Publicaciones

Atrial Imaging and Cardiac Rhythm in Cryptogenic Embolic Stroke: The ARIES Study

Rigual R,Castrejón-Castrejón S, Fernández-Gassó L et al. J Am Heart Assoc. 2024 Sep 3;13(17):e036236. doi: 10.1161/JAHA.124.036236. Epub 2024 Aug 29. PMID: 39206739.

https://pubmed.ncbi.nlm.nih.gov/39206739/

Abstract: BACKGROUND: Unknown cardioembolic sources are frequent causes of cryptogenic stroke. We analyzed the risk of atrial fibrillation (AF) or high burden of ectopic atrial activity (HBEA) in patients with cryptogenic stroke, assessing atrial function and 1- year outcomes. METHODS AND RESULTS: The ARIES (Atrial Imaging and Cardiac Rhythm in Cryptogenic Embolic Stroke) study is an observational study including patients with cryptogenic stroke. We analyzed the frequency of AF and HBEA (>3000 atrial ectopic beats/day or >2 bursts or atrial tachycardia between 3 beats and ≤30 seconds) in two 30- day Holter- ECGs, comparing advanced echocardiography signs of left atrial (LA) dysfunction according to rhythm: AF, HBEA, and normal sinus rhythm. We also evaluated 1- year stroke recurrence and mortality. The study included 109 patients; 35 (32.1%) patients had AF, 27 (24.8%) HBEA, and 47 (43.1%) normal sinus rhythm. Compared with those with normal sinus rhythm, patients with AF presented higher 2- dimensional and 3- dimensional LA indexed volumes (38.8±11.2 versus 27.3±11.8 mL/m2, and 50.6±17.2 versus 34.0±15.4 mL/m2, respectively, P<0.001), lower 3- dimensional LA ejection fraction (50±14.6 versus 62.7±11.8, P=0.001), LA reservoir strain (22.0±8.6 versus 30.4±10.5, P<0.001), and LA contraction strain (10.5±8.18 versus 17.1±7.5, P<0.001), remaining significant in multivariate analysis. Patients with HBEA showed higher LA indexed volumes and lower LA reservoir strain than patients with normal sinus rhythm only in univariate analysis. There were no differences in ischemic recurrence or mortality among the groups. CONCLUSIONS: Patients with cryptogenic stroke showed a high incidence of AF and HBEA. AF is strongly related to LA volume, LA function, and LA reservoir and contraction strain, whereas HBEA showed milder structural changes. Advanced LA echocardiography could help patient selection for long- term ECG monitoring in suspected cardiac sources.

Funding: This project has been supported by a grant from the Stroke Project of the Cerebrovascular Diseases Study Group of the Spanish Society of Neurology, funded by Daiichi- Sankyo. This work was also supported by RICORS (Redes de Investigación Cooperativa Orientadas a Resultados en Salud) network under grant RD21/0006/0012.

Influence of Hospital Type on Outcomes of Patients With Acute Spontaneous Intracerebral Hemorrhage: A Population-Based Study.

Marti-Fabregas J, Ramos-Pachón A, Prats-Sanchez L,et al. Neurology. 2024 Jul 23;103(2):e209539. doi: 10.1212/WNL.0000000000209539. Epub 2024 Jun 14.. PMID: 38875516
Abstract:

Background and objectives: Whether the outcome of patients with spontaneous intracerebral hemorrhage (ICH) differs depending on the type of hospital where they are admitted is uncertain. The objective of this study was to determine influence of hospital type at admission (telestroke center [TSC], primary stroke center [PSC], or comprehensive stroke center [CSC]) on outcome for patients with ICH. We hypothesized that outcomes may be better for patients admitted to a CSC.

Methods: This is a multicenter prospective observational and population-based study of a cohort of consecutively recruited patients with ICH (March 2020-March 2022). We included all patients with spontaneous ICH in Catalonia (Spain) who had a pre-ICH modified Rankin scale (mRS) score of 0-3 and who were admitted to the hospital within 24 hours of onset. We compared patients admitted to a TSC/PSC (n = 641) or a CSC (n = 1,320) and also analyzed the subgroup of patients transferred (n = 331) or not transferred (n = 310) from a TSC/PSC to a CSC. The main outcome was the 3-month mRS score obtained by blinded investigators. Outcomes were compared using adjusted ordinal logistic regression to estimate the common odds ratio (OR) and 95% CI for a shift in mRS scores. A propensity score matching (PSM) analysis was performed for the subgroup of transferred patients.

Results: Relevant data were obtained from 1961 of a total of 2,230 patients, with the mean (SD) age of 70 (14.1) years, and 713 (38%) patients were women. After adjusting for confounders (age, NIH Stroke Scale score, intraventricular hemorrhage, hematoma volume, and pre-ICH mRS score), type of hospital of initial admission (CSC vs TSC/PSC) was not associated with outcome (adjusted common OR 1.13, 95% CI 0.93-1.38). A PSM analysis indicated that transfer to a CSC was not associated with more favorable outcomes (OR 0.77, 95% CI 0.55-1.10; p = 0.16).

Discussion: In this population-based study, we found that, after adjusting for confounders, hospital types were not associated with functional outcomes. In addition, for patients who were transferred from a TSC/PSC to a CSC, PSM indicated that outcomes were similar to nontransferred patients. Our findings suggest that patient characteristics are more important than hospital characteristics in determining outcome after ICH.

Trial registration information: ClinicalTrials.gov Identifier: NCT03956485.

Funding: Fundaciô Ictus, RICORS RD21/006/006

DNA methylation and stroke prognosis: an epigenome-wide association study.

Jiménez-Balado J, Fernández-Pérez I, Gallego-Fábrega C et al. Clin Epigenetics. 2024 Jun 6;16(1):75. doi: 10.1186/s13148-024-01690-2.PMID: 38845005
Abstract:
Background and aims Stroke is the leading cause of adult-onset disability. Although clinical factors infuence stroke outcome, there is a signifcant variability among individuals that may be attributed to genetics and epigenetics, including DNA methylation (DNAm). We aimed to study the association between DNAm and stroke prognosis.
Methods and results To that aim, we conducted a two-phase study (discovery-replication and meta-analysis) in Caucasian patients with ischemic stroke from two independent centers (BasicMar [discovery, N=316] and St. Pau [replication, N=92]). Functional outcome was assessed using the modifed Rankin Scale (mRS) at three months after stroke, being poor outcome defned as mRS>2. DNAm was determined using the 450K and EPIC BeadChips in whole-blood samples collected within the frst 24 h. We searched for diferentially methylated positions (DMPs) in 370,344 CpGs, and candidates below p-value< 10–5 were subsequently tested in the replication cohort. We then meta-analyzed DMP results from both cohorts and used them to identify diferentially methylated regions (DMRs). After doing the epigenome-wide association study, we found 29 DMPs at p-value< 10–5 and one of them was replicated: cg24391982, annotated to thrombospondin-2 (THBS2) gene (p-valuediscovery=1.54·10–6; p-value replication=9.17·10–4; p-valuemeta-analysis=6.39·10–9). Besides, four DMRs were identifed in patients with poor outcome annotated to zinc fnger protein 57 homolog (ZFP57), Arachidonate 12-Lipoxygenase 12S Type (ALOX12), ABI Family Member 3 (ABI3) and Allantoicase (ALLC) genes (p-value<1·10–9 in all cases).
Discussion Patients with poor outcome showed a DMP at THBS2 and four DMRs annotated to ZFP57, ALOX12, ABI3 and ALLC genes. This suggests an association between stroke outcome and DNAm, which may help identify new stroke recovery mechanisms.
Funding: This work was supported by grants from the Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III with the grants “Registro BASICMAR” Funding for Research in Health (PI051737), Fondos de Investigación Sanitaria ISC III (PI12/01238), (PI15/00451), (PI18/00022), (PI21/00593); Sara Borrell program, funded by Instituto de Salud Carlos III (CD22/00001, J.J.-B.); and Fondos FEDER/EDRF Spanish stroke research network INVICTUS+(RD16/0019/0002) and Grant “RICORS-ICTUS” (RD21/0006/0021) funded by Instituto de Salud Carlos III (ISCIII), and by the European Union NextGenerationEU, Mecanismo para la Recuperación y la Resiliencia (MRR). Additional support provided by the Fundació la Marató TV3 with the grant “GOD’s project. Genestroke Consor‑ tium” (76/C/2011) and Recercaixa’13 (JJ086116). Fundings were received from National Institute of Health, SiGN study, The NINDS Stroke Genetics Network Study (U01NS069208) and CaNVAS (1R01NS114045-01).