Keitaro Senoo

Asymptomatic versus symptomatic atrial fibrillation: A systematic review of age/gender differences and cardiovascular outcomes

Up to 40% of atrial fibrillation (AF) patients are asymptomatic. Despite this, scarce data are available about asymptomatic AF, with regard to its clinical profile and relationship to cerebrovascular and cardiovascular risks. Our objective was to conduct a systematic review and meta-analysis was to study the relationship between age and gender with asymptomatic AF and to establish whether patients with asymptomatic AF have a higher risk of death (all-cause and cardiovascular) and stroke/systemic thromboembolism, when compared to symptomatic AF patients. After a comprehensive search, 6 studies (2 randomized clinical trials and 4 observational studies) were entered in the meta-analysis. Despite significant heterogeneity, our data show that the prevalence of females amongst asymptomatic AF group was significantly less compared to the symptomatic AF group (RR, 0.57; 95% CI: 0.52-0.64). No difference in age between asymptomatic and symptomatic AF patients (P=0.72) was seen. No differences were found in all-cause death between patients with asymptomatic and symptomatic AF (RR, 1.38; 95% CI: 0.82-2.17), nor in cardiovascular death (RR, 0.85; 95% CI: 0.53-1.36) or stroke/thromboembolism (RR, 1.72 95% CI: 0.59-5.08). Asymptomatic AF is more associated with male sex, irrespective of age. Both general and cardiovascular death risks as well as thromboembolic risk do not seem to be affected by the asymptomatic clinical status. Symptomatic status should not determine our approach to stroke prevention and other cardiovascular prevention therapies, amongst patients with AF.

Non-vitamin K antagonist oral anticoagulants (NOACs) in patients with concomitant atrial fibrillation and heart failure: a systemic review and meta-analysis of randomized trials

No pooled analysis has been undertaken to assess the efficacy and safety of the non‐vitamin K antagonist oral anticoagulants (NOACs) compared with warfarin in the subgroup of patients with atrial fibrillation (AF) and heart failure (HF), including edoxaban data from recent randomized controlled trials (RCTs).

Residual Risk of Stroke and Death in Anticoagulated Patients According to the Type of Atrial Fibrillation: AMADEUS Trial

Background and Purpose— Atrial fibrillation (AF) and heart failure frequently coexist and are associated with increased morbidity and mortality. We investigated the prognosis of anticoagulated patients with permanent AF and nonpermanent AF according to preexisting heart failure in the AMADEUS (Evaluating the Use of SR34006 Compared to Warfarin or Acenocoumarol in Patients With Atrial Fibrillation) trial. Methods— The primary outcome was a composite of cardiovascular death and stroke or systemic embolism, analyzed using a Cox proportional hazards model, adjusted for baseline age, sex, diabetes mellitus, hypertension, creatinine, and previous cardiovascular diseases. The median follow-up was 11.6 months (interquartile range, 6.2–15.2). Results— Nonpermanent AF was present in 2072 patients (46% of cohort), of which 339 (16%) had preexisting heart failure. A total of 2484 patients had permanent AF (54% of cohort), with a higher burden of heart failure including 730 patients (29%; P<0.001). Overall, death because of cardiovascular causes occurred in 57 patients and 45 had stroke or systemic embolism (1.4/100 person-years for each). Overall, the adjusted incidence of the composite outcome was higher in patients with permanent AF than in patients with nonpermanent AF. In multivariate analysis, permanency of AF, creatinine, prior cerebrovascular events, and previous coronary disease were independently associated with the primary outcome. The hazard ratio for permanent versus nonpermanent AF was 1.68 (95% confidence interval, 1.08–2.55; P=0.02). The presence of heart failure increased the risk of adverse outcomes in a similar way in both permanent and nonpermanent AF (interaction P value=0.76). Conclusions— The risk of cardiovascular death, stroke, or systemic embolism is higher in anticoagulated patients with permanent AF than in those with nonpermanent AF, regardless of preexisting heart failure.

Major Bleeding in Patients with Non-Valvular Atrial Fibrillation: Impact of Time in Therapeutic Range on Contemporary Bleeding Risk Scores

Bleeding risk represents a major concern in anticoagulated patients with atrial fibrillation (AF). Several bleeding prediction scores have been described: HAS-BLED, ATRIA, HEMORR2HAGES and ORBIT. Of these, only HAS-BLED considers quality of anticoagulation control amongst vitamin K antagonist (VKA) users. We hypothesised that predictive value of bleeding risk scores other than HAS-BLED could be improved incorporating time in therapeutic range (TTR) in warfarin-treated patients. Of the 127 adjudicated major bleeding events, 21.3% of events occurred in ‘low-risk’ HAS-BLED category (1.8 per 100 patient-years), compared to higher proportions (≥50% of events; ~2.5 per 100 patient-years) in ‘low-risk’ categories for other scores. Only the ‘low-risk’ HAS-BLED category was associated with the absence of investigator-defined major bleeding events (OR: 1.46;95% CI: 1.00–2.15). ‘High’ or ‘medium/high’ risk categories for the HAS-BLED (p = 0.023) or ORBIT (p = 0.022) scores, respectively, conferred significant risk for adjudicated major bleeding events. On Cox regression analysis, adjudicated major bleeding was associated only with HAS-BLED (HR: 1.62;95% CI: 1.06–2.48) and ORBIT (HR: 1.83;95% CI: 1.08–3.09) ‘high-risk’ categories. Adding ‘labile INR’ (TTR < 65%) to ORBIT, ATRIA and HEMORR2HAGES significantly improved their reclassification and discriminatory performances. In conclusion, HAS-BLED categorised adjudicated major bleeding events in low-risk and high-risk patients appropriately, whilst ORBIT and ATRIA categorised most major bleeds into their ‘low-risk’ patient categories. Adding TTR to ORBIT, ATRIA and HEMORR2HAGES led to improved predictive performance for major bleeding.

Efficacy and Safety of Non-Vitamin K Antagonist Oral Anticoagulants vs. Warfarin in Japanese Patients With Atrial Fibrillation

BACKGROUND Non-vitamin K antagonist oral anticoagulants (NOAC) have been developed as alternatives to warfarin. Until recently, the latter was the standard oral anticoagulant for patients with non-valvular atrial fibrillation (NVAF). The efficacy and safety of NOAC in Japanese patients with NVAF has been investigated in small trials or subgroups from global randomized control trials (RCT). METHODS AND RESULTS We conducted a systematic review and meta-analysis of RCT, to compare the efficacy and safety of NOAC to those of warfarin in Japanese patients with NVAF. Published research was systematically searched for RCT that compared NOAC to warfarin in Japanese patients with NVAF. Random-effects models were used to pool efficacy and safety data across RCT. Three studies, involving 1,940 patients, were identified. Patients randomized to NOAC had a decreased risk for stroke and systemic thromboembolism (relative risk [RR], 0.45; 95% CI: 0.24-0.85), with a non-significant trend for lower major bleeding (RR, 0.66; 95% CI: 0.29-1.47), intracranial bleeding (RR, 0.46; 95% CI: 0.18-1.16) and gastrointestinal bleeding (RR, 0.52; 95% CI: 0.25-1.08). CONCLUSIONS NOAC are more efficacious than warfarin for the prevention of stroke and systemic embolism in Japanese patients with NVAF. The present findings offer clinicians a more comprehensive picture of NOAC as a therapeutic option to reduce the risk of stroke in Japanese NVAF patients.

Body Mass Index and Adverse Outcomes in Elderly Patients With Atrial Fibrillation The AMADEUS Trial

Background and Purpose— Obesity has been associated with increased cardiovascular risk in atrial fibrillation, but little is known in elderly patients with atrial fibrillation. Methods— Post hoc analysis of data from the AMADEUS (Evaluating the Use of SR34006 Compared to Warfarin or Acenocoumarol in Patients With Atrial Fibrillation) trial. Results— We studied 1588 elderly patients, who were categorized as normal body mass index (BMI, 18.5–25 kg/m2; n=515 [32.4%]), overweight (BMI, 25–30 kg/m2; n=711 [44.8%]), and obese (BMI≥30 kg/m2; n=362 [22.8%]). There was a significant reduction in the composite outcome of cardiovascular death and stroke/systemic embolism with increasing BMI category, being 5.0%, 3.2%, and 1.5% per 100 patient-years, respectively (P for trend=0.01). Cox proportional hazards analysis found obesity to be associated with a lower risk of the primary composite outcome (hazard ratio, 0.29; 95% confidence interval, 0.11–0.77; P=0.01). In the warfarin arm (n=814), multivariate logistic regression analysis demonstrated that obesity was independently related to higher odds of time in therapeutic range ≥60% (odds ratio, 1.84; 95% confidence interval, 1.21–2.80; P=0.004). Conclusion— Obesity was associated with a lower stroke and mortality rate in elderly anticoagulated atrial fibrillation patients. Obesity was related to good quality anticoagulation control.

Female Sex, Time in Therapeutic Range, and Clinical Outcomes in Atrial Fibrillation Patients Taking Warfarin

Background and Purpose— Female patients have higher risk for stroke than male patients in nonanticoagulated atrial fibrillation patients, but limited data are available on sex differences in stroke and bleeding outcomes among patients with anticoagulated atrial fibrillation on warfarin, especially in relation to quality of anticoagulation control, as reflected by the time in therapeutic range (TTR). Methods— We investigated adverse outcomes in females (n=791) and males (n=1501) among 2292 patients with atrial fibrillation taking warfarin arm in the AMADEUS (Evaluating the Use of SR34006 Compared to Warfarin or Acenocoumarol in Patients With Atrial Fibrillation) trial. Results— The combined end point of cardiovascular death and stroke/systemic embolism (SSE) was similar in females versus males. There was no sex differences in either cardiovascular death or SSE. Compared with males, females had a lower risk of major bleeding (hazard ratio, 0.39; 95% confidence interval, 0.18–0.87; P=0.02). No differences were seen in mortality and stroke outcomes between females and males either in the prespecified age subgroups or in relation to TTR categories. TTR was negatively correlated with any clinically relevant bleeding in both females (r=−0.86; P=0.03) and males (r=−0.94; P=0.005). On Cox regression, TTR (but not female sex) emerged as an independent predictor for combined cardiovascular death/SSE and clinically relevant bleeding events. Conclusion— Anticoagulated female patients with atrial fibrillation had a similar rate of cardiovascular death and SSE, but a lower risk of major bleeding, compared with males. TTR (but not female sex) was an independent predictor for combined cardiovascular death and SSE and clinically relevant bleeding events.

Updated NICE guideline: management of atrial fibrillation (2014)

There is significant progress made in the field of atrial fibrillation, especially regarding stroke stratification, novel pharmacological agents and interventions for improving symptom control. The Updated NICE Guideline for management of 2014 reflects that and provided an up-to-date appraisal regarding atrial fibrillation treatment, management with consideration to overall healthcare cost economics. It emphasizes the need for individualized, patient-centered package of care, and an robust stroke and bleeding risk before decision regarding choice of oral anticoagulation to be made.

Role of cardiopulmonary dysfunction and left atrial remodeling in development of acute decompensated heart failure in chronic heart failure with preserved left ventricular ejection fraction

BACKGROUND The presence of heart failure (HF) with preserved ejection fraction (HFPEF) is increasingly recognized. However, prognostic factors for HFPEF remain unclear. METHODS AND RESULTS The data were derived from Shinken Database 2004-2010, a prospective cohort study (n=15,227). We examined 301 consecutive HFPEF patients (New York Heart Association Class II or greater) and tracked them for an average 3.5 years. Cardiopulmonary exercise testing (CPX), blood exams, and ultrasound cardiogram (UCG) were performed at the first medical examination. Acute decompensated HF (ADHF) admission was observed in 19 patients (6.3%). CPX showed that the anaerobic threshold was lower (7.3±4.8mL/min/kg vs. 9.7±4.3mL/min/kg, p=0.02) and slope of the increase in ventilation to the increase in CO(2) output (VE-VCO(2) slope) was higher (40.6±8.5 vs. 34.6±7.9, p<0.01) in patients with ADHF admission than those without. Serum brain natriuretic peptide (BNP) tended to be higher and left atrial (LA) dimension was significantly greater (47.0±15.8mm vs. 41.0±9.9mm, p=0.01) in patients with ADHF admission than those without. Multivariate analysis showed that higher VE-VCO(2) slope and greater LA dimension were independent determinants of ADHF admission. CONCLUSION An aggravated CPX parameter and LA dilatation were associated with ADHF admission in patients with symptomatic HFPEF, suggesting the prognostic role of cardiopulmonary dysfunction during exercise and LA remodeling in the pathogenesis of decompensated HF development in HFPEF.

Coronary artery diseases in Japanese patients with nonvalvular atrial fibrillation

BACKGROUND Both the prevalence of atrial fibrillation and coronary artery disease (CAD) is increasing in aged societies. However, limited data are available regarding the prevalence of CAD and the incidence of coronary events in Japanese patients with nonvalvular atrial fibrillation (NVAF). METHODS AND RESULTS The data in this study were derived from Shinken Database 2004-2010, which includes 15,227 new patient visitors to the Cardiovascular Institute between June 2004 and March 2011. In the database, 1835 patients were diagnosed with NVAF (mean age 63 years, mean CHADS2 score 1.1 ± 1.1, and 75% were men). The prevalence of CAD at the initial visit was 118 patients (6.4%). They were older age and had a greater prevalence of men, more history of congestive heart failure and more history of cardiovascular risk factors rather than those without. During the follow-up period of 532 ± 599 days, coronary events (myocardial infarction, unstable angina, and stable angina) occurred in 51 patients (1.9%/year). Multivariate analysis showed that a history of CAD (p<0.001) and older age (p=0.024) were independent predictors of the incidence of future coronary events. CONCLUSIONS In Japanese patients with NVAF, both the presence of CAD and the occurrence of coronary events are not uncommon. History of CAD and older age are strongly associated with the incidence of coronary events.