Orthotopic heart transplantation (OHT) is the most effective long-term therapy for end-stage heart disease, with implanted left ventricular assist devices ('destination therapy') as an alternative for selected patients. The denervation of the transplanted heart with complete loss of autonomic nervous system modulation, the use of immunosuppressant drugs, as well as the risk of allograft rejection (AR) and vasculopathy, all change the incidence, prognosis and treatment of tachyarrhythmias and bradyarrhythmias, as well as the mechanisms of sudden cardiac death (SCD).Arrhythmias post-OHT can be classified according to their underlying mechanisms (see Table 1). Tachyarrhythmias and bradyarrythmias can come from the transplanted heart, be due to the surgery itself or result from AR or vasculopathy. In addition, bradyarrhythmias may be caused by drugs taken by the recipient patient before surgery. This review aims to present the most common causes of arrhythmias in OHT patients, and to highlight the importance of ruling out and treating AR and vasculopathy -transplant coronary artery disease (TCAD), which should always be the first concern. The causative mechanisms represent different risk factors, and overlap is possible, which may increase the occurrence of such arrhythmias.With the increasing success of radiofrequency (RF) ablation techniques, it is important that cardiologists are familiar with tachycardias and bradycardias in this context, which may benefit from a multidisciplinary approach in the management of the patient starting with the underlying mechanisms. Tachyarrhythmias Supraventricular TachycardiaThe most common atrial arrhythmia in OHT patients is atrial flutter AbstractOrthotopic heart transplantation (OHT) is currently the most effective long-term therapy for patients with end-stage cardiac disease, even as left ventricular devices show markedly improved outcomes. As surgical techniques and immunosuppressive regimens have been refined, short-term mortality caused by sepsis has decreased, while morbidity caused by repeated rejection episodes and vasculopathy has increased, and is often manifested by arrhythmias. These chronic transplant complications require early and aggressive multidisciplinary treatment. Understanding the relationship between arrhythmias and these complications in the acute and chronic stages following OHT is critical in improving patient prognosis, as arrhythmias may be the earliest or sole presentation. Finally, decentralised/ denervated hearts represent a unique opportunity to investigate the underlying mechanisms of arrhythmias.

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.