Christopher M. Mullin

Percutaneous closure of the left atrial appendage versus warfarin therapy for prevention of stroke in patients with atrial fibrillation: a randomised non-inferiority trial

BACKGROUND In patients with non-valvular atrial fibrillation, embolic stroke is thought to be associated with left atrial appendage (LAA) thrombi. We assessed the efficacy and safety of percutaneous closure of the LAA for prevention of stroke compared with warfarin treatment in patients with atrial fibrillation. METHODS Adult patients with non-valvular atrial fibrillation were eligible for inclusion in this multicentre, randomised non-inferiority trial if they had at least one of the following: previous stroke or transient ischaemic attack, congestive heart failure, diabetes, hypertension, or were 75 years or older. 707 eligible patients were randomly assigned in a 2:1 ratio by computer-generated randomisation sequence to percutaneous closure of the LAA and subsequent discontinuation of warfarin (intervention; n=463) or to warfarin treatment with a target international normalised ratio between 2.0 and 3.0 (control; n=244). Efficacy was assessed by a primary composite endpoint of stroke, cardiovascular death, and systemic embolism. We selected a one-sided probability criterion of non-inferiority for the intervention of at least 97.5%, by use of a two-fold non-inferiority margin. Serious adverse events that constituted the primary endpoint for safety included major bleeding, pericardial effusion, and device embolisation. Analysis was by intention to treat. This study is registered with Clinicaltrials.gov, number NCT00129545. FINDINGS At 1065 patient-years of follow-up, the primary efficacy event rate was 3.0 per 100 patient-years (95% credible interval [CrI] 1.9-4.5) in the intervention group and 4.9 per 100 patient-years (2.8-7.1) in the control group (rate ratio [RR] 0.62, 95% CrI 0.35-1.25). The probability of non-inferiority of the intervention was more than 99.9%. Primary safety events were more frequent in the intervention group than in the control group (7.4 per 100 patient-years, 95% CrI 5.5-9.7, vs 4.4 per 100 patient-years, 95% CrI 2.5-6.7; RR 1.69, 1.01-3.19). INTERPRETATION The efficacy of percutaneous closure of the LAA with this device was non-inferior to that of warfarin therapy. Although there was a higher rate of adverse safety events in the intervention group than in the control group, events in the intervention group were mainly a result of periprocedural complications. Closure of the LAA might provide an alternative strategy to chronic warfarin therapy for stroke prophylaxis in patients with non-valvular atrial fibrillation. FUNDING Atritech.

Quality of Life Assessment in the Randomized PROTECT AF (Percutaneous Closure of the Left Atrial Appendage Versus Warfarin Therapy for Prevention of Stroke in Patients With Atrial Fibrillation) Trial of Patients at Risk for Stroke With Nonvalvular Atrial Fibrillation

OBJECTIVES This study sought to assess quality of life parameters in a subset of patients enrolled in the PROTECT AF (Percutaneous Closure of the Left Atrial Appendage Versus Warfarin Therapy for Prevention of Stroke in Patients With Atrial Fibrillation) trial. BACKGROUND The PROTECT AF (Percutaneous Closure of the Left Atrial Appendage Versus Warfarin Therapy for Prevention of Stroke in Patients With Atrial Fibrillation) trial demonstrated that in patients with nonvalvular atrial fibrillation (AF) and CHADS2 (congestive heart failure, hypertension, age, diabetes mellitus, and prior stroke, transient ischemic attack, or thromboembolism) score ≥1, a left atrial appendage closure device is noninferior to long-term warfarin for stroke prevention. Given this equivalency, quality of life (QOL) indicators are an important metric for evaluating these 2 different strategies. METHODS QOL using the Short-Form 12 Health Survey, version 2, measurement tool was obtained at baseline and 12 months in a subset of 547 patients in the PROTECT AF trial (361 device and 186 warfarin patients). The analysis cohort consisted of patients for whom either paired quality of life data were available after 12 months of follow-up or for patients who died. RESULTS With the device, the total physical score improved in 34.9% and was unchanged in 29.9% versus warfarin in whom 24.7% were improved and 31.7% were unchanged (p = 0.01). Mental health improvement occurred in 33.0% of the device group versus 22.6% in the warfarin group (p = 0.06). There was a significant improvement in QOL in patients randomized to device for total physical score, physical function, and in physical role limitation compared to control. There were significant differences in the change in total physical score among warfarin naive and not-warfarin naive subgroups in the device group compared to control, but larger gains were seen with the warfarin naive subgroup with a 12-month change of 1.3 ± 8.8 versus -3.6 ± 6.7 (p = 0.0004) device compared to warfarin. CONCLUSIONS Patients with nonvalvular AF at risk for stroke treated with left atrial appendage closure have favorable QOL changes at 12 months versus patients treated with warfarin. (WATCHMAN Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation [WATCHMAN PROTECT]; NCT00129545).

Newly detected atrial fibrillation in patients with an implantable cardioverter-defibrillator is a strong risk marker of increased mortality.

BACKGROUND Atrial fibrillation (AF) has been associated with higher rates of all-cause mortality in patients with heart failure (HF). The risk of newly detected AF in patients receiving implantable cardioverter-defibrillator (ICD) therapy is unknown. METHODS Newly detected AF was evaluated in all patients enrolled in the Inhibition of Unnecessary RV Pacing with AV Search Hysteresis in ICDs (INTRINSIC RV) study. The relationships between AF and endpoints (total mortality, ICD shocks, and HF hospitalizations) were analyzed retrospectively with proportional-hazards models. RESULTS At 108 centers, 1530 patients meeting VITALITY AVT ICD indications were followed for 12 months. Of these, 1356 (89%) had no history of AF at the time of implant. Patients with a history of AF had a higher prevalence of HF (52% vs. 36%; P <.01) and had higher rates of HF hospitalization (hazard ratio [HR] 2.14 [1.29-3.54], P <.01), death (HR 2.22 [1.26-3.92], P <.01), and any ICD shock (HR 1.75 [1.19-2.58], P <.01) compared with those with no history. AF incidence during the first 3 months of implant was available in 1317 (86%; 1170 no AF, 147 history of AF) patients. New-onset AF during the first 3 months of implant (45 of 1170, 4%) was associated with a significant increased risk of death (HR 2.86 [1.02-8.05], P = .05) but not with inappropriate ICD shock (HR 2.43 [0.87-6.75], P = .09) or HF hospitalization (HR 1.17 [0.28-4.82], P = .83). CONCLUSION History of AF at the time of ICD implant identifies additional risk of HF and death. Newly detected AF is associated with significantly higher rates of death. The relationship between newly detected AF and inappropriate ICD shock or HF hospitalization is uncertain and requires further study.

Changes in Heart Rate Variability, Quality of Life, and Activity in Cardiac Resynchronization Therapy Patients: Results of the HF-HRV Registry

Background: Cardiac resynchronization therapy (CRT) is a viable therapy in the treatment of heart failure (HF). Heart rate variability (HRV) is a prognostic marker of HF and mortality and is a sign of autonomic dysfunction. Acute improvements in measures of HRV have been demonstrated after CRT in small clinical studies. The purpose of the present study was to evaluate changes in HRV and patient outcomes over time and the relationship between these changes in a large generalized sample of patients who received CRT with defibrillator (CRT‐D).

Mechanical versus manual chest compressions in out-of-hospital cardiac arrest: a meta-analysis.

Objective:The objective of this study was to conduct a meta-analysis of literature examining rates of return of spontaneous circulation from load-distributing band and piston-driven chest compression devices as compared with manual cardiopulmonary resuscitation. Data Sources:Searches were conducted in MEDLINE, the ClinicalTrials.gov registry, and bibliographies on manufacturer websites for studies written in English. Study Selection:Selection criteria for the meta-analysis required that studies must be human controlled (randomized, historical, or case-control) investigations with confirmed out-of-hospital cases. Data Extraction:A total of 12 studies (load-distributing band cardiopulmonary resuscitation versus manual cardiopulmonary resuscitation = 8, piston-driven cardiopulmonary resuscitation versus manual cardiopulmonary resuscitation = 4), comprising a total of 6,538 subjects with 1,824 return of spontaneous circulation events, met the selection criteria. Data Synthesis:Random effects models were used to assess the relative effect of treatments on return of spontaneous circulation. Compared with manual cardiopulmonary resuscitation, load-distributing band cardiopulmonary resuscitation had significantly greater odds of return of spontaneous circulation (odds ratio, 1.62 [95% CI, 1.36, 1.92], p < 0.001). The treatment effect for piston-driven cardiopulmonary resuscitation was similar to manual cardiopulmonary resuscitation (odds ratio, 1.25 [95% CI, 0.92, 1.68];p = 0.151). The corresponding difference in percentages of return of spontaneous circulation rates from cardiopulmonary resuscitation was 8.3% for load-distributing band cardiopulmonary resuscitation and 5.2% for piston-driven cardiopulmonary resuscitation. Compared with manual cardiopulmonary resuscitation, combining both mechanical cardiopulmonary resuscitation devices produced a significant treatment effect in favor of higher odds of return of spontaneous circulation with mechanical cardiopulmonary resuscitation devices (odds ratio, 1.53 [95% CI, 1.32, 1.78], p < 0.001). Conclusion:The ability to achieve return of spontaneous circulation with mechanical chest compression devices is significantly improved when compared with manual chest compressions. In the case of load-distributing band cardiopulmonary resuscitation, it was superior to manual cardiopulmonary resuscitation as the odds of return of spontaneous circulation were over 1.6 times greater. The robustness of these findings should be tested in large randomized clinical trials.

Device diagnostics and long-term clinical outcome in patients receiving cardiac resynchronization therapy

AIMS This retrospective analysis sought to develop and validate a model using the measured diagnostic variables in cardiac resynchronization therapy (CRT) devices to predict mortality. METHODS AND RESULTS Data used in this analysis came from two CRT studies: Cardiac Resynchronization Therapy Registry Evaluating Patient Response with RENEWAL Family Devices (CRT RENEWAL) (n = 436) and Heart Failure-Heart Rate Variability (HF-HRV) (n = 838). Patients from CRT RENEWAL were used to create a model for risk of death using logistic regression and to create a scoring system that could be used to predict mortality. Results of both the logistic regression and the clinical risk score were validated in a cohort of patients from the HF-HRV study. Diagnostics significantly improved over time post-CRT implant (all P < 0.001) and were correlated with a trend of decreased risk of death. The regression model classified CRT RENEWAL patients into low (2.8%), moderate (6.9%), and high (13.8%) risk of death based on tertiles of their model predicted risk. The clinical risk score classified CRT RENEWAL patients into low (2.8%), moderate (10.1%), and high (13.4%) risk of death based on tertiles of their score. When both the regression model and the clinical risk score were applied to the HF-HRV study, each was able to classify patients into appropriate levels of risk. CONCLUSION Device diagnostics may be used to create models that predict the risk of death.

Clinical Predictors of Risk for Atrial Fibrillation: Implications for Diagnosis and Monitoring

OBJECTIVE To create a risk score using clinical factors to determine whom to screen and monitor for atrial fibrillation (AF). PATIENTS AND METHODS The AF risk score was developed based on the summed odds ratios (ORs) for AF development of 7 accepted clinical risk factors. The AF risk score is intended to assess the risk of AF similar to how the CHA2DS2-VASc score assesses stroke risk. Seven validated risk factors for AF were used to develop the AF risk score: age, coronary artery disease, diabetes mellitus, sex, heart failure, hypertension, and valvular disease. The AF risk score was tested within a random population sample of the Intermountain Healthcare outpatient database. Outcomes were stratified by AF risk score for OR and Kaplan-Meier analysis. RESULTS A total of 100,000 patient records with an index follow-up from January 1, 2002, through December 31, 2007, were selected and followed up for the development of AF through the time of this analysis, May 13, 2013, through September 6, 2013. Mean ± SD follow-up time was 3106±819 days. The ORs of subsequent AF diagnosis of patients with AF risk scores of 1, 2, 3, 4, and 5 or higher were 3.05, 12.9, 22.8, 34.0, and 48.0, respectively. The area under the curve statistic for the AF risk score was 0.812 (95% CI, 0.805-0.820). CONCLUSION We developed a simple AF risk score made up of common clinical factors that may be useful to possibly select patients for long-term monitoring for AF detection.

TCT-615 Do patients with CKD benefit from Left Atrial Appendage Closure (LAAC) with WATCHMAN? Insights from PROTECT AF

Patients (Pts) with chronic kidney disease (CKD) and atrial fibrillation have a greater risk of stroke and death than those with normal renal function and are at higher risk for bleeding with oral anticoagulants (OAC). We analyzed the efficacy of left atrial appendage closure (LAAC) with WATCHMAN