A randomized trial evaluating the accuracy of AF detection by four external ambulatory ECG monitors compared to permanent pacemaker AF detection.

PURPOSE: Several external cardiac monitors (ECMs) have recently been developed. These have never been compared to 'gold standard' monitoring with concurrently implanted DDDRP pacemakers. The accuracy of AF detection of Zio XT Monitor (ZM), NUUBO Vest (NV) and Carnation Ambulatory Monitor (CAM) compared with Novacor 'R' Test 4 (RT) in patients (pts) with DDDRP PPM advanced Holters as the comparator, was evaluated. METHODS: Twenty-one pts. with AF and a DDDRP PPM, each acting as their own control subject, wore every ECM for 2 weeks in randomized order. PPM downloads were performed at application and removal. Device ECGs were compared for AF burden and individual AF episodes with PPM Holters. Pt acceptability, wear time, costs and time expenditure were evaluated. RESULTS: RT AF burden was less accurate than the ZM, NV or CAM (p < 0.05). Probability of inaccurate AF diagnosis was higher for RT than ZM or CAM OR 12.31 and 5.85, respectively (p = 0.025 and p = 0.042). ZM wear time was longer than the RT: 307 h vs. 224 h; p = 0.02. Acceptability was greater for CAM than RT (1.86 ± 2.63 compared with 0.57 ± 1.17 for CAM; p = 0.024). All ECMs were more expensive than RT (p < 0.00001). CONCLUSIONS: All new ECMs were more expensive than the RT system; however, the ZM, NV and CAM are all more accurate than current standard practice RT device in AF burden assessment. The RT is more likely to give inaccurate diagnoses than ZM or CAM. This may have clinical implications.

Atrial high-rate episodes: prevalence, stroke risk, implications for management, and clinical gaps in evidence.

Self-terminating atrial arrhythmias are commonly detected on continuous rhythm monitoring, e.g. by pacemakers or defibrillators. It is unclear whether the presence of these arrhythmias has therapeutic consequences. We sought to summarize evidence on the prevalence of atrial high-rate episodes (AHREs) and their impact on risk of stroke. We performed a comprehensive, tabulated review of published literature on the prevalence of AHRE. In patients with AHRE, but without atrial fibrillation (AF), we reviewed the stroke risk and the potential risk/benefit of oral anticoagulation. Atrial high-rate episodes are found in 10-30% of AF-free patients. Presence of AHRE slightly increases stroke risk (0.8% to 1%/year) compared with patients without AHRE. Atrial high-rate episode of longer duration (e.g. those >24 h) could be associated with a higher stroke risk. Oral anticoagulation has the potential to reduce stroke risk in patients with AHRE but is associated with a rate of major bleeding of 2%/year. Oral anticoagulation is not effective in patients with heart failure or survivors of a stroke without AF. It remains unclear whether anticoagulation is effective and safe in patients with AHRE. Atrial high-rate episodes are common and confer a slight increase in stroke risk. There is true equipoise on the best way to reduce stroke risk in patients with AHRE. Two ongoing trials (NOAH-AFNET 6 and ARTESiA) will provide much-needed information on the effectiveness and safety of oral anticoagulation using non-vitamin K antagonist oral anticoagulants in patients with AHRE.

A trial of three non-invasive blood pressure monitors compared with invasive blood pressure assessment in atrial fibrillation and sinus rhythm.

OBJECTIVE: To investigate the accuracy of three non-invasive blood pressure (BP) devices in atrial fibrillation (AF) compared with invasive arterial BP. METHODS: One hundred patients aged 45-90 years, 63% male (50 in AF and 50 age matched controls in sinus rhythm [SR]) were identified with arterial lines measuring beat-to-beat BP fluctuation. Non-invasive BP measurements utilising the manual sphygmomanometer (MS), PulseCor R6.5 (PC) and automated sphygmomanometer (AS) were taken simultaneously with invasive BP in a randomised sequence. This was repeated three times in each patient. RESULTS: In SR differences in systolic BP (SBP) for MS, AS and PC were -0.34 mm Hg (95% CI -2.31 to 1.63; P = .733), -3.80 mm Hg (95% CI -5.73 to -1.87; P = .0001) and -3.90 mm Hg (95% CI -5.90 to -1.90; P = .0001) and for diastolic BP (DBP) were 6.02 mm Hg (95% CI 4.39-7.64; P < .0001), 8.95 mm Hg (95% CI 7.36-10.55; P < .0001) and 7.54 mm Hg (95% CI 5.89-9.18; P < .0001), respectively. In AF mean differences in SBP for MS, AS and PC were -7.33 mm Hg (95% CI -9.11 to -5.55; P < .0001), -5.29 mm Hg (95% CI -7.08 to -3.50; P < .0001) and -5.75 mm Hg (95% CI -7.54 to -3.96; P < .0001) respectively and for DBP were 5.28 mm Hg (95% CI 4.03-6.54; P < .0001), 6.26 mm Hg (95% CI 5.00-7.52; P < .0001) and 6.89 mm Hg (95% CI 5.64-8.15; P < .0001) respectively. CONCLUSIONS: The MS is accurate in SR because of direct assessment of Korotkoff sounds. Non-invasive BP assessment in AF is significantly less accurate. These findings have important prognostic and therapeutic implications.

First clinical trial of specific IKACh blocker shows no reduction in atrial fibrillation burden in patients with paroxysmal atrial fibrillation: pacemaker assessment of BMS 914392 in patients with paroxysmal atrial fibrillation.

AIMS: To assess the efficacy of BMS 914392 on atrial fibrillation (AF) burden reduction in 20 patients with pacemakers and paroxysmal atrial fibrillation (PAF). BMS 914392 is a potent, selective, oral inhibitor of the IKACh current and has been shown to suppress AF, whilst having no effect on the ventricular refractory period. This is the first efficacy study of BMS 914392 in patients with PAF. METHODS AND RESULTS: The study was a four-way, crossover, double-blind design. A total of 20 patients with PAF and dual-chamber pacemakers were recruited. The pacemakers allowed beat-to-beat monitoring. Anti-arrhythmic drugs were withdrawn. Patients received low-dose (10 mg OD), medium-dose (10 mg TDS), and high-dose (20 mg TDS) BMS 914392 or placebo for 3 weeks before being crossed to the next phase. Patients underwent a washout period, four treatment phases and a final washout phase. Atrial fibrillation burden was downloaded from their pacemakers at the end of each study phase. BMS 914392 did not reduce AF burden when compared with placebo (10 mg OD P = 0.56, 10 mg TDS P = 0.22, 20 mg TDS P = 0.23). Heart rate and corrected QT (QTc) were not affected by BMS 914392. Adverse event (AE) rates did not differ from placebo in any of the treatment groups, with no serious AEs recorded. CONCLUSION: BMS 914932 has not been shown to reduce AF burden in patients with PAF and pacemakers using beat-to-beat pacemaker monitoring throughout the study. BMS 914392 was well tolerated and did not affect QTc or reduce heart rate. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01356914.

The development of AF over time in patients with permanent pacemakers: objective assessment with pacemaker diagnostics demonstrates distinct patterns of AF.

AIMS: To describe the long-term patterns of atrial fibrillation (AF) in patients with permanent pacemakers. METHODS AND RESULTS: A total of 2092 pacemaker Holter downloads were analysed in 323 patients with dual chamber permanent pacemakers, describing a cumulative 1031 patient-years of beat-to-beat monitoring. Four subtypes of AF were applied: (i) non-progressive low-burden PAF (NPLB-PAF, n = 120): such patients never have >1% AF burden throughout follow-up; (ii) chronic progressive PAF (CP-PAF, n = 55): AF burden increases but is never 100%; (iii) relapsing-remitting PAF (RR-PAF, n = 78): AF burden has reduced at least once by more than 2% and is never 100%; (iv) persistent AF (PersAF, n = 70): 100% AF burden for at least 28 days. Overall, mean AF burden rose 0.34% per year (P < 0.0001). After accounting for age, heart failure (HF) had a significant interaction with AF burden (P = 0.0022), but HATCH score and CVA/TIA did not. There were no differences in the frequency or duration of monitoring between the four AF subtypes. Atrial fibrillation episode frequency discriminated between subtypes (P = 0.0004). Eighteen of 70 (26%) patients with PersAF had pacemaker documented episodes of sinus rhythm (i.e. reversion to 'paroxysmal AF') after the onset of PersAF. CONCLUSION: In this cohort, the development of AF over time appears more complex than current definitions suggest. Atrial fibrillation can remain low burden without progression, remit-relapse, or progress as is described in currently accepted definitions. More frequent episodes of AF indicated a favourable subtype. Persistent AF is not inevitable, and can revert to paroxysmal AF. CLINICAL TRIAL REGISTRATION: NCT02016950, http://clinicaltrials.gov/show/NCT02016950.

Implantable diagnostic monitors in the early assessment of syncope and collapse.

The implantable diagnostic monitor, or loop recorder (ILR) is a subcutaneous monitor capable of continuous ECG monitoring up to 3 years. It is an elegant investigative tool for the assessment of patients with recurrent, unexplained syncope in whom an arrhythmic cause needs to be excluded, and is now increasingly utilised very early in the diagnostic work-up of these patients, in line with current guidelines. This review examines the evidence underpinning these recommendations as well as the relevant clinical trials evaluating the use of the ILR in syncope. Continued research will be needed to validate its role as a first line investigation in a sub-select of syncopal patients, especially with the addition of remote monitoring capabilities.

A preliminary assessment of the effects of ATI-2042 in subjects with paroxysmal atrial fibrillation using implanted pacemaker methodology.

AIMS: ATI-2042 (budiodarone) is a chemical analogue of amiodarone with a half life of 7 h. It is electrophysiologically similar to amiodarone, but may not have metabolic and interaction side effects. The sophisticated electrocardiograph logs of advanced DDDRP pacemakers were used to monitor the efficacy of ATI-2042. The aim of this study was to determine the preliminary efficacy and safety of ATI-2042 in patients with paroxsymal atrial fibrillation (PAF) and pacemakers. METHODS AND RESULTS: Six women with AF burden (AFB) between 1 and 50% underwent six sequential 2-week study periods. Patients received 200 mg bid of ATI-2042 during Period 2 (p2), 400 mg bid during p3, 600 mg bid during p4, 800 mg bid during p5, and no drug during baseline and washout (p1 and p6). Pacemaker data for the primary outcome measure AFB were downloaded during each period. Mean AFB decreased between baseline and all doses: AFB at baseline (SD) was 20.3 +/- 14.6% and mean AFB at 200 mg bid was 5.2 +/- 4.2%, at 400 mg bid 5.2 +/- 5.2%, at 600 mg bid 2.8 +/- 3.4%, and at 800 mg bid 1.5 +/- 0.5%. The mean reductions in AFB at all doses of ATI-2042 were statistically significant (P < 0.005). Atrial fibrillation burden increased in washout. Atrial fibrillation episodes tended to increase with ATI-2042, but this was offset by substantial decreases in episode duration. ATI-2042 was generally well tolerated. CONCLUSION: ATI-2042 effectively reduced AFB over all doses studied by reducing mean episode duration. A large-scale study will be required to confirm this effect.

The clinical impact of implantable loop recorders in patients with syncope.

AIMS: Implantable loop recorders (ILR) provide an opportunity to record ECG data from a spontaneous syncopal event. We conducted a randomized study to investigate the impact of the Reveal Plus ILR on an unselected population of patients with recurrent syncope. Initial follow-up (at least 6 months) did not demonstrate a reduction in syncopal events or an improvement in quality of life. We report the planned extension of follow-up to 18 months. METHODS AND RESULTS: All patients presenting acutely with recurrent unexplained syncope over a 16-month period, following a basic clinical work-up, were randomized to receive the ILR or conventional investigation and management. A total of 421 patients presented, 201 were eligible, median age 74, (IQ range 61-81) 54% female, with median syncopes 3 (IQ range 2-6). Median follow-up 17 months (IQ range 9-23). 42 (43%) of ILR patients and 8 (6%) of conventional patients received an ECG diagnosis (hazard ratio 6.53, 95% CI 3.73-11.4, P<0.001). Time to second syncope was significantly longer for ILR patients, although of borderline significance (P=0.04). A greater variety of diagnoses and treatments were seen in ILR patients. ILR patients had fewer post-randomization investigations and fewer days in hospital; however, cost savings were not statistically significant. There was improved quality of life in the ILR group (visual analogue scales, P=0.03) for general wellbeing. Overall mortality was 12% with no difference between the two groups. CONCLUSION: Investigation by the ILR significantly increases the diagnostic rate and ECG directed treatments in a typical unselected syncopal population. Long-term follow-up has demonstrated a significant subsequent reduction in syncopal events with improved quality of life.

Improving the acceptability of the atrial defibrillator for the treatment of persistent atrial fibrillation: the atrial defibrillator sedation assessment study (ADSAS).

BACKGROUND: To compare the acceptability and effectiveness of three pre-medication regimens for manually activated cardioversion of recurrent persistent atrial fibrillation. METHODS: Eighteen patients implanted with the Jewel AF atrial defibrillator for drug-resistant persistent atrial fibrillation only were studied in an open-labelled randomised crossover study. Patients were assigned to sedation (S) with midazolam elixir, analgesia (A) with morphine sulphate or combination therapy (C) with dextromoramide and lorazepam. Pre-medication was taken up to 1 h before cardioversion. Patients rotated through each type of medication after undertaking at least one cardioversion. Visual analogue scales were completed immediately post-cardioversion and 24 h later for pain, anxiety and 'unpleasantness'. Higher scores represented a worse outcome. RESULTS: After 2 years' follow-up, 238 cardioversions were performed with S, 17 with A and 35 with C. The mean immediate combined score for S (10.9, 95% confidence interval (CI) 8.2-13.6) was significantly lower than for A (17.3, 95% CI 15.1-19.5, P = 0.01) and for C (15.9, 95% CI 12.3-19.6, P = 0.02). All patients who used S chose it as the most favourable pre-medicant. All patients who used A found it the least acceptable. CONCLUSION: Sedation rather than analgesia enhanced the acceptability of manually activated atrial defibrillation.

How do we diagnose syncope?

INTRODUCTION: The Eastbourne Syncope Assessment Study aims to increase diagnostic yield in unexplained syncope while reducing investigational costs. The initial study phase was a retrospective analysis of every presentation to the Eastbourne General Hospital (a busy nontertiary center in the United Kingdom serving a population of 250,000; 24% are older than 65 years) with syncope for the year 1998. METHODS AND RESULTS: A total of 1,334 cases with syncopal codes were identified. Six hundred sixty patients (mean age 64 years) had actually suffered an episode of syncope. Forty percent had recurrent syncope, with a mean of 4.7 previous episodes. Twenty-nine percent of syncope cases remained undiagnosed. Forty-four percent were diagnosed as vasovagal, 12% neurologic, 6% due to an arrhythmia, 2% drug related, and 2% due to hemorrhage. Thirteen different types of investigation were undertaken, with an overall total of 3,264 investigations performed at a cost of Pound Sterling 104,285. Diagnosis was achieved by history and examination alone in 61% of cases. Excluding history and examination, the most cost-effective diagnostic tools were the 7-day patient-activated recorder (R test) and tilt testing (Pound Sterling 260 and Pound Sterling 401 per diagnosis, respectively). Investigations also were graded by their relative diagnostic power. Hospital admission alone accounted for 67% of the cost of investigating syncope. CONCLUSION: In syncope, diagnostic rates can be improved and investigational costs reduced by concentrating on the most specific, sensitive, and cost-effective investigations and by minimizing hospital stay. Such a protocol currently is under investigation at our institution.