Clinical decisions for appropriate management of patients with atrial fibrillation.

The management of patients with atrial fibrillation (AF) requires intricate clinical decision-making to optimize outcomes. In everyday clinical practice, physicians undergo difficult choices to better manage patients with AF. They need to balance thromboembolic and bleeding risk to focus on patients' symptoms and to manage a variety of multiple comorbidities. In this review, we aimed to explore the multifaceted dimensions of clinical decision-making in AF patients, encompassing the definition and diagnosis of clinical AF, stroke risk stratification, oral anticoagulant therapy selection, consideration of bleeding risk, and the ongoing debate between rhythm and rate control strategies. We will also focus on possible grey zones for the management of AF patients. In navigating this intricate landscape, clinicians must reconcile the dynamic interplay of patient-specific factors, evolving guidelines, and emerging therapies. The review underscores the need for personalized, evidence-based clinical decision-making to tailor interventions for optimal outcomes according to specific AF patient profiles.

[Optimizing the care management pathway of patients with ischemia and non-obstructive coronary arteries]. / Ottimizzazione del percorso clinico-gestionale del paziente con ischemia in assenza di malattia coronarica ostruttiva.

Ischemia with non-obstructive coronary arteries (INOCA) is defined by the coexistence of anginal symptoms and demonstrable ischemia, with no evidence of obstructive coronary arteries. The underlying mechanism of INOCA is coronary microvascular dysfunction with or without associated vasospasm. INOCA patients have recurrent symptoms, functional limitations, repeated access to the emergency department, impaired quality of life and a higher incidence of cardiovascular events than the general population. Although well described in chronic coronary syndrome guidelines, INOCA remains underdiagnosed in clinical practice because of insufficient awareness, lack of accurate diagnostic tools, and poorly standardized and consistent definitions to diagnose, both invasively and non-invasively, coronary microvascular dysfunction.To disseminate current scientific evidence on INOCA as a distinct clinical entity, during 2022 we conducted at 30 cardiology units all over the country a clinical practice improvement initiative, with the aim of developing uniform and shared management pathways for INOCA patients across different operational settings. The present document highlights the outcomes of this multidisciplinary initiative.

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.

Longer and better lives for patients with atrial fibrillation: the 9th AFNET/EHRA consensus conference.

AIMS: Recent trial data demonstrate beneficial effects of active rhythm management in patients with atrial fibrillation (AF) and support the concept that a low arrhythmia burden is associated with a low risk of AF-related complications. The aim of this document is to summarize the key outcomes of the 9th AFNET/EHRA Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA). METHODS AND RESULTS: Eighty-three international experts met in Münster for 2 days in September 2023. Key findings are as follows: (i) Active rhythm management should be part of the default initial treatment for all suitable patients with AF. (ii) Patients with device-detected AF have a low burden of AF and a low risk of stroke. Anticoagulation prevents some strokes and also increases major but non-lethal bleeding. (iii) More research is needed to improve stroke risk prediction in patients with AF, especially in those with a low AF burden. Biomolecules, genetics, and imaging can support this. (iv) The presence of AF should trigger systematic workup and comprehensive treatment of concomitant cardiovascular conditions. (v) Machine learning algorithms have been used to improve detection or likely development of AF. Cooperation between clinicians and data scientists is needed to leverage the potential of data science applications for patients with AF. CONCLUSIONS: Patients with AF and a low arrhythmia burden have a lower risk of stroke and other cardiovascular events than those with a high arrhythmia burden. Combining active rhythm control, anticoagulation, rate control, and therapy of concomitant cardiovascular conditions can improve the lives of patients with AF.

Conduction system disease management in patients candidate and/or treated for the aortic valve disease: an Italian Survey promoted by Italian Association of Arrhythmology and Cardiac Pacing (AIAC).

BACKGROUND: Conduction system disorders represent a frequent complication in patients undergoing surgical (surgical aortic valve replacement, SAVR) or percutaneous (transcatheter aortic valve implantation, TAVI) aortic valve replacement. The purpose of this survey was to evaluate experienced operators approach in this clinical condition. METHODS: This survey was independently conducted by the Italian Association of Arrhythmology and Cardiac Pacing (AIAC) and it consisted of 24 questions regarding the respondents' profile, the characteristics of participating centres, and conduction disease management in different scenarios. RESULTS: Fifty-five physicians from 55 Italian arrhythmia centres took part in the survey. Prophylactic pacemaker implantation is rare. In case of persistent complete atrioventricular block (AVB), 49% and 73% respondents wait less than one week before implanting a definitive pacemaker after SAVR and TAVI, respectively. In case of second degree AVB, the respondents wait some days more for definitive implantation. Respondents consider bundle branch blocks, in particular pre-existing left bundle branch block (LBBB), the worst prognostic factors for pacemaker implantation after TAVI. The implanted valve type is considered a relevant element to evaluate. In patients with new-onset LBBB and severe/moderate left ventricular systolic dysfunction, respondents would implant a biventricular pacemaker in 100/55% of cases, respectively. CONCLUSIONS: Waiting time before a definitive pacemaker implantation after aortic valve replacement has reduced compared to the past, and it is anticipated in TAVI vs. SAVR. Bundle branch blocks are considered the worse prognostic factor for pacemaker implantation after TAVI. The type of pacemaker implanted in new-onset LBBB patients without severe left ventricular systolic dysfunction is heterogeneous.

Simple scores to predict 1-year mortality in atrial fibrillation.

BACKGROUND: Traditional scores as CHADS2 and CHA2DS2-Vasc are suitable for predicting stroke and systemic embolism in patients with atrial fibrillation (AF) and have shown to be also associated with mortality. Other more complex scores have been recommended for survival prediction. The purpose of our analysis was to test the performance of different clinical scores in predicting 1-year mortality in AF patients. MATERIAL AND METHODS: CHADS2 and CHA2DS2-Vasc scores were calculated for AF patients of the BLITZ-AF register and compared to R2-CHADS2, R2-CHA2DS2-Vasc and CHA2DS2VASc-RAF scores in predicting 1-year survival. Scores including renal function were calculated both with glomerular filtration rate (GFR) and creatinine clearance. RESULTS: One-year vital status (1960 alive and 199 dead) was available in 2159 patients. Receiver-operating characteristic curves displayed an association of each score to all-cause mortality, with R2(ClCrea)-CHADS2 being the best [area under the curve (AUC) 0.734]. Differences among the AUCs of the eight scores were not so evident, and a significant difference was found only between R2(ClCrea)-CHADS2 and CHADS2, CHA2DS2VASc, (ClCrea)-CHA2DS2-VASC-RAF.All the scores showed a similar performance for cardiovascular (CV) mortality, with CHA2DS2VASc-RAF being the best (AUC 0.757), with a significant difference with respect to CHADS2, CHA2DS2VASc, and (ClCrea)CHA2DS2Vasc-RAF. CONCLUSIONS: More complex scores, even if with better statistical performance, do not show a clinically relevant higher capability to discriminate alive or dead patients at 12 months. The classical and well known CHA2DS2VASc score, which is routinely used all around the world, has a high sensitivity in predicting all-cause mortality (AUC 0.695; Sensit. 80.4%) and CV mortality (AUC 0.691; Sensit. 80.0%). GRAPHICAL ABSTRACT: http://links.lww.com/JCM/A632.

The key role of public health in renovating Italian biomedical doctoral programs.

Background: A key renovation of doctoral programs is currently ongoing in Italy. Public health and its competencies may play a pivotal role in high-level training to scientific research, including interdisciplinary and methodological abilities. Methods: As a case study, we used the ongoing renovation of the Clinical and Experimental Medicine doctoral program at the University of Modena and Reggio Emilia. We focused on how the program is designed to meet national requirements as well as students' needs, thus improving educational standards for scientific research in the biomedical field, and on the specific contribution of public health and epidemiology in such an effort. Results: The renovation process of doctoral programs in Italy, with specific reference to the biomedical field, focuses on epidemiologic-statistical methodology, ethics, language and communication skills, and open science from an interdisciplinary and international perspective. In the specific context of the doctoral program assessed in the study and from a broader perspective, public health appears to play a key role, taking advantage of most recent methodological advancements, and contributing to the renovation of the learning process and its systematic quality monitoring. Conclusions: From a comparative assessment of this case study and Italian legislation, the key role of public health has emerged in the renovation process of doctoral programs in the biomedical field.

Efficacy and Safety of Non-Vitamin-K Antagonist Oral Anticoagulants Versus Warfarin Across the Spectrum of Body Mass Index and Body Weight: An Individual Patient Data Meta-Analysis of 4 Randomized Clinical Trials of Patients With Atrial Fibrillation.

BACKGROUND: The efficacy and safety of non-vitamin-K antagonist oral anticoagulants (NOACs) across the spectrum of body mass index (BMI) and body weight (BW) remain uncertain. METHODS: We analyzed data from COMBINE AF (A Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in Atrial Fibrillation), which pooled patient-level data from the 4 pivotal randomized trials of NOAC versus warfarin in patients with atrial fibrillation. The primary efficacy and safety outcomes were stroke or systemic embolic events (stroke/SEE) and major bleeding, respectively; secondary outcomes were ischemic stroke/SEE, intracranial hemorrhage, death, and the net clinical outcome (stroke/SEE, major bleeding, or death). Each outcome was examined across BMI and BW. Because few patients had a BMI <18.5 kg/m2 (n=598), the primary analyses were restricted to those with a BMI ≥18.5 kg/m2. RESULTS: Among 58 464 patients, the median BMI was 28.3 (interquartile range, 25.2-32.2) kg/m2, and the median BW was 81.0 (interquartile range, 70.0-94.3) kg. The event probability of stroke/SEE was lower at a higher BMI irrespective of treatment, whereas the probability of major bleeding was lower at a higher BMI with warfarin but relatively unchanged across BMI with NOACs. NOACs reduced stroke/SEE overall (adjusted hazard ratio [HRadj], 0.80 [95% CI, 0.73-0.88]; P<0.001), with a generally consistent effect across BMI (Ptrend across HRs, 0.48). NOACs also reduced major bleeding overall (HRadj, 0.88 [95% CI, 0.82-0.94]; P<0.001), but with attenuation of the benefit at a higher BMI (trend test across BMI [Ptrend], 0.003). The overall treatment effects of NOACs versus warfarin for secondary outcomes were consistent across BMI, with the exception of the net clinical outcome and death. While these outcomes were overall reduced with NOACs (net clinical outcome, HRadj, 0.91 [95% CI, 0.87-0.95]; P<0.001; death, HRadj, 0.91 [95% CI, 0.86-0.97]; P=0.003), these benefits were attenuated at higher BMI (Ptrend, 0.001 and 0.08, respectively). All findings were qualitatively similar when analyzed across BW. CONCLUSIONS: The treatment effect of NOACs versus warfarin in atrial fibrillation is generally consistent for stroke/SEE across the spectrum of BMI and BW, whereas the reduction in major bleeding is attenuated in those with higher BMI or BW. Death and the net clinical outcome are overall reduced with NOACs over warfarin, although there remain uncertainties for these outcomes at a very high BMI and BW.

Economic analyses in cardiac electrophysiology: from clinical efficacy to cost utility.

Cardiac electrophysiology is an evolving field that relies heavily on costly device- and catheter-based technologies. An increasing number of patients with heart rhythm disorders are becoming eligible for cardiac interventions, not least due to the rising prevalence of atrial fibrillation and increased longevity in the population. Meanwhile, the expansive costs of healthcare face finite societal resources, and a cost-conscious approach to new technologies is critical. Cost-effectiveness analyses support rational decision-making in healthcare by evaluating the ratio of healthcare costs to health benefits for competing therapies. They may, however, be subject to significant uncertainty and bias. This paper aims to introduce the basic concepts, framework, and limitations of cost-effectiveness analyses to clinicians including recent examples from clinical electrophysiology and device therapy.

Practical guide on left atrial appendage closure for the non-implanting physician: an international consensus paper.

A significant proportion of patients who suffer from atrial fibrillation (AF) and are in need of thromboembolic protection are not treated with oral anticoagulation or discontinue this treatment shortly after its initiation. This undertreatment has not improved sufficiently despite the availability of direct oral anticoagulants which are associated with less major bleeding than vitamin K antagonists. Multiple reasons account for this, including bleeding events or ischaemic strokes whilst on anticoagulation, a serious risk of bleeding events, poor treatment compliance despite best educational attempts, or aversion to drug therapy. An alternative interventional therapy, which is not associated with long-term bleeding and is as effective as vitamin K anticoagulation, was introduced over 20 years ago. Because of significant improvements in procedural safety over the years, left atrial appendage closure, predominantly achieved using a catheter-based, device implantation approach, is increasingly favoured for the prevention of thromboembolic events in patients who cannot achieve effective anticoagulation. This management strategy is well known to the interventional cardiologist/electrophysiologist but is not more widely appreciated within cardiology or internal medicine. This article introduces the devices and briefly explains the implantation technique. The indications and device follow-up are more comprehensively described. Almost all physicians who care for adult patients will have many with AF. This practical guide, written within guideline/guidance boundaries, is aimed at those non-implanting physicians who may need to refer patients for consideration of this new therapy, which is becoming increasingly popular.

External Validation of COOL-AF Scores in the Asian Pacific Heart Rhythm Society Atrial Fibrillation Registry.

Background: The COOL-AF (Cohort of Antithrombotic Use and Optimal International Normalized Ratio Levels in Patients with Atrial Fibrillation) risk scores for death, bleeding, and thromboembolic events (TEs) were derived from the COOL-AF cohort from Thailand and require external validation. Objectives: The authors sought to externally validate the COOL-AF scores in the APHRS (Asia-Pacific Heart Rhythm Society) registry and to compare their performance in the ESC-EHRA (European Society of Cardiology-European Heart Rhythm Association) EORP-AF (EURObservational Research Programme in Atrial Fibrillation) General Long-Term Registry. Methods: We studied 3,628 APHRS and 8,825 EORP-AF patients. Receiver operating characteristic (ROC) curves and Cox regression analyses were used to test the predictive value of COOL-AF scores and to compared them with the CHA2DS2-VASc and HAS-BLED scores. Results: Patients in the EORP-AF were older, had a higher prevalence of male sex, and were at higher thromboembolic and hemorrhagic risk than APHRS patients. After 1 year of follow-up in APHRS and EORP-AF, the following events were recorded: 87 (2.4%) and 435 (4.9%) death for any causes, 37 (1.0%) and 111 (1.3%) major bleeding, and 25 (0.7%) and 109 (1.2%) TEs, respectively. In APHRS, the COOL-AF scores showed moderate-to-good predictive value for all-cause mortality (area under the curve [AUC]: 0.77; 95% CI: 0.71-0.83), major bleeding (AUC: 0.68; 95% CI: 0.60-0.76), and TEs (AUC: 0.61; 95% CI: 0.51-0.71), and were similar to the CHA2DS2-VASc and HAS-BLED scores. In EORP-AF, the predictive value of COOL-AF for all-cause mortality (AUC: 0.68; 95% CI: 0.65-0.70) and major bleeding (AUC: 0.61; 95% CI: 0.60-0.62) was modest and lower than in APHRS. In EORP-AF, the COOL-AF score for TE was inferior to the CHA2DS2-VASc score. Conclusions: The COOL-AF risk scores may be an easy tool to identify Asian patients with AF at risk for death and major bleeding and performs better in Asian than in European patients with AF. (Clinical Survey on the Stroke Prevention in Atrial Fibrillation in Asia [AF-Registry]; NCT04807049).

Trends in atrial fibrillation-related mortality in Europe, 2008-2019.

AIMS: Update data regarding the atrial fibrillation (AF)-related mortality trend in Europe remains scant. We assess the age- and sex- specific trends in AF-related mortality in the European states between the years 2008 and 2019. METHODS AND RESULTS: Data on cause-specific deaths and population numbers by sex for European countries were retrieved through the publicly available World Health Organization (WHO) mortality dataset for the years 2008 to 2019. AF-related deaths were ascertained when the ICD-10 code I48 was listed as the underlying cause of death in the medical death certificate. To calculate annual trends, we assessed the average (AAPC) annual % change with relative 95% confidence intervals (CIs) using Joinpoint regression. During the study period, 773 750 AF-related deaths (202 552 males and 571 198 females) occurred in Europe. The age-adjusted mortality rate (AAMR) linearly increased from 12.3 (95% CI: 11.2 to 12.9) per 100 000 population in 2008 to 15.3 (95% CI: 14.7 to 15.7) per 100 000 population in 2019 [AAPC: +2.0% (95% CI: 1.6 to 3.5), p < 0.001] with a more pronounced increased among men [AAPC: +2.7% (95% CI: 1.9 to 3.5), p < 0.001] compared to women [AAPC: +1.7% (95% CI: 1.1 to 2.3), p < 0.001] (p for parallelism 0.01). The higher AAMR increased was observed in some eastern European countries such as Latvia, Lithuania and Poland while the lower were mainly clustered in the central Europe. CONCLUSIONS: Over the last decade, the age-adjusted AF-related mortality has increased in Europe especially among males. Disparities still exist between western and eastern European countries.

Detection of subclinical atrial fibrillation with cardiac implanted electronic devices: What decision making on anticoagulation after the NOAH and ARTESiA trials?

Atrial fibrillation (AF) may be asymptomatic and the extensive monitoring capabilities of cardiac implantable electronic devices (CIEDs) revealed asymptomatic atrial tachi-arrhythmias of short duration (minutes-hours) occurring in patients with no prior history of AF and without AF detection at a conventional surface ECG. Both the terms "AHRE" (Atrial High-Rate Episodes) and subclinical AF were used in a series of prior studies, that evidenced the association with an increased risk of stroke. Two randomized controlled studies were planned in order to assess the risk-benefit profile of anticoagulation in patients with AHRE/subclinical AF: the NOAH and ARTESiA trials. The results of these two trials (6548 patients enrolled, overall) show that the risk of stroke/systemic embolism associated with AHRE/subclinical AF is in the range of 1-1.2 % per patient-year, but with an important proportion of severe/fatal strokes occurring in non-anticoagulated patients. The apparent discordance between ARTESiA and NOAH results may be approached by considering the related study-level meta-analysis, which highlights a consistent reduction of ischemic stroke with oral anticoagulants vs. aspirin/placebo (relative risk [RR] 0.68, 95 % CI 0.50-0.92). Oral anticoagulation was found to increase major bleeding (RR 1.62, 95 % CI 1.05-2.5), but no difference was found in fatal bleeding (RR 0.79, 95 % CI 0.37-1.69). Additionally, no difference was found in cardiovascular death or all-cause mortality. Taking into account these results, clinical decision-making for patients with AHRE/subclinical AF at risk of stroke, according to CHA2DS2-VASc, can now be evidence-based, considering the benefits and related risks of oral anticoagulants, to be shared with appropriately informed patients.