Serum free and esterified carnitine levels as well as lipids were investigated in patients undergoing regular hemodialysis (HD) treatment before and during 12 weeks of treatment with L-carnitine (1 g i.v.) at the end of each HD. The results were compared with those obtained in patients on continuous ambulatory peritoneal dialysis (CAPD; n = 15) or intermittent peritoneal dialysis (IPD; n = 3) and healthy controls (CO; n = 20). In HD patients (n = 23) total carnitine (TC) was 49.9 ± 3.9 (CO: 46.0 ± 2.5; NS), free carnitine (FC) was 31.6 ± 2.8 (CO: 37.4 ± 1.3; p < 0.05), short-chain acylcarnitine (SCC) was 17.0 ± 1.8 (CO: 7.2 ± 0.9; p < 0.0001) and long-chain acylcarnitine (LCC) was 1.2 ± 0.2 μmol/l (CO: 0.6 ± 0.1; p < 0.05). FC was in the normal range in CAPD (35.6 ± 3.2) and IPD (44.5 ± 8.0 μmol/l) patients, whereas SCC (30.1 ± 3.5) and LCC (2.9 ± 0.2) levels were maximal elevated in IPD patients (11.8 ± 0.8 and 1.5 ± 0.2 on CAPD). Therefore, TC was higher in IPD than in CAPD patients (77.5 ± 5.0 vs. 49.0 ± 3.5 μmol/l). 12 weeks after L-carnitine supplementation in HD patients, TC was 313.9 ± 22.6, FC was 207.7 ± 12.4, SCC was 99.6 ± 12.1 and LCC was 7.1 ± 0.6 μmol/l. TC and FC were significantly lower in females compared with males. Total cholesterol and ketone bodies were normal, HDL cholesterol was significantly decreased before and after L-carnitine supplementation. On the other hand, a paradoxical rise in serum triglycerides was observed. Our data indicate abnormalities of free and esterified carnitine in HD, CAPD and IPD patients. The markedly elevated serum levels for TC, FC, SCC and LCC following L-carnitine therapy suggest limited carnitine utilization in chronic uremic patients.

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.

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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.

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