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Background Neurologic events during primary stay in heart transplant (HTx) recipients may be associated with reduced outcome and survival, which we aim to explore with the current study. Methods and Results We screened and included all patients undergoing HTx in our center between September 2010 and December 2022 (n=268) and checked for the occurrence of neurologic events within their index stay. Neurologic events were defined as ischemic stroke, hemorrhage, hypoxic ischemic injury, or acute symptomatic neurologic dysfunction without central nervous system injury. The cohort was then divided into recipients with (n=33) and without (n=235) neurologic events after HTx. Using a multivariable Cox regression model, the association of neurologic events after HTx and survival was assessed. Recipients with neurologic events displayed a longer intensive care unit stay (30 versus 16 days; P =0.009), longer mechanical ventilation (192 versus 48 hours; P <0.001), and higher need for blood transfusion, and need for hemodialysis after HTx was substantially higher (81% versus 55%; P =0.01). Resternotomy (36% versus 26%; P =0.05) and mechanical life support (extracorporeal life support) after HTx (46% versus 24%; P =0.02) were also significantly higher in patients with neurologic events. Covariable-adjusted multivariable Cox regression analysis revealed a significant independent association of neurologic events and increased 30-day (hazard ratio [HR], 2.5 [95% CI, 1.0-6.0]; P =0.049), 1-year (HR, 2.2 [95% CI, 1.1-4.3]; P =0.019), and overall (HR, 2.5 [95% CI, 1.5-4.2]; P <0.001) mortality after HTx and reduced Kaplan-Meier survival up to 5 years after HTx ( P <0.001). Conclusions Neurologic events after HTx were strongly and independently associated with worse postoperative outcome and reduced survival up to 5 years after HTx.

Aims: Ischemic strokes in patients on oral anticoagulant therapy (OAT) despite optimal adherence pose a therapeutic challenge. We assessed the utility of transesophageal echocardiography (TEE) in identifying potential competing cardiac causes for stroke that occurred despite adequate OAT., Methods: This retrospective observational study included patients admitted for acute ischemic stroke between January 2022 and June 2023 who were on OAT for an established long-term indication. Transthoracic and transesophageal echocardiography, along with assessment of OAT adherence, were conducted. Demographic data, OAT details, and stroke characteristics were analysed to determine the influence of TEE findings on therapeutic decisions., Results: We included 26 patients. TEE identified potential cardiac competing stroke mechanisms in 88% of cases, with valvular thrombi and left atrial or appendage thrombus being predominant. Infective endocarditis, often asymptomatic, was unexpectedly prevalent. TEE significantly influenced therapeutic decisions, especially in cases where transthoracic echocardiography was inconclusive., Conclusions: TEE may be crucial for unravelling the mechanisms of ischemic stroke in patients on adequate OAT, guiding precise therapeutic strategies and potentially reducing the risk of recurrent embolic events. Our findings underscore the limitations of standard echocardiography in detecting cardiac embolic sources and emphasize the importance of tailored decision-making in secondary stroke prevention., (Copyright © 2024 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Objectives: The optimal management of acute ischemic stroke (AIS) in patients with oral anticoagulation (OA) is challenging. Our study aimed to analyze the clinical characteristics and outcome of AIS in patients with OA for nonvalvular atrial fibrillation (NVAF)., Methods: We retrospectively analyzed data on NVAF patients with AIS on direct oral anticoagulants (DOAC) or vitamin K antagonists (VKA) admitted to our Stroke Unit from 2017 to 2022. Ninety-day modified Rankin Scale (mRS), 90-day, and 12-month stroke recurrences were recorded., Results: A total of 169 patients (53.2% female, mean age 82.8±6.7 y), 117 (69.2%) on DOAC, and 52 on VKA (30.8%), were enrolled. Mean age, in-hospital mortality, and 90-day mRS ≥4 were significantly higher in VKA patients. 63.4% of VKA patients had subtherapeutic INR, whereas 47.1% of DOAC patients were on low-dose (14.2% off-label). Large vessel occlusion and embolic etiology were more frequent in VKA patients (34.6% vs. 26.4%, P =0.358; 92.3% vs. 74.3%, P =0.007, respectively), whereas lacunar strokes were more frequent in DOAC patients (19.8% vs. 12.2%, P =0.366). Among patients on VKA before AIS 86.4% were switched to DOAC, whereas a DOAC-to-VKA and a DOAC-to-DOAC switch were done in 25.4% and 11.7%, respectively. Stroke recurrence occurred in 6.4% of patients at 90 days and 10.7% at 12 months. Anticoagulant switching was not associated with stroke recurrences., Conclusions: In our study, nonembolic etiology was more frequent in DOAC patients and anticoagulant switching did not reduce the risk of stroke recurrence. Prospective multicentric studies are warranted., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: While direct-acting oral anticoagulants (DOACs) have established efficacy in reducing the risk of ischemic stroke, they still leave a residual risk of stroke, which may be greater in practice (0.7–2.3%) than in controlled clinical trial settings. This meta-analysis examines four therapeutic approaches following a stroke in patients already on DOACs: continuing with the same DOAC, changing to a different DOAC, increasing the current DOAC dosage, or switching to a vitamin K antagonist (VKA), such as warfarin. Methods: Systematic review of literature from the MEDLINE, Embase, and Cochrane databases, was conducted in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The analysis focused on six studies with varied patient demographics, examining as outcomes as recurrent ischemic stroke, intracranial hemorrhage, other bleeding events, and mortality. Results: Six studies comprising 12,159 patients were included, all of them were observational. Patients who remained on their initial DOAC regimen had a lower risk of experiencing ischemic strokes (risk ratio (RR) 0.55; 95% confidence interval (CI) 0.43–0.70; p < 0.001; I2 = 0%), intracranial hemorrhage (RR 0.37; 95% CI 0.25–0.55; p < 0.001; I2 = 0%), and hemorrhagic events (RR 0.44; 95% CI 0.30–0.63; p < 0.001; I2 = 6%) compared to those who were switched to warfarin, with an increase in mortality rates (hazard ratio (HR) 1.85; 95% CI 1.06–3.24; p = 0.03; I2 = 84%). In contrast, neither changing to a different DOAC nor adjusting the dose proved to be more effective than the original regimen. Conclusion: Post-stroke adjustments to anticoagulation therapy—whether altering the drug or its dosage—do not yield additional benefits. In addition, the results suggest that warfarin may be less effective than DOACs for preventing stroke recurrence, bleeding complications, and death in this patient population. [ABSTRACT FROM AUTHOR]

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Background/Objectives: Despite the widespread use of oral anticoagulants (OACs), acute ischemic stroke (AIS) remains a significant risk for patients with atrial fibrillation (AF). The real-world effectiveness of OACs in preventing recurrent strokes, particularly following an initial stroke of cardioembolic (CE) origin, continues to be a major challenge for clinicians managing AF patients. This study evaluated the efficacy of OACs in secondary stroke prevention and investigated the influence of anticoagulation type and quality on recurrence risk. Methods: We analyzed data from 128 AF patients in the prospective Transzlációs Idegtudományi Nemzeti Laboratórium (TINL) STROKE-registry, admitted with CE stroke between February 2023 and September 2024. Patients were categorized by anticoagulation status at admission (OAC-users, n = 89; anticoagulation-naïve, n = 39). Recurrence rates were assessed using logistic regression models, adjusted for age, sex, hypertension, diabetes, and pre-stroke disability. Subgroup analyses explored the effects of anticoagulation type and quality. Results: Recurrence rates were similar between the OAC-treated and anticoagulation-naïve patients after adjusting for confounders (19.10% vs. 17.95%, p = 0.870). Among the anticoagulated patients, neither anticoagulation type nor quality alone significantly influenced the recurrence risk. However, their interaction was statistically significant (p = 0.049), suggesting that the effectiveness of anticoagulation in preventing strokes is strongly affected by treatment quality. Conclusions: Although OACs are a cornerstone of stroke prevention in patients with AF, their efficacy in reducing recurrence depends on optimal management. These findings highlight that adequate anticoagulation, not just its use, is critical to minimize recurrence risk. To effectively prevent strokes in high-risk AF patients, future strategies must focus on standardized protocols, tailored monitoring, and individualized dosing regimens. [ABSTRACT FROM AUTHOR]

Background: Patients with atrial fibrillation (AF) have a high risk for recurrent clinical events after an ischemic stroke. Direct oral anticoagulants (DOAC) are prescribed for secondary prevention. Adherence to DOAC is crucial mainly because of their short elimination half-life. Non-adherence to DOAC can negatively impact patients' outcomes. The relationship between (non-)adherence and recurrent clinical events is unknown in AF patients after initial stroke. We investigated adherence to DOAC in stroke survivors with AF who were included in the MAAESTRO study at the University Hospital Basel, Switzerland, between 2008 and 2022. Methods: This study is a secondary analysis of data from MAAESTRO with a matched nested case-control design and 1:2 ratio. DOAC intake was measured with a small electronic device (Time4MedTM). We defined two arbitrary intervals of 17 days and 95 days as the longest time spans with electronic monitoring data per patient to maximize the number of participants with adequate amount of observation time available for analysis. Taking and timing adherence were calculated retrospectively i.e., prior to the recurrent event for cases. Trendline analysis of adherence over 95 days was calculated. Linear regression analysis was performed after adjusting for the co-variables age and daily pill burden. Sensitivity analysis was performed with controls for intervals in the reverse direction (prospectively). Results: We analyzed 11 cases and 22 matched controls (mean age: 75.9 ± 9.2 years vs. 73.1 ± 8.4 years; n.s.) with similar stroke characteristics (NIHSS, mRS, MoCA) and 36.4% women in each group. Mean adherence values were high and similar between cases and controls (95 days taking: 87.0 ± 18.9% (cases) vs. 90.8 ± 9.8% (controls), n.s.; similar values for timing adherence). Six hemorrhagic and five ischemic events had occurred. Compared to controls, a significantly higher 95 days taking adherence was observed for hemorrhagic events (96.0 ± 5.0% (cases) vs. 88.1 ± 11.5% (controls); p<0.01) and a significantly lower 95 days taking adherence was observed for ischemic events (75.7 ± 24.8% (cases) vs. 94.2 ± 6.2% (controls), p = 0.024). Values for timing adherence were similar. A non-significant downward linear trend of adherence was observed over 95 days independently of the clinical events. The sensitivity analysis showed that the direction of the interval had negligible impact on the 95 days adherence. Conclusion: Because recurrent ischemic events after an AF-related stroke were associated with low adherence to DOAC <76%, adherence enhancing interventions seem crucial in anticoagulated AF-patients. However, AF-patients with high adherence might benefit from a regular re-assessment of the bleeding risk as hemorrhagic complications were associated with adherence to DOAC >96%. Trial registration: ClinicalTrials.gov NCT03344146. [ABSTRACT FROM AUTHOR]

Antiphospholipid syndrome (APS) is known as a rare etiology of embolic ischemic stroke. In individuals below 50 years, up to 20% of strokes are associated with APS, whereas in patients >50 years, it is considered a very seldom cause of stroke. We describe the course of a 66-year-old white woman, who experienced four embolic strokes with large vessel occlusion over a period of 2 years, which were repeatedly and successfully treated by mechanical thrombectomy. Initially attributed to atrial fibrillation and treated with direct oral anticoagulants, the patient was finally diagnosed with primary APS due to isolated anti-beta 2-glycoprotein antibodies and successfully treated after several stroke recurrences. After initiation of Vitamin K antagonist therapy, no further strokes occurred. For recurrent embolic stroke despite oral anticoagulation, late-onset APS might be considered a rare etiology also in the elderly. [ABSTRACT FROM AUTHOR]

Introduction. Direct oral anticoagulants (DOAC) are the first-line treatment for primary and secondary acute ischaemic stroke (AIS) prevention in patients with nonvalvular atrial fibrillation (NVAF), but a significant percentage of patients develop AIS despite being treated with DOAC. As the number of DOAC-treated patients is growing, so is the number of patients with AIS on DOAC. The aim of the study was to assess the incidence of AIS with prestroke DOAC treatment among patients hospitalised in the University Hospital in Kraków, to analyse the clinical characteristics of AIS occurring in patients on DOAC, and to identify potential causes of treatment ineffectiveness in this group. Materials and Methods. In the study, we included all patients hospitalised in the Department of Neurology of the University Hospital in Kraków within one year (July 2022 to June 2023) with the diagnosis of AIS. The group was divided into two subgroups of patients with and without prestroke DOAC treatment. Based on medical files, we retrospectively analysed the profile of cardiovascular risk factors, stroke severity (assessed with National Institutes of Health Stroke Scale, NIHSS), use of causative stroke treatment and short-term outcomes (defined as NIHSS score, modified Rankin scale (mRS) score at discharge, in-hospital mortality, and secondary intracerebral haemorrhage among patients treated with mechanical thrombectomy, MT). Within the DOAC-treated subgroup, we looked for potential causes of AIS occurring despite DOAC treatment (valvular AF, poor adherence to treatment, underdosing, other prothrombotic conditions, aetiology of stroke other than thromboembolic, and drug-drug interactions). Results. In the study, we included 768 AIS patients. 109 (14.2%) had a history of prestroke DOAC treatment. A potential cause of DOAC treatment failure was identified in the majority of them (n = 63 , 57.8%). Patients with prestroke DOAC treatment had worse functional condition before stroke and higher stroke severity on admission but similar short-term outcomes and similar short-term effects of treatment with MT. DOAC (+) and DOAC (-) patients had different profiles of cardiovascular risk factors and different factors associated with short-term outcome. Conclusions and Clinical Implications. A potential cause of AIS occurring in DOAC-treated patients can be identified in most cases and in many of them prevented. [ABSTRACT FROM AUTHOR]

Introduction: Patients with ischemic stroke (IS) and atrial fibrillation (AF) face a higher risk of recurrent vascular events. This study evaluates the impact of atherosclerotic vascular disease burden across different vascular territories on the risk of vascular events in patients with recent ischemic stroke and AF within 90 days. Patients and Methods: We included patients with IS and AF from the International RAF network in a prospective 90-day follow-up. Atherosclerotic vascular disease was identified by at least one of the following: Symptomatic ischemic heart disease, symptomatic peripheral artery disease, internal carotid stenosis ≥50%, or the presence of plaques in the aorta. The primary outcome was a composite of stroke, transient ischemic attack, systemic embolism, cerebral bleeding, and major extracranial bleeding within 90 days postacute stroke. Patients were categorized into 5 groups based on the number of affected atherosclerotic vascular territories, with those with no atherosclerotic vascular disease as the reference. Kaplan–Meier curves were generated and compared using the log-rank test to determine the predictive value of the number of diseased territories for the risk of events. Data analysis was performed with SPSS/PC Win Package 25.0. Results: Of the 2148 patients (mean age 77.59; 53.86% female), 744 (34.60%) had atherosclerosis. Multivariable analysis revealed that involvement of 3 (hazard ratio [HR] 2.80, 95% confidence interval [CI]: 1.20-6.53) or 4 (HR 6.81, 95% CI: 1.02-36.24) vascular territories was significantly associated with the risk of combined events. Conclusions: In patients with recent ischemic stroke and AF, atherosclerosis across multiple territories correlates with a higher risk of future vascular events. [ABSTRACT FROM AUTHOR]

Background and Aims: Non-valvular atrial fibrillation (NVAF) patients face a 3– 5 times greater risk of acute ischemic stroke (AIS) compared to those without NVAF. This study aims to establish a novel clinical prediction model for AIS in elderly patients with NVAF by incorporating relevant biomarker indicators.Methods: A total of 301 individuals diagnosed with NVAF were selected for this investigation at the Third Affiliated Hospital of Anhui Medical University. Based on the presence of AIS, patients were categorized into two groups: the Stroke Cohort and the Non-Stroke Cohort. Predictor screening was performed using the least absolute shrinkage and selection operation (LASSO) regression algorithm. The binary logistic regression equation was applied to fit the model, followed by internal validation using the bootstrap resampling method (1000 times). Receiver operating characteristic (ROC) curve, calibration degree curve plots, and clinical decision curve analysis (DCA) were generated, respectively. Finally, a nomogram was constructed to present the prediction model.Results: The final results of this study revealed that neutrophil-to-lymphocyte ratio (NLR), red cell distribution width (RDW), lipoprotein(a) (Lp(a)), systolic pressure, history of stroke, hyperlipidemia were independent risk factors for AIS in elderly patients with NVAF (P< 0.05). And the high-density lipoprotein cholesterol (HDL-C) was an independent protective factor (P< 0.05). By incorporating these indicators, a nomogram prediction model for predicting AIS in elderly patients with NVAF was constructed. Comparative analysis between the nomogram predictive model and CHA2DS2-VASc score revealed that the AUC of the nomogram predictive model surpassed that of the CHA2DS2-VASc score (AUC: 0.881vs 0.850).Conclusion: NLR, RDW, Lp(a), SP, history of stroke, hyperlipidemia, and HDL-C emerge as independent prognostic factors for acute ischemic stroke in elderly patients with non-valvular atrial fibrillation. The predictive utility of the nomogram model may potentially surpass that of the CHA2DS2-VASc scoring system. [ABSTRACT FROM AUTHOR]

Patients with atrial fibrillation (AF) experiencing ischemic stroke despite oral anticoagulation (OAC), i.e., breakthrough strokes, are not uncommon, and represent an important clinical subgroup in view of the consistently high risk of stroke recurrence and mortality. The understanding of the heterogenous potential mechanism underlying OAC failure is essential in order to implement specific therapeutic measures aimed at reducing the risk of recurrent ischemic stroke. However, due to the incomplete comprehension of this phenomenon and the limited available data, secondary stroke prevention in such high-risk patients represents a clinical dilemma. There are several available strategies to prevent ischemic stroke recurrence in AF patients with breakthrough stroke in the absence of competing causes unrelated to AF, and these include continuation or change in the type of OAC, addition of antiplatelet therapy, left atrial appendage closure, or any combination of the above options. However, due to the limited available data, the latest guidelines do not provide any specific recommendations about which of the above strategies may be preferred. This review describes the incidence, the clinical impact and the potential mechanisms underlying OAC failure in AF patients. Furthermore, the evidence supporting each of the above therapeutic options for secondary stroke prevention and the potential future directions will be discussed. [ABSTRACT FROM AUTHOR]

Copyright of Turkish Journal of Neurology / Turk Noroloji Dergisi is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Atrial fibrillation (AF) is an important risk factor for ischemic stroke (IS). Oral anticoagulation (OAC) significantly reduces the risk of IS in AF but also increases the risk of systemic bleeding, including intracerebral hemorrhage (ICH). AF-related strokes are associated with greater disability and mortality compared to non-AF strokes. The management of patients with AF-related strokes is challenging, and it involves weighing individual risks and benefits in the acute treatment and preventive strategies of these patients. This review summarizes the current knowledge of the acute management of ischemic and hemorrhagic stroke in patients with AF, and the prognosis and potential implications for management both in the acute and long-term setting. [ABSTRACT FROM AUTHOR]

Background: Atrial fibrillation (AF) known before ischemic stroke (KAF) has been postulated to be an independent category with a recurrence risk higher than that of AF detected after stroke (AFDAS). However, it is unknown whether this risk difference is confounded by pre‐existing anticoagulation, which is most common in KAF and also indicates a high ischemic stroke recurrence risk. Methods: Individual patient data analysis from 5 prospective cohorts of anticoagulated patients following AF‐associated ischemic stroke. We compared the primary (ischemic stroke recurrence) and secondary outcome (all‐cause death) among patients with AFDAS versus KAF and among anticoagulation‐naïve versus previously anticoagulated patients using multivariable Cox, Fine‐Gray models, and goodness‐of‐fit statistics to investigate the relative independent prognostic importance of AF‐category and pre‐existing anticoagulation. Results: Of 4,357 patients, 1,889 (43%) had AFDAS and 2,468 (57%) had KAF, while 3,105 (71%) were anticoagulation‐naïve before stroke and 1,252 (29%) were previously anticoagulated. During 6,071 patient‐years of follow‐up, we observed 244 recurrent strokes and 661 deaths. Only pre‐existing anticoagulation (but not KAF) was independently associated with a higher hazard for stroke recurrence in both Cox and Fine‐Gray models. Models incorporating pre‐existing anticoagulation showed better fit than those with AF category; adding AF‐category did not result in better model fit. Neither pre‐existing anticoagulation nor KAF were independently associated with death. Conclusion: Our findings challenge the notion that KAF and AFDAS are clinically relevant and distinct prognostic entities. Instead of attributing an independently high stroke recurrence risk to KAF, future research should focus on the causes of stroke despite anticoagulation to develop improved preventive treatments. ANN NEUROL 2023;94:43–54 [ABSTRACT FROM AUTHOR]

Aims The prognosis of patients with atrial fibrillation (AF) and ischemic stroke while taking oral anticoagulation is poorly understood. This study aimed to characterize the outcomes of patients following a stroke event while on oral anticoagulation. Methods and results Individual participant data from five pivotal randomized trials of antithrombotic therapy in AF were used to assess the outcomes of patients with a post-randomization ischemic stroke while on study medication (warfarin, standard-, or lower-dose direct oral anticoagulant regimen) during trial follow-up. The primary outcome was recurrent ischemic stroke after the first post-randomization ischemic stroke. The primary analysis included 1163 patients with a first post-randomization ischemic stroke while on study medication (median age 73 years, 39.3% female, 35.4% history of stroke before trial enrollment). During a median continued follow-up of 337 days, 74 patients had a recurrent ischemic stroke [cumulative incidence at 1 year: 7.0%, 95% confidence interval (CI) 5.2%–8.7%]. The cumulative incidence of mortality at 3 months after stroke was 12.4% (95% CI 10.5%–14.4%). Consistent results for the incidence of recurrent ischemic stroke at 1 year were obtained in an analysis accounting for the competing risk of death (6.2%, 95% CI 4.8%–7.9%) and in a landmark analysis excluding the first 2 weeks after the index stroke and only including patients without permanent study drug discontinuation since then (6.8%, 95% CI 4.6%–8.9%). Conclusion Patients with AF and ischemic stroke while on oral anticoagulation are at increased risk of recurrent ischemic stroke and death. These patients currently have an unmet medical need. [ABSTRACT FROM AUTHOR]

Graph: Graphical Abstract A-C-T-I-O-N items that should be considered in atrial fibrillation (AF) patients suffering an ischaemic stroke while on oral anticoagulation (OAC). Recurrent ischaemic stroke risk was higher in study patients with a history of any stroke prior to randomization when compared with patients without prior stroke. During a median follow-up of 337 days, 74 (6.3%) patients suffered recurrent ischaemic stroke and 235 (20.2%) patients died.[3] As secondary haemorrhagic transformation of the index stroke may have been falsely classified as haemorrhagic stroke, respective frequencies were not reported. [Extracted from the article]

Neurological events (NE) during primary stay in heart transplant (HTx) recipients may be associated with reduced outcome and survival. We screened all patients undergoing HTx in our center between 09/2010 and 04/2022 (n=241), and included 237 patients with complete data on occurrence of NE during primary stay. NE were defined as ischemic stroke, hemorrhage, hypoxic ischemic injury or acute symptomatic neurological dysfunction without CNS injury. The cohort (table 1) was divided in recipients with (n=35) and without (n=202) NE after HTx. Using linear regression analysis, association of NE after HTx and survival, was assessed. Functional disability after strokes was classified by the modified Rankin Scale (mRS). Recipients with NE showed worse outcome (details in Table 1), including longer ICU stay, longer mechanical ventilation and more severe infections. Re-sternotomy and mechanical life support (ECLS) post HTx was also significantly higher. Covariable-adjusted regression revealed significant independent association of NE and reduced 30-day (adj. HR 3.8, 95% CI 1.4-10.1, p=.008) and 1-year (adj. HR 3.4, 95% CI 1.3-9.2, p=.013) survival after HTx, confirmed by Kaplan-Meier survival (p <.001, see figure 1A). Those surviving show high severity of functional disability (58% mRS 5). Only a minority recovers completely one year after the event, with 66% at least still mildly disabled (mRS ≥2; see figure 1B). Neurological events post HTx were strongly and independently associated with worse postoperative outcome and reduced survival up to 5 years after heart transplantation. [ABSTRACT FROM AUTHOR]