Pharmacological and non-pharmacological treatments and outcomes for new-onset atrial fibrillation in ICU patients: the CAFE scoping review and database analyses.

BACKGROUND: New-onset atrial fibrillation occurs in around 10% of adults treated in an intensive care unit. New-onset atrial fibrillation may lead to cardiovascular instability and thromboembolism, and has been independently associated with increased length of hospital stay and mortality. The long-term consequences are unclear. Current practice guidance is based on patients outside the intensive care unit; however, new-onset atrial fibrillation that develops while in an intensive care unit differs in its causes and the risks and clinical effectiveness of treatments. The lack of evidence on new-onset atrial fibrillation treatment or long-term outcomes in intensive care units means that practice varies. Identifying optimal treatment strategies and defining long-term outcomes are critical to improving care. OBJECTIVES: In patients treated in an intensive care unit, the objectives were to (1) evaluate existing evidence for the clinical effectiveness and safety of pharmacological and non-pharmacological new-onset atrial fibrillation treatments, (2) compare the use and clinical effectiveness of pharmacological and non-pharmacological new-onset atrial fibrillation treatments, and (3) determine outcomes associated with new-onset atrial fibrillation. METHODS: We undertook a scoping review that included studies of interventions for treatment or prevention of new-onset atrial fibrillation involving adults in general intensive care units. To investigate the long-term outcomes associated with new-onset atrial fibrillation, we carried out a retrospective cohort study using English national intensive care audit data linked to national hospital episode and outcome data. To analyse the clinical effectiveness of different new-onset atrial fibrillation treatments, we undertook a retrospective cohort study of two large intensive care unit databases in the USA and the UK. RESULTS: Existing evidence was generally of low quality, with limited data suggesting that beta-blockers might be more effective than amiodarone for converting new-onset atrial fibrillation to sinus rhythm and for reducing mortality. Using linked audit data, we showed that patients developing new-onset atrial fibrillation have more comorbidities than those who do not. After controlling for these differences, patients with new-onset atrial fibrillation had substantially higher mortality in hospital and during the first 90 days after discharge (adjusted odds ratio 2.32, 95% confidence interval 2.16 to 2.48; adjusted hazard ratio 1.46, 95% confidence interval 1.26 to 1.70, respectively), and higher rates of subsequent hospitalisation with atrial fibrillation, stroke and heart failure (adjusted cause-specific hazard ratio 5.86, 95% confidence interval 5.33 to 6.44; adjusted cause-specific hazard ratio 1.47, 95% confidence interval 1.12 to 1.93; and adjusted cause-specific hazard ratio 1.28, 95% confidence interval 1.14 to 1.44, respectively), than patients who did not have new-onset atrial fibrillation. From intensive care unit data, we found that new-onset atrial fibrillation occurred in 952 out of 8367 (11.4%) UK and 1065 out of 18,559 (5.7%) US intensive care unit patients in our study. The median time to onset of new-onset atrial fibrillation in patients who received treatment was 40 hours, with a median duration of 14.4 hours. The clinical characteristics of patients developing new-onset atrial fibrillation were similar in both databases. New-onset atrial fibrillation was associated with significant average reductions in systolic blood pressure of 5 mmHg, despite significant increases in vasoactive medication (vasoactive-inotropic score increase of 2.3; p < 0.001). After adjustment, intravenous beta-blockers were not more effective than amiodarone in achieving rate control (adjusted hazard ratio 1.14, 95% confidence interval 0.91 to 1.44) or rhythm control (adjusted hazard ratio 0.86, 95% confidence interval 0.67 to 1.11). Digoxin therapy was associated with a lower probability of achieving rate control (adjusted hazard ratio 0.52, 95% confidence interval 0.32 to 0.86) and calcium channel blocker therapy was associated with a lower probability of achieving rhythm control (adjusted hazard ratio 0.56, 95% confidence interval 0.39 to 0.79) than amiodarone. Findings were consistent across both the combined and the individual database analyses. CONCLUSIONS: Existing evidence for new-onset atrial fibrillation management in intensive care unit patients is limited. New-onset atrial fibrillation in these patients is common and is associated with significant short- and long-term complications. Beta-blockers and amiodarone appear to be similarly effective in achieving cardiovascular control, but digoxin and calcium channel blockers appear to be inferior. FUTURE WORK: Our findings suggest that a randomised controlled trial of amiodarone and beta-blockers for management of new-onset atrial fibrillation in critically ill patients should be undertaken. Studies should also be undertaken to provide evidence for or against anticoagulation for patients who develop new-onset atrial fibrillation in intensive care units. Finally, given that readmission with heart failure and thromboembolism increases following an episode of new-onset atrial fibrillation while in an intensive care unit, a prospective cohort study to demonstrate the incidence of atrial fibrillation and/or left ventricular dysfunction at hospital discharge and at 3 months following the development of new-onset atrial fibrillation should be undertaken. TRIAL REGISTRATION: Current Controlled Trials ISRCTN13252515. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 71. See the NIHR Journals Library website for further project information.

BACKGROUND: Atrial fibrillation can cause heart failure and stroke. It can also affect heart rate in different ways. It is common for patients admitted to intensive care units to develop atrial fibrillation. When patients have never had atrial fibrillation before, this is called 'new-onset atrial fibrillation'. We do not know how new-onset atrial fibrillation in patients treated in an intensive care unit affects heart rate and blood pressure, what the best treatments are or how treatments affect how people recover. METHODS: We looked at studies of new-onset atrial fibrillation treatments in intensive care units to see if some treatments have been shown to work better. We used a national database to see what happens to intensive care unit patients in the UK who develop new-onset atrial fibrillation. We also used two databases from intensive care units in the UK and the USA to see how many patients in the intensive care units have new-onset atrial fibrillation, how atrial fibrillation affects heart rate and blood pressure, and whether or not some treatments work better than others. RESULTS: Between 6% and 11% of intensive care unit patients develop new-onset atrial fibrillation. These patients are more likely to die in hospital and in the first 90 days after discharge than those who do not. They are also more likely to be readmitted to hospital with atrial fibrillation, stroke and heart failure. The evidence for new-onset atrial fibrillation treatments is limited, but suggests that beta-blockers or amiodarone may work better than calcium channel blockers or digoxin. CONCLUSIONS: New-onset atrial fibrillation in intensive care units is common, and outcomes are worse in patients who develop new-onset atrial fibrillation than in those who do not. Our research shows that some new-onset atrial fibrillation treatments work better than others. This information will help us to plan a study to improve health after new-onset atrial fibrillation.

Barriers to patients eligible for screening investigations and insertion of primary prevention implantable cardioverter defibrillators.

AIMS: Primary prevention (PP) implantable cardioverter defibrillator (ICD) implant rates in the UK are below national targets and barriers to this are not well known. This study was designed to identify the stages along the referral pathway from general to specialist care that eligible patients reach and what proportion eventually receive an ICD. METHODS AND RESULTS: A single institution database search was performed to identify all adults with severe left ventricular systolic dysfunction (left ventricular ejection fraction, LVEF≤35%), documented in the calendar year 2007. Medical records were assessed for age, heart failure aetiology, QRS duration, evidence of non-sustained ventricular tachycardia on Holter, electrophysiological study, and records of consultation with general physicians, cardiologists, and electrophysiologists (EPs) and reference to assessment of risk of sudden cardiac death and the role of ICD implantation. Three hundred twenty-six patients with LVEF ≤ 35% were identified from three electronic databases. Mean age was 72 ± 12 years. Seventy-two patients satisfied UK National Institute for Clinical Excellence guidelines for PP ICD implantation and 63 eligible for further screening. Of the 135 patients, 76 (56%) patients reviewed by a general cardiologist did not receive ICD implantation or referral for further assessment. When offered, ICD acceptance rate was high (35 vs. 3 patients who refused ICD). After seeing an EP, 8 of 47 (17%) patients were not offered ICD or further screening. The average age was 66.5 ± 6.2 years and no patient greater than 80 years had a PP ICD. CONCLUSIONS: Failure to refer from the general physician to cardiology and from the cardiologist to EP is the principle reason for low PP ICD implant rates among eligible patients in the UK.

Validation of coronary sinus activation pattern during left atrial appendage pacing for beat-to-beat assessment of mitral isthmus conduction/block.

INTRODUCTION: Mitral isthmus (MI) ablation for treatment of perimitral flutter is often performed during atrial fibrillation (AF) ablation but is technically challenging. Traditional assessment of MI conduction by left atrial activation mapping while pacing from either side of the line is time-consuming, and cannot be performed during ongoing ablation. Analysis of the coronary sinus (CS) activation pattern during left atrial appendage (LAA) pacing has been proposed as a simpler technique for evaluating MI conduction, enabling beat-to-beat assessment of conduction during ablation procedures and prompt identification of conduction block. METHODS: MI conduction was evaluated in 40 patients undergoing MI ablation using both: ((i) endocardial activation mapping and other standard techniques, and (ii) CS activation pattern during LAA pacing (change from distal-to-proximal activation to proximal-to-distal taken to signify the onset of MI block). RESULTS: CS activation sequence was used to assess conduction in 39 of 40 patients (unable to advance CS catheter distally in one case). MI block was achieved in 36 of 39 cases. The mean MI conduction time (LAA to distal CS) was 92.9 +/- 25.9 ms prior to ablation and 178.4 +/- 59.9 ms after MI block was confirmed. The mean step-out in conduction time at point of block was 80.8 +/- 40.6 ms. In all individuals in whom CS activation indicated block, there was concordance with endocardial activation, differential pacing and, where detectable, presence of widely split double potentials. CS lesions were required to achieve block in 24 of 36 (67%) successful cases. Radiofrequency application time and procedure time to achieve MI block were 10.8 +/- 6.0 minutes and 21.1 +/- 15.3 minutes, respectively.

A randomized trial to compare atrial fibrillation ablation using a steerable vs. a non-steerable sheath.

AIMS: Catheter positioning and stability are recognized challenges in catheter ablation of atrial fibrillation (AF). This prospective randomized study assessed whether routinely using a steerable sheath affects procedure outcomes. METHODS AND RESULTS: Fifty-six AF patients were randomized to ablation using either an Agilis NXT (St Jude Medical, St Paul, MN, USA) steerable sheath or a fixed-curve Mullins sheath (Cook Medical Inc., Bloomington, IN, USA) for the ablation catheter. A mapping system with CT integration was used to isolate the pulmonary veins (PVs) in pairs and further ablation performed if AF persisted. There was no significant difference in time to gain trans-septal access, CT registration time, time to isolate PVs, fluoroscopy time for PV isolation, total procedure time, or total fluoroscopy time. A learning curve was seen for the steerable sheath, and after correcting for this, CT registration time and right PV isolation were quicker in this group. One patient crossed over from fixed-curve to steerable. Acute, 3-, and 6-month single procedure success were similar in both groups. CONCLUSION: Allowing for the usage learning curve, a steerable sheath reduced time for some elements of AF ablation. Although this did not result in improved success, it may be useful for inexperienced operators, but at increased procedure cost.

Accuracy of manual QRS duration assessment: its importance in patient selection for cardiac resynchronization and implantable cardioverter defibrillator therapy.

AIMS: Patients with left ventricular systolic dysfunction and electrocardiographic QRS duration (QRSd) >or=120 ms may obtain symptomatic and prognostic benefits from cardiac resynchronization therapy (CRT). However, clinical trials do not describe the methods used to measure QRSd. We investigated the effect of electrocardiogram (ECG) display format and paper speed on the accuracy of manual QRSd assessment and concordance of manual QRSd with computer-calculated mean and maximal QRSd. METHODS AND RESULTS: Six cardiologists undertook QRSd measurements on ECGs, with computer-calculated mean QRSd close to 120 ms. Display formats were 12-lead, 6-limb, and 6-precordial leads, each at 25 and 50 mm/s. When the computer-calculated mean was used to define QRSd, manual assessment demonstrated 97 and 83% concordance at categorizing QRSd as < and >or=120 ms, respectively. Using the computer-calculated maximal QRSd, manual assessment demonstrated 83% concordance when QRSd was <120 ms and 19% concordance when QRSd was >or=120 ms. The six-precordial lead format demonstrated significantly less intra and inter-observer variabilities than the 12-lead, but this did not improve concordance rates. CONCLUSION: Manual QRSd assessments demonstrate significant variability, and concordance with computer-calculated measurement depends on whether QRSd is defined as the mean or maximal value. Consensus is required both on the most appropriate definition of QRSd and its measurement.

Impairment of coronary flow reserve in aortic stenosis.

Coronary flow reserve (CFR) is markedly reduced in patients with severe aortic valve stenosis (AS), but the exact mechanisms underlying this impairment of CFR in AS remain unclear. Reduced CFR is the key mechanism leading to myocardial ischemia symptoms and adverse outcomes in AS patients. The objective of this study was to develop an explicit mathematical model formulated with a limited number of parameters that describes the effect of AS on left coronary inflow patterns and CFR. We combined the mathematical V(3) (ventricular-valvular-vascular) model with a new lumped-parameter model of coronary inflow. One thousand Monte-Carlo computational simulations with AS graded from mild up to very severe were performed within a wide range of physiological conditions. There was a good agreement between the CFR values computed with this new model and those measured in 24 patients with isolated AS (r = 0.77, P < 10(-4)). A global sensitivity analysis showed that the valve effective orifice area (EOA) was the major physiological determinant of CFR (total sensitivity index = 0.87). CFR was markedly reduced when AS became severe, i.e., when EOA was <1.0 cm(2), and was generally exhausted when the EOA was <0.5-0.6 cm(2). The reduction of CFR that is associated with AS can be explained by the concomitance of 1) reduced myocardial supply as a result of decreased coronary perfusion pressure, and 2) increased myocardial metabolic demand as a result of increased left ventricular workload.

Assessment of left ventricular mass regression after aortic valve replacement--cardiovascular magnetic resonance versus M-mode echocardiography.

OBJECTIVE: In patients with aortic valve disease, the presence of left ventricular hypertrophy (LVH) carries a significant risk of adverse cardiovascular events. Regression of hypertrophy after aortic valve replacement (AVR) is associated with a reduction in risk. In general, M-mode echocardiography has been used for quantitative assessment of left ventricular mass (LVM) and regression, but this technique is believed to have limitations from which cardiovascular magnetic resonance (CMR) does not suffer. The objective of this study therefore was to determine whether quantitative assessment of LVM and regression after AVR using the two techniques was comparable. METHODS: Thirty-nine patients with aortic valve disease were studied before and 1 year after AVR. Transthoracic M-mode echocardiography and four different formulae were used to calculate left ventricular mass index (LVMI), and then compared with CMR measurements. RESULTS: Overall, correlation between the techniques for single measurement of LVMI was moderate (r-values from 0.64 to 0.69), with a tendency for overestimation by echocardiography; there was no agreement in degree of regression (r-values from 0.004 to 0.18). The Bland-Altman limits of agreement ranged from 85 to 131% for single measurement of LVMI, and 328-470% for regression. The change in LVMI with CMR was 43+/-28 g/m2, vs. 27 to 54+/-19 to 41 g/m2 using echocardiography. CONCLUSIONS: M-mode echocardiography does not provide reliable quantification of regression of LVH in individuals, and for accurate measurement CMR is superior. The use of CMR in future studies may reduce costs since fewer subjects are needed to accurately detect significant changes in LVMI after AVR.