Apixaban versus Aspirin for Embolic Stroke of Undetermined Source.

BACKGROUND: Rivaroxaban and dabigatran were not superior to aspirin in trials of patients with embolic stroke of undetermined source (ESUS). It is unknown whether apixaban is superior to aspirin in patients with ESUS and known risk factors for cardioembolism. METHODS: We conducted a multicenter, randomized, open-label, blinded-outcome trial of apixaban (5 mg twice daily) compared with aspirin (100 mg once daily) initiated within 28 days after ESUS in patients with at least one predictive factor for atrial fibrillation or a patent foramen ovale. Cardiac monitoring was mandatory, and aspirin treatment was switched to apixaban in case of atrial fibrillation detection. The primary outcome was any new ischemic lesion on brain magnetic resonance imaging (MRI) during 12-month follow-up. Secondary outcomes included major and clinically relevant nonmajor bleeding. RESULTS: A total of 352 patients were randomly assigned to receive apixaban (178 patients) or aspirin (174 patients) at a median of 8 days after ESUS. At 12-month follow-up, MRI follow-up was available in 325 participants (92.3%). New ischemic lesions occurred in 23 of 169 (13.6%) participants in the apixaban group and in 25 of 156 (16.0%) participants in the aspirin group (adjusted odds ratio, 0.79; 95% confidence interval, 0.42 to 1.48; P=0.57). Major and clinically relevant nonmajor bleeding occurred in five and seven participants, respectively (1-year cumulative incidences, 2.9 and 4.2; hazard ratio, 0.68; 95% confidence interval, 0.22 to 2.16). Serious adverse event rates were 43.9 per 100 person-years in those given apixaban and 45.7 per 100 person-years in those given aspirin. The Apixaban for the Treatment of Embolic Stroke of Undetermined Source trial was terminated after a prespecified interim analysis as a result of futility. CONCLUSIONS: Apixaban treatment was not superior to cardiac monitoring-guided aspirin in preventing new ischemic lesions in an enriched ESUS population. (Funded by Bristol-Myers Squibb and Medtronic Europe; ClinicalTrials.gov number, NCT02427126.)

Prevention of cerebral thromboembolism by oral anticoagulation with dabigatran after pulmonary vein isolation for atrial fibrillation: the ODIn-AF trial.

BACKGROUND AND OBJECTIVES: Long-term oral anticoagulation (OAC) following successful catheter ablation of atrial fibrillation (AF) remains controversial. Prospective data are missing. The ODIn-AF study aimed to evaluate the effect of OAC on the incidence of silent cerebral embolic events and clinically relevant cardioembolic events in patients at intermediate to high risk for embolic events, free from AF after pulmonary vein isolation (PVI). METHODS: This prospective, randomized, multicenter, open-label, blinded endpoint interventional trial enrolled patients who were scheduled for PVI to treat paroxysmal or persistent AF. Six months after PVI, AF-free patients were randomized to receive either continued OAC with dabigatran or no OAC. The primary endpoint was the incidence of new silent micro- and macro-embolic lesions detected on brain MRI at 12 months of follow-up compared to baseline. Safety analysis included bleedings, clinically evident cardioembolic, and serious adverse events (SAE). RESULTS: Between 2015 and 2021, 200 patients were randomized into 2 study arms (on OAC: n = 99, off OAC: n = 101). There was no significant difference in the occurrence of new cerebral microlesions between the on OAC and off OAC arm [2 (2%) versus 0 (0%); P = 0.1517] after 12 months. MRI showed no new macro-embolic lesion, no clinical apparent strokes were present in both groups. SAE were more frequent in the OAC arm [on OAC n = 34 (31.8%), off OAC n = 18 (19.4%); P = 0.0460]; bleedings did not differ. CONCLUSION: Discontinuation of OAC after successful PVI was not found to be associated with an elevated risk of cerebral embolic events compared with continued OAC after a follow-up of 12 months.

A leadless pacemaker in the real-world setting: Patient profile and performance over time.

Background: While prior Micra trials demonstrated a high implant success rate and favorable safety and efficacy results, changes in implant populations and safety over time is not well studied. The objective of this analysis was to report the performance of Micra in European and Middle Eastern patients and compare to the Micra Investigational Device Exemption (IDE) and Micra Post Approval Registry (PAR) studies. Methods: The prospective, single-arm Micra Acute Performance European and Middle Eastern (MAP EMEA) registry was designed to further study the performance of Micra in patients from EMEA. The primary endpoint was to characterize acute (30-day) major complications. Electrical performance was analyzed. The major complication rate through 12 months was compared with the IDE and PAR studies. Results: The MAP EMEA cohort (n = 928 patients) had an implant success rate of 99.9% and were followed for an average of 9.7 ± 6.5 months. Compared to prior studies, MAP EMEA patients were more likely to have undergone dialysis and have a condition which precluded the use of a transvenous pacemaker (p < .001). Within 30 days of implantation, the MAP EMEA cohort had a major complication rate of 2.59%. Mean pacing thresholds were low and stable through 12 months (0.61 ± 0.40 V at 0.24 ms at implant and 12 months). Through 12 months post-implantation, the major complication rate for MAP EMEA was not significantly different from IDE (p = .56) or PAR (p = .79). Conclusion: Despite patient differences over time, the Micra leadless pacemaker was implanted with a high success rate and low complication rate, in-line with prior reports.

Single beta-blocker or combined amiodarone therapy in implantable cardioverter-defibrillator and cardiac resynchronization therapy-defibrillator patients: Insights from the German DEVICE registry.

BACKGROUND: Because of its antiarrhythmic potency and due to the lack of alternatives, amiodarone is often used for antiarrhythmic therapy in patients with implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy-defibrillator systems. To date, robust data on the safety and clinical benefit of amiodarone therapy in these patients are missing. OBJECTIVE: The purpose of this study was to assess the periprocedural and postprocedural outcomes of combined therapy with beta-blockers plus amiodarone compared to treatment with single beta-blockers in the "real-life" cohort of ICD recipients of the German DEVICE registry. METHODS: A total of 4499 patients who underwent ICD implantation, revision, or upgrade in 49 centers participating in the German DEVICE registry were enrolled from March 2007 to February 2014. RESULTS: Amiodarone had no significant effect on the success of defibrillation testing. Early implantation-associated complications were similar between the groups. However, 1-year overall mortality was significantly higher in the beta-blocker plus amiodarone cohort (adjusted hazard ratio 2.09; P <.001). Interestingly, among the surviving patients, amiodarone was not associated with a significantly reduced risk of ICD discharges or syncopal events. Furthermore, the occurrence of ventricular tachycardia (VT) storm or incessant VTs and the number of patients scheduled for intracardiac ablation did not differ among both groups, whereas the rate of rehospitalization was lower in the cohort with only beta-blockers. CONCLUSIONS: Although amiodarone has no adverse effect on the success of defibrillation testing, our data suggest an increased all-cause mortality under amiodarone therapy, especially in the subgroups of patients with sinus rhythm or severely reduced left ventricular function. In surviving patients, rates of arrhythmic events were comparable.

Cardiac glycosides are not associated with increased mortality or hospitalization rates in ICD and CRT-ICD patients after adjustment for baseline-characteristics at one-year follow-up: Results from the German DEVICE registry.

AIMS: Despite lacking supporting randomized trials, cardiac glycosides (CGs) are widely used in heart failure and/or atrial fibrillation. Moreover, several pro- and retrospective studies and registry-data have recently raised serious concerns in terms of efficacy and safety of CGs in this field. We have therefore examined the association between CGs and clinical outcome of implantable cardioverter-defibrillator (ICD) and cardiac resynchronization (CRT-ICD) patients of the large German DEVICE registry. METHODS AND RESULTS: Between 2007 and 2014, 3782 ICD and 1529 CRT-ICD patients were enrolled in the German DEVICE registry. Those two groups were analyzed independently according to medication with or without CGs. After adjustment for patient characteristics, CGs were not significantly associated with increased one-year mortality (HR 1.27, 95%-CI 0.91-1.76, p = 0.162), major adverse cardiac and cerebrovascular events (OR 1.36, 95%-CI 0.98-1.89, p = 0.063), ICD-shocks (OR 1.29, 95%-CI 0.95-1.74, p = 0.104) or the need for rehospitalization in ICD patients at one-year-follow-up. Similar findings were obtained in CRT-ICD patients. Regarding possible determinants for glycoside treatment, atrial fibrillation at enrollment was found to be most strongly associated with the prescription of glycosides in ICD (adjusted OR 3.25, 95%-CI 2.63-4.02) and CRT-ICD patients (adjusted OR 3.17, 95%-CI 2.39-4.19). CONCLUSION: Overall harmful effects of CGs in ICD- and CRT-ICD patients could not be confirmed in DEVICE. Further large and randomized-controlled trials that investigate dose-dependent effects of CGs in addition to contemporary therapy of heart failure and atrial fibrillation are needed.

Distribution and impact of age in patients with implantable cardioverter-defibrillators regarding early complications and 1-year clinical outcome: results from the German Device Registry.

BACKGROUND: Patients receiving implantable-cardioverter-defibrillators (ICD) in clinical practice are often older or younger than in clinical trials. Whether older patients benefit from ICD-therapy in a similar way as younger patients is under debate. The objective of this study was to provide real-world data regarding outcomes with respect to age in a large cohort in the German Device Registry. METHODS: Within the registry data from 50 German centers were collected between January 2007 and February 2014. RESULTS: Our analysis included 3239 ICD patients representing a group of young (28%; group I: < 58 years), intermediate aged (50%; group II: 58-74 years), and elderly patients (22%; group III: 75-92 years). Intergroup comparison of all groups was performed followed by individual comparison vs. group II serving as age-reference group. Procedure-related complications did not differ between all groups. Analysis of the primary endpoint, 1-year all-cause mortality, revealed an increased mortality in the elderly and a decreased mortality in the young cohort vs. the reference group II (group I 2.1%, group II 6.2%, group III 13.2%; p < 0.001). While all-cause rehospitalizations did not differ, we observed a difference in reported device revisions showing more device revisions required in younger patients (group I 8.9%, group II 6.8%, group III 4.0%; p = 0.001). CONCLUSIONS: One-year mortality was doubled in elderly ICD patients probably due to non-cardiac causes. These results further underpin the need for re-evaluating the primary prevention ICD indication in octo- and nonagenarians. Young patients show lower mortality rates but seem to bear higher risk of device-related complications, which highlights the need for improved measures to reduce device-related complications in the young.

Impact of diabetes on clinical outcome of patients with heart failure undergoing ICD and CRT procedures: results from the German Device Registry.

AIMS: Diabetes mellitus (DM) has a negative impact on prognosis in patients with heart failure (HF). The role impact of DM in HF patients with implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy (CRT) devices might differ and remains unclear. The aim of our study was to investigate the impact of DM on periprocedural complications and clinical outcome in HF patients undergoing ICD or CRT implantation. METHODS AND RESULTS: Within the German Device Registry, data from 50 German centres were collected between January 2007 and February 2014. A retrospective analysis of n = 5329 patients undergoing ICD implantation was conducted. Patients' characteristics, procedural data, periprocedural complications, and post-procedural clinical outcome, including a composite clinical endpoint of all-cause mortality, stroke, and myocardial infarction (MACCE), were analysed. Subgroup analysis were performed for ICD and CRT implantations. Median follow-up was 15.7 (12.9; 20.0) and 16.2 (12.8; 21.2) months in DM and non-DM patients. Of 5329 patients enrolled, n = 1448 (27.2%) had a diagnosis of DM. Within the cohort, 94% of DM and 90% of non-DM patients had a diagnosis of HF. Patients with DM were older, had higher body mass index, and higher rate of cardiovascular comorbidities compared with non-DM patients. Unadjusted and adjusted analyses revealed similar all-over intrahospital periprocedural complication rates in both groups (4.1% vs 3.9%). Unadjusted Kaplan-Meier survival analysis showed higher all-cause mortality after 1 year (9.0% vs 6.3%; log-rank P = 0.001) with higher MACCE rates (10.0% vs 7.3%; P < 0.001) in the DM group versus non-DM patients. After multivariable adjustment for relevant covariates, the association of DM to MACCE disappeared [HR 1.11 (0.89-1.38)]. Because chronic kidney disease (CKD) was clearly associated with increased 1 year MACCE after multivariate adjustment [odds ratio (OR) 2.11 (1.68-2.64)], a subgroup analysis was performed showing a strong trend towards more perioperative complications in DM patients with CKD [OR 2.16 (0.9-5.21)], while no effect of DM was observed in patients without CKD [OR 0.73 (0.42-1.28)]. CONCLUSIONS: The overall risk of periprocedural complications and short-term (1 year) clinical outcome in patients with DM and HF undergoing ICD or CRT defibrillator (CRT-D) implantation was not increased. In contrast, CKD was associated with an increased risk of 1 year MACCE in HF patients undergoing ICD/CRT-D implantation.

Impact of ticagrelor monotherapy on two-year clinical outcomes in patients with long stenting: a post hoc analysis of the GLOBAL LEADERS trial.

AIMS: The aim of this study was to evaluate the impact of a novel antiplatelet regimen in patients with increasing total stent length (TSL). METHODS AND RESULTS: This is a post hoc analysis of the GLOBAL LEADERS trial, a prospective, multicentre, open-label, randomised trial, investigating the impact of the experimental strategy (one-month dual antiplatelet therapy [DAPT] followed by 23-month ticagrelor monotherapy) versus the reference regimen (12-month DAPT followed by 12-month aspirin monotherapy) in patients with a Biolimus A9-eluting stent (BES). The primary endpoint was the composite of all-cause death and new Q-wave myocardial infarction (MI), and the secondary endpoint was Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding at two years. To investigate the association between total stent length and outcomes, groups were compared in quartiles according to TSL; the fourth quartile group was at significantly higher ischaemic risk at two years. In that stratum (TSL ≥46 mm), the experimental strategy significantly reduced the risk of the primary endpoint (hazard ratio [HR] 0.67, 95% confidence interval [CI]: 0.49-0.90; pinteraction=0.043), while demonstrating a similar risk of BARC type 3 or 5 bleeding (HR 0.99, 95% CI: 0.66-1.49; pinteraction=0.975). CONCLUSIONS: Ticagrelor monotherapy could potentially balance ischaemic and bleeding risks, thereby achieving a net clinical benefit in patients with a TSL ≥46 mm with a BES.

Determinants of inappropriate implantable cardioverter-defibrillator shocks: the German Device Registry perspective.

BACKGROUND: In the present study, we have focused upon rates and clinical determinants of inappropriate shock (IS) after implantable cardioverter-defibrillator (ICD). METHODS: Data were collected prospectively in the German Device II Registry. RESULTS: A total of 783 patients were included. Three sub-groups were identified: non-shock (NS) included 725 patients (92.6%), IS 24 (3.1%), and appropriate shock (AS) 34 (4.3%). IS patients were younger (AS 68 (58-77); IS 59 (51-68); NS 66 (56-75) years; p = 0.03), had been mainly referred for primary prophylaxis (AS 42.4%; IS 70.8%; NS 67.3%; p = 0.01), had a higher resting heart rate (AS 70 (63-80); IS 80 (71-98); NS 70 (60-81) BPM; p = 0.003), had more often atrial fibrillation (AF) (AS 14.7%; IS 45.8%; NS 18.8%; p = 0.006), and shorter QRS duration (AS 100 (90-120); IS 95 (90-100); NS 120 (98-150) msec.; p = 0.001). VVI-ICD was more common in IS (AS 64.7%; IS 83.3%; NS 49.8%; p = 0.002). At a follow-up of 18.2 months (75% IQR 13.6-22.4), no deaths were observed in the IS group, one (2.9%) in the AS, and 36 (4.9%) in the NS (p = 0.9). At logistic regression, VVI-ICD implantation was the strongest IS independent determinant (OR 5.0; 95% CI 1.6-15.9; p = 0.004) together with age < 70 years (OR 4.6; CI 1.4-14.7; p = 0.009), AF at time of ICD implantation (OR 3.5; CI 1.3-9.1; p = 0.01), and resting heart rate > 70/min (OR 2.8; CI 1.0-7.3; p = 0.03). CONCLUSION: In a contemporary setting, some specific conditions such as VVI-ICD, younger age, and faster resting heart rates remain important IS determinants after ICD implantation.

Evaluation of thoracic impedance trends for implant-based remote monitoring in heart failure patients - Results from the (J-)HomeCARE-II Study.

AIMS: Remote monitoring by implantable devices substantially improves management of heart failure (HF) patients by providing diagnostic day-to-day data. The use of thoracic impedance (TI) as a surrogate measure of fluid accumulation is still strongly debated. The multicenter HomeCARE-II study evaluated clinically apparent HF events in the context of remote device diagnostics, focusing on the controversial role of TI. METHODS AND RESULTS: We followed 497 patients (66.6 ±â€¯10.1 years, 77% male, QRS 139.8 ±â€¯36.0 ms, ejection fraction 26.8 ±â€¯7.0%) implanted with a CRT-D (67%) or an ICD (33%) for 21.4 ±â€¯8.1 months. An independent event committee confirmed 171 HF events of which 82 were used to develop a TI-based algorithm for the prediction of imminent cardiac decompensation. Highly inter-individual variations in patterns of TI trends were observed. The algorithm resulted in a sensitivity of 41.5% (50.0%) with 0.95 (1.34) false alerts per patient year, and a positive predictive value of 7.9% overall and 27.9% in the HF event group of patients. Averaged ratio statistics showed a significant pre-hospital decrease and a highly significant in-hospital increase in TI after intensified diuresis. Recurrent decompensations turned out to be preceded by a significantly stronger decrease of TI compared to first events with a higher chance for detection (63.6% sensitivity, p < 0.05). CONCLUSIONS: Overall performance in predicting imminent decompensation by monitoring TI alone is limited due to its high inter-patient variability. TI stand-alone applications should be redirected towards a target population with more advanced symptoms where post-hospital observation aimed to maintain the patient's discharge status might be the most valuable approach. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT00711360 (HomeCARE-II) and NCT01221649 (J-HomeCARE-II).

Clinical outcomes in unselected patients treated with the PROMUS Element platinum-chromium, everolimus-eluting stent: Final five-year results from the PE PROVE Study.

OBJECTIVES: The goal of this analysis was to evaluate the final 5-year safety and effectiveness of the PROMUS Element platinum-chromium everolimus-eluting stent in unselected patients treated in routine clinical practice. BACKGROUND: The prospective, open-label PROMUS Element™ European Post-Approval Surveillance Study (PE-PROVE) enrolled 1,010 "real-world" patients who received the PROMUS Element stent. Adverse event rates were low at 1-year, and the incidence of stent thrombosis was 0.6%. METHODS: The primary endpoint was target vessel failure (TVF; overall and PE stent-related), a composite of cardiac death, myocardial infarction (MI) related to the target vessel, or target vessel revascularization (TVR) at 1-year post-implantation. Five-year clinical outcomes were evaluated in overall as well as high-risk patient subgroups. RESULTS: The overall 5-year TVF rate was 14.9%, with 7.0% being related to the study stent. Cardiac death, MI and TVR related to the study stent occurred in 0.5%, 3.2%, and 5.7%, respectively. Stent thrombosis through 5-year follow-up was 1.0%. The rates of overall and study stent related TVF were numerically higher in patients with medically treated diabetes, long lesions (≥28 mm), and small diameter vessels (≤2.5 mm) compared to the overall study population. Additionally, favorable stent thrombosis rates through 5 years were reported for the PROMUS Element stent in these high-risk subgroups. CONCLUSIONS: The final 5-year data from the PE-PROVE study demonstrate favorable outcomes and low rates of adverse events with the PE stent when used in "real-world" patients with coronary artery disease.

Angiographic and clinical performance of a paclitaxel-coated balloon compared to a second-generation sirolimus-eluting stent in patients with in-stent restenosis: the BIOLUX randomised controlled trial.

AIMS: Although several studies have shown positive outcomes after the use of drug-coated balloons (DCB) for in-stent restenosis (ISR), data on randomised controlled trials versus latest-generation drug-eluting stents (DES) are limited. Therefore, in this randomised trial, we sought to evaluate whether a butyryl-tri-hexyl citrate (BTHC)-based paclitaxel DCB is non-inferior to a biodegradable polymer sirolimus-eluting stent (BP-SES) therapy in patients with ISR in either a bare metal stent (BMS) or DES. METHODS AND RESULTS: A total of 229 patients with ISR in BMS or DES from 13 German centres and one Latvian centre were 2:1 randomly allocated to DCB (n=157) or DES (n=72). The primary efficacy endpoint was defined as in-stent late lumen loss (LLL) at six months, and the primary safety endpoint was target lesion failure (TLF) at 12 months. LLL in the DCB arm was 0.03±0.40 mm compared to 0.20±0.70 mm in the DES arm (p=0.40). DCB proved to be non-inferior to DES (Δ = -0.17±0.52 mm, 97.5% CI -∞; -0.01]; p<0.0001). At 12 months, Kaplan-Meier TLF estimates were 16.7% in the DCB arm and 14.2% in the DES arm (p=0.65) and remained similar at 18 months (DCB versus DES: 17.4% versus 19.5%, p=0.88). CONCLUSIONS: In patients with DES or BMS ISR, treatment with a paclitaxel DCB showed similar LLL at six months and TLF rates up to 18 months compared to a second-generation sirolimus DES.

[Left atrial appendage clusure in nonvalvular atrial fibrillation : Clinical evidence 2017]. / Der Verschluss des linken Vorhofohrs bei nichtvalvulärem Vorhofflimmern zur Prophylaxe von Tod, Schlaganfall und Blutungen : Klinische Evidenz 2017.

Nonvalvular atrial fibrillation (AF) is the most common arrhythmia with a prevalence of 1-2% and affects approximately 15-20% of all octogenarians. Patients are at increased risk of thromboembolic stroke, with an overall risk of 5% per year. Thrombi form almost exclusively in the left atrial appendage (LAA), a blind sac-like heterogeneous structure trabeculated by pectinate muscles. In the past five decades, life-long oral anticoagulation (OAC) with vitamin K antagonists (VKA) has been the state-of-the art treatment to prevent stroke and systemic embolism from thrombi in AF. In the last decade, nonvitamin K dependent oral anticoagulants (NOAC) have been shown to be superior to VKA. Given the safety issues of indefinite OAC with either VKA or NOAC, it is plausible to consider left atrial appendage closure (LAAC) as an alternative strategy to prevent death, stroke or other systemic embolization, and bleeding. In recent years, LAAC has been compared to VKA in prospective randomized trials, yielding superior results regarding efficacy and noninferiority regarding safety in the mid-term. This review provides an update on the current state of LAAC in the field of prevention of death, stroke, and bleedings in patients suffering from nonvalvular AF. We elucidate the evidence and limitations of anticoagulation as the classical treatment paradigm, and review devices and techniques for LAAC. Most importantly, the current clinical evidence on efficacy and safety is outlined.

Left atrial appendage closure for prevention of death, stroke, and bleeding in patients with nonvalvular atrial fibrillation.

Nonvalvular atrial fibrillation (AF) is the most frequent arrhythmia with a prevalence of 1%-2% in the general population. Its prevalence increases with age and its diagnosis benefits of improvement and simplification of technologies for its detection. Today, AF affects approximately 7% of individuals age>65years and 15%-20% of octogenarians. Due to stasis and activation of coagulation in a fibrillating atrium, patients are at increased risk of thromboembolism, in particular ischemic stroke, with an overall stroke risk of 5% per year. Since the left atrium itself is round and smooth-walled, thrombi typically do not form there, but almost exclusively in the left atrial appendage (LAA), a blind sac-like heterogeneous structure trabeculated by pectinate muscles. In the past five decades, oral anticoagulation (OAC) with vitamin K antagonists (VKA) has been the state-of-the art treatment to prevent stroke and systemic embolism from thrombi in AF. In the last decade, nonvitamin K dependant oral anticoagulants (NOAC) have been shown to be overall superior to VKA with respect to efficacy and safety in large trials and registries. Given the safety issues of indefinite OAC with either VKA or NOAC, it is plausible to consider left atrial appendage closure (LAAC) as an alternative strategy for prevention of all three catastrophes for patients with AF on anticoagulation: death, stroke or other systemic embolization, and bleeding. In the past years, LAAC has been compared to VKA in prospective randomized trials, yielding superior results regarding efficacy and non-inferiority regarding safety in the mid-term. Today, the decision to provide the most appropriate treatment for a patient with AF (OAC, NOAC, or LAAC) is complex and needs to be individualized. This review provides a comprehensive update on the current state of LAAC in the field of prevention of death, stroke and bleedings in patients suffering from nonvalvular AF. We describe the pathophysiology of the LAA with regard to stroke, elucidate the evidence and limitations of anticoagulation as the classical treatment paradigm, and review devices and techniques for LAAC. Most importantly, the current clinical evidence on efficacy and safety is outlined and finally, contemporary recommendations for patient selection are provided.

Activation of remote monitoring for cardiac implantable electronic devices: small dog for tall weeds.

BACKGROUND: Remote monitoring (RM) of cardiac implantable electronic devices (CIEDs) has been popularized as a precious patients' management tool. We have investigated RM within the premises of a multicenter, prospective, real-world registry, i.e., the German Device II. METHODS: We have focused on: (1) CIEDs with RM capabilities implantation rate and (2) actual rate of RM features activation. RESULTS: A cohort of 1223 CIEDs patients were treated from 04/11 to 02/14. Of these, 720 (58.8%) were implanted with RM-capable devices and were presenting significantly more often a clinical diagnosis of dilatative cardiomyopathy and an indication for cardiac resynchronization. At discharge, the RM feature was activated in only 12.6% (91/720) of the total number of patients implanted with RM-capable CIEDs. After adjusting for implanting center, there was no significant correlation between any of the patient clinical characteristics and RM activation. One-year estimated mortality was 9.0% in patients with activated RM, 5.6% in those with not activated RM, and 7.7% in those without RM capability (p = 0.3). The RM feature was still activated in 13.8% of the patients surviving at follow-up. Patients undergoing RM had a trend for higher re-hospitalization rate and less visits in the device outpatient clinic. CONCLUSIONS: Although RM in CIEDs may be a clinically valuable technological armamentarium, its activation does not reflect patients' clinical profile. In fact, RM is often not activated, most probably because it is still recognized as a source of increased workload in a reality where reimbursement plans for dedicated human resources are not yet optimized.

Cardiovascular magnetic resonance-GUIDEd management of mild to moderate left ventricular systolic dysfunction (CMR GUIDE): Study protocol for a randomized controlled trial.

BACKGROUND: The majority of sudden cardiac death (SCD) in patients with heart failure occurs in those with mild-moderate left ventricular (LV) systolic dysfunction (LVEF 36-50%) who under current guidelines are ineligible for primary prevention implantable cardiac defibrillator (ICD) therapy. Recent data suggest that cardiac magnetic resonance (CMR) evidence of replacement fibrosis forms a substrate for malignant arrhythmia and therefore potentially identifies a subgroup at increased risk of SCD. Our hypothesis is that among patients with mild-moderate LV systolic dysfunction, a CMR-guided management strategy for ICD insertion based on the presence of scar or fibrosis is superior to a current strategy of standard care. METHODS/DESIGN: CMR GUIDE is a prospective, multicenter randomized control trial enrolling patients with mild-moderate LV systolic dysfunction and CMR evidence of fibrosis on optimal heart failure therapy. Participants will be randomized to receive either a primary prevention ICD or an implantable loop recorder (ILR). The primary endpoint is the time to SCD or hemodynamically significant ventricular arrhythmia (VF or VT) during an average 4-year follow-up. Secondary endpoints include quality of life assessed by Minnesota Living with Heart Failure Questionnaire, heart failure related hospitalizations, and a cost-utility analysis. Clinical trials.gov identifier NCT01918215. DISCUSSION: CMR GUIDE trial will add substantially to our understanding of the role of myocardial fibrosis and the risk of developing life-threatening ventricular arrhythmias. If the superiority of a CMR-guided approach over standard care is proven, it may change international clinical guidelines, with the potential to considerably increase survival in this growing patient population.

An optimized approach for right atrial flutter ablation: a post hoc analysis of the AURUM 8 study.

PURPOSE: Radiofrequency catheter ablation of typical atrial flutter can vary largely in duration from patient to patient. The purpose of this work was to determine optimal combination of ablation settings leading to the highest procedural efficacy. METHODS: Our retrospective multivariate analysis comprised 448 patients undergoing atrial flutter ablation with nonirrigated 8-mm catheters at 19 clinical centers. Four procedural variables were included in the prognostic model: preset maximum temperature, preset maximum power, catheter-tip material (gold vs. platinum-iridium), and ablation technique (maximum voltage-guided vs. conventional anatomical approach). Univariate and multivariate analyses were performed using the logistic regression (for acute ablation success) and Cox constant proportional hazard models (for cumulative ablation time). RESULTS: Significant multivariate predictors of acute ablation success were a higher preset maximum temperature (odds 1.083 per 1 °C, P < 0.05) and gold-tip catheter (odds 2.096, P < 0.05). Predictors of cumulative ablation time were the maximum voltage-guided ablation technique (hazard ratio 1.856, P < 0.001), higher preset maximum temperature (hazard ratio 1.039 per 1 °C, P < 0.001), and gold-tip catheter (hazard ratio 1.225, P < 0.05). The combination of optimal settings (70 °C, 70 W, gold-tip catheter, maximum voltage-guided technique) increased the acute success rate from 91.7 % (for the entire study cohort) to 100 %, and reduced median cumulative ablation time from 8.3 to 4.3 min, median total procedure duration from 76 to 55 min, and median fluoroscopy time from 14 to 7 min. CONCLUSIONS: The combination of maximum voltage-guided gold-tip ablation at 70 °C and 70 W was associated with 100 % ablation success and minimal ablation times for nonirrigated ablation of atrial flutter.

Apixaban for treatment of embolic stroke of undetermined source (ATTICUS randomized trial): Rationale and study design.

Rationale Optimal secondary prevention of embolic stroke of undetermined source is not established. The current standard in these patients is acetylsalicylic acid, despite high prevalence of yet undetected paroxysmal atrial fibrillation. Aim The ATTICUS randomized trial is designed to determine whether the factor Xa inhibitor apixaban administered within 7 days after embolic stroke of undetermined source, is superior to acetylsalicylic acid for prevention of new ischemic lesions documented by brain magnetic resonance imaging within 12 months after index stroke. Design Prospective, randomized, blinded, parallel-group, open-label, German multicenter phase III trial in approximately 500 patients with embolic stroke of undetermined source. A key inclusion criterion is the presence or the planned implantation of an insertable cardiac monitor. Patients are 1:1 randomized to apixaban or acetylsalicylic acid and treated for a 12-month period. It is an event-driven trial aiming for core-lab adjudicated primary outcome events. Study outcomes The primary outcome is the occurrence of at least one new ischemic lesion identified by axial T2-weighted FLAIR magnetic resonance imaging and/or axial DWI magnetic resonance imaging at 12 months when compared with the baseline magnetic resonance imaging. Key secondary outcomes are the combination of recurrent ischemic strokes, hemorrhagic strokes, systemic embolism; combination of MACE including recurrent stroke, myocardial infarction, and cardiovascular death and combination of major and clinically relevant non-major bleeding defined according to ISTH, and change of cognitive function and quality of life (EQ-5D, Stroke Impact Scale). Discussion Embolic stroke of undetermined source is caused by embolic disease and associated with a high risk of recurrent ischemic strokes and clinically silent cerebral ischemic lesions. ATTICUS will investigate the impact of atrial fibrillation detected by insertable cardiac monitor and the effects of early anticoagulation with apixaban compared with antiplatelet therapy with acetylsalicylic acid on the incidence of new ischemic lesion after embolic stroke of undetermined source.