Consumer-led screening for atrial fibrillation using consumer-facing wearables, devices and apps: A survey of health care professionals by AF-SCREEN international collaboration.

AIM: A variety of consumer-facing wearables, devices and apps are marketed directly to consumers to detect atrial fibrillation (AF). However, their management is not defined. Our aim was to explore their role for AF screening via a survey. METHODS AND RESULTS: An anonymous web-based survey was undertaken by 588 health care professionals (HCPs) (response rate 23.7%). Overall, 57% HCPs currently advise wearables/apps for AF detection in their patients: this was much higher for electrophysiologists and nurses/allied health professionals (74-75%) than cardiologists (57%) or other physicians (34-38%). Approximately 46% recommended handheld (portable) single-lead dedicated ECG devices, or, less frequently, wristband ECG monitors with similar differentials between HCPs . Only 10-15% HCPs advised photoplethysmographic wristband monitors or smartphone apps. In over half of the HCP consultations for AF detected by wearables/apps, the decision to screen was entirely the patient's. About 45% of HCPs perceive a potential role for AF screening in people aged >65 years or in those with risk factors. Almost 70% of HCPs believed we are not yet ready for mass consumer-initiated screening for AF using wearable devices/apps, with patient anxiety, risk of false positives and negatives, and risk of anticoagulant-related bleeding perceived as potential disadvantages, and perceived need for appropriate management pathways. CONCLUSIONS: There is a great potential for appropriate use of consumer-facing wearables/apps for AF screening. However, it appears that there is a need to better define suitable individuals for screening and an appropriate mechanism for managing positive results before they can be recommended by HCPs.

Screening for Atrial Fibrillation: A Report of the AF-SCREEN International Collaboration.

Approximately 10% of ischemic strokes are associated with atrial fibrillation (AF) first diagnosed at the time of stroke. Detecting asymptomatic AF would provide an opportunity to prevent these strokes by instituting appropriate anticoagulation. The AF-SCREEN international collaboration was formed in September 2015 to promote discussion and research about AF screening as a strategy to reduce stroke and death and to provide advocacy for implementation of country-specific AF screening programs. During 2016, 60 expert members of AF-SCREEN, including physicians, nurses, allied health professionals, health economists, and patient advocates, were invited to prepare sections of a draft document. In August 2016, 51 members met in Rome to discuss the draft document and consider the key points arising from it using a Delphi process. These key points emphasize that screen-detected AF found at a single timepoint or by intermittent ECG recordings over 2 weeks is not a benign condition and, with additional stroke factors, carries sufficient risk of stroke to justify consideration of anticoagulation. With regard to the methods of mass screening, handheld ECG devices have the advantage of providing a verifiable ECG trace that guidelines require for AF diagnosis and would therefore be preferred as screening tools. Certain patient groups, such as those with recent embolic stroke of uncertain source (ESUS), require more intensive monitoring for AF. Settings for screening include various venues in both the community and the clinic, but they must be linked to a pathway for appropriate diagnosis and management for screening to be effective. It is recognized that health resources vary widely between countries and health systems, so the setting for AF screening should be both country- and health system-specific. Based on current knowledge, this white paper provides a strong case for AF screening now while recognizing that large randomized outcomes studies would be helpful to strengthen the evidence base.

A phase I study of quisinostat (JNJ-26481585), an oral hydroxamate histone deacetylase inhibitor with evidence of target modulation and antitumor activity, in patients with advanced solid tumors.

PURPOSE: To determine the maximum-tolerated dose (MTD), dose-limiting toxicities (DLT), and pharmacokinetic and pharmacodynamic profile of quisinostat, a novel hydroxamate, pan-histone deacetylase inhibitor (HDACi). EXPERIMENTAL DESIGN: In this first-in-human phase I study, quisinostat was administered orally, once daily in three weekly cycles to patients with advanced malignancies, using a two-stage accelerated titration design. Three intermittent schedules were subsequently explored: four days on/three days off; every Monday, Wednesday, Friday (MWF); and every Monday and Thursday (M-Th). Toxicity, pharmacokinetics, pharmacodynamics, and clinical efficacy were evaluated at each schedule. RESULTS: Ninety-two patients were treated in continuous daily (2-12 mg) and three intermittent dosing schedules (6-19 mg). Treatment-emergent adverse events included: fatigue, nausea, decreased appetite, lethargy, and vomiting. DLTs observed were predominantly cardiovascular, including nonsustained ventricular tachycardia, ST/T-wave abnormalities, and other tachyarhythmias. Noncardiac DLTs were fatigue and abnormal liver function tests. The maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) of quisinostat increased proportionally with dose. Pharmacodynamic evaluation showed increased acetylated histone 3 in hair follicles, skin and tumor biopsies, and in peripheral blood mononuclear cells as well as decreased Ki67 in skin and tumor biopsies. A partial response lasting five months was seen in one patient with melanoma. Stable disease was seen in eight patients (duration 4-10.5 months). CONCLUSIONS: The adverse event profile of quisinostat was comparable with that of other HDACi. Intermittent schedules were better tolerated than continuous schedules. On the basis of tolerability, pharmacokinetic predictions, and pharmacodynamic effects, the recommended dose for phase II studies is 12 mg on the MWF schedule.

Preoperative high-dose atorvastatin for prevention of atrial fibrillation after cardiac surgery: a randomized controlled trial.

OBJECTIVE: The preventative effect of statins on postoperative atrial fibrillation has been hypothesized. However, all studies to date have examined patients who did not receive statins before their further allocation to treatment or no treatment. Because guidelines recommend the routine use of statins in patients with coronary artery disease, we set out to examine the effect of intensive statin pretreatment versus continuation of usual statin dose on atrial fibrillation after cardiac surgery. METHODS: Patients receiving routine statin treatment and undergoing coronary artery bypass surgery or aortic valve replacement with no history of atrial fibrillation or antiarrhythmic medication were randomized to receive atorvastatin 80 mg or atorvastatin 10 mg for 7 days before surgery in a single-blind fashion. The primary end point was the development of postoperative atrial fibrillation during hospital stay. RESULTS: A total of 104 consecutive patients were included. Postoperative atrial fibrillation occurred in 33 patients (32.4%). No significant differences were found in demographics, medical history, or intraoperative variables between treatment groups, with the exception of higher rate of ß-blocker use in the atorvastatin 10 mg group (75% vs 53%, P = .002) and previous myocardial infarction (62% vs 42%, P = .049). The incidence of postoperative atrial fibrillation was lower in the atorvastatin 80 mg group when compared with the atorvastatin 10 mg group, but this difference did not reach statistical significance (29% vs 36%, P = .43). CONCLUSIONS: High-dose atorvastatin for 7 days before cardiac surgery conferred a nonsignificant reduction in postoperative atrial fibrillation when compared with a low-dose regimen. A larger study would be necessary to confirm the beneficial effect of high-dose statins in this setting.

EHRA Expert Consensus Statement on the management of cardiovascular implantable electronic devices in patients nearing end of life or requesting withdrawal of therapy.

The purpose of this Consensus Statement is to focus on implantable cardioverter-defibrillator (ICD) deactivation in patients with irreversible or terminal illness. This statement summarizes the opinions of the Task Force members, convened by the European Heart Rhythm Association (EHRA) and the Heart Rhythm Society (HRS), based on ethical and legal principles, as well as their own clinical, scientific, and technical experience. It is directed to all healthcare professionals who treat patients with implanted ICDs, nearing end of life, in order to improve the patient dying process. This statement is not intended to recommend or promote device deactivation. Rather, the ultimate judgement regarding this procedure must be made by the patient (or in special conditions by his/her legal representative) after careful communication about the deactivation's consequences, respecting his/her autonomy and clarifying that he/she has a legal and ethical right to refuse it. Obviously, the physician asked to deactivate the ICD and the industry representative asked to assist can conscientiously object to and refuse to perform device deactivation.

Postoperative atrial fibrillation - what do we really know?

Postoperative atrial fibrillation (POAF) is a common complication following cardiac surgery, occurring in 20% to 60% of patients. Advanced age, history of atrial fibrillation (AF), heart failure, peripheral arterial disease and chronic obstructive pulmonary disease are predictors of POAF. The pathogenesis of AF seems to be multifactorial, and includes electrical and structural remodeling as well as inflammation (a systemic response caused by cardiopulmonary bypass and cardiotomy). Numerous pharmacologic agents can decrease the incidence of POAF. It is also necessary to evaluate an agent's ability to decrease stroke, mortality, length of stay and hospital costs. Currently, the use of beta-blockers with adjunctive amiodarone has been shown to reduce POAF and several of its complications. Two therapeutic choices exist in patients with POAF: rate control and rhythm control. The decision which is more important to target should be based on the symptoms of the individual patient. Unlike in patients with chronic AF, POAF is generally transient, and the risks of anticoagulation may outweigh the benefits. Surgical ablation techniques and ablation devices have progressed considerably. This made the procedures quicker and simpler, and therefore feasible in virtually all clinical contexts. In turn, this has raised the issue of post-ablation arrhythmias. Although relapsing AF is generally addressed conservatively, it may require ablation, frequently transseptal. Further research is needed to identify the predictors of POAF and the most effective pharmacological and invasive methods for the prevention and treatment of POAF.

Effect of fish oil on ventricular tachyarrhythmia in three studies in patients with implantable cardioverter defibrillators.

AIMS: To determine the effects of omega-3 polyunsaturated fatty acids (omega-3 PUFAs) from fish on the incidence of recurrent ventricular arrhythmia in implantable cardioverter defibrillator (ICD) patients by combining results from published trials. METHODS AND RESULTS: We searched in the Medline, EMBASE, and Cochrane databases and performed a meta-analysis on all three available trials on fish oil and ventricular arrhythmia. Furthermore, we pooled individual data of two of these randomized, double-blind, placebo-controlled trials (Raitt et al. Fish oil supplementation and risk of ventricular tachycardia and ventricular fibrillation in patients with implantable defibrillators: a randomized controlled trial. JAMA 2005;293:2884-2891 and Brouwer et al. Effect of fish oil on ventricular tachyarrhythmia and death in patients with implantable cardioverter defibrillators: the Study on Omega-3 Fatty Acids and Ventricular Arrhythmia (SOFA) randomized trial. JAMA 2006;295:2613-2619). The main outcome was time to first confirmed ventricular fibrillation (VF) or ventricular tachycardia (VT) combined with death for the meta-analysis, and time to first spontaneous confirmed VF or VT for the pooled analysis. The meta-analysis (n = 1148) showed no convincing protective effect of fish oil (RR 0.90; 95% CI 0.67-1.22). The hazard ratio for the subgroup of patients with coronary artery disease at baseline (0.79; 0.60-1.06) tended towards a protective effect. The pooled analysis (n = 722) showed that time to appropriate ICD intervention was similar for fish oil and placebo treatment (log-rank P = 0.79). CONCLUSION: These findings do not support a protective effect of omega-3 PUFAs from fish oil on cardiac arrhythmia in all patients with an ICD. Current data neither prove nor disprove a beneficial or a detrimental effect for subgroups of patients with specific underlying pathologies.

Dose-related effect of statins on atrial fibrillation after cardiac surgery.

BACKGROUND: Atrial fibrillation (AF) is the most common heart rhythm abnormality after cardiac surgery. It increases morbidity and prolongs hospital stay. A role for statins in the prevention of AF has been suggested. We hypothesized that the incidence of postoperative AF due to statin therapy is dose-related. METHODS: A retrospective study of 680 consecutive patients undergoing coronary bypass graft surgery and/or aortic valve replacement was done. Excluded were 57 patients (8.4%) with history of AF, permanent pacemakers, and those receiving antiarrhythmic medication. Preoperative statin treatment and occurrence of postoperative AF were examined using propensity score matching to adjust for differences in patient characteristics between the statin and no-statin groups. RESULTS: The cohort comprised 623 patients. The statin group had a 27.1% incidence of postoperative AF vs 38.3% in the no-statin group (adjusted odds ratio [OR], 2.00; 95% confidence interval, 1.24 to 3.24; p = 0.004). Simvastatin (40 mg) and atorvastatin (40 mg) demonstrated the greatest effect on postoperative AF at 15.6% and 21.2%, respectively, vs no statins (respective adjusted ORs, 3.89 [p < 0.0001] and 2.76 [p = 0.012]). Intermediate-dose (20 mg) statins were also effective against AF, at 24.4% for simvastatin (adjusted OR, 2.32; p = 0.004) and 26.4% for atorvastatin (adjusted OR, 1.99, p = 0.047). Low-dose statins, simvastatin or atorvastatin (10 mg), did not influence postoperative AF. CONCLUSIONS: Statin treatment may reduce the incidence of AF after cardiac surgery. Higher-dose statins have the greatest preventative effect, whereas low-dose statins do not influence postoperative AF.

Web-based virtual cardiac symposia: a new approach for worldwide professional medical education.

AIM: The Internet is an extremely powerful tool for the transmission of data and knowledge, and the question is whether this technology can be used effectively in continuing medical education. We present our experience with worldwide, web-based virtual symposia for practicing physicians. METHODS: The International Society for Holter and Noninvasive Electrocardiography (ISHNE) decided four years ago to conduct a series of cardiology-related educational activities for physicians utilizing a web-based approach. Six educational events under the format of virtual symposia were held on the Internet during the years 2002 to 2006. These Internet events included symposia on Brugada syndrome (2002), the long QT syndrome (2004), arrhythmogenic right ventricular dysplasia (2005), atrial fibrillation (2005), heart failure (2006), and sudden cardiac death (2006). RESULTS: During the past four years, there has been a dramatic and progressive increase in the number of physician registrants, the number of countries represented, and the number of lectures downloaded with each subsequent virtual symposium. For example, during the month of October 2006, the Internet-based sudden cardiac death symposium involved 14,087 physician registrants from 120 countries with 64,939 lectures downloaded. The top lecture was downloaded 11,251 times, and over 200 e-mail questions and replies were exchanged. The average time per visit to the web site was 12.5 minutes. CONCLUSION: The progressively increasing numbers of physician registrants from around the world who participated in these web-based, virtual symposia suggest that this approach is answering an unmet professional educational need. This Internet approach adds an important, new, low-cost dimension to continuing medical education.

Current strategies in the management of atrial fibrillation.

Treatment of atrial fibrillation (AF) has been undergoing significant changes recently. This is due partly to different mechanisms proposed for persistent and permanent AF and partly due to the introduction of energy-based techniques, providing less invasive procedures. This article aims to review the mechanisms of AF leading to the changes in clinical practice and to review the results of surgery, energy-based, and percutaneous techniques. It is difficult to compare and contrast the results of reported series in the literature due to different definitions of AF; freedom from and recurrence of it. Furthermore, in most series it is difficult to distinguish results of surgery for lone AF and AF associated with valvular heart disease and coronary artery disease.

Trial to evaluate the management of paroxysmal supraventricular tachycardia during an electrophysiology study with tecadenoson.

BACKGROUND: Tecadenoson is a potent selective A1-adenosine receptor agonist with a dose-dependent negative dromotropic effect on the AV node. Tecadenoson terminates induced paroxysmal supraventricular tachycardia (PSVT) without the clinically significant side effects caused by stimulation of other adenosine receptors. This trial was designed to determine a safe and effective tecadenoson bolus for termination of electrophysiologically induced PSVT. METHODS AND RESULTS: Patients with a history of symptomatic PSVT and inducible PSVT at the time of a clinically indicated electrophysiology study were randomized into a multicenter, double-blind, placebo-controlled trial. Five 2-dose tecadenoson bolus regimens were evaluated versus placebo (75/150, 150/300, 300/600, 450/900, 900 microg/900 microg). The second bolus was administered only if PSVT persisted for 1 minute after the first bolus. Each tecadenoson regimen resulted in a significant therapeutic conversion rate compared with placebo (range, 50.0% to 90.3%, analysis of all patients dosed; n=181; P<0.0005). Conversion by the first bolus was dose related (range: placebo, 3.3% to 86.7% for 900 microg/900 microg). Time to conversion was dose dependent, with a median time of <1 minute for the 3 highest dose regimens. Postconversion arrhythmias were transient, requiring no additional treatment in 4 regimens (including placebo). Transient second- and third-degree heart block occurred at higher doses (300/600, 450/900, 900 microg/900 microg) and was supported with backup pacing when needed. No effect on blood pressure was observed. Ten patients with a history of asthma or chronic obstructive pulmonary disease tolerated tecadenoson without bronchospasm. CONCLUSIONS: We identified an optimal tecadenoson regimen (300 microg/600 microg) that effectively and rapidly converted 90% (28 of 31) of PSVT patients to normal sinus rhythm with no significant adverse effects.