Anticoagulation with edoxaban in patients with long atrial high-rate episodes ≥24†h.

BACKGROUND AND AIMS: Patients with long atrial high-rate episodes (AHREs) ≥24 h and stroke risk factors are often treated with anticoagulation for stroke prevention. Anticoagulation has never been compared with no anticoagulation in these patients. METHODS: This secondary pre-specified analysis of the Non-vitamin K antagonist Oral anticoagulants in patients with Atrial High-rate episodes (NOAH-AFNET 6) trial examined interactions between AHRE duration at baseline and anticoagulation with edoxaban compared with placebo in patients with AHRE and stroke risk factors. The primary efficacy outcome was a composite of stroke, systemic embolism, or cardiovascular death. The safety outcome was a composite of major bleeding and death. Key secondary outcomes were components of these outcomes and electrocardiogram (ECG)-diagnosed atrial fibrillation. RESULTS: Median follow-up of 2389 patients with core lab-verified AHRE was 1.8 years. AHRE ≥24 h were present at baseline in 259/2389 patients (11%, 78 ± 7 years old, 28% women, CHA2DS2-VASc 4). Clinical characteristics were not different from patients with shorter AHRE. The primary outcome occurred in 9/132 patients with AHRE ≥24 h (4.3%/patient-year, 2 strokes) treated with anticoagulation and in 14/127 patients treated with placebo (6.9%/patient-year, 2 strokes). Atrial high-rate episode duration did not interact with the efficacy (P-interaction = .65) or safety (P-interaction = .98) of anticoagulation. Analyses including AHRE as a continuous parameter confirmed this. Patients with AHRE ≥24 h developed more ECG-diagnosed atrial fibrillation (17.0%/patient-year) than patients with shorter AHRE (8.2%/patient-year; P < .001). CONCLUSIONS: This hypothesis-generating analysis does not find an interaction between AHRE duration and anticoagulation therapy in patients with device-detected AHRE and stroke risk factors. Further research is needed to identify patients with long AHRE at high stroke risk.

Anticoagulation with Edoxaban in Patients with Atrial High-Rate Episodes.

BACKGROUND: Device-detected atrial high-rate episodes (AHREs) are atrial arrhythmias detected by implanted cardiac devices. AHREs resemble atrial fibrillation but are rare and brief. Whether the occurrence of AHREs in patients without atrial fibrillation (as documented on a conventional electrocardiogram [ECG]) justifies the initiation of anticoagulants is not known. METHODS: We conducted an event-driven, double-blind, double-dummy, randomized trial involving patients 65 years of age or older who had AHREs lasting for at least 6 minutes and who had at least one additional risk factor for stroke. Patients were randomly assigned in a 1:1 ratio to receive edoxaban or placebo. The primary efficacy outcome was a composite of cardiovascular death, stroke, or systemic embolism, evaluated in a time-to-event analysis. The safety outcome was a composite of death from any cause or major bleeding. RESULTS: The analysis population consisted of 2536 patients (1270 in the edoxaban group and 1266 in the placebo group). The mean age was 78 years, 37.4% were women, and the median duration of AHREs was 2.8 hours. The trial was terminated early, at a median follow-up of 21 months, on the basis of safety concerns and the results of an independent, informal assessment of futility for the efficacy of edoxaban; at termination, the planned enrollment had been completed. A primary efficacy outcome event occurred in 83 patients (3.2% per patient-year) in the edoxaban group and in 101 patients (4.0% per patient-year) in the placebo group (hazard ratio, 0.81; 95% confidence interval [CI], 0.60 to 1.08; P = 0.15). The incidence of stroke was approximately 1% per patient-year in both groups. A safety outcome event occurred in 149 patients (5.9% per patient-year) in the edoxaban group and in 114 patients (4.5% per patient-year) in the placebo group (hazard ratio, 1.31; 95% CI, 1.02 to 1.67; P = 0.03). ECG-diagnosed atrial fibrillation developed in 462 of 2536 patients (18.2% total, 8.7% per patient-year). CONCLUSIONS: Among patients with AHREs detected by implantable devices, anticoagulation with edoxaban did not significantly reduce the incidence of a composite of cardiovascular death, stroke, or systemic embolism as compared with placebo, but it led to a higher incidence of a composite of death or major bleeding. The incidence of stroke was low in both groups. (Funded by the German Center for Cardiovascular Research and others; NOAH-AFNET 6 ClinicalTrials.gov number, NCT02618577; ISRCTN number, ISRCTN17309850.).

MEDEA randomised intervention study protocol in Cyprus, Greece and Israel for mitigation of desert dust health effects in adults with atrial fibrillation.

INTRODUCTION: Mediterranean countries experience frequent desert dust storm (DDS) events originating from neighbouring Sahara and Arabian deserts, which are associated with significant increase in mortality and hospital admissions, mostly from cardiovascular and respiratory diseases. Short-term exposure to ambient air pollution is considered as a trigger for symptomatic exacerbations of pre-existing paroxysmal atrial fibrillation (AF) and other types of heart arrhythmia. The Mitigating the Health Effects of Desert Dust Storms Using Exposure-Reduction Approaches clinical randomised intervention study in adults with AF is funded by EU LIFE+programme to evaluate the efficacy of recommendations aiming to reduce exposure to desert dust and related heart arrhythmia effects. METHODS AND ANALYSIS: The study is performed in three heavily exposed to desert dust regions of the Eastern Mediterranean: Cyprus, Israel and Crete-Greece. Adults with paroxysmal AF and implanted pacemaker are recruited and randomised to three parallel groups: (a) no intervention, (b) interventions to reduce outdoor exposure to desert dust, (c) interventions to reduce both outdoor and indoor exposure to particulate matter during desert dust episodes. Eligible participants are enrolled on a web-based platform which communicates, alerts and makes exposure reduction recommendations during DDS events. Exposure changes are assessed by novel tools (smartwatches with Global Positioning System and physical activity sensors, air pollution samplers assessing air quality inside and outside participant's homes, etc). Clinical outcomes include the AF burden expressed as the percentage of time with paroxysmal AF over the total study period, the incidence of ventricular arrhythmia episodes as recorded by the participants' pacemakers or cardioverters/defibrillators and the disease-specific Atrial Fibrillation Effect on QualiTy-of-Life questionnaire. ETHICS AND DISSEMINATION: Local bioethics' authorities approved the study at all sites, according to national legislations (Cyprus: National Bioethics Committee, Data Protection Commissioner and Ministry of Health; Greece, Scientific Committee and Governing Board of the University General Hospital of Heraklion; Israel: Institutional Review Board ('Helsinki committee') of the Soroka University Medical Center). The findings will be publicised in peer-reviewed scientific journals, in international conferences and in professional websites and newsletters. A summary of the results and participants' interviews will be included in a documentary in English, Greek and Hebrew. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier; NCT03503812.

Impact of Sustained Cardiac Tachyarrhythmias Recorded in Coronary Intensive Care Unit on Short- and Long-Term Mortality and Duration of Hospitalization.

BACKGROUND: Studies conducted in coronary intensive care units (CICUs) have demonstrated that tachyarrhythmias are associated with increased mortality after acute coronary syndromes (ACSs). However, the data for tachyarrhythmias occurred in CICUs due to a variety of cardiovascular disorders are limited. METHODS: We conducted a single-center prospective observational study, which included consecutive CICU patients (January 1, 2014 to May 31, 2018). We recorded the ventricular arrhythmias (VAs), supraventricular tachycardias (SVTs), and days of CICU hospitalization. The patients were followed up for 6 months after CICU discharge. RESULTS: A total of 943 patients (age: 66.37 ±15.4 years; 673 males [71.4%]) were included. Patients with tachyarrhythmias had higher in-CICU mortality (8.0% vs 4.1%, P = .029, odds ratio [OR]: 2.04, 95% confidence interval [CI]: 1.08-3.86) and higher 6-month all-cause mortality (12.8% vs 6.1%, P = .002, OR: 2.27, 95% CI: 1.35-3.83) than those who did not develop tachyarrhythmias. Ventricular arrhythmias was significantly associated with higher all-cause mortality than no tachyarrhythmia (15.4% vs 6.1%; P = .001) or SVTs (15.4% vs 7.0%; P = .001). The mean duration of hospitalization for the patients with tachyarrhythmias was 3.89 ± 4.90 days, while for the patients without was 2.79 ± 3.31 days (P < .001). Patients without ACS had higher short- and long-term mortality compared to patients with ACS (9.2% vs 2.9%, P < .001 and 12.9% vs 4.9%, P < .001). CONCLUSIONS: Tachyarrhythmias were associated with prolonged CICU hospitalization, while non-ACS cardiovascular disorders and the occurrence of VAs were associated with increased short- and long-term mortality.

Long-term rhythm monitoring with an implantable loop recorder in patients after the first clinical atrial fibrillation episode. Towards an individualized management.

Although atrial fibrillation (AF) is an arrhythmia with a variable clinical profile (symptomatic and asymptomatic episodes), the first symptomatic episode leads to its initial diagnosis in most cases. Nowadays, continuous and remote long-term cardiac rhythm monitoring is feasible by the use of implantable loop recorders. The data concerning the AF recurrences and progression after the first electrocardiographic-documented clinical AF episode demonstrates that a high percentage of patients may not suffer any other AF recurrence, or may present a low recurrence rate of the arrhythmia in the future. The AF burden may play a key role in the management of the arrhythmia as far as the decision-making for anticoagulation, rate and/or rhythm control therapy is concerned. There is evidence that a higher AF burden is associated with a higher risk of ischemic stroke. Non-vitamin K antagonists (NOACs) anticoagulants are increasingly used in the management of AF, providing a more predictable effect with rapid onset and offset of their action. The use of these agents in combination with devices that provide a continuous remote rhythm monitoring capability has encouraged anticoagulation strategies based on the AF burden. Data from tailored anticoagulation studies in AF are in favor of the long-term rhythm monitoring, ensuring a patient-centered approach with a better evaluation and more individualized management of AF, especially in patients with intermediate thromboembolic risk and high bleeding risk. Further large randomized trials are needed, not only to evaluate such strategies but also to elucidate the long-term cardiac rhythm monitoring in the AF management.

Non-typhoidal Salmonella myocarditis in an immunocompetent young adult with diarrhea.

Myocarditis is the inflammation of the heart muscle and it is caused by a wide range of infectious and non-infectious conditions. Non-typhoidal Salmonella infection, a common foodborne illness worldwide, only rarely causes myocarditis. We describe a case of an immunocompetent adult with Salmonella enterica serovar Typhimurium myocarditis who had a favorable outcome due to early recognition of the causative factor and prompt initiation of appropriate treatment.

Recurrence rate of atrial fibrillation after the first clinical episode: A prospective evaluation using continuous cardiac rhythm monitoring.

BACKGROUND: Decision making regarding a patient who has experienced a first clinical episode of atrial fibrillation (AF) is challenging, and the AF recurrences should be a significant consideration. Continuous long-term rhythm monitoring via implantable loop recorders (ILRs) has enabled us to evaluate the AF recurrence profile after the first clinical episode and to investigate clinical parameters associated with the course of the arrhythmia. HYPOTHESIS: Continuous rhythm monitoring via ILRs in AF patients after the first clinical episode is of clinical significance and precisely evaluate the AF recurrence profile. METHODS: Thirty consecutive patients with paroxysmal AF received an ILR after their first symptomatic episode. We evaluated the maximum duration of episodes and the recurrence rate of the arrhythmia during a follow-up period of 3 years. RESULTS: Three patients (10%) had no AF recurrence, whereas 4 patients (13.3%) presented only 1 episode. Almost half of the patients (46.7%) had a low recurrence rate (<5 episodes/year), whereas the majority of patients (19/30) suffered from episodes with maximum duration ≤24 hours. Eleven patients (36.7%) presented either no episode or a low recurrence rate with episodes lasting ≤24 hours. The use of statins was greater in patients with a low recurrence rate (P = 0.025). CONCLUSIONS: A significant percentage of patients either suffer no AF recurrence after their first symptomatic episode or show a low recurrence rate. Most patients present episodes of short duration. If these findings are confirmed in larger studies, they could have clinical implications ensuring individualized management of the arrhythmia in the future.

Probing oral anticoagulation in patients with atrial high rate episodes: Rationale and design of the Non-vitamin K antagonist Oral anticoagulants in patients with Atrial High rate episodes (NOAH-AFNET 6) trial.

Oral anticoagulation prevents ischemic strokes in patients with atrial fibrillation (AF). Early detection of AF and subsequent initiation of oral anticoagulation help to prevent strokes in AF patients. Implanted cardiac pacemakers and defibrillators allow seamless detection of atrial high rate episodes (AHRE), but the best antithrombotic therapy in patients with AHRE is not known. RATIONALE: Stroke risk is higher in pacemaker patients with AHRE than in those without, but the available data also show that stroke risk in patients with AHRE is lower than in patients with AF. Furthermore, only a minority of patients with AHRE will develop AF, many strokes occur without a temporal relation to AHRE, and AHRE can reflect other arrhythmias than AF or artifacts. An adequately powered controlled trial of oral anticoagulation in patients with AHRE is needed. DESIGN: The Non-vitamin K antagonist Oral anticoagulants in patients with Atrial High rate episodes (NOAH-AFNET 6 ) trial tests whether oral anticoagulation with edoxaban is superior to prevent the primary efficacy outcome of stroke or cardiovascular death compared with aspirin or no antithrombotic therapy based on evidence-based indications. The primary safety outcome will be major bleeding. NOAH-AFNET 6 will randomize 3,400 patients with AHRE, but without documented AF, aged ≥65 years with at least 1 other stroke risk factor, to oral anticoagulation therapy (edoxaban) or no anticoagulation. All patients will be followed until the end of this investigator-driven, prospective, parallel-group, randomized, event-driven, double-blind, multicenter phase IIIb trial. Patients will be censored when they develop AF and offered open-label anticoagulation. The sponsor is the Atrial Fibrillation NETwork (AFNET). The trial is supported by the DZHK (German Centre for Cardiovascular Research), the BMBF (German Ministry of Education and Research), and Daiichi Sankyo Europe. CONCLUSION: NOAH-AFNET 6 will provide robust information on the effect of oral anticoagulation in patients with atrial high rate episodes detected by implanted devices.

Atrial high-rate episodes and stroke prevention.

While the benefit of oral anticoagulants (OACs) for stroke prevention in patients with atrial fibrillation (AF) is well established, it is not known whether oral anticoagulation is indicated in patients with atrial high-rate episodes (AHRE) recorded on a cardiac implantable electronic device, sometimes also called subclinical AF, and lasting for at least 6 min in the absence of clinically diagnosed AF. Clinical evidence has shown that short episodes of rapid atrial tachycarrhythmias are often detected in patients presenting with stroke and transient ischaemic attack. Patients with AHRE have a higher likelihood of suffering from subsequent strokes, but their stroke rate seems lower than in patients with diagnosed AF, and not all AHRE episodes correspond to AF. The prognostic and pathological significance of AHRE is not yet fully understood. Clinical trials of OAC therapy are being conducted to determine whether therapeutic intervention would be beneficial to patients experiencing AHRE in terms of reducing the risk of stroke.

Cardiac resynchronization therapy (CRT) device replacement considerations: upgrade or downgrade? A complex decision in the current clinical setting.

There are limited data about the management of patients presenting for elective generator replacements in the setting of previously implanted cardiac resynchronization therapy (CRT) devices that are nearing end-of-life. The individual patient's clinical status and concomitant morbidities may evolve so that considerations may include not only replacement of the pulse generator, but also potentially changing the type of device [e.g. downgrading CRT-defibrillator (CRT-D) to CRT-pacemaker (CRT-P) or ICD or upgrading of CRT-P to CRT-D]. Moreover, the clinical evidence for CRT-D/CRT-P implantation may change over time, with ongoing research and availability of new trial data. In this review we discuss the ethical, clinical and financial implications related to CRT generator replacements and the need for additional clinical trials to better understand which patients should undergo CRT device downgrading or upgrading at the time of battery depletion.

Long-term clinical outcomes in implantable cardioverter defibrillator recipients on the island of Crete.

PURPOSE: The aim of the current study is to disseminate long-term "real-world" data on mortality and device therapies in primary and secondary prevention implantable cardioverter defibrillator (ICD) recipients on the island of Crete. METHODS: We analyzed data for all consecutive patients who received an ICD in our tertiary university hospital from 1993 until December 2013. Follow-up visits were performed every 6 months or more frequently when indicated. Survival status was recorded, and all stored episodes during interrogation were registered and classified as appropriate or inappropriate. RESULTS: In total, 854 patients received an ICD; 623 (73%) for primary and 231 (27%) for secondary prevention. Most of these patients (490) suffered from ischemic cardiomyopathy. During the mean follow-up of 12.4±7.8 years, 218 (25.5%) patients died; 19.7% in the primary prevention group (p=0.008) and 41.1% in the secondary prevention group. Overall, 248 patients (29%) received appropriate therapy; however, the percentage was significantly higher in the secondary prevention group (44.2%) than in primary prevention group (23.4%). The cumulative incidence of inappropriate therapies during the mean follow-up period was 11.6%. Lead-related complications were noted in 49 patients (5.7%), while only 13 patients (1.5%) suffered device-related infections. CONCLUSIONS: The long-term data related to clinical outcomes in ICD recipients in our center are in accordance with those of other international centers and confirm the high efficacy and safety of these devices in preventing sudden cardiac death.

Complications Related to Cardiac Rhythm Management Device Therapy and Their Financial Implication: A Prospective Single-Center TwoYear Survey.

INTRODUCTION: Cardiac rhythm management devices (CRMDs) have proven their clinical effectiveness for patients with heart rhythm disorders. Little is known about safety and complication rates during the implantation of these devices. This study demonstrated the complication rates related to CRMD implantation, and estimated the additional hospital stay and cost associated with the management of complications. METHODS: During a period of one year, a total of 464 consecutive recipients underwent CRMD implantation and were followed for 2 years. Finally, data were analyzed for 398 patients who completed the two-year follow up, resulting in a total of 796 patient-years. RESULTS: Of the 201 patients with initial pacemaker (PM) implantations, 6 (2.99%) had seven complications (5 patients had lead dislodgement, 1 of them twice), and 1 patient developed pocket infection. Of the 117 PM replacements, 1 (0.85%) patient developed a complication (pocket erosion). Two patients with complications (1 with an initial PM and 1 with a replacement) died before completing the follow up for reasons unrelated to cardiac causes. There were no complications in either initial implantations (69 patients) or replacements (11 patients) of implantable cardioverter-defibrillators. The average prolongation of the hospital stay was 7 days, ranging from 1 to 35 days, resulting in 17,411 of total additional direct hospital costs. CONCLUSION: This study found relatively low rates of complications in patients undergoing CRMD implantation, initial or replacement, in our center, compared with other studies. The additional hospitalization days and costs attributable to these complications depend on the nature of the complication.

Diabetic Cranio-Cervico-Radiculoplexus Neuropathy.

We describe a case of a 53-year-old man with type 2 diabetes mellitus in whom cervical-radiculoplexus neuropathy developed, with concomitant cranial and phrenic nerve involvement, occurring as a stepwise, monophasic course. The patient had a presumed remote history of idiopathic cervical-radiculoplexus neuropathy.

Alterations in the expression of genes related to contractile function and hypertrophy of the left ventricle in chronically paced patients from the right ventricular apex.

AIM: Long-term right ventricular apical (RVA) pacing may lead to left ventricular (LV) remodelling and heart failure. This study assessed changes in the expression of genes regulating LV contractile function and hypertrophy, after permanent RVA pacing and investigated whether such changes proceed or even predict LV remodelling. METHODS AND RESULTS: We enrolled 52 consecutive patients (age 79.1 ± 7.7 years, 34 males) who underwent pacemaker implantation for bradycardic indications: Group A, 24 individuals with atrioventricular conduction disturbances and group B, 28 patients with sinus node disease. In group A, peripheral blood mRNA levels of gene sarcoplasmic reticulum calcium ATPase decreased at 3, 6, and 12 months' follow-up, while α-myosin heavy chain (MHC) decreased and ß-MHC increased until 6 months follow-up. In this group, 25% of patients demonstrated significant LV remodelling. At 4 years, LV end-systolic diameter increased from 29.67 ± 3.39 mm at baseline to 35.38 ± 4.22 mm, LV end-diastolic diameter increased from 50 ± 4.95 to 56.71 ± 5.52 mm, and ejection fraction declined from 63.04 ± 10.22 to 52.83 ± 10.81%. Early alterations in gene expression were associated with a deterioration in LV function and geometry that became apparent months later. In group B, echocardiographic indexes and mRNA levels of the evaluated genes demonstrated no statistically significant changes. CONCLUSIONS: Permanent RVA pacing in patients with preserved ejection fraction is associated with alterations in the expression of genes regulating LV contractile function and hypertrophy, measured in the peripheral blood. These alterations are traceable at an early stage, before echocardiographic changes are apparent and are associated with LV remodelling that becomes evident in the long term.