Health-related quality of life and healthcare costs of symptoms and cardiovascular disease events in patients with atrial fibrillation: a longitudinal analysis of 27 countries from the EURObservational Research Programme on Atrial Fibrillation general long-term registry.

AIMS: We examine the effects of symptoms and cardiovascular disease (CVD) events on health-related quality of life (HRQOL) and healthcare costs in a European population with atrial fibrillation (AF). METHODS AND RESULTS: In the EURObservational Research Programme on AF long-term general registry, AF patients from 250 centres in 27 European countries were enrolled and followed for 2 years. We used fixed effects models to estimate the association of symptoms and CVD events on HRQOL and annual healthcare costs. We found significant decrements in HRQOL in AF patients in whom ST-segment elevation myocardial infarction (STEMI) [-0.075 (95% confidence interval -0.144, -0.006)], angina or non-ST-elevation myocardial infarction (NSTEMI) [-0.037 (-0.071, -0.003)], new-onset/worsening heart failure [-0.064 (-0.088, -0.039)], bleeding events [-0.031 (-0.059, -0.003)], thromboembolic events [-0.071 (-0.115, -0.027)], mild symptoms [0.037 (-0.048, -0.026)], or severe/disabling symptoms [-0.090 (-0.108, -0.072)] occurred during the follow-up. During follow-up, annual healthcare costs were associated with an increase of €11 718 (€8497, €14 939) in patients with STEMI, €5823 (€4757, €6889) in patients with angina/NSTEMI, €3689 (€3219, €4158) in patients with new-onset or worsening heart failure, €3792 (€3315, €4270) in patients with bleeding events, and €3182 (€2483, €3881) in patients with thromboembolic events, compared with AF patients without these events. Healthcare costs were primarily driven by inpatient costs. There were no significant differences in HRQOL or healthcare resource use between EU regions or by sex. CONCLUSION: Symptoms and CVD events are associated with a high burden on AF patients and healthcare systems throughout Europe.

MicroRNAs in Atrial Fibrillation: Mechanisms, Vascular Implications, and Therapeutic Potential.

Atrial fibrillation (AFib), the most prevalent arrhythmia in clinical practice, presents a growing global health concern, particularly with the aging population, as it is associated with devastating complications and an impaired quality of life. Its pathophysiology is multifactorial, including the pathways of fibrosis, inflammation, and oxidative stress. MicroRNAs (miRNAs), small non-coding RNA molecules, have emerged as substantial contributors in AFib pathophysiology, by affecting those pathways. In this review, we explore the intricate relationship between miRNAs and the aforementioned aspects of AFib, shedding light on the molecular pathways as well as the potential diagnostic applications. Recent evidence also suggests a possible role of miRNA therapeutics in maintenance of sinus rhythm via the antagonism of miR-1 and miR-328, or the pharmacological upregulation of miR-27b and miR-223-3p. Unraveling the crosstalk between specific miRNA profiles and genetic predispositions may pave the way for personalized therapeutic approaches, setting the tone for precision medicine in atrial fibrillation.

The Society of Thoracic Surgeons 2023 Clinical Practice Guidelines for the Surgical Treatment of Atrial Fibrillation.

The Society of Thoracic Surgeons 2023 clinical practice guidelines for the surgical management of atrial fibrillation incorporate the most recent evidence for surgical ablation and left atrial appendage occlusion in different clinical scenarios. Substantial new evidence regarding the risks and benefits of surgical left atrial appendage occlusion and the long-term benefits of surgical ablation has been produced in the last five years. In comparison to the 2017 clinical practice guideline, the current update has an emphasis on surgical ablation in first-time, non-emergent cardiac surgery and its long-term benefits, an extension of the recommendation to perform surgical ablation in all patients with atrial fibrillation undergoing first-time, non-emergent cardiac surgery and a new class I recommendation for left atrial appendage occlusion in all patients with atrial fibrillation undergoing first-time, non-emergent cardiac surgery. Further guidance is provided for patients with structural heart disease and atrial fibrillation being considered for transcatheter valve repair or replacement, as well as patients in need of isolated left atrial appendage management who are not candidates for surgical ablation. The importance of a multidisciplinary team assessment, treatment planning, and long-term follow-up are reiterated in this clinical practice guideline with a class I recommendation, along with the other recommendations from the 2017 guidelines which remained unchanged in their class of recommendation and level of evidence.

Cardiovascular disease burden due to productivity losses in European Society of Cardiology countries.

OBJECTIVE: Cardiovascular disease (CVD) is the leading cause of death across Europe. We estimated lost earnings (productivity losses) associated with premature mortality due to CVD, and separately for its main sub-categories of coronary heart disease and cerebrovascular disease, across 54 country members of the European Society of Cardiology (ESC). METHODS AND RESULTS: We used a standardized approach to estimate working years and earnings lost due to premature death resulting from CVD across the 54 ESC member countries in 2018. Our population-based approach was based on national data on the number of deaths, employment rates, and earnings by age group and sex. We discounted future working years and earnings lost to present values using a 3.5% annual rate. In 2018, there were 4.4 million deaths due to CVD across the 54 countries, with 7.1 million working years lost. This represented productivity losses due to premature death of €62 billion in 2018. Deaths due to coronary heart disease accounted for 47% (€29 billion) of all CVD costs, and cerebrovascular disease accounted for 18% (€11 billion). Approximately 60% (€37 billion) of all productivity losses occurred in the 28 European Union member states, despite accounting for only 42% (1.8 million) of deaths and 21% (1.5 million) of working years lost across the 54 countries. CONCLUSION: Our study provides a snapshot of the economic consequences posed by premature mortality due to CVD across 54 countries in 2018. The considerable variation across countries highlights the potential gains from policies targeting prevention and care of cardiovascular diseases.

Anticoagulation with edoxaban in patients with long atrial high-rate episodes ≥24†h.

BACKGROUND AND AIMS: Patients with long atrial high-rate episodes (AHREs) ≥24 h and stroke risk factors are often treated with anticoagulation for stroke prevention. Anticoagulation has never been compared with no anticoagulation in these patients. METHODS: This secondary pre-specified analysis of the Non-vitamin K antagonist Oral anticoagulants in patients with Atrial High-rate episodes (NOAH-AFNET 6) trial examined interactions between AHRE duration at baseline and anticoagulation with edoxaban compared with placebo in patients with AHRE and stroke risk factors. The primary efficacy outcome was a composite of stroke, systemic embolism, or cardiovascular death. The safety outcome was a composite of major bleeding and death. Key secondary outcomes were components of these outcomes and electrocardiogram (ECG)-diagnosed atrial fibrillation. RESULTS: Median follow-up of 2389 patients with core lab-verified AHRE was 1.8 years. AHRE ≥24 h were present at baseline in 259/2389 patients (11%, 78 ± 7 years old, 28% women, CHA2DS2-VASc 4). Clinical characteristics were not different from patients with shorter AHRE. The primary outcome occurred in 9/132 patients with AHRE ≥24 h (4.3%/patient-year, 2 strokes) treated with anticoagulation and in 14/127 patients treated with placebo (6.9%/patient-year, 2 strokes). Atrial high-rate episode duration did not interact with the efficacy (P-interaction = .65) or safety (P-interaction = .98) of anticoagulation. Analyses including AHRE as a continuous parameter confirmed this. Patients with AHRE ≥24 h developed more ECG-diagnosed atrial fibrillation (17.0%/patient-year) than patients with shorter AHRE (8.2%/patient-year; P < .001). CONCLUSIONS: This hypothesis-generating analysis does not find an interaction between AHRE duration and anticoagulation therapy in patients with device-detected AHRE and stroke risk factors. Further research is needed to identify patients with long AHRE at high stroke risk.

Cardiovascular disease care and outcomes in West and South European countries.

Variations in cardiovascular disease (CVD) burden between West and South European countries are rarely reported. To address this knowledge gap, The Lancet Regional Health-Europe convened experts from a broad range of countries to assess the current state of knowledge of cardiovascular disease inequalities across Europe. This Review is specifically focused on West and South European countries. Mortality, risk factor and economic data for nine West European and six South European countries were sourced from the World Health Organisation, the Global Burden of Disease study and the World Bank. Healthcare data were collected by survey of participating countries. A key finding was of declines in age-standardised mortality rates (ASMRs) across all countries since 1990. In 2019 rates per 100,000 were lower in West European countries in males (279.7 (264.1-335.9) vs 337.2 (323.7-367.2)) and females (196.2 (183.3-228.8) vs 247.3 (232.2-268.3)). Differences in risk factor exposures were small, with the exception of physical activity and dietary factors, but across all countries the prevalence of obesity has increased, affecting >20% of adults in 2019. Healthcare delivery in 2019 showed inequalities with cardiovascular procedure rates lower in South compared with West European countries. Further declines in ASMRs in West and South European countries will require population strategies to reduce obesity and address inequalities in physical activity and dietary factors. Reducing the gap in procedure rates is unlikely to match the beneficial effects of population strategies for reducing CVD burden in South European countries.

Five critical quality criteria for artificial intelligence-based prediction models.

To raise the quality of clinical artificial intelligence (AI) prediction modelling studies in the cardiovascular health domain and thereby improve their impact and relevancy, the editors for digital health, innovation, and quality standards of the European Heart Journal propose five minimal quality criteria for AI-based prediction model development and validation studies: complete reporting, carefully defined intended use of the model, rigorous validation, large enough sample size, and openness of code and software.

Personalized lifetime prediction of survival and treatment benefit in patients with heart failure with reduced ejection fraction: The LIFE-HF model.

AIMS: Although trials have proven the group-level effectiveness of various therapies for heart failure with reduced ejection fraction (HFrEF), important differences in absolute effectiveness exist between individuals. We developed and validated the LIFEtime-perspective for Heart Failure (LIFE-HF) model for the prediction of individual (lifetime) risk and treatment benefit in patients with HFrEF. METHODS AND RESULTS: Cox proportional hazards functions with age as the time scale were developed in the PARADIGM-HF and ATMOSPHERE trials (n = 15 415). Outcomes were cardiovascular death, heart failure (HF) hospitalization or cardiovascular death, and non-cardiovascular mortality. Predictors were age, sex, New York Heart Association class, prior HF hospitalization, diabetes mellitus, extracardiac vascular disease, systolic blood pressure, left ventricular ejection fraction, N-terminal pro-B-type natriuretic peptide, and glomerular filtration rate. The functions were combined in life-tables to predict individual overall and HF hospitalization-free survival. External validation was performed in the SwedeHF registry, ASIAN-HF registry, and DAPA-HF trial (n = 51 286). Calibration of 2- to 10-year risk was adequate, and c-statistics were 0.65-0.74. An interactive tool was developed combining the model with hazard ratios from trials to allow estimation of an individual's (lifetime) risk and treatment benefit in clinical practice. Applying the tool to the development cohort, combined treatment with a mineralocorticoid receptor antagonist, sodium-glucose cotransporter 2 inhibitor, and angiotensin receptor-neprilysin inhibitor was estimated to afford a median of 2.5 (interquartile range [IQR] 1.7-3.7) and 3.7 (IQR 2.4-5.5) additional years of overall and HF hospitalization-free survival, respectively. CONCLUSION: The LIFE-HF model enables estimation of lifelong overall and HF hospitalization-free survival, and (lifetime) treatment benefit for individual patients with HFrEF. It could serve as a tool to improve the management of HFrEF by facilitating personalized medicine and shared decision-making.

The role of intravascular imaging in chronic total occlusion percutaneous coronary intervention.

Chronic total occlusions (CTOs) represent the most complex subset of coronary artery disease and therefore careful planning of CTO percutaneous coronary recanalization (PCI) strategy is of paramount importance aiming to achieve procedural success, and improve patient's safety and post CTO PCI outcomes. Intravascular imaging has an essential role in facilitating CTO PCΙ. First, intravascular ultrasound (IVUS), due to its higher penetration depth compared to optical coherence tomography (OCT), and the additional capacity of real-time imaging without need for contrast injection is considered the preferred imaging modality for CTO PCI. Secondly, IVUS can be used to resolve proximal cap ambiguity, facilitate wire re-entry when dissection and re-entry strategies are applied and most importantly to guide stent deployment and optimization post implantation. The role of OCT during CTO PCI is currently limited to stent sizing and optimization, however, due to its high spatial resolution, OCT is ideal for detecting stent edge dissections and strut malapposition. In this review, we describe the use of intravascular imaging for lesion crossing, plaque characterization and wire tracking, extra- or intra-plaque, and stent sizing and optimization during CTO PCI and summarize the findings of the major studies in this field.

Anticoagulation with Edoxaban in Patients with Atrial High-Rate Episodes.

BACKGROUND: Device-detected atrial high-rate episodes (AHREs) are atrial arrhythmias detected by implanted cardiac devices. AHREs resemble atrial fibrillation but are rare and brief. Whether the occurrence of AHREs in patients without atrial fibrillation (as documented on a conventional electrocardiogram [ECG]) justifies the initiation of anticoagulants is not known. METHODS: We conducted an event-driven, double-blind, double-dummy, randomized trial involving patients 65 years of age or older who had AHREs lasting for at least 6 minutes and who had at least one additional risk factor for stroke. Patients were randomly assigned in a 1:1 ratio to receive edoxaban or placebo. The primary efficacy outcome was a composite of cardiovascular death, stroke, or systemic embolism, evaluated in a time-to-event analysis. The safety outcome was a composite of death from any cause or major bleeding. RESULTS: The analysis population consisted of 2536 patients (1270 in the edoxaban group and 1266 in the placebo group). The mean age was 78 years, 37.4% were women, and the median duration of AHREs was 2.8 hours. The trial was terminated early, at a median follow-up of 21 months, on the basis of safety concerns and the results of an independent, informal assessment of futility for the efficacy of edoxaban; at termination, the planned enrollment had been completed. A primary efficacy outcome event occurred in 83 patients (3.2% per patient-year) in the edoxaban group and in 101 patients (4.0% per patient-year) in the placebo group (hazard ratio, 0.81; 95% confidence interval [CI], 0.60 to 1.08; P = 0.15). The incidence of stroke was approximately 1% per patient-year in both groups. A safety outcome event occurred in 149 patients (5.9% per patient-year) in the edoxaban group and in 114 patients (4.5% per patient-year) in the placebo group (hazard ratio, 1.31; 95% CI, 1.02 to 1.67; P = 0.03). ECG-diagnosed atrial fibrillation developed in 462 of 2536 patients (18.2% total, 8.7% per patient-year). CONCLUSIONS: Among patients with AHREs detected by implantable devices, anticoagulation with edoxaban did not significantly reduce the incidence of a composite of cardiovascular death, stroke, or systemic embolism as compared with placebo, but it led to a higher incidence of a composite of death or major bleeding. The incidence of stroke was low in both groups. (Funded by the German Center for Cardiovascular Research and others; NOAH-AFNET 6 ClinicalTrials.gov number, NCT02618577; ISRCTN number, ISRCTN17309850.).

Economic burden of cardiovascular diseases in the European Union: a population-based cost study.

BACKGROUND AND AIMS: Cardiovascular disease (CVD) impacts significantly health and social care systems as well as society through premature mortality and disability, with patients requiring care from relatives. Previous pan-European estimates of the economic burden of CVD are now outdated. This study aims to provide novel, up-to-date evidence on the economic burden across the 27 European Union (EU) countries in 2021. METHODS: Aggregate country-specific resource use data on morbidity, mortality, and health, social and informal care were obtained from international sources, such as the Statistical Office of the European Communities, enhanced by data from the European Society of Cardiology Atlas programme and patient-level data from the Survey of Health, Ageing and Retirement in Europe. Country-specific unit costs were used, with cost estimates reported on a per capita basis, after adjustment for price differentials. RESULTS: CVD is estimated to cost the EU €282 billion annually, with health and long-term care accounting for €155 billion (55%), equalling 11% of EU-health expenditure. Productivity losses accounted for 17% (€48 billion), whereas informal care costs were €79 billion (28%). CVD represented a cost of €630 per person, ranging from €381 in Cyprus to €903 in Germany. Coronary heart disease accounted for 27% (€77 billion) and cerebrovascular diseases for 27% (€76 billion) of CVD costs. CONCLUSIONS: This study provides contemporary estimates of the wide-ranging impact of CVD on all aspects of the economy. The data help inform evidence-based policies to reduce the impact of CVD, promoting care access and better health outcomes and economic sustainability.

Global epidemiology of acute coronary syndromes.

This Review provides an epidemiological overview of global mortality from acute coronary syndromes (ACS). Across the regions of the world where data are available, mortality from ACS - including premature (age <70 years) mortality from ACS - was higher in men than in women. In both sexes, age-standardized mortality rates (ASMRs) for ACS in 2020 were highest in lower-income global regions. However, 20 years earlier, ASMRs for ACS were highest in higher-income global regions, including Europe, Northern America and Oceania. These higher-income regions have seen progressive reductions in mortality from ACS during the past 20 years, which is in contrast to the more stable levels of mortality from ACS in Asia and in Latin America and the Caribbean. In the seven African countries with data available, a small upwards trend in ASMRs for ACS was observed, reflecting an epidemiological transition that is already well advanced in these regions. Consistent with these changes during the past 20 years were >50% reductions in ASMRs for ACS in the high-income countries of the world compared with <15% reductions in lower-middle-income countries. Policymakers need more complete epidemiological data across and within global regions to identify those countries in which the burden of death from ACS is greatest and the need to implement preventive strategies is most pressing.

The burden of atrial fibrillation and heart failure in hospitalized patients: A real-world survey in a nationwide snapshot.

PURPOSE: Atrial fibrillation (AF) and heart failure (HF) are common and commonly coexisting cardiovascular diseases in hospitalized patients. We report the absolute number and interrelation between AF and HF, assess the daily burden of both diseases on the healthcare system, and describe the medical treatment in a real-world, nationwide conducted snapshot survey. METHODS: A questionnaire was equally distributed to various healthcare institutions. Data on the baseline characteristics, prior hospitalizations, and medical treatments of all hospitalized patients with AF and HF at a predefined date were collected and analyzed. RESULTS: Seventy-five cardiological departments participated in this multicenter Greek nationwide study. A total of 603 patients (mean age, 74.5 ± 11.4 years) with AF, HF, or the combination of both were nationwide admitted. AF, HF, and the combination of both were registered in 122 (20.2%), 196 (32.5%), and 285 (47.3%) patients, respectively. First-time hospital admission was recorded in 273 (45.7%) of 597 patients, whereas 324 (54.3%) of 597 patients had readmissions in the past 12 months. Of the entire population, 453 (75.1%) were on beta-blockers (BBs), and 430 (71.3%) were on loop diuretics. Furthermore, 315 patients with AF (77.4%) were on oral anticoagulation, of whom 191 (46.9%) were on a direct oral anticoagulant and 124 (30.5%) were on a vitamin K antagonist. CONCLUSION: Hospitalized patients with AF and/or HF have more than one admission within a year. Coexistence of AF and HF is more common. BBs and loop diuretics are the most commonly used drugs. More than three-quarters of the patients with AF were on oral anticoagulation.

Ablation of residual potentials along the circumferential line reduces acute pulmonary vein reconnection.

INTRODUCTION: Acute pulmonary vein (PV) reconnection is frequently encountered in patients undergoing PV isolation (PVI) procedure for the treatment of atrial fibrillation. In this study, we investigated whether the identification and ablation of residual potentials (RPs), after the initial achievement of PVI, reduces acute PV reconnection rate. METHODS: Following PVI in 160 patients, mapping along the ablation line was performed to identify RPs, defined as bipolar amplitude ≥0.2 mV or 0.1-0.19 mV combined with a negative component of the unipolar electrogram. Ipsilateral PV sets with RPs were randomized to either no further ablation (Group B) or to additional ablation of the identified RPs (Group C). The primary study endpoint was spontaneous or adenosine-mediated acute PV reconnection after a 30-min waiting period and was also evaluated in ipsilateral PV sets without RPs (Group A). RESULTS: After isolation of 287 PV pairs, 135 had no RPs (Group A), whereas the remaining PV pairs were randomized to either Group B (n = 75) or Group C (n = 77). Ablation of RPs resulted in a reduction of spontaneous or adenosine-mediated PV reconnection rate (16.9% in Group C vs 48.0% in Group B; p < 0.001). Group A was associated with a significantly lower percentage of acute PV reconnection as compared to Group B (5.9% vs 48.0%; p < 0.001) and Group C (5.9% vs 16.9%; p = 0.016). CONCLUSION: After PVI achievement, the absence of RPs along the circumferential line is associated with a low likelihood of acute PV reconnection rate. Ablation of RPs significantly reduces spontaneous or adenosine-mediated acute PV reconnection rate.

Cost-effectiveness of early rhythm control vs. usual care in atrial fibrillation care: an analysis based on data from the EAST-AFNET 4 trial.

AIMS: The randomized, controlled EAST-AFNET 4 trial showed that early rhythm control (ERC) reduces the rate of a composite primary outcome (cardiovascular death, stroke, or hospitalization for worsening heart failure or acute coronary syndrome) by ∼20%. The current study examined the cost-effectiveness of ERC compared to usual care. METHODS AND RESULTS: This within-trial cost-effectiveness analysis was based on data from the German subsample of the EAST-AFNET 4 trial (n = 1664/2789 patients). Over a 6-year time horizon and from a healthcare payer's perspective, ERC was compared to usual care regarding costs (hospitalization and medication) and effects (time to primary outcome; years survived). Incremental cost-effectiveness ratios (ICERs) were calculated. Cost-effectiveness acceptability curves were constructed to visualize uncertainty. Early rhythm control was associated with higher costs [+€1924, 95% CI (-€399, €4246)], resulting in ICERs of €10 638 per additional year without a primary outcome and €22 536 per life year gained. The probability of ERC being cost-effective compared to usual care was ≥95% or ≥80% at a willingness-to-pay value of ≥€55 000 per additional year without a primary outcome or life year gained, respectively. CONCLUSION: From a German healthcare payer's perspective, health benefits of ERC may come at reasonable costs as indicated by the ICER point estimates. Taking statistical uncertainty into account, cost-effectiveness of ERC is highly probable at a willingness-to-pay value of ≥€55 000 per additional life year or year without a primary outcome. Future studies examining the cost-effectiveness of ERC in other countries, subgroups with higher benefit from rhythm control therapy, or cost-effectiveness of different modes of ERC are warranted.