Liverpool Heart and Chest Hospital

Atrial fibrillation (AF) is the most common arrhythmia in older people, with an increasing prevalence of various geriatric conditions, such as multimorbidity, and frailty. A contemporary integrated approach is effective in reducing the risk of clinical adverse events, particularly when streamlined through the application of the Atrial Fibrillation Better Care (ABC) pathway, as proven in 2 non-European trials. The atrial fibrillation integrated approach in frail, multimorbid and polymedicated older people (AFFIRMO) trial, a European multicenter, open-label, cluster-randomized study, will examine whether a mobile-health integrated care approach based on the ABC pathway combined with a multidimensional Comprehensive Geriatric Assessment (CGA) can reduce the 12-month risk of unplanned all-cause hospitalizations in patients with AF ≥65 years with ≥1 concomitant chronic condition(s). The AFFIRMO trial enrolled 1,260 patients with AF (mean age 74 [SD 6] years; 44.4% female) across 6 European countries (Bulgaria, Denmark, Italy, Romania, Serbia, and Spain). At baseline, the median (IQR) CHA2DS2-VASc score was 4 (3-5), and the median (IQR) HAS-BLED score was 1 (1-2). Hypertension was reported in 992 (78.7%) patients, and diabetes mellitus in 369 (29.3%) patients. Among the enrolled patients, 507 (40.5%) were prefrail, and 171 (13.7%) were frail. Oral anticoagulants (OACs) were prescribed for 1,225 (97.2%) patients, with 1,149 (91.2%) patients receiving non-VKAs oral anticoagulants (NOACs). Follow-up is ongoing and planned to be completed in January 2026. The AFFIRMO trial will provide evidence on the efficacy of the ABC pathway in conjunction with the CGA approach in reducing the risk of unplanned all-cause hospitalizations and other clinical adverse events in older, multimorbid patients with AF. ClinicalTrials.gov identifier: NCT06775028.

Thromboembolic cardiovascular diseases (CVD), including acute coronary syndromes, ischemic stroke, and venous thromboembolism, remain a leading cause of morbidity and mortality worldwide. Despite significant improvements in prevention and diagnosis, thromboembolic CVD remains a major global health challenge, reflecting the incomplete control of multifactorial vascular risk. Growing evidence indicates that air, noise, and light pollution are important yet underrecognized contributors to cardiovascular morbidity. Exposure to particulate matter (PM2.5, PM10), gaseous pollutants (NO2, SO2, CO, O3), chronic noise, and artificial light at night promotes endothelial dysfunction, oxidative stress, inflammation, and platelet activation-key mechanisms fostering a prothrombotic setting. Although regulatory progress has been achieved, air pollution remains the most significant environmental determinant of cardiovascular health globally, and the combined effects of coexisting pollutants are not fully understood. The convergence of urbanization, industrialization, and increasing light exposure further amplifies environmental impacts on vascular health. This scientific statement aims to synthesize current epidemiological and mechanistic evidence, highlight the complex interactions among air, noise, and light pollution, identify critical research gaps, and provide a comprehensive conceptual framework for understanding how environmental stress contributes to thromboembolic cardiovascular complications. Strengthening multidisciplinary research, integrating exposome-based data, and implementing effective prevention policies are essential steps toward mitigating the cardiovascular burden of environmental pollution.

Pharmacotherapy combinations have been shown to improve survival and reduce hospitalisations in adults with chronic heart failure with reduced ejection fraction (HFrEF); however, their cost-effectiveness when used as first-line treatment remains uncertain. A lifetime cohort Markov model was developed from the perspective of the NHS in England to assess the cost-effectiveness of five first-line pharmacotherapy combinations: (i) angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) and beta-blocker (BB) (NICE-recommended treatment at the time of analysis); (ii) ACEI/ARB, BB and mineralocorticoid receptor antagonists (MRA); (iii) angiotensin receptor-neprilysin inhibitor (ARNI), BB and MRA; (iv) ACEI/ARB, BB, MRA and sodium-glucose cotransporter-2 inhibitor (SGLT2i); and (v) ARNI, BB, MRA and SGLT2i. Baseline hospitalisation and mortality rates were informed by real-world data, while treatment effects (HRs) were derived from a review of randomised controlled trials. Among individuals able to tolerate an ACEI, the combination of ACEI, BB, MRA and SGLT2i (cost, £12 124; quality-adjusted life years (QALYs), 5.72) was found to be the most cost-effective first-line treatment option with an incremental cost-effectiveness ratio (ICER) of £7699.Among individuals unable to tolerate an ACEI, the combination of ARNI, BB, MRA and SGLT2i (cost, £18 950; QALYs, 6.04) was found to be the most cost-effective first-line treatment option with an ICER of £15 821. The next most cost-effective first-line treatment option was the combination of ARB, BB, MRA and SGLT2i (cost, £11 842; QALYs, 5.59). These findings were primarily driven by the greater relative QALY gain of ARNI compared with ARB. This study demonstrates that a first-line quadruple pharmacotherapy combination is cost-effective compared with a stepwise approach for treating people with HFrEF, suggesting that wider adoption of early initiation of quadruple pharmacotherapy may improve health outcomes and optimise healthcare resource use.

Antiphospholipid antibodies (aPL) are directed against phospholipids and phospholipid-binding proteins. Laboratory assays used to detect aPL include serological tests for aPL against β2-glycoprotein 1, cardiolipin and other molecules, as well as functional assays for lupus anticoagulant. The presence of aPL can lead to endothelial dysfunction or a hypercoagulable state through prothrombotic and antifibrinolytic mechanisms. These processes, often in conjunction with a 'second hit', such as trauma, surgery, or other causes of hypercoagulability or stasis, can lead to venous or arterial thrombosis. The thrombotic risk associated with aPL is best recognized in thrombotic antiphospholipid syndrome, characterized by a persistently positive test for lupus anticoagulant or seropositivity for aPL associated with venous, arterial or microvascular thrombosis. However, aPL seropositivity and its clinical effect on thrombotic events have been increasingly recognized in a broader group of individuals who do not meet traditional research criteria for thrombotic antiphospholipid syndrome. In this Review, we provide an overview of the evidence related to aPL seropositivity in individuals with or without previous thrombosis and the clinical relevance of aPL seropositivity in predicting the risk of thrombotic cardiovascular events. We discuss potential management strategies and identify key knowledge gaps that warrant further research.

Background/Objectives: Atrial fibrillation (AF) is currently the most common arrhythmia worldwide, and it is linked to increased mortality and morbidity, hence the need for a better clinical stratification of AF patients. Histone complexes or nucleosomes, released into the blood circulation, are found elevated in acute conditions such as stroke, trauma, and sepsis. The aim of this pilot single-centre study was to assess whether circulating histone levels could be used for diagnostic purposes in patients with AF. Methods: A total of 40 patients, well characterised for their biochemical and clinical characteristics, were recruited from outpatient clinics. Patients were randomly recruited into two groups (n = 20 per group), i.e., persistent AF and hypertensive controls. A multi-channel flow imaging methodology based on ImageStreamX was used with a well-optimised protocol to image and quantify five individual histones (H2A, H2B, H3, H4, and macroH2A1.1) together with the dimers (H2A/H2B, and H3/H4). Results: In the AF groups, plasma levels of histone dimers H2A/H2B and H3/H4 were elevated compared to hypertensive controls, 1.8% vs. 1.06% (p-value = 0.03). H2A/H2B dimer levels were increased in AF patients irrespective of gender, smoking status, diabetes, and pharmacological therapy. In the overall population, an inverse correlation between H2A and BMI was detected. Conclusions: Our pilot study, although limited in sample size, suggests that circulating histone complexes may be epigenetic sentinels for AF, offering mechanistic insights while addressing unmet needs in risk stratification.

The present study aimed to report the early and late clinical outcomes of patients who underwent surgical repair for acute type A aortic dissection requiring concomitant coronary artery bypass grafting (CABG), and to explore potential risk factors associated with the need for this additional procedure. Data were retrieved from the multicenter European Registry of Type A Aortic Dissection (ERTAAD). Bootstrapped least absolute shrinkage and selection operator logistic regression and multilevel multivariate logistic regression were performed for variable selection to identify predictors of hospital death, and logistic regression was used for the prediction of CABG. A total of 292 (8.04%) of 3633 patients required additional CABG. The in-hospital mortality rate was 33% for patients undergoing CABG vs 16% of non-CABG recipients (P < .001; odds ratio [OR], 2.52; 95% CI, 1.93-3.35). Dissection of the aortic root involving the right coronary cusp (P < .001; OR, 7.83; 95% CI, 5.55-11.0), a tear in the aortic root (P = .002; OR, 2.08; 95% CI, 1.29-3.32), mitral valve insufficiency (P = .034; OR, 1.33; 95% CI, 1.01-1.71), and a genetic syndrome (P < .001; OR, 3.23; 95% CI, 1.66-5.99) independently predicted the need for CABG. The need for additional CABG is not a rare occurrence during repair of type A aortic dissection and is associated with an increased mortality risk. Intimal tear localization and right coronary sinus dissection should be carefully examined in the preoperative image evaluation to stratify the risk of revascularization and plan the most appropriate approach.