Heart rate and death and hospitalization for heart failure in patients with persistent or permanent atrial fibrillation: Insights from the ARISTOTLE trial.

Rate control is fundamental in the treatment of patients with atrial fibrillation (AF). The independent association of heart rate with outcomes and range of heart rate associated with best outcomes remains uncertain. We assessed the relationship between heart rate and clinical outcomes in patients with persistent or permanent AF enrolled in the randomized, double-blind ARISTOTLE trial. In patients with persistent or permanent AF, a faster heart rate is associated with a modest, but statistically significant increase in death and heart failure hospitalizations. TRIAL REGISTRATION: ClinicalTrials.gov (NCT00412984).

Effect of Catheter Ablation vs Antiarrhythmic Drug Therapy on Mortality, Stroke, Bleeding, and Cardiac Arrest Among Patients With Atrial Fibrillation: The CABANA Randomized Clinical Trial.

Importance: Catheter ablation is effective in restoring sinus rhythm in atrial fibrillation (AF), but its effects on long-term mortality and stroke risk are uncertain. Objective: To determine whether catheter ablation is more effective than conventional medical therapy for improving outcomes in AF. Design, Setting, and Participants: The Catheter Ablation vs Antiarrhythmic Drug Therapy for Atrial Fibrillation trial is an investigator-initiated, open-label, multicenter, randomized trial involving 126 centers in 10 countries. A total of 2204 symptomatic patients with AF aged 65 years and older or younger than 65 years with 1 or more risk factors for stroke were enrolled from November 2009 to April 2016, with follow-up through December 31, 2017. Interventions: The catheter ablation group (n = 1108) underwent pulmonary vein isolation, with additional ablative procedures at the discretion of site investigators. The drug therapy group (n = 1096) received standard rhythm and/or rate control drugs guided by contemporaneous guidelines. Main Outcomes and Measures: The primary end point was a composite of death, disabling stroke, serious bleeding, or cardiac arrest. Among 13 prespecified secondary end points, 3 are included in this report: all-cause mortality; total mortality or cardiovascular hospitalization; and AF recurrence. Results: Of the 2204 patients randomized (median age, 68 years; 37.2% female; 42.9% had paroxysmal AF and 57.1% had persistent AF), 89.3% completed the trial. Of the patients assigned to catheter ablation, 1006 (90.8%) underwent the procedure. Of the patients assigned to drug therapy, 301 (27.5%) ultimately received catheter ablation. In the intention-to-treat analysis, over a median follow-up of 48.5 months, the primary end point occurred in 8.0% (n = 89) of patients in the ablation group vs 9.2% (n = 101) of patients in the drug therapy group (hazard ratio [HR], 0.86 [95% CI, 0.65-1.15]; P = .30). Among the secondary end points, outcomes in the ablation group vs the drug therapy group, respectively, were 5.2% vs 6.1% for all-cause mortality (HR, 0.85 [95% CI, 0.60-1.21]; P = .38), 51.7% vs 58.1% for death or cardiovascular hospitalization (HR, 0.83 [95% CI, 0.74-0.93]; P = .001), and 49.9% vs 69.5% for AF recurrence (HR, 0.52 [95% CI, 0.45-0.60]; P < .001). Conclusions and Relevance: Among patients with AF, the strategy of catheter ablation, compared with medical therapy, did not significantly reduce the primary composite end point of death, disabling stroke, serious bleeding, or cardiac arrest. However, the estimated treatment effect of catheter ablation was affected by lower-than-expected event rates and treatment crossovers, which should be considered in interpreting the results of the trial. Trial Registration: ClinicalTrials.gov Identifier: NCT00911508.

Effect of Apixaban on All-Cause Death in Patients with Atrial Fibrillation: a Meta-Analysis Based on Imputed Placebo Effect.

PURPOSE: Vitamin K antagonists (VKAs) are the standard of care for stroke prevention in patients with atrial fibrillation (AF); therefore, there is not equipoise when comparing newer oral anticoagulants with placebo in this setting. METHODS: To explore the effect of apixaban on mortality in patients with AF, we performed a meta-analysis of apixaban versus placebo using a putative placebo analysis based on randomized controlled clinical trials that compared warfarin, aspirin, and no antithrombotic control. We used data from two prospective randomized controlled trials for our comparison of apixaban versus warfarin (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) and apixaban versus aspirin (Apixaban Versus Acetylsalicylic Acid to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment). Using meta-analysis approaches, we indirectly compared apixaban with an imputed placebo with respect to the risk of death in patients with AF. We used results from meta-analyses of randomized trials as our reference for the comparison between warfarin and placebo/no treatment, and aspirin and placebo/no treatment. RESULTS: In these meta-analyses, a lower rate of death was seen both with warfarin (odds ratio [OR] 0.74, 95% confidence interval [CI] 0.57-0.97) and aspirin (OR 0.86, 95% CI 0.69-1.07) versus placebo/no treatment. Using data from ARISTOTLE and AVERROES, apixaban reduced the risk of death by 34% (95% CI 12-50%; p = 0.004) and 33% (95% CI 6-52%; p = 0.02), respectively, when compared with an imputed placebo. The pooled reduction in all-cause death with apixaban compared with an imputed placebo was 34% (95% CI 18-47%; p = 0.0002). CONCLUSIONS: In patients with AF, indirect comparisons suggest that apixaban reduces all-cause death by approximately one third compared with an imputed placebo.

The Long-Term Multicenter Observational Study of Dabigatran Treatment in Patients With Atrial Fibrillation (RELY-ABLE) Study.

BACKGROUND: During follow-up of between 1 and 3 years in the Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) trial, 2 doses of dabigatran etexilate were shown to be effective and safe for the prevention of stroke or systemic embolism in patients with atrial fibrillation. There is a need for longer-term follow-up of patients on dabigatran and for further data comparing the 2 dabigatran doses. METHODS AND RESULTS: Patients randomly assigned to dabigatran in RE-LY were eligible for the Long-term Multicenter Extension of Dabigatran Treatment in Patients with Atrial Fibrillation (RELY-ABLE) trial if they had not permanently discontinued study medication at the time of their final RE-LY study visit. Enrolled patients continued to receive the double-blind dabigatran dose received in RE-LY, for up to 28 months of follow up after RE-LY (median follow-up, 2.3 years). There were 5851 patients enrolled, representing 48% of patients originally randomly assigned to receive dabigatran in RE-LY and 86% of RELY-ABLE-eligible patients. Rates of stroke or systemic embolism were 1.46% and 1.60%/y on dabigatran 150 and 110 mg twice daily, respectively (hazard ratio, 0.91; 95% confidence interval, 0.69-1.20). Rates of major hemorrhage were 3.74% and 2.99%/y on dabigatran 150 and 110 mg (hazard ratio, 1.26; 95% confidence interval, 1.04-1.53). Rates of death were 3.02% and 3.10%/y (hazard ratio, 0.97; 95% confidence interval, 0.80-1.19). Rates of hemorrhagic stroke were 0.13% and 0.14%/y. CONCLUSIONS: During 2.3 years of continued treatment with dabigatran after RE-LY, there was a higher rate of major bleeding with dabigatran 150 mg twice daily in comparison with 110 mg, and similar rates of stroke and death.

Bleeding during treatment with aspirin versus apixaban in patients with atrial fibrillation unsuitable for warfarin: the apixaban versus acetylsalicylic acid to prevent stroke in atrial fibrillation patients who have failed or are unsuitable for vitamin K antagonist treatment (AVERROES) trial.

BACKGROUND AND PURPOSE: Apixaban reduces stroke with comparable bleeding risks when compared with aspirin in patients with atrial fibrillation who are unsuitable for vitamin k antagonist therapy. This analysis explores patterns of bleeding and defines bleeding risks based on stroke risk with apixaban and aspirin. METHODS: The Apixaban versus Acetylsalicylic Acid to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin k Antagonist Treatment (AVERROES) trial randomized 5599 patients with atrial fibrillation and risk factors to receive either apixaban or aspirin. Bleeding events were defined as the first occurrence of either major bleeding or clinically relevant nonmajor bleeding. RESULTS: The rate of a bleeding event was 3.8%/year with aspirin and 4.5%/year with apixaban (hazard ratio with apixaban, 1.18; 95% CI, 0.92-1.51; P=0.19). The anatomic site of bleeding did not differ between therapies. Risk factors for bleeding common to apixaban and aspirin were use of nonstudy aspirin>50% of the time and a history of daily/occasional nosebleeds. The rates of both stroke and bleeding increased with higher CHADS2 scores but apixaban compared with aspirin was associated with a similar relative risk of bleeding (P interaction 0.21) and a reduced relative risk of stroke (P interaction 0.37) irrespective of CHADS2 category. CONCLUSIONS: Anatomic sites and predictors of bleeding are similar for apixaban and aspirin in these patients. Higher CHADS2 scores are associated with increasing rates of bleeding and stroke, but the balance between risks and benefits of apixaban compared with aspirin is favorable irrespective of baseline stroke risk. Clinical Trial Registration Information- www.clinicaltrials.gov. Unique identifier: NCT 00496769.

Trends in Oral Anticoagulant Use Among 436 864 Patients With Atrial Fibrillation in Community Practice, 2011 to 2020.

Background Among patients with nonvalvular atrial fibrillation (AF) and an elevated stroke risk, guidelines recommend direct oral anticoagulants (DOACs) over warfarin for stroke prevention. Changes in DOAC use over the past decade have not been well described. Methods and Results We evaluated trends in use of DOACs and warfarin from 2011 to 2020 among adults with AF and a CHA2DS2-VASc score ≥2 based on electronic health record data from 88 health systems in the United States contributing to Cerner Real World Data. The use of DOACs and warfarin was described over time, by age, sex, race, and ethnicity, and at the health-system level. We identified 436 864 patients with AF at risk for stroke (median age, 78 years; 52.1% men). From 2011 to 2020, overall anticoagulation rates increased from 56.3% to 64.7%, as DOAC use increased steadily (from 4.7% to 47.9%), while warfarin use declined (from 52.4% to 17.7%). DOAC uptake was similar across age, sex, and race and ethnicity groups but varied by health system. In 2020, the median health-system-level proportion of patients with AF on a DOAC was 49% (interquartile range, 40%-54%). Conclusions Over the past decade, anticoagulation rates for patients with AF have increased modestly as DOACs largely replaced warfarin, though significant gaps remain: One in 3 high-risk patients with AF is not on any anticoagulant. While DOAC adoption was generally consistent across major demographic groups, use between health systems remained highly variable, suggesting that provider and system factors influence DOAC uptake use more than patient-level factors.

High prevalence of iatrogenic hyperthyroidism in elderly patients with atrial fibrillation in an anticoagulation clinic.

In elderly patients with established atrial fibrillation (AF) who are receiving thyroid replacement, regular testing for thyroid function is often not performed, placing the patient at risk for iatrogenic hyperthyroidism. Of 215 patients followed in an anticoagulation clinic, 41 were receiving thyroid replacement and 15 of these were found to have hyperthyroidism. Eight had documented AF coincident with abnormal thyroid function. In addition, only 22 patients on thyroid replacement had an annual TSH. In conclusion, iatrogenic hyperthyroidism may frequently be missed in AF patients because of inadequate monitoring of serum TSH. Thyroid replacement is common in elderly patients with AF followed in an anticoagulation clinic. Laboratory evidence of hyperthyroidism occurred in 37%, usually in patients with higher doses of thyroid replacement, and often associated with AF. The frequency of iatrogenic hyperthyroidism may be underestimated in patients with AF since many patients who receive thyroid replacement therapy are not monitored regularly with serum TSH.

Siddha fasting in morbidly obese heart failure patients achieves significant weight loss and reduces hospitalization.

Two thirds of heart failure (HF) patients are overweight or obese. Current guidelines are unclear about weight reduction goals. We explored impact of Heartful Living (HL,) a cardiologist-led Self-Inquiry (Si) mindfulness program targeting deeper insight and resilience to promote intentional weight loss in morbidly obese HF patients. The primary outcome was >10% intentional weight loss in HF achieved in 6 males and 4 females, BMI 40 (± 8.11)Kg/m2, age of 67.1 (± 10.02) years, who participated in HL and were followed for 10 months to 3 years. Two patients had systolic dysfunction, with a reduced ejection fraction of 25 and 40%. All had diabetes (7) or metabolic syndrome (3). The fasting was unsupervised, at home and intuitive without prespecified parameters. The average weight loss through HUGE fasting was 17.5% of total body weight for all 10 patients, and 25.5% for the 5 patients followed over 2 years. Diabetes, hypertension and renal parameters improved allowing reduction of medications. This prospective case series followed ten morbidly obese patients with HF, and demonstrates intentional weight loss can be achieved with mindfulness. Clinical improvement occurs when HF patients reach over 15% weight loss. Prospective studies are needed to evaluate outcomes in broader HF populations.

Quality of life effects of automatic external defibrillators in the home: results from the Home Automatic External Defibrillator Trial (HAT).

BACKGROUND: Public access automatic external defibrillators (AEDs) can save lives, but most deaths from out-of-hospital sudden cardiac arrest occur at home. The Home Automatic External Defibrillator Trial (HAT) found no survival advantage for adding a home AED to cardiopulmonary resuscitation (CPR) training for 7,001 patients with a prior anterior wall myocardial infarction. Quality of life (QOL) outcomes for both the patient and spouse/companion were secondary end points. METHODS: A subset of 1,007 study patients and their spouse/companions was randomly selected for ascertainment of QOL by structured interview at baseline and 12 and 24 months after enrollment. The primary QOL measures were the Medical Outcomes Study 36-Item Short-Form psychological well-being (reflecting anxiety and depression) and vitality (reflecting energy and fatigue) subscales. RESULTS: For patients and spouse/companions, the psychological well-being and vitality scales did not differ significantly between those randomly assigned an AED plus CPR training and controls who received CPR training only. None of the other QOL measures collected showed a clinically and statistically significant difference between treatment groups. Patients in the AED group were more likely to report being extremely or quite a bit reassured by their treatment assignment. Spouse/companions in the AED group reported being less often nervous about the possibility of using AED/CPR treatment than those in the CPR group. CONCLUSIONS: Adding access to a home AED to CPR training did not affect QOL either for patients with a prior anterior myocardial infarction or their spouse/companion but did provide more reassurance to the patients without increasing anxiety for spouse/companions.

Electrocardiographic clues to identify nonresponders to cardiac resynchronization therapy.

BACKGROUND: The aim of cardiac resynchronization therapy (CRT) is to restore myocardial electromechanical synchrony. Achieving this in patients with chronic severe heart failure due to poor left ventricular (LV) systolic function and cardiac dyssynchrony on optimal medical therapy, is associated with improved clinical performance and outcomes. Up to one-third of patients undergoing CRT do not benefit from implantation. Ensuring LV capture is essential and can be at times difficult to confirm. METHODS: Described herein, are six patients who underwent biventricular pacemaker implantation but failed to experience an improvement in LV systolic function or functional capacity. RESULTS: In each case, the 12-lead electrocardiogram (ECG) was helpful in unmasking loss of LV capture in patients who were presumed to have biventricular pacing. CONCLUSIONS: Despite the technical wizardry behind CRT and patient system analyzers, the surface ECG should continue to be an invaluable tool for evaluating patients who have undergone CRT.