Patterns of comorbidities in patients with atrial fibrillation and impact on management and long-term prognosis: an analysis from the Prospective Global GLORIA-AF Registry.

BACKGROUND: Clinical complexity, as the interaction between ageing, frailty, multimorbidity and polypharmacy, is an increasing concern in patients with AF. There remains uncertainty regarding how combinations of comorbidities influence management and prognosis of patients with atrial fibrillation (AF). We aimed to identify phenotypes of AF patients according to comorbidities and to assess associations between comorbidity patterns, drug use and risk of major outcomes. METHODS: From the prospective GLORIA-AF Registry, we performed a latent class analysis based on 18 diseases, encompassing cardiovascular, metabolic, respiratory and other conditions; we then analysed the association between phenotypes of patients and (i) treatments received and (ii) the risk of major outcomes. Primary outcome was the composite of all-cause death and major adverse cardiovascular events (MACE). Secondary exploratory outcomes were also analysed. RESULTS: 32,560 AF patients (mean age 70.0 ± 10.5 years, 45.4% females) were included. We identified 6 phenotypes: (i) low complexity (39.2% of patients); (ii) cardiovascular (CV) risk factors (28.2%); (iii) atherosclerotic (10.2%); (iv) thromboembolic (8.1%); (v) cardiometabolic (7.6%) and (vi) high complexity (6.6%). Higher use of oral anticoagulants was found in more complex groups, with highest magnitude observed for the cardiometabolic and high complexity phenotypes (odds ratio and 95% confidence interval CI): 1.76 [1.49-2.09] and 1.57 [1.35-1.81], respectively); similar results were observed for beta-blockers and verapamil or diltiazem. We found higher risk of the primary outcome in all phenotypes, except the CV risk factor one, with highest risk observed for the cardiometabolic and high complexity groups (hazard ratio and 95%CI: 1.37 [1.13-1.67] and 1.47 [1.24-1.75], respectively). CONCLUSIONS: Comorbidities influence management and long-term prognosis of patients with AF. Patients with complex phenotypes may require comprehensive and holistic approaches to improve their prognosis.

Educational status affects prognosis of patients with heart failure with reduced ejection fraction: A post-hoc analysis from the WARCEF trial.

AIMS: The influence of social determinants of health (SDOH) on the prognosis of Heart Failure and reduced Ejection Fraction (HFrEF) is increasingly reported. We aim to evaluate the contribution of educational status on outcomes in patients with HFrEF. METHODS: We used data from the WARCEF trial, which randomized HFrEF patients with sinus rhythm to receive Warfarin or Aspirin; educational status of patients enrolled was collected at baseline. We defined three levels of education: low, medium and high level, according to the highest qualification achieved or highest school grade attended. We analysed the impact of the educational status on the risk of the primary composite outcome of all-cause death, ischemic stroke (IS) and intracerebral haemorrhage (ICH); components of the primary outcome were also analysed as secondary outcomes. RESULTS: 2295 patients were included in this analysis; of these, 992 (43.2%) had a low educational level, 947 (41.3%) had a medium education level and the remaining 356 (15.5%) showed a high educational level. Compared to patients with high educational level, those with low educational status showed a high risk of the primary composite outcome (adjusted hazard ratio [aHR]: 1.31, 95% confidence intervals [CI] 1.02-1.69); a non-statistically significant association was observed in those with medium educational level (aHR: 1.20, 95%CI: .93-1.55). Similar results were observed for all-cause death, while no statistically significant differences were observed for IS or ICH. CONCLUSION: Compared to patients with high educational levels, those with low educational status had worse prognosis. SDOH should be considered in patients with HFrEF. CLINICAL TRIAL REGISTRATION: NCT00041938.

Impact of chronic obstructive pulmonary disease in patients with atrial fibrillation: an analysis from the GLORIA-AF registry.

AIMS: Chronic obstructive pulmonary disease (COPD) may influence management and prognosis of atrial fibrillation (AF), but this relationship has been scarcely explored in contemporary global cohorts. We aimed to investigate the association between AF and COPD, in relation to treatment patterns and major outcomes. METHODS AND RESULTS: From the prospective, global GLORIA-AF registry, we analysed factors associated with COPD diagnosis, as well as treatment patterns and risk of major outcomes in relation to COPD. The primary outcome was the composite of all-cause death and major adverse cardiovascular events (MACEs). A total of 36 263 patients (mean age 70.1 ± 10.5 years, 45.2% females) were included; 2,261 (6.2%) had COPD. The prevalence of COPD was lower in Asia and higher in North America. Age, female sex, smoking, body mass index, and cardiovascular comorbidities were associated with the presence of COPD. Chronic obstructive pulmonary disease was associated with higher use of oral anticoagulant (OAC) [adjusted odds ratio (aOR) and 95% confidence interval (CI): 1.29 (1.13-1.47)] and higher OAC discontinuation [adjusted hazard ratio (aHR) and 95% CI: 1.12 (1.01-1.25)]. Chronic obstructive pulmonary disease was associated with less use of beta-blocker [aOR (95% CI): 0.79 (0.72-0.87)], amiodarone and propafenone, and higher use of digoxin and verapamil/diltiazem. Patients with COPD had a higher hazard of primary composite outcome [aHR (95% CI): 1.78 (1.58-2.00)]; no interaction was observed regarding beta-blocker use. Chronic obstructive pulmonary disease was also associated with all-cause death [aHR (95% CI): 2.01 (1.77-2.28)], MACEs [aHR (95% CI): 1.41 (1.18-1.68)], and major bleeding [aHR (95% CI): 1.48 (1.16-1.88)]. CONCLUSION: In AF patients, COPD was associated with differences in OAC treatment and use of other drugs; Patients with AF and COPD had worse outcomes, including higher mortality, MACE, and major bleeding.

Remote monitoring and telemedicine in heart failure: implementation and benefits.

PURPOSE OF REVIEW: Remote monitoring (RM) of cardiac implantable electronic devices (CIEDs) is recommended as part of the individualized multidisciplinary follow-up of heart failure (HF) patients. Aim of this article is to critically review recent findings on RM, highlighting potential benefits and barriers to its implementation. RECENT FINDINGS: Device-based RM is useful in the early detection of CIEDs technical issues and cardiac arrhythmias. Moreover, RM allows the continuous monitoring of several patients' clinical parameters associated with impending HF decompensation, but there is still uncertainty regarding its effectiveness in reducing mortality and hospitalizations. Implementation of RM strategies, together with a proactive physicians' attitude towards clinical actions in response to RM data reception, will make RM a more valuable tool, potentially leading to better outcomes.

Performance of HAS-BLED and DOAC scores to predict major bleeding events in atrial fibrillation patients treated with direct oral anticoagulants: A report from a prospective European observational registry.

BACKGROUND: The DOAC score has been recently proposed for bleeding risk stratification of patients with atrial fibrillation treated with direct oral anticoagulants (DOAC). OBJECTIVE: To compare the performance of HAS-BLED and DOAC score in predicting major bleeding events in a contemporary cohort of European AF patients treated with DOAC. METHODS: We included patients derived from a prospective observational registry of European AF patients. HAS-BLED and DOAC scores were calculated as per the original schemes. Our primary endpoint was major bleeding events. Receiver operating characteristic (ROC) curves were used to compare the predictive ability of the scores. RESULTS: A total of 2834 AF patients (median age [IQR] 69 [62-77] years; 39.6 % female) treated with DOAC were included in the analysis. According to the HAS-BLED score, 577 patients (20.4 %) were categorized as very low risk of bleeding, as compared to 1276 (45.0 %) according to DOAC score. A total of 55 major bleeding events occurred with an overall incidence of 1.04 per 100 patient-years. Both scores showed only a modest ability for the prediction of bleeding events (HAS-BLED area under the curve [AUC], 0.65, 95 % confidence interval [CI] 0.55-0.70; DOAC score AUC 0.62, 95 % CI 0.59-0.71, p for difference = 0.332]. At calibration analysis, the DOAC score showed modest calibration, especially for patients at high risk, when compared to HAS-BLED. CONCLUSION: In a contemporary cohort of DOAC-treated AF patients, both HAS-BLED and DOAC scores only modestly predicted the occurrence of major bleeding events. Our results do not support the preferential use of DOAC score over HAS-BLED.

Cardiac resynchronization therapy (CRT) nonresponders in the contemporary era: A state-of-the-art review.

In the 2000s, cardiac resynchronization therapy (CRT) became a revolutionary treatment of heart failure with reduced left ventricular ejection fraction (HFrEF) and wide QRS. However, about one-third of CRT recipients do not show a favorable response. This review of the current literature aims to better define the concept of CRT response/nonresponse. The diagnosis of CRT nonresponder should be viewed as a continuum, and it cannot rely solely on a single parameter. Moreover, baseline features of some patients might predict an unfavorable response. A strong collaboration between heart failure specialists and electrophysiologists is key to overcoming this challenge with multiple strategies. In the contemporary era, new pacing modalities, such as His-bundle pacing and left bundle branch area pacing, represent a promising alternative to CRT. Observational studies have demonstrated their potential; however, several limitations should be addressed. Large randomized controlled trials are needed to prove their efficacy in HFrEF with electromechanical dyssynchrony.

Single-lead VDD pacing: a literature review on short-term and long-term performance.

INTRODUCTION: VDD pacing system was introduced more than 30 years ago. Its use is considered by the 2021 European Society of Cardiology guidelines on cardiac pacing as a potential alternative to dual chambers system for patients with atrioventricular block and normal sinus node function. AREAS COVERED: In this article, we performed a narrative review of current literature in order to identify the strengths and weaknesses of this pacing system. VDD system allows the maintenance of AV synchronous pacing and its hemodynamic advantages. Some disadvantages may be related to the non-negligible incidence of atrial undersensing and the possible subsequent need for upgrade to DDD system. On the other hand, shorter implantation time and lower complications rate may be advantages. EXPERT OPINION: In the modern pacing era, VDD pacing system struggles to find its own space. However, it may still be considered as a valuable alternative to a dual-chamber pacemaker for selected patients, in specific clinical scenarios.

Clinical Outcomes in Metabolically Healthy and Unhealthy Obese and Overweight Patients With Atrial Fibrillation: Findings From the GLORIA-AF Registry.

OBJECTIVE: To explore the association between metabolic status, body mass index (BMI), and natural history of patients with atrial fibrillation (AF). METHODS: The global, prospective GLORIA-AF Registry Phase II and III included patients with recent diagnosis of AF between November 2011 and December 2014 for Phase II and between January 2014 and December 2016 for Phase III. With this analysis, we categorized patients with AF according to BMI (normal weight [18.5 to 24.9 kg/m2], overweight [25.0 to 29.9 kg/m2], obese [30.0 to 60.0 kg/m2]) and metabolic status (presence of hypertension, diabetes, and hyperlipidemia). We analyzed risk of major outcomes using multivariable Cox regression analyses; the primary outcome was the composite of all-cause death and major adverse cardiovascular events. RESULTS: There were 24,828 (mean age, 70.1±10.3 years; 44.6% female) patients with AF included. Higher BMI was associated with metabolically unhealthy status and higher odds of receiving oral anticoagulants and other treatments. Normal-weight unhealthy patients showed a higher risk of the primary composite outcome (adjusted hazard ratio [aHR], 1.20; 95% CI, 1.01 to 1.42) and thromboembolism, whereas a lower risk of cardiovascular death (aHR, 0.35; 95% CI, 0.14 to 0.88) and major adverse cardiovascular events (aHR, 0.56; 95% CI, 0.33 to 0.93) was observed in metabolically healthy obese individuals. Unhealthy metabolic groups were also associated with increased risk of major bleeding (aHR, 1.51 [95% CI, 1.04 to 2.20] and aHR, 1.96 [95% CI, 1.34 to 2.85] in overweight and obese groups, respectively). CONCLUSION: Increasing BMI was associated with poor metabolic status and with more intensive treatment. Prognosis was heterogeneous between BMI groups, with metabolically unhealthy patients showing higher risk of adverse events.

Low Occurrence of Infections and Death in a Real-World Cohort of Patients with Cardiac Implantable Electronic Devices.

BACKGROUND: The incidence of infections and death in patients implanted with cardiac implantable electronic devices (CIEDs) is not fully known yet. AIM: To describe the incidence of CIED-related infection and death, and their potential predictors in a contemporary cohort of CIED patients. METHODS: All consecutive patients implanted with a CIED at our institution were prospectively enrolled. Follow-up visits were performed 2 weeks after CIED implantation for all patients, and then every 6 months for implantable cardioverter defibrillator (ICD)/cardiac resynchronization therapy (CRT) patients and every 12 months for pacemaker (PM) patients. The adjudication of CIED-related infections was performed by two independent investigators and potential disagreement was resolved by a senior investigator. RESULTS: Between September 2016 and August 2020, a total of 838 patients were enrolled (34.6% female; median age 77 (69.6-83.6); median PADIT score 2 (2-4)). PMs were implanted in 569 (68%) patients and ICD/CRT in 269 (32%) patients. All patients had pre-implant antibiotic prophylaxis and 5.5% had an antibiotic-eluting envelope. Follow-up data were available for 832 (99.2%) patients. After a median follow-up of 42.3 (30.2-56.4) months, five (0.6%) patients had a CIED-related infection and 212 (25.5%) patients died. Using multivariate Cox regression analysis, end-stage chronic kidney disease (CKD) requiring dialysis and therapy with corticosteroids was independently associated with a higher risk of infection (hazard ratio (HR): 14.20; 95% confidence interval (CI) 1.48-136.62 and HR: 14.71; 95% CI 1.53-141.53, respectively). Age (HR: 1.07; 95% CI 1.05-1.09), end-stage CKD requiring dialysis (HR: 6.13; 95% CI 3.38-11.13) and history of atrial fibrillation (HR: 1.47; 95% CI 1.12-1.94) were independently associated with all-cause death. CONCLUSIONS: In a contemporary cohort of CIED patients, mortality was substantially high and associated with clinical factors depicting a population at risk. On the other hand, the incidence of CIED-related infections was low.

Sex-related differences in presentation, treatment, and outcomes of Asian patients with atrial fibrillation: a report from the prospective APHRS-AF Registry.

We aimed to investigate the sex-related differences in the clinical course of patients with Atrial Fibrillation (AF) enrolled in the Asia-Pacific-Heart-Rhythm-Society Registry. Logistic regression was utilized to investigate the relationship between sex and oral anticoagulant, rhythm control strategies and the 1-year chance to maintain sinus rhythm. Cox-regression was utilized to assess the 1-year risk of all-cause, and cardiovascular death, thromboembolic events, acute coronary syndrome, heart failure, and major bleeding. In the whole cohort (4121 patients, 69 ± 12 years,34.3% female), females had different cardiovascular risk factors, clinical manifestations, and disease perceptions than men, with more advanced age (72 ± 11 vs 67 ± 12 years, p < 0.001) and dyslipidemia (36.7% vs 41.7%, p = 0.002). Coronary artery disease was more prevalent in males (21.1% vs 16.1%, p < 0.001) as well as the use of antiplatelet drugs. Females had a higher use of oral anticoagulant (84.9% vs 81.3%, p = 0.004) but this difference was non-significant after adjustment for confounders. On multivariable analyses, females were less often treated with rhythm control strategies (Odds Ratio [OR] 0.44,95% Confidence Interval [CI] 0.38-0.51) and were less likely to maintain sinus rhythm (OR 0.27, 95% CI 0.22-0.34) compared to males. Cox-regressions analysis showed no sex-related differences for the risk of death, cardiovascular, and bleeding. The clinical management of Asian AF patients should consider several sex-related differences.

Patterns of oral anticoagulant use and outcomes in Asian patients with atrial fibrillation: a post-hoc analysis from the GLORIA-AF Registry.

Background: Previous studies suggested potential ethnic differences in the management and outcomes of atrial fibrillation (AF). We aim to analyse oral anticoagulant (OAC) prescription, discontinuation, and risk of adverse outcomes in Asian patients with AF, using data from a global prospective cohort study. Methods: From the GLORIA-AF Registry Phase II-III (November 2011-December 2014 for Phase II, and January 2014-December 2016 for Phase III), we analysed patients according to their self-reported ethnicity (Asian vs. non-Asian), as well as according to Asian subgroups (Chinese, Japanese, Korean and other Asian). Logistic regression was used to analyse OAC prescription, while the risk of OAC discontinuation and adverse outcomes were analysed through Cox-regression model. Our primary outcome was the composite of all-cause death and major adverse cardiovascular events (MACE). The original studies were registered with ClinicalTrials.gov, NCT01468701, NCT01671007, and NCT01937377. Findings: 34,421 patients were included (70.0 ± 10.5 years, 45.1% females, 6900 (20.0%) Asian: 3829 (55.5%) Chinese, 814 (11.8%) Japanese, 1964 (28.5%) Korean and 293 (4.2%) other Asian). Most of the Asian patients were recruited in Asia (n = 6701, 97.1%), while non-Asian patients were mainly recruited in Europe (n = 15,449, 56.1%) and North America (n = 8378, 30.4%). Compared to non-Asian individuals, prescription of OAC and non-vitamin K antagonist oral anticoagulant (NOAC) was lower in Asian patients (Odds Ratio [OR] and 95% Confidence Intervals (CI): 0.23 [0.22-0.25] and 0.66 [0.61-0.71], respectively), but higher in the Japanese subgroup. Asian ethnicity was also associated with higher risk of OAC discontinuation (Hazard Ratio [HR] and [95% CI]: 1.79 [1.67-1.92]), and lower risk of the primary composite outcome (HR [95% CI]: 0.86 [0.76-0.96]). Among the exploratory secondary outcomes, Asian ethnicity was associated with higher risks of thromboembolism and intracranial haemorrhage, and lower risk of major bleeding. Interpretation: Our results showed that Asian patients with AF showed suboptimal thromboembolic risk management and a specific risk profile of adverse outcomes; these differences may also reflect differences in country-specific factors. Ensuring integrated and appropriate treatment of these patients is crucial to improve their prognosis. Funding: The GLORIA-AF Registry was funded by Boehringer Ingelheim GmbH.

Comparing atrial fibrillation guidelines: Focus on stroke prevention, bleeding risk assessment and oral anticoagulant recommendations.

Clinical practice in atrial fibrillation (AF) patient management is constantly evolving. In the past 3 years, various new AF guidelines or focused updates have been published, given this rapidly evolving field. In 2019, the American College of Cardiology/American Heart Association published a focused update of the 2014 guidelines. In 2020, both the European Society of Cardiology and the Canadian Cardiovascular Society released their new guidelines. Finally, the most recent guidelines were those published in 2021 by the Asian Pacific Heart Rhythm Society, which updates their 2017 version and the 2021 National Institute for Health and Care Excellence (NICE) guidelines. In the present narrative review, we compare these guidelines, emphasizing similarities and differences in the following mainstay elements of patient care: thromboembolic risk assessment, oral anticoagulants (OACs) prescription, bleeding risk evaluation, and integrated patient management. A formal evaluation of baseline thromboembolic and bleeding risks and their reassessment during follow-up is evenly recommended, although some differences in using risk stratification scores. OACs prescription is highly encouraged where appropriate, and prescription algorithms are broadly similar. The importance of an integrated and multidisciplinary approach to patient care is emerging, aiming to address several different aspects of a multifaceted disease.

Atrial High-Rate Episodes Detected by Cardiac Implantable Electronic Devices: Dynamic Changes in Episodes and Predictors of Incident Atrial Fibrillation.

BACKGROUND: Atrial high rate episodes (AHRE) detected by cardiac implantable electronic devices (CIEDs) may be associated with a risk of progression towards long-lasting episodes (≥24 h) and clinical atrial fibrillation (AF). METHODS: Consecutive CIED patients presenting AHRE (with confirmation of an arrhythmia lasting 5 min-23 h 59 min, atrial rate ≥175/min, with no AF at 12-lead ECG and no prior clinical AF) were retrospectively enrolled. The aims of this study were to describe patients' characteristics and the incidence of adverse events, and second, to identify potential predictors of the composite outcome of clinical AF and/or AHRE episodes lasting ≥24 h. RESULTS: 104/107 (97.2%) patients (median age 79.7 (74.0-84.2), 33.7% female) had available follow-up data. Over a median follow-up of 24.3 (10.6-40.3) months, 31/104 (29.8%) patients experienced the composite outcome of clinical AF or AHRE episodes lasting ≥24 h. Baseline CHA2DS2-VASc score and the longest AHRE episode at enrollment lasting 12 h-23 h 59 min were independently associated with the composite outcome (Hazard ratio (HR); 95% CI: 1.40; 1.07-1.83 and HR: 8.15; 95% CI 2.32-28.65, respectively). Baseline CHA2DS2-VASc score and the longest AHRE episode at enrollment lasting 12 h-23 h 59 min were the only independent predictors of incident clinical AF (HR: 1.45; 95% CI 1.06-2.00 and HR: 4.25; 95% CI 1.05-17.20, respectively). CONCLUSIONS: In patients with AHRE, the incidence of clinical AF or AHRE episodes lasting ≥24 h is high in a two-year follow-up. Baseline patients' characteristics (CHA2DS2-VASc score) and AHRE duration may help to intensify monitoring and decision-making, being independently associated with clinical AF at follow-up.

DIGItal Health Literacy after COVID-19 Outbreak among Frail and Non-Frail Cardiology Patients: The DIGI-COVID Study.

BACKGROUND: Telemedicine requires either the use of digital tools or a minimum technological knowledge of the patients. Digital health literacy may influence the use of telemedicine in most patients, particularly those with frailty. We aimed to explore the association between frailty, the use of digital tools, and patients' digital health literacy. METHODS: We prospectively enrolled patients referred to arrhythmia outpatient clinics of our cardiology department from March to September 2022. Patients were divided according to frailty status as defined by the Edmonton Frail Scale (EFS) into robust, pre-frail, and frail. The degree of digital health literacy was assessed through the Digital Health Literacy Instrument (DHLI), which explores seven digital skill categories measured by 21 self-report questions. RESULTS: A total of 300 patients were enrolled (36.3% females, median age 75 (66-84)) and stratified according to frailty status as robust (EFS ≤ 5; 70.7%), pre-frail (EFS 6-7; 15.7%), and frail (EFS ≥ 8; 13.7%). Frail and pre-frail patients used digital tools less frequently and accessed the Internet less frequently compared to robust patients. In the logistic regression analysis, frail patients were significantly associated with the non-use of the Internet (adjusted odds ratio 2.58, 95% CI 1.92-5.61) compared to robust and pre-frail patients. Digital health literacy decreased as the level of frailty increased in all the digital domains examined. CONCLUSIONS: Frail patients are characterized by lower use of digital tools compared to robust patients, even though these patients would benefit the most from telemedicine. Digital skills were strongly influenced by frailty.