BACKGROUND:Atrial fibrillation (AF) is common in heart failure (HF), but the outcome by type of AF is largely unknown. OBJECTIVES:This study investigated outcomes related to type of AF (paroxysmal, persistent or permanent, or new onset) in 2 recent large trials in patients with HF with reduced ejection fraction. METHODS:The study analyzed patients in the PARADIGM-HF (Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure) and ATMOSPHERE (Aliskiren Trial to Minimize Outcomes in Patients with Heart Failure) trials. Multivariable Cox regression models were used to estimate hazard ratios (HRs) for outcomes related to AF type. RESULTS:Of 15,415 patients, 5,481 (35.6%) had a history of AF at randomization, and of these, 1,645 (30.0%) had paroxysmal AF. Compared with patients without AF, patients with paroxysmal AF at randomization had a higher risk of the primary composite endpoint of cardiovascular death or HF hospitalization (HR: 1.20; 95% confidence interval [CI]: 1.09 to 1.32; p < 0.001), HF hospitalization (HR: 1.34; 95% CI: 1.19 to 1.51; p < 0.001), and stroke (HR: 1.34; 95% CI: 1.02 to 1.76; p = 0.037), whereas the corresponding risks in patients with persistent or permanent AF were not elevated. Neither type of AF was associated with higher mortality. New onset AF was associated with the greatest risk of adverse outcomes: primary endpoint (HR: 2.21; 95% CI: 1.80 to 2.71), HF hospitalization (HR: 2.11; 95% CI: 1.58 to 2.81), stroke (HR: 2.20; 95% CI: 1.25 to 3.88), and all-cause mortality (HR: 2.26; 95% CI: 1.86 to 2.74), all p values < 0.001, compared with patients without AF. Anticoagulants were used less often in patients with paroxysmal (53%) and new onset (16%) AF than in patients with persistent or permanent AF (71%). CONCLUSIONS:Among HF patients with a history of AF, those with paroxysmal AF were at greater risk of HF hospitalization and stroke than were patients with persistent or permanent AF, underlining the importance of anticoagulant therapy. New onset AF was associated with increased risk of all outcomes. (Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure [PARADIGM-HF]; NCT01035255) (Aliskiren Trial to Minimize Outcomes in Patients with Heart Failure [ATMOSPHERE]; NCT00853658).

AIMS:To assess the association between atrial fibrillation (AF) and mortality, and also the association between resting heart rate (HR) and mortality in both sinus rhythm (SR) and AF in patients with heart failure with preserved ejection fraction (HFpEF). METHODS AND RESULTS:A total of 9090 patients with HFpEF (ejection fraction ≥ 50%) were included from the Swedish Heart Failure registry; 4296 (47%) had SR and 4794 (53%) had AF. Patients with AF were older (80.3 vs. 75.0 years) and more symptomatic compared with patients in SR. The outcome measure was all-cause mortality. The adjusted hazard ratio (95% confidence interval) for AF vs. SR was 1.21 (1.11-1.32). Compared with HR ≤ 60 b.p.m., the adjusted hazard ratios (95% confidence interval) were in SR: 1.06 (0.92-1.21) for HR 61-70 b.p.m., 1.30 (1.12-1.52) for HR 71-80 b.p.m., 1.27 (1.07-1.51) for HR 81-90 b.p.m., and 1.77 (1.45-2.17) for HR > 90 b.p.m. Due to non-proportional hazards in AF, hazard ratios were estimated in three time periods. Compared with HR ≤ 60 b.p.m., the adjusted hazard ratios (95% confidence interval) were in AF: 1.30 (1.07-1.57), 1.07 (0.83-1.39), and 1.01 (0.70-1.48) for HR 61-70 b.p.m., 1.35 (1.12-1.62), 0.99 (0.77-1.27), and 0.96 (0.66-1.40) for HR 71-80 b.p.m., 1.41 (1.16-1.73), 1.01 (0.76-1.36), and 0.79 (0.51-1.22) for HR 81-90 b.p.m., and 1.78 (1.46-2.17), 1.08 (0.80-1.46), and 0.73 (0.46-1.17) for HR > 90 b.p.m., during 0-2, 2-4, and 4-6 years of follow-up, respectively. CONCLUSION:In a large and unselected cohort of patients with HFpEF, AF was independently associated with all-cause mortality. A higher HR was associated with increased mortality in SR. In AF, the effect of a higher HR on mortality was only present during the first years of follow-up, with convergence in outcomes according to baseline HR groups over long-term follow-up.

Heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF) are very common conditions, particularly in the elderly. However, the mechanisms underlying the two disorders, including their intricate interaction have not been fully resolved. Here, our aim is to review the evidence on the role of the two types of senile amyloidosis in this connection. Two types of senile amyloidosis can be identified: wild-type transthyretin (TTR)-derived amyloidosis (ATTRwt) and isolated atrial amyloidosis (IAA). ATTRwt is an underlying condition that is being increasingly recognized in patients with HFpEF and often accompanied by AF. IAA is an established cause of AF, adding to the mechanism problem. New diagnostic and therapeutic possibilities have emerged that may facilitate clinical management of (senile) amyloidosis, which in turn may have implications for the management of HFpEF and AF.

Background In contemporary atrial fibrillation trials most deaths are cardiac related, whereas stroke and bleeding represent only a small subset of deaths. We aimed to evaluate the long-term risk of cardiac events and all-cause mortality in individuals with atrial fibrillation compared to no atrial fibrillation. Design A systematic review and meta-analysis of studies published between 1 January 2006 and 21 October 2016. Methods Four databases were searched. Studies had follow-up of at least 500 stable patients for either cardiac endpoints or all-cause mortality for 12 months or longer. Publication bias was evaluated and random effects models were used to synthesise the results. Heterogeneity between studies was examined by subgroup and meta-regression analyses. Results A total of 15 cohort studies was included. Analyses indicated that atrial fibrillation was associated with an increased risk of myocardial infarction (relative risk (RR) 1.54, 95% confidence interval (CI) 1.26-1.85), all-cause mortality (RR 1.95, 95% CI 1.50-2.54) and heart failure (RR 4.62, 95% CI 3.13-6.83). Coronary heart disease at baseline was associated with a reduced risk of myocardial infarction and explained 57% of the heterogeneity. A prospective cohort design accounted for 25% of all-cause mortality heterogeneity. Due to there being fewer than 10 studies, sources of heterogeneity were inconclusive for heart failure. Conclusions Atrial fibrillation seems to be associated with an increased risk of subsequent myocardial infarction in patients without coronary heart disease and an increased risk of, all-cause mortality and heart failure in patients with and without coronary heart disease.