Catheter ablation of atrial fibrillation: a treatment frontier.
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Atrial Fibrillation↗
Biomedical subjects
Albert L Waldo
Publications and source records attributed to Albert L Waldo.
A perspective on antiarrhythmic drug therapy to treat atrial fibrillation: there remains an unmet need.
Because presently available antiarrhythmic drugs are neither as highly efficacious nor as safe as desirable for the prevention of atrial fibrillation (AF), rate control-versus-rhythm control trials for the treatment of AF were evaluated. They demonstrated that rate control is not simply a therapeutic fallback option if rhythm control should fail, but rather, it is a legitimate primary therapeutic option. Nevertheless, there remain many reasons to consider maintenance of sinus rhythm (rhythm control) over AF (rate control) if only there were antiarrhythmic agents that could provide this treatment more effectively and safely. In fact, an important analysis of the AFFIRM trial data indicated that rhythm control offers a significant survival advantage over rate control if it could be safely achieved. Therein lie an important clinical dilemma and an unmet need. Sinus rhythm is good, but we need better ways to maintain it effectively and safely.
Anti-Arrhythmia Agents↗
Use of fast fourier transform analysis of atrial electrograms for rapid characterization of atrial activation-implications for delineating possible mechanisms of atrial tachyarrhythmias.
INTRODUCTION: Different analysis techniques have been developed to help understand and characterize the mechanisms responsible for atrial arrhythmias. We tested the hypothesis that Fast Fourier Transform (FFT) analysis of recorded atrial electrograms (AEGs) will rapidly and accurately identify regular and irregular patterns of atrial activation, and, thereby, may provide evidence suggestive of underlying mechanisms of atrial tachyarrhythmias. METHODS AND RESULTS: During induced atrial tachyarrhythmias in both the canine sterile pericarditis model and canine rapid ventricular pacing-induced congestive heart failure model; 380-404 AEGs were recorded simultaneously from epicardial electrodes on both atria. From AEGs, atrial activation sequences were determined during atrial flutter (AFL), focal atrial tachycardia (AT), and atrial fibrillation (AF). Four-second recording segments of each AEG were subjected to FFT analysis. Frequencies found during FFT analyses in all studies precisely corresponded to the cycle lengths of the AEGs. In AFL and AT, one dominant frequency peak was found throughout both atria. In AF due to multiple unstable reentry circuits, multiple and broad frequency peaks were found in both atria. In AF due to a stable rapid rhythm (driver) in the left atrium with fibrillatory conduction to the rest of the atria, one dominant frequency peak in areas with 1:1 conduction from the driver, and multiple and/or broad frequency peaks in areas with fibrillatory conduction produced by the driver were found. Computation time for all FFT analyses took <5 minutes. CONCLUSION: FFT analysis accurately and rapidly identifies global atrial activation patterns during AFL, AT, and AF, thereby assisting in determining arrhythmia mechanisms.
Animals↗
Hospitalized patients with atrial fibrillation and a high risk of stroke are not being provided with adequate anticoagulation.
OBJECTIVES: The purpose of this study was to determine both treatment gaps and predictors of warfarin use in atrial fibrillation (AF) patients enrolled in a national multicenter study. BACKGROUND: The National Anticoagulation Benchmark Outcomes Report (NABOR) is a performance improvement program designed to benchmark anticoagulation prophylaxis, treatment, and outcomes among participating hospitals. METHODS: A retrospective cohort study of inpatients was performed at 21 teaching, 13 community, and 4 Veterans Administration hospitals in the U.S. Patients with an ICD-9-CM code for AF (427.31) were randomly selected. RESULTS: Among the 945 patients studied, the mean age was 71.5 (+/- 13.5) years; 43% were >75 years of age, 54.5% were men, and 67% had a history of hypertension. Most (86%) had factors that stratified them as at high risk of stroke, and only 55% of those received warfarin. Neither warfarin nor aspirin were prescribed in 21% of high-risk patients, including 18% of those with a previous stroke, transient ischemic attack, or systemic embolic event. Age >80 years (p = 0.008) and perceived bleeding risk (p = 0.022) were negative predictors of warfarin use. Persistent/permanent AF (p < 0.001) and history of stroke, transient ischemic attack, or systemic embolus (p = 0.014) were positive predictors of warfarin use, whereas high-risk stratification was not. CONCLUSIONS: This study confirms the under-use of warfarin, but also adds to published reports in several regards. It showed that risk stratification, the guidepost for treatment in international guidelines, had little effect on warfarin use, and that age >80 years and AF classification (permanent/persistent) are factors that influence warfarin use.
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Antithrombotic therapy practices in US hospitals in an era of practice guidelines.
BACKGROUND: Antithrombotic therapy is efficacious for the prevention of thromboembolic disease, but it necessitates careful risk-benefit assessment. METHODS: Antithrombotic therapy data were retrospectively collected from inpatient medical records at 38 US hospitals. Patients treated for atrial fibrillation, acute myocardial infarction, deep vein thrombosis, or pulmonary embolism and patients given prophylaxis for total knee replacement, total hip replacement, or hip fracture surgery between July 1, 2000, and June 30, 2003, were randomly selected. RESULTS: The medical records of 3778 patients (53.3% men) were included. The mean patient age was 66.1 years. Of patients with atrial fibrillation at high risk for stroke, only 54.7% received warfarin sodium, and 20.6% received neither aspirin nor warfarin. Of patients with acute myocardial infarction, only 75.5% received aspirin on hospital arrival. After orthopedic surgery procedures, only 85.6% of patients received prophylaxis with a parenteral anticoagulant agent or warfarin. In 49.4% of patients with deep vein thrombosis, pulmonary embolism, or both, unfractionated or low-molecular-weight heparin use was discontinued before an international normalized ratio of 2.0 or greater was achieved for 2 consecutive days. Patients with deep vein thrombosis or pulmonary embolism were rarely discharged from the hospital with bridge therapy (an injectable anticoagulant agent plus warfarin), although the length of hospitalization was significantly shorter than if discharged taking warfarin alone (4.0 vs 8.1 days; P < .001). CONCLUSIONS: A significant percentage of hospitalized patients do not receive adequate antithrombotic therapy for the primary and secondary prevention of thromboembolic disease.
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Occurrence and characteristics of stroke events in the Atrial Fibrillation Follow-up Investigation of Sinus Rhythm Management (AFFIRM) study.
BACKGROUND: Atrial fibrillation (AF) is a risk factor for stroke, especially when accompanied by other high-risk cardiovascular predictors. The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Study was a multicenter comparison of high-risk patients with AF who were randomized to either a sinus rhythm control or a rate control strategy. METHODS: Physicians were encouraged to continue anticoagulation therapy for their patients. Patients in the sinus rhythm control group could stop warfarin sodium therapy after 4 (preferably a minimum of 12) weeks if they maintained sinus rhythm while receiving an antiarrhythmic drug. RESULTS: The AFFIRM Study enrolled 4060 patients. Mortality was the same in both groups. Two hundred eleven patients (8.2%) had a stroke event. Ischemic stroke occurred in 157 patients (6.3%), primary intraparenchymal hemorrhage in 34 (1.2%), and subdural or subarachnoid hemorrhage in 24 (0.8%). The most frequently determined ischemic stroke mechanism was cardioembolic (35/71 [49%]). Treatment assignment had no significant effect on the occurrence of ischemic stroke. Patients in AF at the time of the stroke event had a 60% greater chance of having an ischemic stroke, and those taking warfarin at the time of follow-up had a 69% decrease in the risk of having an ischemic stroke. CONCLUSIONS: In the AFFIRM Study, stroke rates were not significantly different in the rate control and sinus rhythm control arms. However, several clinical and therapeutic variables were associated with stroke risk. In patients with a history of AF at high risk for stroke or death, the presence of AF increases the risk of having a stroke, and warfarin therapy reduces the risk of having a stroke. The beneficial effect of warfarin therapy is seen not only in patients in AF but also in patients with a history of AF but who presumably remain in sinus rhythm.
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Comparative effects of single- and linear triple-site rapid bipolar pacing on atrial activation in canine models.
Nonuniform conduction may cause block and/or delay, thereby providing a substrate for the onset and maintenance of reentrant atrial arrhythmias. We tested the hypothesis that linear triple-site, bipolar, rapid pacing (LTSBRP) of the right atrium generates more uniform wave-front propagation compared with single-site, bipolar, rapid pacing (SSBRP), thereby reducing and/or eliminating conduction block and delay that is otherwise present. Five dogs with pericarditis and three normal dogs were studied. Three plunge-wire electrode pairs were placed 5-7 mm apart in both perpendicular and parallel configurations at the superior aspect of the crista terminalis and were used to pace at 200- and 300-ms cycle lengths for < or =6 s. During pacing, 380 electrograms were recorded simultaneously from electrode arrays placed epicardially on the atria, which produced activation sequence maps for each pacing episode. Local conduction-velocity vectors were computed for each site during each episode. Histograms of absolute velocity vector angles from the x-axis (of the crista terminalis) were plotted to assess uniformity of wave-front propagation, and the magnitude of each vector was computed to assess the local speed. LTSBRP showed 1) more uniform linear activation wave fronts compared with SSBRP, 2) velocity vectors with a more uniform magnitude and direction compared with SSBRP, 3) a predominant absolute velocity vector angle vs. a scattered angle distribution with SSBRP, and 4) shorter right atrial activation time and faster mean epicardial speed than SSBRP for each pacing cycle length. LTSBRP created a more uniform wave-front propagation with less or no conduction block and/or delay compared with SSBRP.
Animals↗
Role of permanent pacing to prevent atrial fibrillation: science advisory from the American Heart Association Council on Clinical Cardiology (Subcommittee on Electrocardiography and Arrhythmias) and the Quality of Care and Outcomes Research Interdisciplinary Working Group, in collaboration with the Heart Rhythm Society.
This advisory summarizes the current database on pacing modalities and algorithms used to prevent and terminate atrial fibrillation (AF). On the basis of the evidence indicating that ventricular pacing is associated with a higher incidence of AF in patients with sinus node dysfunction, a patient who has a history of AF and needs a pacemaker for bradycardia should receive a physiological pacemaker (dual chamber or atrial) rather than a single-chamber ventricular pacemaker. For patients who need a dual-chamber pacemaker, efforts should be made to program the device to minimize the amount of ventricular pacing when atrioventricular conduction is intact. Many pacemakers and implantable defibrillators have features designed to prevent AF and to terminate AF with rapid atrial pacing. The evidence to support their use is limited, although these algorithms appear to be safe and usually add little additional cost. For patients who have a bradycardia indication for pacing and also have AF, no consistent data from large randomized trials support the use of alternative single-site atrial pacing, multisite right atrial pacing, biatrial pacing, overdrive pacing, or antitachycardia atrial pacing. Even fewer data support the use of atrial pacing in the management of AF in patients without symptomatic bradycardia. At present, permanent pacing to prevent AF is not indicated; however, additional studies are ongoing, which will help to clarify the role of permanent pacing for AF.
Algorithms↗
Clinical factors that influence response to treatment strategies in atrial fibrillation: the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study.
BACKGROUND: The AFFIRM Study was a randomized multicenter comparison of 2 treatment strategies, rate-control versus rhythm-control, in high-risk patients with atrial fibrillation (AF). The primary outcome of the trial showed no overall difference in survival between strategies. However, there may be important patient subgroups for which there are identifiable differences in outcome with 1 of the 2 strategies. METHODS AND RESULTS: Subgroups that were prespecified for analysis from the main AFFIRM Study were age, sex, coronary artery disease (CAD), hypertension, congestive heart failure (CHF), left ventricular ejection fraction (LVEF), rhythm at randomization, first episode of AF, and duration of the qualifying episode of AF. Baseline characteristics were analyzed for each subgroup. Adjusted hazard ratios for each subgroup and for each stratum were generated using Cox models, and these models were used to determine whether treatment strategy affected overall survival differentially by subgroup. Adjusted survival was worse for patients > or =65 years and for patients with a history of CHF, CAD, or an abnormal LVEF. In the adjusted analyses, the effect of treatment strategy was similar within all of the prespecified subgroups. When each subgroup stratum was analyzed separately, patients > or =65 years and patients without a history of CHF had significantly better outcome with rate-control therapy (each P < .01). CONCLUSIONS: Overall, treatment effect for rate control versus rhythm control was the same within each subgroup. However, certain selected patient categories may have better survival with one particular strategy for management of AF.
Age Factors↗
Factors affecting bleeding risk during anticoagulant therapy in patients with atrial fibrillation: observations from the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study.
BACKGROUND: Stroke and systemic thromboembolism are serious problems for patients with atrial fibrillation (AF), but their incidence can be substantially reduced by appropriate anticoagulation. Bleeding is the major complication of anticoagulant treatment, and the relative risks for bleeding vs stroke must be considered when starting anticoagulation. METHODS: The AFFIRM trial included patients with AF and at least one risk factor for stroke, randomly assigning them to either a rate-control or rhythm-control strategy. All patients were initially treated with warfarin. The incidence of protocol-defined major and minor bleeding was documented during follow-up. Variables associated with bleeding were determined using a Cox proportional hazards model, using baseline and time-dependent covariates. RESULTS: The 4060 patients in the AFFIRM trial were followed for an average of 3.5 years. Major bleeding occurred in 260 patients, an annual incidence of approximately 2% per year, with no significant difference between the rate-control and rhythm-control groups. Increased age, heart failure, hepatic or renal disease, diabetes, first AF episode, warfarin use, and aspirin use were significantly associated with major bleeding. Minor bleeding was common in both treatment arms, with 738 patients reporting this problem in one or more visits. CONCLUSIONS: Bleeding is a significant problem that complicates management of patients with AF. Risk factors for bleeding can be identified, and knowledge of these risk factors can be used to plan therapy.
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Electrocardiographic imaging (ECGI), a novel diagnostic modality used for mapping of focal left ventricular tachycardia in a young athlete.
We report the first clinical application of electrocardiographic imaging (ECGI), a new, noninvasive imaging modality for arrhythmias, in an athlete with focal ventricular tachycardia (VT) originating from a left ventricular (LV) diverticulum. A reconstructed map of the epicardial activation sequence during a single premature ventricular complex (PVC) of an identical QRS morphology to the clinical VT, generated from 224-electrode body surface ECGs and a chest CT (ECGI), localized the PVC to the site of the diverticulum. This correlated with subsequent maps obtained using standard techniques. We describe the first case that used ECGI to guide diagnosis and therapy of a clinical tachyarrhythmia.
Adult↗
Treatment of venous thromboembolism: adherence to guidelines and impact of physician knowledge, attitudes, and beliefs.
OBJECTIVES: To assess the treatment of venous thromboembolism (VTE) in hospitalized patients enrolled in a national, multicenter database. METHODS: This was a retrospective, cohort study that randomly selected VTE patients from 38 academic/teaching, community, and Veterans Administration (VA) hospitals. The study included a physician survey component. The patients selected were those treated between January 2002 and June 2003 who had an ICD-9-CM code for pulmonary embolus (PE), deep vein thrombosis (DVT), or pregnancy-related PE or DVT. RESULTS: The study included 939 patients: 52.7% with DVT, 28.4% with PE, and 18.8% with PE and DVT. Mean age was 59.5 years. Risk factors included obesity (body mass index > 30) in 30.1%, history of VTE in 28.0%, malignancy in 27.4%, surgery in 21.1%, and immobility in 18.5%. Only 56.1% of patients were treated with low-molecular-weight heparin (LMWH). Bridging from LMWH or unfractionated heparin (UFH) to warfarin was completed during hospitalization in 486 (68.6%), but only 246 (50.6%) had an international normalized ratio (INR) > or = 2 for 48 hours before discontinuation of the injectable anticoagulant. Length of stay in patients discharged on bridge therapy was 4.0 +/- 3.7 days vs 8.1 +/- 5.8 days for patients discharged on warfarin therapy (P < .001). Ninety-two (10.1%) patients were discharged with neither oral nor injectable anticoagulation and had a mean duration of treatment of only 10.6 +/- 16.2 days. Of 245 physicians surveyed from participating hospitals, 84% and 53%, respectively, indicated that LMWH was their preferred agent for treatment of DVT and treatment of PE. With regard to warfarin, 30% did not believe it was necessary to have a therapeutic INR for > or = 2 days before discontinuing LMWH or UFH, and 27% responded that it was necessary to keep DVT patients in the hospital until they were therapeutic. CONCLUSIONS: In this cross-section of United States hospitals, lower than anticipated use of LMWH, insufficient bridging from UFH or LMWH to warfarin, and continuation of anticoagulation after hospitalization were all problems discovered with the treatment of VTE. Physician knowledge, attitudes, and beliefs are partially responsible for the gap between actual practice and international guidelines. These results suggest that hospitals should evaluate their adherence to international VTE treatment guidelines and develop strategies to optimize antithrombotic therapy.
Anticoagulants↗
Epicardial mapping of chronic atrial fibrillation in patients: preliminary observations.
BACKGROUND: The mechanisms of chronic atrial fibrillation (AF) are not well understood. We performed epicardial mapping of chronic AF in patients undergoing open heart surgery to test the hypothesis that chronic AF is due to a left atrial "driver" with a regular, short cycle length, resulting in fibrillatory conduction to the rest of the atria. METHODS AND RESULTS: Nine patients with chronic AF (1 month to >15 years' duration) were studied at open heart surgery, 8 before and 1 during cardiopulmonary bypass. During AF, atrial electrograms (AEGs) were recorded for 1 to 5 minutes from 404 epicardial electrodes arranged in bipoles along with ECG lead II or ventricular electrogram. Four-second segments of each bipolar AEG were also subjected to fast Fourier transform analysis. Two patterns of atrial activation were present during AF. In pattern 1 (7/9 patients), AEGs from parts of the atria demonstrated a short, regular cycle length with identical beat-to-beat morphology, and the rest of the atria were activated irregularly, and AEGs that demonstrated constant morphology and cycle length were localized to parts of the left atria (5/7), the right atria (1/7), or both atria (1/7). In pattern 2 (2/9 patients), AEGs showed no evidence of regular activation or constant morphology. CONCLUSIONS: In 9 patients with chronic AF, the commonest recorded AEG pattern showed an area of regular, rapid rhythm, consistent with the possibility that a driver causing fibrillatory conduction is one mechanism of AF in these patients.
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Relationships between sinus rhythm, treatment, and survival in the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) Study.
BACKGROUND: The AFFIRM Study showed that treatment of patients with atrial fibrillation and a high risk for stroke or death with a rhythm-control strategy offered no survival advantage over a rate-control strategy in an intention-to-treat analysis. This article reports an "on-treatment" analysis of the relationship of survival to cardiac rhythm and treatment as they changed over time. METHODS AND RESULTS: Modeling techniques were used to determine the relationships among survival, baseline clinical variables, and time-dependent variables. The following baseline variables were significantly associated with an increased risk of death: increasing age, coronary artery disease, congestive heart failure, diabetes, stroke or transient ischemic attack, smoking, left ventricular dysfunction, and mitral regurgitation. Among the time-dependent variables, the presence of sinus rhythm (SR) was associated with a lower risk of death, as was warfarin use. Antiarrhythmic drugs (AADs) were associated with increased mortality only after adjustment for the presence of SR. Consistent with the original intention-to-treat analysis, AADs were no longer associated with mortality when SR was removed from the model. CONCLUSIONS: Warfarin use improves survival. SR is either an important determinant of survival or a marker for other factors associated with survival that were not recorded, determined, or included in the survival model. Currently available AADs are not associated with improved survival, which suggests that any beneficial antiarrhythmic effects of AADs are offset by their adverse effects. If an effective method for maintaining SR with fewer adverse effects were available, it might be beneficial.
Adrenergic beta-Antagonists↗
The impact of asymptomatic atrial fibrillation.
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Atrial Fibrillation↗
A perspective on rate control in the treatment of atrial fibrillation.
Until recently, the standard approach to therapy of atrial fibrillation (AF) in most cases was restoration and maintenance of sinus rhythm (rhythm control). Although difficult to accomplish, and associated with potential serious adverse effects of antiarrhythmic agents, this therapeutic approach was influenced by the belief that rhythm control was associated with better survival, fewer symptoms, better exercise tolerance, lower risk of stroke, better quality of life, and absence of need for long-term anticoagulation. However, four clinical trials comparing rate control with rhythm control have failed to demonstrate these advantages, indicating that rate control should be considered a legitimate primary therapeutic option, particularly in patients at risk for stroke. Pursuit of rate or rhythm control should be decided on a case-by-case basis.
Anti-Arrhythmia Agents↗
From bedside to bench: entrainment and other stories.
The concepts of transient entrainment of reentrant rhythms started with studies of overdrive pacing of atrial flutter (AFL) in patients in the immediate period after open heart surgery. Initial studies demonstrated the need to achieve a critical pacing rate and a critical duration of pacing at the critical pacing rate to interrupt AFL. Further pacing studies of AFL, ventricular tachycardia, atrioventricular (AV) reentrant tachycardia, AV nodal reentrant tachycardia, and atrial tachycardia refined the understanding of what occurs during overdrive pacing of reentrant tachycardias, and permitted a mechanistic understanding of transient entrainment as continuous resetting of a reentrant tachycardia to a pacing rate that is faster than the rate of the tachycardia, but which fails to interrupt it. The demonstration of transient entrainment of a tachycardia provides a reliable clinical tool to establish the presence of a reentrant rhythm. Moreover, the principles of entrainment have also been applied clinically to assist in effective application of antitachycardia pacing and catheter ablation techniques.
Arrhythmias, Cardiac↗