Matthew R. Reynolds

Comparison of antiarrhythmic drug therapy and radiofrequency catheter ablation in patients with paroxysmal atrial fibrillation: A randomized controlled trial

CONTEXT Antiarrhythmic drugs are commonly used for prevention of recurrent atrial fibrillation (AF) despite inconsistent efficacy and frequent adverse effects. Catheter ablation has been proposed as an alternative treatment for paroxysmal AF. OBJECTIVE To determine the efficacy of catheter ablation compared with antiarrhythmic drug therapy (ADT) in treating symptomatic paroxysmal AF. DESIGN, SETTING, AND PARTICIPANTS A prospective, multicenter, randomized (2:1), unblinded, Bayesian-designed study conducted at 19 hospitals of 167 patients who did not respond to at least 1 antiarrhythmic drug and who experienced at least 3 AF episodes within 6 months before randomization. Enrollment occurred between October 25, 2004, and October 11, 2007, with the last follow-up on January 19, 2009. INTERVENTION Catheter ablation (n = 106) or ADT (n = 61), with assessment for effectiveness in a comparable 9-month follow-up period. MAIN OUTCOME MEASURES Time to protocol-defined treatment failure. The proportion of patients who experienced major treatment-related adverse events within 30 days of catheter ablation or ADT was also reported. RESULTS At the end of the 9-month effectiveness evaluation period, 66% of patients in the catheter ablation group remained free from protocol-defined treatment failure compared with 16% of patients treated with ADT. The hazard ratio of catheter ablation to ADT was 0.30 (95% confidence interval, 0.19-0.47; P < .001). Major 30-day treatment-related adverse events occurred in 5 of 57 patients (8.8%) treated with ADT and 5 of 103 patients (4.9%) treated with catheter ablation. Mean quality of life scores improved significantly in patients treated by catheter ablation compared with ADT at 3 months; improvement was maintained during the course of the study. CONCLUSION Among patients with paroxysmal AF who had not responded to at least 1 antiarrhythmic drug, the use of catheter ablation compared with ADT resulted in a longer time to treatment failure during the 9-month follow-up period. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00116428.

Treatment of atrial fibrillation with antiarrhythmic drugs or radiofrequency ablation: two systematic literature reviews and meta-analyses

Background—Although radiofrequency catheter ablation (RFA) has evolved from an experimental procedure to an important treatment option for atrial fibrillation, the relative safety and efficacy of catheter ablation relative to that of antiarrhythmic drug (AAD) therapy has not been established. Methods and Results—Two separate systematic reviews were conducted: one on RFA and the other on AAD to provide accurate and broadly representative estimates of the clinical efficacy and safety of both therapies in the treatment of atrial fibrillation. Electronic searches were conducted in EMBASE and MEDLINE from 1990 to 2007. For the RFA review, all study designs were accepted. For the AAD review, articles were limited to prospective studies on the following drugs of interest: amiodarone, dofetilide, sotalol, flecainide, and propafenone. Data were extracted by 1 reviewer, with a second reviewer performing independent confirmation of extracted data. Sixty-three RFA and 34 AAD studies were included in the reviews. Patients enrolled in RFA studies tended to be younger (mean age, 55 versus 62 years), had longer duration of atrial fibrillation (6.0 versus 3.1 years), and had failed a greater number of prior drug trials (2.6 versus 1.7). The single-procedure success rate of ablation off AAD therapy was 57% (95% CI, 50% to 64%), the multiple procedure success rate off AAD was 71% (95% CI, 65% to 77%), and the multiple procedure success rate on AAD or with unknown AAD usage was 77% (95% CI, 73% to 81%). In comparison, the success rate for AAD therapy was 52% (95% CI, 47% to 57%). A major complication of catheter ablation occurred in 4.9% of patients. Adverse events for AAD studies, although more common (30% versus 5%), were less severe. Conclusions—Studies of RFA for treatment of atrial fibrillation report higher efficacy rates than do studies of AAD therapy and a lower rate of complications.Background— Although radiofrequency catheter ablation (RFA) has evolved from an experimental procedure to an important treatment option for atrial fibrillation, the relative safety and efficacy of catheter ablation relative to that of antiarrhythmic drug (AAD) therapy has not been established. Methods and Results— Two separate systematic reviews were conducted: one on RFA and the other on AAD to provide accurate and broadly representative estimates of the clinical efficacy and safety of both therapies in the treatment of atrial fibrillation. Electronic searches were conducted in EMBASE and MEDLINE from 1990 to 2007. For the RFA review, all study designs were accepted. For the AAD review, articles were limited to prospective studies on the following drugs of interest: amiodarone, dofetilide, sotalol, flecainide, and propafenone. Data were extracted by 1 reviewer, with a second reviewer performing independent confirmation of extracted data. Sixty-three RFA and 34 AAD studies were included in the reviews. Patients enrolled in RFA studies tended to be younger (mean age, 55 versus 62 years), had longer duration of atrial fibrillation (6.0 versus 3.1 years), and had failed a greater number of prior drug trials (2.6 versus 1.7). The single-procedure success rate of ablation off AAD therapy was 57% (95% CI, 50% to 64%), the multiple procedure success rate off AAD was 71% (95% CI, 65% to 77%), and the multiple procedure success rate on AAD or with unknown AAD usage was 77% (95% CI, 73% to 81%). In comparison, the success rate for AAD therapy was 52% (95% CI, 47% to 57%). A major complication of catheter ablation occurred in 4.9% of patients. Adverse events for AAD studies, although more common (30% versus 5%), were less severe. Conclusions— Studies of RFA for treatment of atrial fibrillation report higher efficacy rates than do studies of AAD therapy and a lower rate of complications. Received October 6, 2008; accepted April 28, 2009. # CLINICAL PERSPECTIVE {#article-title-2}

Premature Induction of an Immunosuppressive Regulatory T Cell Response during Acute Simian Immunodeficiency Virus Infection

Here we report the results of an investigation into the possibility that one mechanism responsible for the establishment of persistent human immunodeficiency virus infection is an early regulatory T (Treg) cell response that blunts virus-specific responses. Using the simian immunodeficiency virus (SIV)-infected rhesus macaque model, we show that, indeed, viral replication and immune activation in lymphatic tissue drive a premature immunosuppressive response, with dramatic increases in the frequencies of CD4+CD25+FOXP3+ Treg cells, transforming growth factor- beta 1+ cells, interleukin-10+ cells, and indoleamine 2,3-dioxygenase+CD3+ cells. When we compared SIV infection with rhesus cytomegalovirus (RhCMV) infection, we found that the frequency of Treg cells paralleled the magnitude of immune activation during both infections but that the magnitude of immune activation and of the Treg cell response were lower and peaked much later during RhCMV infection. Importantly, the frequency of Treg cells inversely correlated with the magnitude of the SIV-specific cytotoxic T lymphocyte response. We conclude that an early Treg cell response during acute SIV infection may contribute to viral persistence by prematurely limiting the antiviral immune response before infection is cleared.

Vaccine-Induced Cellular Immune Responses Reduce Plasma Viral Concentrations after Repeated Low-Dose Challenge with Pathogenic Simian Immunodeficiency Virus SIVmac239

ABSTRACT The goal of an AIDS vaccine regimen designed to induce cellular immune responses should be to reduce the viral set point and preserve memory CD4 lymphocytes. Here we investigated whether vaccine-induced cellular immunity in the absence of any Env-specific antibodies can control viral replication following multiple low-dose challenges with the highly pathogenic SIVmac239 isolate. Eight Mamu-A*01-positive Indian rhesus macaques were vaccinated with simian immunodeficiency virus (SIV) gag, tat, rev, and nef using a DNA prime-adenovirus boost strategy. Peak viremia (P = 0.007) and the chronic phase set point (P = 0.0192) were significantly decreased in the vaccinated cohort, out to 1 year postinfection. Loss of CD4+ memory populations was also ameliorated in vaccinated animals. Interestingly, only one of the eight vaccinees developed Env-specific neutralizing antibodies after infection. The control observed was significantly improved over that observed in animals vaccinated with SIV gag only. Vaccine-induced cellular immune responses can, therefore, exert a measure of control over replication of the AIDS virus in the complete absence of neutralizing antibody and give us hope that a vaccine designed to induce cellular immune responses might control viral replication.

Health-Related Quality of Life After Transcatheter Aortic Valve Replacement in Inoperable Patients With Severe Aortic Stenosis

Background— Transcatheter aortic valve replacement (TAVR) has been shown to improve survival compared with standard therapy in patients with severe aortic stenosis who cannot have surgery. The effects of TAVR on health-related quality of life have not been reported from a controlled study. Methods and Results— The Placement of Aortic Transcatheter Valves (PARTNER) trial randomized patients with symptomatic, severe aortic stenosis who were not candidates for surgical valve replacement to TAVR (n=179) or standard therapy (n=179). Health-related quality of life was assessed at baseline and at 1, 6, and 12 months with the Kansas City Cardiomyopathy Questionnaire (KCCQ) and the 12-item Short Form-12 General Health Survey (SF-12). The primary end point was the KCCQ overall summary score (range, 0–100; higher=better). At baseline, mean KCCQ summary scores (35±20) and SF-12 physical summary scores (28±7) were markedly depressed. Although the KCCQ summary score improved from baseline in both groups, the extent of improvement was greater after TAVR compared with control at 1 month (mean between-group difference, 13 points; 95% confidence interval, 8–19; P<0.001) with larger benefits at 6 months (mean difference, 21 points; 95% confidence interval, 15–27; P<0.001) and 12 months (mean difference, 26 points; 95% confidence interval, 19–33; P<0.001). At 12 months, TAVR patients also reported higher SF-12 physical and mental health scores with mean differences compared with standard care of 5.7 and 6.4 points, respectively (P<0.001 for both comparisons). Conclusions— Among inoperable patients with severe aortic stenosis, compared with standard care, TAVR resulted in significant improvements in health-related quality of life that were maintained for at least 1 year. Clinical Trials Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00530894.

Supervised Exercise Versus Primary Stenting for Claudication Resulting From Aortoiliac Peripheral Artery Disease Six-Month Outcomes From the Claudication: Exercise Versus Endoluminal Revascularization (CLEVER) Study

Background— Claudication is a common and disabling symptom of peripheral artery disease that can be treated with medication, supervised exercise (SE), or stent revascularization (ST). Methods and Results— We randomly assigned 111 patients with aortoiliac peripheral artery disease to receive 1 of 3 treatments: optimal medical care (OMC), OMC plus SE, or OMC plus ST. The primary end point was the change in peak walking time on a graded treadmill test at 6 months compared with baseline. Secondary end points included free-living step activity, quality of life with the Walking Impairment Questionnaire, Peripheral Artery Questionnaire, Medical Outcomes Study 12-Item Short Form, and cardiovascular risk factors. At the 6-month follow-up, change in peak walking time (the primary end point) was greatest for SE, intermediate for ST, and least with OMC (mean change versus baseline, 5.8±4.6, 3.7±4.9, and 1.2±2.6 minutes, respectively; P <0.001 for the comparison of SE versus OMC, P =0.02 for ST versus OMC, and P =0.04 for SE versus ST). Although disease-specific quality of life as assessed by the Walking Impairment Questionnaire and Peripheral Artery Questionnaire also improved with both SE and ST compared with OMC, for most scales, the extent of improvement was greater with ST than SE. Free-living step activity increased more with ST than with either SE or OMC alone (114±274 versus 73±139 versus −6±109 steps per hour), but these differences were not statistically significant. Conclusions— SE results in superior treadmill walking performance than ST, even for those with aortoiliac peripheral artery disease. The contrast between better walking performance for SE and better patient-reported quality of life for ST warrants further study. Clinical Trial Registration— URL: . Unique identifier: [NCT00132743][1]. # Clinical Perspective {#article-title-36} [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00132743&atom=%2Fcirculationaha%2F125%2F1%2F130.atomBackground Claudication is a common and disabling symptom of peripheral artery disease that can be treated with medication, supervised exercise or stent revascularization.Background— Claudication is a common and disabling symptom of peripheral artery disease that can be treated with medication, supervised exercise (SE), or stent revascularization (ST). Methods and Results— We randomly assigned 111 patients with aortoiliac peripheral artery disease to receive 1 of 3 treatments: optimal medical care (OMC), OMC plus SE, or OMC plus ST. The primary end point was the change in peak walking time on a graded treadmill test at 6 months compared with baseline. Secondary end points included free-living step activity, quality of life with the Walking Impairment Questionnaire, Peripheral Artery Questionnaire, Medical Outcomes Study 12-Item Short Form, and cardiovascular risk factors. At the 6-month follow-up, change in peak walking time (the primary end point) was greatest for SE, intermediate for ST, and least with OMC (mean change versus baseline, 5.8±4.6, 3.7±4.9, and 1.2±2.6 minutes, respectively; P<0.001 for the comparison of SE versus OMC, P=0.02 for ST versus OMC, and P=0.04 for SE versus ST). Although disease-specific quality of life as assessed by the Walking Impairment Questionnaire and Peripheral Artery Questionnaire also improved with both SE and ST compared with OMC, for most scales, the extent of improvement was greater with ST than SE. Free-living step activity increased more with ST than with either SE or OMC alone (114±274 versus 73±139 versus −6±109 steps per hour), but these differences were not statistically significant. Conclusions— SE results in superior treadmill walking performance than ST, even for those with aortoiliac peripheral artery disease. The contrast between better walking performance for SE and better patient-reported quality of life for ST warrants further study. Clinical Trial Registration— URL: http://clinicaltrials.gov/ct/show/NCT00132743?order=1. Unique identifier: NCT00132743.

The National Cardiovascular Data Registry (NCDR) Data Quality Brief : The NCDR Data Quality Program in 2012

OBJECTIVES The National Cardiovascular Data Registry (NCDR) developed the Data Quality Program to meet the objectives of ensuring the completeness, consistency, and accuracy of data submitted to the observational clinical registries. The Data Quality Program consists of 3 main components: 1) a data quality report; 2) a set of internal quality assurance protocols; and 3) a yearly data audit program. BACKGROUND Since its inception in 1997, the NCDR has been the basis for the development of performance and quality metrics, site-level quality improvement programs, and peer-reviewed health outcomes research. METHODS Before inclusion in the registry, data are filtered through the registry-specific algorithms that require predetermined levels of completeness and consistency for submitted data fields as part of the data quality report. Internal quality assurance protocols enforce data standards before reporting. Within each registry, 300 to 625 records are audited annually in 25 randomly identified sites (i.e., 12 to 25 records per audited site). RESULTS In the 2010 audits, the participant average raw accuracy of data abstraction for the CathPCI Registry, ICD Registry, and ACTION Registry-GWTG were, respectively, 93.1% (range, 89.4% minimum, 97.4% maximum), 91.2% (range, 83.7% minimum, 95.7% maximum), and 89.7.% (range, 85% minimum, 95% maximum). CONCLUSIONS The 2010 audits provided evidence that many fields in the NCDR accurately represent the data from the medical charts. The American College of Cardiology Foundation is undertaking a series of initiatives aimed at creating a quality assurance rapid learning system, which, when complete, will monitor, evaluate, and improve data quality.

Cost-effectiveness of transcatheter aortic valve replacement compared with standard care among inoperable patients with severe aortic stenosis: results from the placement of aortic transcatheter valves (PARTNER) trial (Cohort B).

Background— In patients with severe aortic stenosis who cannot have surgery, transcatheter aortic valve replacement (TAVR) has been shown to improve survival and quality of life compared with standard therapy, but the costs and cost-effectiveness of this strategy are not yet known. Methods and Results— The PARTNER trial randomized patients with symptomatic, severe aortic stenosis who were not candidates for surgery to TAVR (n=179) or standard therapy (n=179). Empirical data regarding survival, quality of life, medical resource use, and hospital costs were collected during the trial and used to project life expectancy, quality-adjusted life expectancy, and lifetime medical care costs to estimate the incremental cost-effectiveness of TAVR from a US perspective. For patients treated with TAVR, mean costs for the initial procedure and hospitalization were

Health-Related Quality of Life After Transcatheter or Surgical Aortic Valve Replacement in High-Risk Patients With Severe Aortic Stenosis: Results From the PARTNER (Placement of AoRTic TraNscathetER Valve) Trial (Cohort A)

42 806 and

Tau truncation during neurofibrillary tangle evolution in Alzheimer's disease.

78 542, respectively. Follow-up costs through 12 months were lower with TAVR (