Introduction. Heart failure (HF) and systemic inflammation are interdependent processes that continuously potentiate each other. Distinct pathophysiological pathways are activated, resulting in increased neutrophil count and reduced lymphocyte numbers, making the neutrophil to lymphocyte ratio (NLR) a potential indirect marker of severity. We conducted this comprehensive review to characterize the role of NLR in HF. Methods. We searched the PubMed (MEDLINE) database using the key words “neutrophil”, “lymphocyte”, “heart failure”, “cardiomyopathy”, “implantable cardioverter defibrillator”, “cardiac resynchronization therapy” and “heart transplant”. Results. We identified 241 publications. 31 were selected for this review, including 12,107 patients. NLR was correlated to HF severity expressed by clinical, biological, and imaging parameters, as well as to short and long-term prognosis. Most studies reported its survival predictive value. Elevated NLR (>2.1–7.6) was an independent predictor of in-hospital mortality [adjusted HR 1.13 (95% CI 1.01–1.27) – 2.8 (95% CI 1.43–5.53)] as well as long-term all-cause mortality [adjusted HR 1.43 (95% CI 1.1–1.85) – 2.403 (95% CI 1.076–5.704)]. Higher NLR levels also predicted poor functional capacity [NLR > 2.26/2.74, HR 3.93 (95% CI 1.02–15.12) / 3.085 (95% CI 1.52–6.26)], hospital readmissions [NLR > 2.9/7.6, HR 1.46 (95% CI 1.10–1.93) / 3.46 (95% CI 2.11–5.68)] cardiac resynchronization therapy efficacy [NLR > 3.45/unit increase, HR 12.22 (95% CI 2.16–69.05) / 1.51 (95% CI 1.01–2.24)] and appropriate implantable cardioverter defibrillator shocks (NLR > 2.93), as well as mortality after left ventricular assist device implantation [NLR > 4.4 / quartiles, HR 1.67 (95% CI 1.03–2.70) / 1.22 (95% CI 1.01–1.47)] or heart transplant (NLR > 2.41, HR 3.403 (95% CI 1.04–11.14)]. Conclusion. Increased NLR in HF patients can be a valuable auxiliary biomarker of severity, and most of all, of poor prognosis.

Background Clinical complexity is increasingly prevalent among patients with atrial fibrillation (AF). The ‘Atrial fibrillation Better Care’ (ABC) pathway approach has been proposed to streamline a more holistic and integrated approach to AF care; however, there are limited data on its usefulness among clinically complex patients. We aim to determine the impact of ABC pathway in a contemporary cohort of clinically complex AF patients. Methods From the ESC-EHRA EORP-AF General Long-Term Registry, we analysed clinically complex AF patients, defined as the presence of frailty, multimorbidity and/or polypharmacy. A K-medoids cluster analysis was performed to identify different groups of clinical complexity. The impact of an ABC-adherent approach on major outcomes was analysed through Cox-regression analyses and delay of event (DoE) analyses. Results Among 9966 AF patients included, 8289 (83.1%) were clinically complex. Adherence to the ABC pathway in the clinically complex group reduced the risk of all-cause death (adjusted HR [aHR]: 0.72, 95%CI 0.58–0.91), major adverse cardiovascular events (MACEs; aHR: 0.68, 95%CI 0.52–0.87) and composite outcome (aHR: 0.70, 95%CI: 0.58–0.85). Adherence to the ABC pathway was associated with a significant reduction in the risk of death (aHR: 0.74, 95%CI 0.56–0.98) and composite outcome (aHR: 0.76, 95%CI 0.60–0.96) also in the high-complexity cluster; similar trends were observed for MACEs. In DoE analyses, an ABC-adherent approach resulted in significant gains in event-free survival for all the outcomes investigated in clinically complex patients. Based on absolute risk reduction at 1 year of follow-up, the number needed to treat for ABC pathway adherence was 24 for all-cause death, 31 for MACEs and 20 for the composite outcome. Conclusions An ABC-adherent approach reduces the risk of major outcomes in clinically complex AF patients. Ensuring adherence to the ABC pathway is essential to improve clinical outcomes among clinically complex AF patients.

Aims The 4S-AF classification scheme comprises of four domains: stroke risk (St), symptoms (Sy), severity of atrial fibrillation (AF) burden (Sb), and substrate (Su). We sought to examine the implementation of the 4S-AF scheme in the EORP-AF General Long-Term Registry and compare outcomes in AF patients according to the 4S-AF-led decision-making process. Methods and results  Atrial fibrillation patients from 250 centres across 27 European countries were included. A 4S-AF score was calculated as the sum of each domain with a maximum score of 9. Of 6321 patients, 8.4% had low (St), 47.5% EHRA I (Sy), 40.5% newly diagnosed or paroxysmal AF (Sb), and 5.1% no cardiovascular risk factors or left atrial enlargement (Su). Median follow-up was 24 months. Using multivariable Cox regression analysis, independent predictors of all-cause mortality were (St) [adjusted hazard ratio (aHR) 8.21, 95% confidence interval (CI): 2.60–25.9], (Sb) (aHR 1.21, 95% CI: 1.08–1.35), and (Su) (aHR 1.27, 95% CI: 1.14–1.41). For CV mortality and any thromboembolic event, only (Su) (aHR 1.73, 95% CI: 1.45–2.06) and (Sy) (aHR 1.29, 95% CI: 1.00–1.66) were statistically significant, respectively. None of the domains were independently linked to ischaemic stroke or major bleeding. Higher 4S-AF score was related to a significant increase in all-cause mortality, CV mortality, any thromboembolic event, and ischaemic stroke but not major bleeding. Treatment of all 4S-AF domains was associated with an independent decrease in all-cause mortality (aHR 0.71, 95% CI: 0.55–0.92). For each 4S-AF domain left untreated, the risk of all-cause mortality increased substantially (aHR 1.35, 95% CI: 1.16–1.56). Conclusion  Implementation of the novel 4S-AF scheme is feasible, and treatment decisions based on this scheme improve mortality rates in AF.

Background Frailty is a medical syndrome characterised by reduced physiological reserve and increased vulnerability to stressors. Data regarding the relationship between frailty and atrial fibrillation (AF) are still inconsistent. Objectives We aim to perform a comprehensive evaluation of frailty in a large European cohort of AF patients. Methods A 40-item frailty index (FI) was built according to the accumulation of deficits model in the AF patients enrolled in the ESC-EHRA EORP-AF General Long-Term Registry. Association of baseline characteristics, clinical management, quality of life, healthcare resources use and risk of outcomes with frailty was examined. Results Among 10,177 patients [mean age (standard deviation) 69.0 (11.4) years, 4,103 (40.3%) females], 6,066 (59.6%) were pre-frail and 2,172 (21.3%) were frail, whereas only 1,939 (19.1%) were considered robust. Baseline thromboembolic and bleeding risks were independently associated with increasing FI. Frail patients with AF were less likely to be treated with oral anticoagulants (OACs) (odds ratio 0.70, 95% confidence interval 0.55–0.89), especially with non-vitamin K antagonist OACs and managed with a rhythm control strategy, compared with robust patients. Increasing frailty was associated with a higher risk for all outcomes examined, with a non-linear exponential relationship. The use of OAC was associated with a lower risk of outcomes, except in patients with very/extremely high frailty. Conclusions In this large cohort of AF patients, there was a high burden of frailty, influencing clinical management and risk of adverse outcomes. The clinical benefit of OAC is maintained in patients with high frailty, but not in very high/extremely frail ones.