no LVEF recovery, independent of prior MI or CABG, baseline LVEF, MI location and QRS duration or axis. Of 113 patients undergoing CMR, fQRS was associated with increased peri-infarct zone late gadolinium enhancement (13 ±â€¯5% vs 11 ±â€¯4%, p = 0.02), but not core infarct. CONCLUSIONS: Despite contemporary post-MI therapy, >1 in 4 patients will show a decline in LVEF during follow-up. Fragmented QRS complexes on 12­lead surface ECG early post-MI may be a valuable marker of unfavorable LV remodeling and correlate to increased peri-infarct scar on CMR imaging.

Assessing physician knowledge regarding indications for a primary prevention implantable defibrillator and potential barriers for referral.

BACKGROUND: Although there is clear evidence to demonstrate that primary prevention implantable defibrillators (ICDs) reduce mortality in high-risk patients, ICDs are underutilized. Limited data exist assessing referring physicians' knowledge about guideline indications and attitudes towards ICDs, which may influence decision for referral. METHODS AND RESULTS: The Arrhythmia Working Group from the Alberta Cardiovascular and Stroke Strategic Clinical Network developed a web-based survey consisting of case scenarios regarding primary prevention ICD indications and a list of barriers for referral to aid in the design of a complex device care pathway. We invited referring physicians to participate in the survey including internists and cardiologists and cardiology residents. The survey was completed by 109 of 799 (response rate = 14%) of physicians. Of those, 55% were internists, 32% cardiologists, and 13% cardiology residents. The majority of physicians were male (62%), practicing in a university hospital (66%). Overall, complete guideline-concordant answers were provided by 34% of physicians. In multivariable analysis, predictors of complete guideline concordance were being a cardiologist (odd ratio [OR] 5.9, confidence interval [CI] 2.1-16.4, P = 0.001) and cardiology resident (OR 6.7, CI 1.7-27.3, P = 0.007). The most common barrier for referral for internists was lack of confidence in knowledge of guideline recommendations; while cardiologists reported concerns about cost-effectiveness and cardiology residents were most concerned with inappropriate shocks. CONCLUSION: Knowledge regarding indications for primary prevention ICD is limited and varies significantly among referring physicians. The barriers for referral differ among physician groups and addressing these identified barriers may help to improve appropriate ICD utilization.

Heart Rate Turbulence and T-Wave Alternans in Patients with Coronary Artery Disease: The Influence of Diabetes.

BACKGROUND: Patients with diabetes mellitus (DM) have a higher risk of sudden cardiac death. Factors associated with the risk profiles of coronary artery disease (CAD) patients with DM are not well established. Heart rate turbulence (HRT) and T-wave alternans (TWA) are often used to predict arrhythmia events. METHODS AND RESULTS: HRT and TWA were measured in two independent groups: the ARTEMIS cohort study and the REFINE-ICD randomized trial. ARTEMIS assesses risk 3-12 months after coronary angiography in patients with CAD. The initial 1001 patients in ARTEMIS, 526 with and 475 without DM, are included in this analysis. REFINE-ICD compares usual care versus usual care plus ICD therapy in patients with left ventricular (LV) ejection fraction (EF) values of 36-50% assessed 2-15 months after myocardial infarction. The initial 275 patients screened in REFINE ICD are included in this analysis. Abnormal HRT plus TWA was more common in patients with versus without DM in ARTEMIS (125/526, 24% vs 63/475, 13%; P < 0.001) and REFINE-ICD (43/55, 78% vs 55/220, 25%; P < 0.001), respectively. Abnormal HRT plus TWA was also more common in patients with LVEF values < 50% (28%) vs ≥ 50% (18%; P < 0.001) in ARTEMIS and LVEF values below the population median of 42% (60/138, 43%) versus above the median (38/137, 28%; P < 0.01) in REFINE-ICD. CONCLUSIONS: Abnormal HRT plus TWA is more common in CAD patients with DM compared with the patients without DM and is related to the severity of LV dysfunction. CLINICAL TRIAL REGISTRATION INFORMATION: http://www.clinicaltrials.gov, NCT01426685; http://www.clinicaltrials.gov, NCT00673842.