Gender differences in procedure-related adverse events in patients receiving implantable cardioverter-defibrillator therapy.

BACKGROUND: Women are at higher risk than men for adverse events with certain invasive cardiac procedures. Our objective was to compare rates of in-hospital adverse events in men and women receiving implantable cardioverter- defibrillator (ICD) therapy in community practice. METHODS AND RESULTS: Using the National Cardiovascular Data Registry ICD Registry, we identified patients undergoing first-time ICD implantation between January 2006 and December 2007. Outcomes included in-hospital adverse events after ICD implantation. Multivariable analysis assessed the association between gender and in-hospital adverse events, with adjustment for demographic, clinical, procedural, physician, and hospital characteristics. Of 161,470 patients, 73% were male, and 27% were female. Women were more likely to have a history of heart failure (81% versus 77%, P<0.01), worse New York Heart Association functional status (57% versus 50% in class III and IV, P<0.01), and nonischemic cardiomyopathy (44% versus 27%, P<0.01) and were more likely to receive biventricular ICDs (39% versus 34%, P<0.01). In unadjusted analyses, women were more likely to experience any adverse event (4.4% versus 3.3%, P<0.001) and major adverse events (2.0% versus 1.1%, P<0.001). In multivariable models, women had a significantly higher risk of any adverse event (OR 1.32, 95% CI 1.24 to 1.39) and major adverse events (OR 1.71, 95% CI 1.57 to 1.86). CONCLUSIONS: Women are more likely than men to have in-hospital adverse events related to ICD implantation. Efforts are needed to understand the reasons for higher ICD implantation-related adverse event rates in women and to develop strategies to reduce the risk of these events.

Atrial flutter versus atrial fibrillation in a general population: differences in comorbidities associated with their respective onset.

OBJECTIVE: Determine and compare the prevalence of known risk factors for cardiovascular disease among unselected individuals presenting with their first ever episode of atrial flutter (AFL) and atrial fibrillation (AF). STUDY DESIGN AND SETTING: We evaluated 11 pre-selected clinical variables including age, sex, smoking history and other potential cardiac risk factors. Using the resources of the Marshfield Epidemiologic Study Area, a population-based database, all newly diagnosed cases of either AFL or AF in the region during a 4-year period were identified. RESULTS: Among the 472 incident cases, 76 (16.1%) had AFL and 396 (83.9%) had AF. Compared to those with AF, subjects with AFL were more likely to have had a history of chronic obstructive pulmonary disease (25% vs. 12%, P = 0.006), heart failure (28% vs. 17%, P = 0.05), and smoking (49% vs. 37%, P = 0.06). Hypertension, on the other hand, was more common among individuals with AF (63% vs. 47%, P = 0.01). CONCLUSION: This study represents the first report to evaluate potential differences in the conditions associated with the development of AFL versus AF. Research into the mechanisms of atrial arrhythmogenesis may lead to improved preventive and therapeutic interventions.

Discrimination against international medical graduates in the United States residency program selection process.

BACKGROUND: Available evidence suggests that international medical graduates have improved the availability of U.S. health care while maintaining academic standards. We wondered whether studies had been conducted to address how international graduates were treated in the post-graduate selection process compared to U.S. graduates. METHODS: We conducted a Medline search for research on the selection process. RESULTS: Two studies provide strong evidence that psychiatry and family practice programs respond to identical requests for applications at least 80% more often for U.S. medical graduates than for international graduates. In a third study, a survey of surgical program directors, over 70% perceived that there was discrimination against international graduates in the selection process. CONCLUSIONS: There is sufficient evidence to support action against discrimination in the selection process. Medical organizations should publish explicit proscriptions of discrimination against international medical graduates (as the American Psychiatric Association has done) and promote them in diversity statements. They should develop uniform and transparent policies for program directors to use to select applicants that minimize the possibility of non-academic discrimination, and the accreditation organization should monitor whether it is occurring. Whether there should be protectionism for U.S. graduates or whether post-graduate medical education should be an unfettered meritocracy needs to be openly discussed by medicine and society.

Use of implantable cardioverter defibrillators for primary prevention in the community: do women and men equally meet trial enrollment criteria?

BACKGROUND: Fewer women than men undergo implantable cardioverter defibrillator (ICD) implantation for the primary prevention of sudden cardiac death. The criteria used to select patients for ICD implantation may be more permissive among men than for women. We hypothesized that women who undergo primary prevention ICD implantation more often meet strict trial enrollment criteria for this therapy. METHODS: We studied 59,812 patients in the National Cardiovascular Data Registry ICD registry undergoing initial primary prevention ICD placement between January 2005 and April 2007. Patients were classified as meeting or not meeting enrollment criteria of either the MADIT-II or SCD-HeFT trials. Multivariable analyses assessed the association between gender and concordance with trial criteria adjusting for demographic, clinical, and system characteristics. RESULTS: Among the cohort, 27% (n = 16,072) were women. Overall, 85.2% of women and 84.5% of men met enrollment criteria of either trial (P = .05). In multivariable analyses, women were equally likely to meet trial criteria (OR 1.04, 95% CI 0.99-1.10) than men. Significantly more women than men met the trial enrollment criteria among patients older than age 65 (86.6% of women vs 85.3% of men, OR 1.11, 95% CI 1.03-1.19), but this difference was not found among younger patients (82.5% of women vs 83.0% of men, OR 0.97, 95% CI 0.89-1.07). CONCLUSIONS: In a national cohort undergoing primary prevention ICD implantation, older women were only slightly more likely then men to meet the enrollment criteria for MADIT II or SCD-HeFT. Relative overutilization in men is not an important explanation for gender differences in ICD implantation.

Influence of Multimorbidity on Burden and Appropriateness of Implantable Cardioverter-Defibrillator Therapies.

OBJECTIVE: To determine whether burden of multiple chronic conditions (MCCs) influences the risk of receiving inappropriate vs appropriate device therapies. DESIGN: Retrospective cohort study. SETTING: Seven US healthcare delivery systems. PARTICIPANTS: Adults with left ventricular systolic dysfunction receiving an implantable cardioverter-defibrillator (ICD) for primary prevention. MEASUREMENTS: Data on 24 comorbid conditions were captured from electronic health records and categorized into quartiles of comorbidity burden (0-3, 4-5, 6-7 and 8-16). Incidence of ICD therapies (shock and antitachycardia pacing [ATP] therapies), including appropriateness, was collected for 3 years after implantation. Outcomes included time to first ICD therapy, total ICD therapy burden, and risk of inappropriate vs appropriate ICD therapy. RESULTS: Among 2235 patients (mean age = 69 ± 11 years, 75% men), the median number of comorbidities was 6 (interquartile range = 4-8), with 98% having at least two comorbidities. During a mean 2.2 years of follow-up, 18.3% of patients experienced at least one appropriate therapy and 9.9% experienced at least one inappropriate therapy. Higher comorbidity burden was associated with an increased risk of first inappropriate therapy (adjusted hazard ratio [HR] = 1.94 [95% confidence interval {CI} = 1.14-3.31] for 4-5 comorbidities; HR = 2.25 [95% CI = 1.25-4.05] for 6-7 comorbidities; and HR = 2.91 [95% CI = 1.54-5.50] for 8-16 comorbidities). Participants with 8-16 comorbidities had a higher total burden of ICD therapy (adjusted relative risk [RR] = 2.12 [95% CI = 1.43-3.16]), a higher burden of inappropriate therapy (RR = 3.39 [95% CI = 1.67-6.86]), and a higher risk of receiving inappropriate vs appropriate therapy (RR = 1.74 [95% CI = 1.07-2.82]). Comorbidity burden was not significantly associated with receipt of appropriate ICD therapies. Patterns were similar when separately examining shock or ATP therapies. CONCLUSIONS: In primary prevention ICD recipients, MCC burden was independently associated with an increased risk of inappropriate but not appropriate device therapies. Comorbidity burden should be considered when engaging patients in shared decision making about ICD implantation.

Assessing the impact of censoring of costs and effects on health-care decision-making: an example using the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study.

OBJECTIVES: Losses to follow-up and administrative censoring can cloud the interpretation of trial-based economic evaluations. A number of investigators have examined the impact of different levels of adjustment for censoring, including nonadjustment, adjustment of effects only, and adjustment for both costs and effects. Nevertheless, there is a lack of research on the impact of censoring on decision-making. The objective of this study was to estimate the impact of adjustment for censoring on the interpretation of cost-effectiveness results and expected value of perfect information (EVPI), using a trial-based analysis that compared rate- and rhythm-control treatments for persons with atrial fibrillation. METHODS: Three different levels of adjustment for censoring were examined: no censoring of cost and effects, censoring of effects only, and censoring of both costs and effects. In each case, bootstrapping was used to estimate the uncertainty incosts and effects, and the EVPI was calculated to determine the potential worth of further research. RESULTS: Censoring did not impact the adoption decision. Nevertheless, this was not the case for the decision uncertainty or the EVPI. For a threshold of $50,000 per life-year, the EVPI varied between $626,000 (partial censoring) to $117 million (full censoring) for the eligible US population. CONCLUSIONS: The level of adjustment for censoring in trial-based cost-effectiveness analyses can impact on the decisions to fund a new technology and to devote resources for further research. Only when censoring is taken into account for both costs and effects are these decisions appropriately addressed.

Device Therapies Among Patients Receiving Primary Prevention Implantable Cardioverter-Defibrillators in the Cardiovascular Research Network.

BACKGROUND: Primary prevention implantable cardioverter-defibrillators (ICDs) reduce mortality in selected patients with left ventricular systolic dysfunction by delivering therapies (antitachycardia pacing or shocks) to terminate potentially lethal arrhythmias; inappropriate therapies also occur. We assessed device therapies among adults receiving primary prevention ICDs in 7 healthcare systems. METHODS AND RESULTS: We linked medical record data, adjudicated device therapies, and the National Cardiovascular Data Registry ICD Registry. Survival analysis evaluated therapy probability and predictors after ICD implant from 2006 to 2009, with attention to Centers for Medicare and Medicaid Services Coverage With Evidence Development subgroups: left ventricular ejection fraction, 31% to 35%; nonischemic cardiomyopathy <9 months' duration; and New York Heart Association class IV heart failure with cardiac resynchronization therapy defibrillator. Among 2540 patients, 35% were <65 years old, 26% were women, and 59% were white. During 27 (median) months, 738 (29%) received ≥1 therapy. Three-year therapy risk was 36% (appropriate, 24%; inappropriate, 12%). Appropriate therapy was more common in men (adjusted hazard ratio [HR], 1.84; 95% confidence interval [CI], 1.43-2.35). Inappropriate therapy was more common in patients with atrial fibrillation (adjusted HR, 2.20; 95% CI, 1.68-2.87), but less common among patients ≥65 years old versus younger (adjusted HR, 0.72; 95% CI, 0.54-0.95) and in recent implants (eg, in 2009 versus 2006; adjusted HR, 0.66; 95% CI, 0.46-0.95). In Centers for Medicare and Medicaid Services Coverage With Evidence Development analysis, inappropriate therapy was less common with cardiac resynchronization therapy defibrillator versus single chamber (adjusted HR, 0.55; 95% CI, 0.36-0.84); therapy risk did not otherwise differ for Centers for Medicare and Medicaid Services Coverage With Evidence Development subgroups. CONCLUSIONS: In this community cohort of primary prevention patients receiving ICD, therapy delivery varied across demographic and clinical characteristics, but did not differ meaningfully for Centers for Medicare and Medicaid Services Coverage With Evidence Development subgroups.

Implantable cardiac defibrillator placement in a patient with persistent left superior vena cava and Brugada syndrome.

A 45-year-old man was diagnosed with new-onset atrial fibrillation. Control of ventricular rate led to spontaneous conversion to sinus rhythm. Subsequent electrocardiograms revealed ST segment changes characteristic of Brugada syndrome. Electrophysiology study demonstrated inducible ventricular fibrillation. During the placement of an implantable cardiac defibrillator the patient was found to have a persistent left superior vena cava. Persistent left superior vena cava is present in 0.3% of cases in autopsy series. To date, persistent left superior vena cava has not been reported in association with Brugada syndrome. We report such a case.

Prevalence and mortality of patients with myocardial infarction and reduced left ventricular ejection fraction in a defined community: relation to the second multicenter automatic defibrillator implantation trial.

OBJECTIVES: We compared characteristics and mortality of patients from a community population meeting enrollment criteria of the second Multicenter Automatic Defibrillator Implantation Trial (MADIT II) to those of the MADIT II subjects. BACKGROUND: MADIT II showed that implantable cardioverter-defibrillators (ICDs) reduce mortality in patients with myocardial infarction (MI) and low left ventricular ejection fraction (LVEF)

Kidney function and appropriateness of device therapies in adults with implantable cardioverter defibrillators.

OBJECTIVE: Patients with chronic kidney disease (CKD) have higher risk of sudden cardiac death; however, they may not receive implantable cardioverter defibrillators (ICDs), in part due to higher risk of complications. We evaluated whether CKD is associated with greater risk of device-delivered shocks/antitachycardia pacing (ATP) therapies among patients receiving a primary prevention ICD. METHODS: We studied participants in the observational Cardiovascular Research Network Longitudinal Study of Implantable Cardioverter Defibrillators. CKD was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. Outcomes included all delivered shocks/ATPs therapies and type of shock/ATP therapies (inappropriate or appropriate, determined by physician adjudication) within the 3 years. We evaluated the associations between CKD and time to first device therapy, burden of device therapy, and inappropriate versus appropriate device therapy, adjusting for demographics, comorbidity, laboratory values and medication use. RESULTS: Among 2161 participants, 1066 (49.3%) had CKD (eGFR 44±11 mL/min/1.73 m2) at ICD implantation. During mean of 2.26±0.89 years, 9.8% and 18.5% of participants had at least one inappropriate and appropriate shock/ATP therapies, respectively. CKD was not associated with time to first shock/ATP therapies (adjusted HR 0.87, 95% CI 0.73 to 1.05), overall burden of shock/ATP therapies (adjusted relative rate 0.93, 95% CI 0.74 to 1.17) or inappropriate versus appropriate shock/ATP therapies (adjusted relative risk 0.88, 95% CI 0.68 to 1.14) compared with not having CKD. CONCLUSIONS: In adults receiving a primary prevention ICD, mild-to-moderate CKD was not associated with the timing, burden or appropriateness of subsequent device therapy. Potential concern for inappropriate ICD-delivered therapies should not preclude ICDs among eligible patients with CKD.

Comparison of Inappropriate Shocks and Other Health Outcomes Between Single- and Dual-Chamber Implantable Cardioverter-Defibrillators for Primary Prevention of Sudden Cardiac Death: Results From the Cardiovascular Research Network Longitudinal Study of Implantable Cardioverter-Defibrillators.

BACKGROUND: In US clinical practice, many patients who undergo placement of an implantable cardioverter-defibrillator (ICD) for primary prevention of sudden cardiac death receive dual-chamber devices. The superiority of dual-chamber over single-chamber devices in reducing the risk of inappropriate ICD shocks in clinical practice has not been established. The objective of this study was to compare risk of adverse outcomes, including inappropriate shocks, between single- and dual-chamber ICDs for primary prevention. METHODS AND RESULTS: We identified patients receiving a single- or dual-chamber ICD for primary prevention who did not have an indication for pacing from 15 hospitals within 7 integrated health delivery systems in the Longitudinal Study of Implantable Cardioverter-Defibrillators from 2006 to 2009. The primary outcome was time to first inappropriate shock. ICD shocks were adjudicated for appropriateness. Other outcomes included all-cause hospitalization, heart failure hospitalization, and death. Patient, clinician, and hospital-level factors were accounted for using propensity score weighting methods. Among 1042 patients without pacing indications, 54.0% (n=563) received a single-chamber device and 46.0% (n=479) received a dual-chamber device. In a propensity-weighted analysis, device type was not significantly associated with inappropriate shock (hazard ratio, 0.91; 95% confidence interval, 0.59-1.38 [P=0.65]), all-cause hospitalization (hazard ratio, 1.03; 95% confidence interval, 0.87-1.21 [P=0.76]), heart failure hospitalization (hazard ratio, 0.93; 95% confidence interval, 0.72-1.21 [P=0.59]), or death (hazard ratio, 1.19; 95% confidence interval, 0.93-1.53 [P=0.17]). CONCLUSIONS: Among patients who received an ICD for primary prevention without indications for pacing, dual-chamber devices were not associated with lower risk of inappropriate shock or differences in hospitalization or death compared with single-chamber devices. This study does not justify the use of dual-chamber devices to minimize inappropriate shocks.

A randomized, controlled trial of RSD1235, a novel anti-arrhythmic agent, in the treatment of recent onset atrial fibrillation.

OBJECTIVES: The purpose of this study was to determine the efficacy and safety of intravenous RSD1235 in terminating recent onset atrial fibrillation (AF). BACKGROUND: Anti-arrhythmic drugs currently available to terminate AF have limited efficacy and safety. RSD1235 is a novel atrial selective anti-arrhythmic drug. METHODS: This was a phase II, multi-centered, randomized, double-blinded, step-dose, placebo-controlled, parallel group study. Fifty-six patients from 15 U.S. and Canadian sites with AF of 3 to 72 h duration were randomized to one of two RSD1235 dose groups or to placebo. The two RSD1235 groups were RSD-1 (0.5 mg/kg followed by 1 mg/kg) or RSD-2 (2 mg/kg followed by 3 mg/kg), by intravenous infusion over 10 min; a second dose was given only if AF was present. The primary end point was termination of AF during infusion or within 30-min after the last infusion. Secondary end points included the number of patients in sinus rhythm at 0.5, 1, and 24 h post-last infusion and time to conversion to sinus rhythm. RESULTS: The RSD-2 dose showed significant differences over placebo in: 1) termination of AF (61% vs. 5%, p < 0.0005); 2) patients in sinus rhythm at 30 min (56% vs. 5%, p < 0.001); 3) sinus rhythm at 1 h (53% vs. 5%, p = 0.0014); and 4) median time to conversion to SR (14 vs. 162 min, p = 0.016). There were no serious adverse events related to RSD1235. CONCLUSIONS: RSD1235, a new atrial-selective anti-arrhythmic agent, appears to be efficacious and safe for converting recent onset AF to sinus rhythm.

Asymptomatic atrial fibrillation: demographic features and prognostic information from the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study.

BACKGROUND: Atrial fibrillation (AF) may occur without symptoms. Little is known about demographic features and prognostic information in patients with asymptomatic AF. METHODS: In the AFFIRM study, 4060 patients were randomized to either rhythm or rate control. At baseline, patients were identified as asymptomatic if they answered "no" to a 15-item questionnaire related to cardiac symptoms during AF in the 6 months before study entry. RESULTS: There were 481 (12%) asymptomatic patients at baseline. Compared with symptomatic patients, asymptomatic patients were more often men and had a lower incidence of coronary artery disease and congestive heart failure, but had more cerebrovascular events. Asymptomatic patients had a longer duration of AF, a lower maximum heart rate, and better left ventricular function. They received fewer cardiac medications and fewer therapies to maintain sinus rhythm. At 5 years, there was a trend for better survival in asymptomatic patients (81% vs 77%, P = .058), and they were more likely to be free from disabling stroke or anoxic encephalopathy, major bleeding, and cardiac arrest (79% vs 67%, P = .024). However, mortality and major events were similar after correction for baseline differences. CONCLUSIONS: Patients with asymptomatic AF have less serious heart disease but more cerebrovascular disease. Asymptomatic patients receive different therapies than symptomatic patients. However, the absence of symptoms and the differences in treatment does not confer a more favorable prognosis when differences in baseline clinical parameters are considered. Anticoagulation should be considered in these patients.

Clinical factors associated with abandonment of a rate-control or a rhythm-control strategy for the management of atrial fibrillation in the AFFIRM study.

OBJECTIVE: The objective of the current study was to determine the clinical factors that were associated with abandonment of a rate-control or a rhythm-control strategy in patients with atrial fibrillation (AF). BACKGROUND: Although the AFFIRM Study demonstrated that outcomes are similar with a primary strategy of rate-control or rhythm-control for AF, there may be clinical or demographic factors associated with abandonment of the initial treatment strategy. Knowledge of these risk factors would be useful so that patients may be given appropriate initial therapy and, as appropriate, switched to alternative treatments earlier. METHODS: Patients in the AFFIRM Study were subdivided into those who were maintained on their initial treatment strategy versus those who abandoned initial treatment strategy for alternative therapies. We determined the clinical and demographic factors associated with change in initial treatment strategy. RESULTS: At 5 years the original treatment strategy was maintained in 85% of the patients in the rate-control arm versus 62% of those in the rhythm-control arm (P <.0001). Length of the qualifying episode of AF was associated with abandonment of both rhythm-control and rate-control strategies. Antiarrhythmic drug failure before randomization and a history of thyroid disease also were associated with abandonment of rhythm-control. Patients were more likely to maintain rate-control if they already had an implanted pacemaker or if they were older than 75 years, while an ejection fraction <30% was associated with abandonment of the rate-control strategy. CONCLUSIONS: In patients with AF, rhythm-control strategies are abandoned significantly more often than rate-control strategies. Patients with long durations of AF on presentation or previous antiarrhythmic drug failure might be considered for rate-control as initial treatment.

Comparison of management patterns and clinical outcomes in patients with atrial fibrillation in Canada and the United States (from the analysis of the Atrial Fibrillation Follow-up Investigation of Rhythm Management [AFFIRM] database).

Little is known about differences in practice patterns or outcomes in the management of patients who have atrial fibrillation in Canada compared with those in the United States (US). We evaluated the effect that the country of enrollment may have on the management patterns and clinical outcomes in patients who participated in the AFFIRM study. Three thousand four hundred patients came from the US and 660 from Canada. In the US, patients were more likely to have a history of coronary artery disease (39% vs 35%, p = 0.03), hypertension (72% vs 67%, p = 0.01), or congestive heart failure (24% vs 18%, p = 0.0002). More US participants were <65 years of age (25% vs 19%, p = 0.003). Although at randomization the use of warfarin was comparable, during follow-up Canadians were more likely to be treated with warfarin and to be therapeutically anticoagulated. Mortality rate at 5 years was higher in US patients (24% vs 16%, p = 0.001), and the composite end point (death, disabling stroke, major bleeding, cardiac arrest, or anoxic encephalopathy) was also higher in US patients (30% vs 22%, p = 0.0005). Even after adjusting for known differences in baseline characteristics, the risk of death was lower in Canada (hazard ratio 0.70, p = 0.02). In conclusion, in the AFFIRM study, US subjects were more likely to have preexisting cardiovascular diseases despite being younger (<65 years old) than those in Canada. Effective warfarin therapy was more commonly employed in Canada. After correcting for the known differences in baseline characteristics, Canadian patients who had atrial fibrillation had a lower mortality risk.

Cost-effectiveness of rhythm versus rate control in atrial fibrillation.

BACKGROUND: Atrial fibrillation is the most common type of sustained cardiac arrhythmia, but recent trials have identified no clear advantage of rhythm control over rate control. Consequently, economic factors often play a role in guiding treatment selection. OBJECTIVE: To estimate the cost-effectiveness of rhythm-control versus rate-control strategies for atrial fibrillation in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM). DESIGN: Retrospective economic evaluation. Nonparametric bootstrapping was used to estimate the distribution of incremental costs and effects on the cost-effectiveness plane. DATA SOURCES: Data on survival and use of health care resources were obtained for all 4060 AFFIRM participants. Unit costs were estimated from various U.S. databases. TARGET POPULATION: Patients with atrial fibrillation who were 65 years of age or who had other risk factors for stroke or death, similar to those enrolled in AFFIRM. TIME HORIZON: Mean follow-up of 3.5 years. PERSPECTIVE: Third-party payer. INTERVENTIONS: Management of patients with atrial fibrillation with antiarrhythmic drugs (rhythm control) compared with drugs that control heart rate (rate control). OUTCOME MEASURES: Mean survival, resource use, costs, and cost-effectiveness. RESULTS OF BASE-CASE ANALYSIS: A mean survival gain of 0.08 year (P = 0.10) was observed for rate control. Patients in the rate-control group used fewer resources (hospital days, pacemaker procedures, cardioversions, and short-stay and emergency department visits). Rate control costs 5077 dollars less per person than rhythm control. RESULTS OF SENSITIVITY ANALYSIS: Cost savings ranged from 2189 dollars o 5481 dollars per person. Rhythm control was more costly and less effective than rate control in 95% of the bootstrap replicates over a wide range of cost assumptions. LIMITATIONS: Resource use was limited to key items collected in AFFIRM, and the results are generalizable only to similar patient populations with atrial fibrillation. CONCLUSION: Rate control is a cost-effective approach to the management of atrial fibrillation compared with maintenance of sinus rhythm in patients with atrial fibrillation similar to those enrolled in AFFIRM.

Rate control vs. rhythm control in the management of atrial fibrillation in elderly persons.

Antiarrhythmic medications used to maintain sinus rhythm have long been the treatment of choice in atrial fibrillation. The results of five prospective randomized trials comparing the efficacy and safety of rhythm-control to rate-control strategies are now available. Reflecting the epidemiology of atrial fibrillation in the real world, most subjects enrolled in these investigations were elderly persons at increased risk of stroke or death. All of these trials have had similar results; these studies have failed to demonstrate a clear advantage of one treatment strategy over the other. A prespecified subgroup analysis among 3091 elderly patients in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study revealed that rhythm control was associated with a higher risk of death than rate control. This review examines developments leading to and the implications and limitations of these trials and discusses recently issued practice guidelines and the justification for ongoing efforts to develop nonpharmacologic approaches to rhythm management in atrial fibrillation.

Effect of omega-three polyunsaturated fatty acids on inflammation, oxidative stress, and recurrence of atrial fibrillation.

The efficacy of omega-3 polyunsaturated fatty acids (n-3 PUFAs) in preventing recurrence of atrial fibrillation (AF) is controversial and their effects on inflammation and oxidative stress in this population are not known. This study examined the effects of high-dose marine n-3 PUFAs added to conventional therapy on the recurrence of AF and on markers of inflammation and oxidative stress. Patients with paroxysmal or persistent AF were randomized to n-3 PUFAs (4 g/day; n = 126) or placebo (n = 64) in a 2:1 ratio in a prospective, double-blind, placebo-controlled, parallel group study. The primary outcome was time to recurrence of AF. Secondary outcomes were changes in biomarkers of inflammation (serum interleukin [IL]-6, IL-8, IL-10, tissue necrosis factor alpha, monocyte chemoattractant protein-1, and vascular endothelial growth factor), N-terminal-pro-brain-type natriuretic peptide, and oxidative stress (urinary F2-isoprostanes). AF recurred in 74 patients (58.7%) randomized to n-3 PUFAs and in 30 patients (46.9%) who received placebo; time to recurrence of AF did not differ significantly in the 2 groups (hazard ratio 1.20; 95% confidence interval 0.76 to 1.90, adjusted p = 0.438). Compared with placebo, n-3 PUFAs did not result in clinically meaningful changes in concentrations of inflammatory markers, N-terminal-pro-brain-type natriuretic peptide or F2-isoprostanes. In conclusion, in patients with paroxysmal or persistent AF, treatment with n-3 PUFAs 4 g/day did not reduce the recurrence of AF, nor was it associated with clinically important effects on concentrations of markers of inflammation and oxidative stress. (Clinical trial registration number, NCT 00552084.).

Age and sex differences in long-term outcomes following implantable cardioverter-defibrillator placement in contemporary clinical practice: findings from the Cardiovascular Research Network.

BACKGROUND: Patient sex and age may influence rates of death after receiving an implantable cardioverter-defibrillator for primary prevention. Differences in outcomes other than mortality and whether these differences vary by heart failure symptoms, etiology, and left ventricular ejection fraction are not well characterized. METHODS AND RESULTS: We studied 2954 patients with left ventricular ejection fraction ≤0.35 undergoing first-time implantable cardioverter-defibrillator for primary prevention within the Cardiovascular Research Network; 769 patients (26%) were women, and 2827 (62%) were aged >65 years. In a median follow-up of 2.4 years, outcome rates per 1000 patient-years were 109 for death, 438 for hospitalization, and 111 for heart failure hospitalizations. Procedure-related complications occurred in 8.36%. In multivariable models, women had significantly lower risks of death (hazard ratio 0.67, 95% CI 0.56 to 0.80) and heart failure hospitalization (hazard ratio 0.82, 95% CI 0.68 to 0.98) and higher risks for complications (hazard ratio 1.38, 95% CI 1.01 to 1.90) than men; patients aged >65 years had higher risks of death (hazard ratio 1.55, 95% CI 1.30 to 1.86) and heart failure hospitalization (hazard ratio 1.25, 95% CI 1.05 to 1.49) than younger patients. Age and sex differences were generally consistent in strata according to symptoms, etiology, and severity of left ventricular systolic dysfunction, except the higher risk of complications in women, which differed by New York Heart Association classification (P=0.03 for sex-New York Heart Association interaction), and the risk of heart failure hospitalization in older patients, which differed by etiology of heart failure (P=0.05 for age-etiology interaction). CONCLUSIONS: The burden of adverse outcomes after receipt of an implantable cardioverter-defibrillator for primary prevention is substantial and varies according to patient age and sex. These differences in outcome generally do not vary according to baseline heart failure characteristics.

A population-based study of mortality among patients with atrial fibrillation or flutter.

PURPOSE: To determine the mortality associated with atrial flutter and atrial fibrillation in the general population. SUBJECTS AND METHODS: Using the Marshfield Epidemiologic Study Area, a database that captures nearly all medical care and deaths among its 58,820 residents, we identified patients diagnosed with atrial flutter or atrial fibrillation from July 1, 1991, through June 30, 1995. Patients were followed prospectively and compared with a group of controls without these arrhythmias. RESULTS: A total of 4775 person-years of follow-up were completed in 577 patients and 577 controls. Compared with controls, mortality among patients with atrial fibrillation or flutter was nearly 7.8-fold higher at 6 months (95% confidence interval [CI]: 4.1 to 15) and 2.5-fold higher (95% CI: 2.0 to 3.1; P < 0.0001) at the last follow-up (mean [+/- SD] of 3.6 +/- 2.3 years; range, 1 day to 7.3 years). At 6 months, mortality among patients with atrial flutter alone was somewhat greater than in controls and less than one third that of those with atrial fibrillation (with or without atrial flutter) (P = 0.02). At the last follow-up, however, mortality was greater among patients with atrial flutter (hazard ratio [HR] = 1.7; 95% CI: 1.2 to 2.6; P = 0.007), atrial fibrillation (HR = 2.4; 95% CI: 1.9 to 3.1; P < 0.0001), or both atrial arrhythmias (HR = 2.5; 95% CI: 1.9 to 3.3; P < 0.0001) when compared with controls in models that adjusted for cardiovascular risk factors. CONCLUSION: In the general population, both atrial flutter and atrial fibrillation are independent predictors of increased late mortality. The relatively benign course during the 6-month period after the initial diagnosis of atrial flutter suggests that early diagnosis and treatment of these patients may improve their long-term survival.