Factors associated with 'caregiver burden' for atrial fibrillation patients.

BACKGROUND: The burden on caregivers providing support to atrial fibrillation (AF) patients has not been evaluated. OBJECTIVE: To examine the interrelationship between unpaid caregiver, patient and thromboprophylaxis characteristics and caregiver burden in AF. METHODS: We conducted a cross-sectional survey study of AF patient-caregiver dyads recruited from cardiology clinics at an urban teaching hospital. Eligible patients had a diagnosis of AF, received thromboprophylaxis to prevent stroke, lived in the community and had an adult, unpaid, English-speaking caregiver. Hierarchical multivariate regression was used to evaluate the association between caregiver, patient and thromboprophylaxis characteristics and caregiver burden as measured by the 'Caregiver Reaction Assessment' (CRA). RESULTS: Eighty patient-caregiver dyads were surveyed. The mean ± standard deviation scores for each CRA domain were 'Disrupted schedule' (2.4 ± 1.0), 'Financial problems' (2.1 ± 0.8), 'Lack of family support' (1.9 ± 0.7), 'Health problems' (1.9 ± 0.7) and 'Self-esteem' (0.9 ± 0.5). Significantly greater caregiver burden due to 'Disrupted schedule' was seen in those spending > 4 h/week providing care and when caring for frail, sick or disabled patients, with higher CHADS2 scores and requiring help with their medications. 'Financial problems' burden scores were significantly associated with caring for frail patients and those requiring more frequent office follow-up. 'Lack of family support' scores were inversely associated with having somebody else to help provide care and increased as patients CHADS2 score increased. Lower 'Health problem' burden scores were associated with female gender and higher scores with the need to spend > 4 h/week providing care. CONCLUSION: The greatest burden to caregivers of AF patients occurs due to schedule disruption.

Effect of pharmacological therapies for stroke prevention on major gastrointestinal bleeding in patients with atrial fibrillation.

Various antiplatelet and anticoagulation options are available for stroke prevention in patients with atrial fibrillation (AF). Currently, it is unclear whether these agents differ in their propensity to cause major gastrointestinal bleeding (MGIB). To our knowledge, no systematic evaluation of MGIB rates from randomised controlled trials (RCTs) of pharmacological stroke prevention in patients with AF has been conducted. Two independent investigators conducted systematic literature searches in MEDLINE and CENTRAL from the earliest possible date through November 2010. To be included, RCTs had to evaluate an adult population with AF or flutter and report data on the incidence of MGIB. Peto's odds ratios (ORs) with associated 95% confidence intervals (CIs) were calculated for all possible pair-wise comparisons of pharmacological stroke prevention alternatives. A total of 16 unique trials (n = 42,983) met inclusion criteria. The reported incidence of MGIB in placebo or control arms of identified trials was as high as 1.5%. Upon pair-wise meta-analysis of different pharmacological strategies, adjusted-dose vitamin K antagonists (VKAs) were found to be associated with a higher odds of MGIB compared with placebo/control (OR 3.21, 95% CI 1.32-7.82) and aspirin (or triflusal or indobufen) (OR 1.92, 95% CI 1.08-3.41). The addition of aspirin (or triflusal) to an adjusted-dose VKA resulted in greater odds of MGIB compared with aspirin alone (OR 4.72, 95% CI 1.35-16.49) and adjusted-dose VKA alone (OR 2.66, 95% CI 1.05-6.74). While aspirin increased the odds of MBIG by 3.23-fold compared with placebo/control, this finding did not reach statistical significance. The combination of aspirin and clopidogrel increased patients' odds of MGIB compared with aspirin alone (OR 1.93, 95% CI 1.46-2.56). Dabigatran was associated with a 30% increased odds of MGIB compared with adjusted-dose VKA (OR 1.30, 95% CI 1.06-1.59); however, ximelagatran was not. Low-intensity VKA therapy, alone or in combination with aspirin, was not associated with increased odds of MGIB compared with any (active-) comparator. The MGIB is a concern for patients with AF receiving pharmacological stroke prevention. Current RCT data suggest that dabigatran and adjusted-dose VKA therapy are associated with the highest odds of MGIB. Aspirin was not found to increase patients' odds of MGIB; however, this finding may be the result of type 2 error. Dual therapy resulting from the addition of an antiplatelet agent was typically associated with further increased odds of MGIB compared with monotherapy.

Are the risk factors listed in warfarin prescribing information associated with anticoagulation-related bleeding? A systematic literature review.

Warfarin significantly reduces thromboembolic risk, but perceptions of associated bleeding risk limit its use. The evidence supporting the association between bleeding and individual patient risks factors is unclear. This systematic review aims to determine the strength of evidence supporting an accentuated bleeding risk when patients with risk factors listed in the warfarin prescribing information are prescribed the drug. A systematic literature search of MEDLINE and Cochrane CENTRAL was conducted to identify studies reporting multivariate relationships between prespecified covariates and the risk of bleeding in patients receiving warfarin. The prespecified covariates were identified based on patient characteristics for bleeding listed in the warfarin package insert. Each covariate was evaluated for its association with specific types of bleeding. The quality of individual evaluations was rated as 'good', 'fair' or 'poor' using methods consistent with those recommended by the Agency for Healthcare Research and Quality (AHRQ). Overall strength of evidence was determined using the Grading of Recommendations Assessment, Development (GRADE) criteria and categorised as 'insufficient', 'very low', 'low', 'moderate' or 'high'. Thirty-four studies, reporting 134 multivariate evaluations of the association between a covariate and bleeding risk were identified. The majority of evaluations had a low strength of evidence for the association between covariates and bleeding and none had a high strength of evidence. Malignancy and renal insufficiency were the only two covariates that had a moderate strength of evidence for their association with major and minor bleeding respectively. The associations between covariates listed in the warfarin prescribing information and increased bleeding risk are not well supported by the medical literature.

Lack of effect of statins on maintenance of normal sinus rhythm following electrical cardioversion of persistent atrial fibrillation.

Randomised controlled trials evaluating the effect of statin use on maintenance of normal sinus rhythm (NSR) after electrical cardioversion (ECV) of persistent atrial fibrillation (AF) have demonstrated conflicting results. However, many of these trials were of relatively small size and thus underpowered to adequately evaluate this end-point. The aim of this study was to conduct a meta analysis evaluating the effect of statin use on maintenance of NSR after ECV of persistent AF. Randomised controlled trials evaluating the use of statins to maintain NSR after ECV of AF were identified through a systematic search including Medline (1950 through December 2009), the Cochrane CENTRAL Register (4th quarter, 2009) and a manual review of references without any language restrictions. Pooled estimates of effect are reported as relative risks (RRs) with accompanying 95% confidence intervals (CIs) using a random-effects model. Four trials (n = 424; range: 48-212) were identified and subject to meta analysis. Evaluated statins included atorvastatin 10 and 80 mg and pravastatin 40 mg/day. Over a mean of 2.1 months (range: 1-3 months) statins did not increase the likelihood of maintaining NSR following ECV (RR, 1.12; 95%CI, 0.85-1.46) compared with control. Current evidence does not suggest that statins are associated with an increased probability of maintaining NSR following ECV of persistent AF.

Understanding heterogeneity in meta-analysis: the role of meta-regression.

BACKGROUND: Meta-regression has grown in popularity in recent years, paralleling the increasing numbers of systematic reviews and meta-analysis published in the biomedical literature. However, many clinicians and decision-makers may be unfamiliar with the underlying principles and assumptions made within meta-regression leading to incorrect interpretation of their results. AIMS: This paper reviews the appropriate use and interpretation of meta-regression in the medical literature, including cautions and caveats to its use. MATERIALS & METHODS: A literature search of MEDLINE (OVID) from 1966-February 2009 was conducted to identify literature relevant to the topic of heterogeneity and/or meta-regression in systematic reviews and meta-analysis. RESULTS: Meta-analysis, a statistical method of pooling data from studies included in a systematic review, is often compromised by heterogeneity of its results. This could include clinical, methodological or statistical heterogeneity. Meta-regression, said to be a merging of meta-analytic and linear regression principles, is a more sophisticated tool for exploring heterogeneity. It aims to discern whether a linear relationship exists between an outcome measure and on or more covariates. The associations found in a meta-regression should be considered hypothesis generating and not regarded as proof of causality. CONCLUSIONS: The current review will enable clinicians and healthcare decision-makers to appropriately interpret the results of meta-regression when used within the constructs of a systematic review, and be able to extend it to their clinical practice.

The impact of gender on survival amongst patients with implantable cardioverter defibrillators for primary prevention against sudden cardiac death.

BACKGROUND: Implantable cardioverter defibrillators (ICDs) are a life-saving therapy for many patients with cardiovascular disease at increased risk of fatal dysrhythmias. As men comprise the majority of the study population (67-92%) in clinical trials, the benefit to women is unknown. We performed a meta-analysis of primary prevention trials to evaluate the impact of ICDs in men and women on death from any cause. METHODS: Included trials met the following criteria: (i) randomized controlled trials versus standard of care, (ii) ICD used as primary prevention in a well-described protocol and (iii) data provided on risk of death from any cause for both male and female patients. RESULTS: Five clinical trials were included in this meta-analysis. The risk of death from any cause was significantly reduced by 26% in male patients who received ICD therapy compared to control, hazard ratio (HR) 0.74 (95% CI 0.60-0.91) but not amongst female patients, HR 0.81 (95% CI 0.60-1.09). As the COMPANION trial evaluated the combination of biventricular pacemaker with ICD therapy we conducted a separate analysis without the inclusion of this study. Male patients receiving ICD therapy demonstrated a similar 24% reduction in risk of death from any cause, HR 0.76 (95% CI 0.58-0.99) whilst female patients demonstrated a reduction of only 12%, HR 0.88 (95% CI 0.63-1.22). CONCLUSIONS: Unlike their male counterparts, females did not significantly benefit from ICD therapy and without concurrent biventricular pacing, appear only to achieve a nonsignificant 12% reduction in risk of death.

Changes in P-wave dispersion and P-wave duration after open heart surgery are associated with the peak incidence of atrial fibrillation.

BACKGROUND: Increased P-wave dispersion (P-disp) and maximum P-wave duration (P-max) predict the development of atrial fibrillation (AF) in the general population. The present study evaluates the time-dependent relationship of P-disp and P-max after open heart surgery. METHODS AND RESULTS: P-disp and P-max were measured in the perioperative period of open heart surgery (one day before surgery through postoperative day 4). Compared with the baseline, P-max decreased immediately after open heart surgery (112.63 +/- 7.4 ms vs 106.9 +/- 8.2 ms, P =.005). An increase in P-disp was observed between postoperative days 1 and 2 (37.5 +/- 6.8 ms vs 43.1 +/- 4.5 ms, P <.05), and postoperative days 1 and 3 (37.5 +/- 6.8 ms vs 44.1 +/- 6.6 ms, P <.05). There was also an increase in the P-max between postoperative day 1 and 3 (103 +/- 8.3 ms vs 110 +/- 7.7 ms, P <.05). CONCLUSIONS: Nonuniform atrial conduction (P-disp) is greatest on days 2 and 3 after open heart surgery, and the longest atrial conduction time (P-max) is greatest on day 3 after open heart surgery, findings that coincide with the time of greatest risk for AF. (Heart Lung((R)) 2001;30:466-71.)

A comparison of the QT and QTc dispersion among patients with sustained ventricular tachyarrhythmias and different etiologies of heart disease.

OBJECTIVES: To determine if etiology of heart disease is associated with differences in QT and QTc dispersion among patients with ventricular tachyarrhythmias. METHODS: This study was undertaken in 145 patients undergoing electrophysiological testing for sustained ventricular tachycardia or ventricular fibrillation. Patients were divided into groups based on etiology of heart disease determined by history, ECG, coronary angiography, and echocardiography. The groups included patients with: dilated cardiomyopathy (n = 29), myocardial infarction (n = 90), established coronary artery disease without a myocardial infarction (n = 11), or hypertension induced left ventricular hypertrophy (n = 15). The QT intervals on a 12--lead ECG were determined and Bazett's formula was used to derive the QTc intervals. The QT and QTc dispersion were determined by subtracting the shortest QT(c) interval from the longest on each 12-lead recording. RESULTS: The patients with dilated cardiomyopathy had significantly higher QT and QTc dispersion values as compared to any of the other three groups (P < 0.05 for both). No other differences in electrocardiographic variables were found between groups. CONCLUSIONS: In a group of patients with a history of ventricular tachycardia or ventricular fibrillation, QT and QTc dispersion are significantly greater among patients with dilated cardiomyopathy than for patients with a previous myocardial infarction, established coronary artery disease without a myocardial infarction, or hypertensive left ventricular hypertrophy.

Amiodarone in the new AHA guidelines for ventricular tachyarrhythmias.

OBJECTIVE: To delineate amiodarone's role in the new American Heart Association guidelines for ventricular tachyarrhythmias, review the literature that supports the use of amiodarone in ventricular tachyarrhythmias, describe the pharmaceutical properties of amiodarone and elucidate their clinical implications, and discuss the dosing, preparation, and administration of amiodarone. DATA SOURCES: A search of MEDLINE (1966-October 2000) database and EMBASE Drugs and Pharmacology database (1980-October 2000) was performed. References from published articles and tertiary references were used to gather additional data. DATA EXTRACTION: All articles were screened, and pertinent studies were identified and evaluated. DATA SYNTHESIS: Recent trials have demonstrated amiodarone's usefulness in the setting of ventricular tachyarrhythmias. Based on these investigations and contrary to past guidelines, amiodarone is included in the 2000 advanced cardiovascular life support guidelines as a possible agent for hemodynamically stable monomorphic ventricular tachycardia (VT), non-QT prolonged polymorphic VT, and ventricular fibrillation (VF)/pulseless VT. Although not specifically evaluated in the setting of hemodynamically stable monomorphic VT and non-QT prolonged polymorphic VT, investigations by the intravenous Amiodarone Multicenter Trial Group and other clinical trials make amiodarone an acceptable choice for these arrythmia categories. The results of the ARREST (Resuscitation of Refractory Sustained Ventricular Tachyarrhythmias) trial prove amiodarone to be the antiarrhythmic of choice for VF/pulseless VT. CONCLUSIONS: Amiodarone is classified as a IIb therapeutic intervention for all three arrhythmia categories, which makes it an acceptable, safe, and useful agent with fair to good evidence to support its use. In addition, amiodarone requires careful preparation and delivery to achieve safe and effective outcomes.

Hematologic and chemical changes observed during and after cardiac arrest in a canine model--a pilot study.

STUDY OBJECTIVE: To evaluate the effect of cardiac arrest and cardiopulmonary resuscitation (CPR) on blood chemistry in a canine model. DESIGN: Evaluative canine animal study. SETTING: Animal laboratory accredited by the Association for Assessment and Accreditation of Laboratory Animals. SUBJECTS: Twenty-six adult mongrel dogs. INTERVENTION: The dogs underwent an episode of induced fibrillatory cardiac arrest for 3 minutes followed by 10 minutes of standard CPR. Blood samples were taken at baseline (before cardiac arrest), after 10 minutes of ventricular fibrillation, and 10 minutes after successful resuscitation for determination of blood chemistries and hematologic parameters. MEASUREMENTS AND MAIN RESULTS: Glucose, blood urea nitrogen, serum creatinine, sodium, potassium, chloride, calcium, phosphorus, uric acid, alkaline phosphatase, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, protein, albumin, cholesterol, triglycerides, iron, white blood cell count, red blood cell count, and hematocrit were measured. Significant changes (p<0.05) in values obtained during CPR versus baseline values were noted for all laboratory parameters except blood urea nitrogen, chloride, and alkaline phosphatase. Eighteen dogs achieved return of spontaneous circulation (ROSC); their laboratory values were obtained after CPR. Significant changes (p<0.05) after ROSC compared with baseline were noted for all laboratory values except chloride, blood urea nitrogen, uric acid, alkaline phosphatase, glucose, potassium, calcium, triglycerides, iron, red blood cell count, and hematocrit. CONCLUSION: Results indicate that significant changes in blood chemistries and hematologic parameters occur during and after CPR. Clinicians should note these normal laboratory parameter changes when interpreting laboratory data in patients who experience cardiac arrest.

An evaluation of the change in electrocardiographic P-wave variables after acute caffeine ingestion in normal volunteers.

BACKGROUND: Caffeine's effect on supraventricular dysrhythmias is poorly understood, and establishing a marker to predict atrial fibrillation may help to explain supraventricular dysrhythmias caused by caffeine. OBJECTIVE: To evaluate the effects of caffeine (mean 6.1 mg/kg) on maximum P-wave duration and P-wave dispersion in normal volunteers. METHOD: A randomised, double-blind, placebo-controlled, crossover study in 10 healthy volunteers at least 17 years of age at the University of Connecticut. Participants abstained from caffeinated products for at least 2 days before study initiation and were randomly allocated on different days to receive placebo or caffeine 400 mg. For each of the study phases, a baseline 12-lead electrocardiogram (ECG) was performed and a subsequent 12-lead ECG was performed 3 h after ingesting the study drug. RESULTS: No significant changes were found within intra- or intergroup comparisons for any P-wave variables measured. CONCLUSION: Single dose caffeine (400 mg) does not affect average P-wave duration, maximum P-wave duration or P-wave dispersion in normal individuals.