Analysis of cause-specific mortality in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study.

BACKGROUND: Expectations that reestablishing and maintaining sinus rhythm in patients with atrial fibrillation might improve survival were disproved in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study. This report describes the cause-specific modes of death in the AFFIRM treatment groups. METHODS AND RESULTS: All deaths in patients enrolled in AFFIRM underwent blinded review by the AFFIRM Events Committee, and a mode of death was assigned. In AFFIRM, 2033 patients were randomized to a rhythm-control strategy and 2027 patients to a rate-control strategy. During a mean follow-up of 3.5 years, there were 356 deaths in the rhythm-control patients and 310 deaths in the rate-control patients (P=0.07). In the rhythm-control group, 129 patients (9%) died of a cardiac cause, and in the rate-control group, 130 patients (10%) died (P=0.95). Both groups had similar rates of arrhythmic and nonarrhythmic cardiac deaths. The numbers of vascular deaths were similar in the 2 groups: 35 (3%) in the rhythm-control group and 37 (3%) in the rate-control group (P=0.82). There were no differences in the rates of ischemic stroke and central nervous system hemorrhage. In the rhythm-control group, there were 169 noncardiovascular deaths (47.5% of the total number of deaths), whereas in the rate-control arm, there were 113 noncardiovascular deaths (36.5% of the total number of deaths) (P=0.0008). Differences in noncardiovascular death rates were due to pulmonary and cancer-related deaths. CONCLUSIONS: Management of atrial fibrillation with a rhythm-control strategy conferred no advantage over a rate-control strategy in cardiac or vascular mortality and may be associated with an increased noncardiovascular death rate.

Use of amiodarone for atrial fibrillation in patients with preexisting pulmonary disease in the AFFIRM study.

In the Atrial Fibrillation Follow-up Investigation of Rhythm Management study, preexisting pulmonary disease did not preclude the use of amiodarone. Preexisting pulmonary disease was associated with a higher risk of pulmonary death and had a higher risk of diagnosed amiodarone pulmonary toxicity. However, use of amiodarone in the presence of preexisting pulmonary disease did not increase pulmonary death and all-cause mortality rates. Cautious use of amiodarone to treat atrial fibrillation appears acceptable in elderly patients with atrial fibrillation, even if preexisting pulmonary disease is present.

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.

Left Atrial Appendage Thrombus Resolution with Reduced Dose Apixaban.

A 63 year old woman with a history of persistent atrial fibrillation and CHADSVASC score of 2, suffered a massive stroke with a hemorrhagic transformation, 2 days following an appendectomy and reversal of warfarin anticoagulation with vitamin K. A left atrial appendage occlusive device (LAAOD) was considered for stroke prevention given the risk of recurrent cerebral hemorrhage. A transesophageal echocardiography (TEE) however, revealed left atrial appendage (LAA) clots which precluded the use of a LAAOD. A computed tomography revealed only partial resolution of the right hemispheric hematoma. Apixaban 2.5 mg twice daily was successful in resolving the LAA clots within 2 months without aggravating her cerebral hematoma which continued to resolve. This is the first case, to our knowledge showing reduced-dose Apixaban to completely resolve left atrial thrombus. Our case also addresses the issue of bridging following reversal of warfarin anticoagulation with vitamin K.

Variations in Anticoagulation Practices Following the Maze Procedure.

The current real-world anticoagulation practices following left atrial appendectomy in the context of the Maze procedure are unknown. This is a cohort study of all patients who underwent the Maze procedure with amputation of the left atrial appendage from June 2005 to November 2012. Data was prospectively collected at regular intervals with an interview and Holter monitoring. All patients received anticoagulation for 3 months. Those then kept on anticoagulation and those for whom anticoagulation was stopped were compared in terms of death, bleeding and incidence of stroke. In total, there were 113 patients, of whom 66 were treated with anticoagulation (Group A) and 47 were not (Group B). There were no significant baseline differences between the two groups, including the presence of atrial fibrillation (A:19.7%, B:10.6%, p=0.30), CHADS2 score (A:1.41±1.05, B:1.15±1.08, p=0.19), and left atrial size (A:48.3±7.1mm, B:47.6±7.8 mm, p=0.57). There were 275 patient-years of follow-up, with an average of 2.43 years per patient. Only two patients experienced strokes, both in Group A (p=0.27). Of the 5 bleeding events, 4 occurred in the first 3 months while on anticoagulation and the remaining event occurred in Group A at 3 years post-operatively (p=0.10). No standardized approach to anticoagulation after the Maze procedure is apparent in real-world practice in an urban Canadian setting. Patients who undergo the Maze procedure with amputation of the left atrial appendage are at a low risk of stroke, but the optimal anticoagulation strategy requires further investigation.

Incidence, predictors, and procedural results of upgrade to resynchronization therapy: the RAFT upgrade substudy.

BACKGROUND: The resynchronization-defibrillation for ambulatory heart failure trial (RAFT) study demonstrated that adding cardiac resynchronization therapy (CRT) in selected patients requiring de novo implantable cardiac defibrillators (ICD) reduced mortality as compared with ICD therapy alone, despite an increase in procedure-related adverse events. Data are lacking regarding the management of patients with ICD therapy who develop an indication for CRT upgrade. METHODS AND RESULTS: Participating RAFT centers provided data regarding de novo CRT-D (CRT with ICD) implant, upgrade to CRT-D during RAFT (study upgrade), and upgrade within 6 months after presentation of study results (substudy). Substudy centers enrolled 1346 (74.9%) patients in RAFT, including 644 de novo, 80 study upgrade, and 60 substudy CRT attempts. The success rate (initial plus repeat attempts) was 95.2% for de novo versus 96.3% for study upgrade and 90.0% for substudy CRT attempts (P=0.402). Acute complications occurred among 26.2% of de novo versus 18.8% of study upgrade and 3.4% of substudy CRT implantation attempts (P<0.001). The most common complication was left ventricular lead dislodgement. The principal reasons for not yet attempting upgrade in the substudy were patient preference (31.9%), New York Heart Association Class I (17.0%), and a QRS<150 ms (13.1%). CONCLUSIONS: Among a broad group of implant physicians, CRT upgrades were performed in patients with an ICD in situ with no difference in implant success rate and a reduced acute complication rate as compared with a de novo CRT implant. Decisions to upgrade were influenced by predictors of benefit in subgroup analyses of the RAFT study and other trials.