PRediction and detection of Occult Atrial fibrillation in patients after acute Cryptogenic stroke and Transient Ischemic Attack (PROACTIA)

Abstract Background Studies with implantable cardiac rhythm monitors (ICRM) have shown that a 1/3 of patients with cryptogenic stroke/transitory ischemic attack (TIA) have episodes of subclinical atrial fibrillation (SCAF) as one of the potential risk factor for cerebral embolism. However, ICRM are costly and resource demanding. Purpose The PROACTIA study seeks to test a pre-specified scoring system to assess individual risk of SCAF in order to offer tailored therapy to patients after cryptogenic stroke/TIA. Methods Patients admitted with first time cryptogenic stroke or TIA were eligible for the study and underwent blood sampling, cerebral CT/MRI, carotid Doppler ultrasound, ECG, 24h-HolterECG, transthoracic transesophageal echocardiography, registration of medical history and implantation of ICRM during the index hospitalization The scoring system was composed of variables that have previously been found associated with AF occurrence: CHA2DS2-VASc, P-wave duration (P-dur), premature atrial contractions (PAC)/24h, supraventricular runs (SVR)/24h, left atrial end-systolic volume index (LAVI), and the biomarkers TnT, NT-proBNP and D-dimer. Data are presented as median (inter quartile range). Results Within 25 months, 434 patients screened and 251 patients were included in the present study and had an ICRM implanted. Eleven patients were later excluded yielding a study cohort of 176 patients with cerebral infarction and 61 with TIA that were followed for 833 (633–1028) days. AF was detected in 36%. It took 113 (25–336) days to detect AF, and 5 (2–14) days from AF-detection to initiation of NOAC. All variables were significantly increased in AF patients: no-AF vs AF: CHADS-VASC: 4 (3–5) vs 5 (4–6)*, LAVI mL/m2: 35 (28–40) vs 40 (35–50)**, PAC/24h: 69 (29–211) vs 347 (59–1917)**, SVR / 24-h: 1 (0–3) vs 3 (1–17)**, P-dur ms: 100 (100–120) vs 120 (100–120)**, D-dimer mg/L: 0,3 (0,2–0,6) vs 0,5 (0,3–0,9)**, TnT ng/L: 10 (7–16) vs 15 (9–27)**, NT-proBNP ng/L: 103 (49–283) vs 245 (102–774)**. *p&amp;lt;0.01, **p&amp;lt;0.001. Multivariate analysis yielded the following model: −8.524 + 0.057*LAVI (p&amp;lt;0.001) + 0.035*P-dur (p&amp;lt;0.001) + 0.873*LogPAC/24h (p&amp;lt;0.001). ROC analysis using leave-one-out cross validation: AUC=0.77. Applying the model to our population, it would identify a high-risk group (&amp;gt;80% true positive) consisting of 17 true positive and 4 false positive, and a low-risk group (&amp;lt;5% false negative) consisting of 17 true negative and 1 false negative. Conclusions ICRM detected SCAF in 36% of cryptogenic stroke/TIA patients within 27 months. LAVI, PAC/24h and P-duration were strong independent predictors of SCAF enabling a meaningful risk stratification that can be used for tailoring therapy in cryptogenic stroke/TIA patients. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Stiftelsen Dam </jats:sec

Biomarkers in patients with cryptogenic stroke/TIA and subclinical atrial fibrillation

Abstract Background A large proportion of patients with cryptogenic stroke or transitory ischemic attack (TIA) have underlying subclinical atrial fibrillation (SCAF) detected on follow up. It is not clear whether SCAF is the underlying primary entity in the pathogenesis of stroke in these patients, or merely a marker of atrial myopathy associated with left atrial remodeling, fibrosis and inflammation. Purpose As a hypothesis generating study, we investigated a panel of selected biomarkers involved in fibrosis, inflammation, and thrombosis: growth differentiation factor 15 (GDF-15), transforming growth factor b (TGFb), galectin-3, soluble suppressor of tumorgenicity2 (sST2), von Willebrand factor (vWF), Tissue metalloprotease1 (TIMP1), Matrix metalloprotease9 (MMP9), Emmprin, Interleukin6 (IL6), C-reactive protein (CRP), Tissue factor (TF), Plasminogen activator inhibitor (PAI1), and their relation to the occurrence of SCAF during follow-up in patients after cryptogenic stroke or TIA. We hypothized that biomarker levels were increased in patients with subclinical AF. Methods 236 patients, median age 71 years (range 21–94) of which 38% were women, with their first cryptogenic stroke or TIA were included 2–4 days after the index event and followed with an Implantable Cardiac Rhythm Monitor for &amp;gt;1 year. Echocardiography and blood sampling were performed at inclusion. ELISA methods were used. Results SCAF occurred in 84 patients (36%). Only GDF-15 was significantly increased in AF- vs no-AF patients: 1010 pg/mL (inter quartile range: 814–1416) vs 860 pg/mL (inter quartile range: 622–1197) (p=0.018), and correlated with the number of premature atrial contractions (PAC)/24h (by Holter ECG during index hospitalization) (rs=0.314, p&amp;lt;0.001) and AF-burden during follow-up (rs=0.149, p=0.022). Furthermore, there was a significant trend across quartiles of GDF-15 for having AF, and patients in the three highest quartiles (Q2–4) compared with Q1 had an odd ratio of having AF of 2.16 (95% CI 1.10–4.25), adjusted for sex and body mass index. The significance, however, was lost when adjusting for age, which correlated significantly to GDF-15 (rs=0.283; p&amp;lt;0.001). ROC curve analyses showed an AUC of 0.593 (0.52–0.68) for GDF-15 compared to 0.617 (0.54–0.69) for age. GDF-15 was also associated with co-morbidities such as hypertension (p&amp;lt;0.001), diabetes (p&amp;lt;0.001), and vascular disease (p&amp;lt;0.001). Conclusion In patients with a cryptogenic stroke or TIA experiencing SCAF during follow up, only levels of GDF-15 were elevated and correlated with PAC/24h and AF-burden. However, GDF-15 was highly related to age and co-morbidities and did not add significantly to the prediction of AF in a multivariate analysis. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Stiftelsen Dam, Norwegian Atrial Fibrillation Research Network </jats:sec

Left atrial appendage function by strain predicts subclinical atrial fibrillation in patients with cryptogenic stroke/TIA

Abstract Background Left atrial (LA) function by strain has shown to be promising to predict clinical atrial fibrillation (AF) in patients with cryptogenic stroke/TIA. However, there is little knowledge, if this novel method may prospectively predict subclinical AF (SCAF) and moreover, if left atrial appendage (LAA) function by strain and mechanical dispersion may be more sensitive to improve prediction of SCAF. Purpose The aim of the present study was to investigate if LA and LAA function by strain could improve the prediction of SCAF in patients at risk. Methods In this prospective study (mean follow-up 859±226 days), 185 patients with cryptogenic stroke/TIA, mean age 68±13 years, 33% female and no history of clinical AF or SCAF, were included. All participants underwent 2D and 3D transesophageal and transthoracic echocardiography in sinus rhythm after index cryptogenic stroke/TIA (mean 5±3days). LAA and LA functions by phasic strain, including reservoir strain (Sr), conduit strain (Scd) and contraction strain (Sct) and mechanical dispersion of Sr were assessed. SCAF episodes were detected by cardiac monitoring during follow up (mean 257±273 days). Results LAA function by strain was decreased in those with SCAF (60/32% of all patients) compared to those without: Sr: 19.2±4.5% vs. 25.6±6.5% (p&amp;lt;0.001), Scd: −11.0±3.1% vs. −14.4±4.5% (p&amp;lt;0.001), Sct: −7.9±4.0% vs. −11.2±4% (p&amp;lt;0.001), respectively, while mechanical dispersion by Sr strain was increased, 34±24ms vs. 26±20ms (p=0.02). However, LA function by strain and mechanical dispersion did not differ in patients with SCAF compared to patients without. By ROC analyses, LAA strain and mechanical dispersion were highly significant in prediction of SCAF. LAA reservoir strain showed the best AUC of 0.80 (95% CI 0.73–0.87) with a cut-off value of 22.2%, sensitivity of 80%, and specificity of 73%, p&amp;lt;0.001. (Figure) Conclusions For the first time, we showed, that left atrial appendage function by strain and mechanical dispersion predicts SCAF, as opposed to left atrial function. Left atrial appendage function by strain may be useful in risk prediction in patients at considerable AF risk. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Department of Cardiology, Akershus University Hospital, Oslo/Lørenskog, Norway </jats:sec

Physiological Monitoring in Acute Stroke: A Literature Review

Aim. This paper is a report of a review of the literature that considers how physiological parameters may affect outcome after stroke and the implications of this evidence for monitoring. Background. Throughout the world, the incidence of first-ever stroke is approximately 200 per 100,000 people per year [Sudlow et al. (1997) Stroke 28, 491]. Stroke is the third most common cause of mortality [Sarti et al. (2000) Stroke 31, 1588] and causes 5.54 million deaths worldwide [Murray & Lopez (1997) Lancet 349, 268]. Physiological monitoring is considered a fundamental component of acute stroke care. Currently, the strength of evidence to support its use and identify its components is unclear. Nurse-led physiological assessment and subsequent interventions in acute stroke may have the potential to improve survival and reduce disability. Data sources. Online bibliographic databases from 1966 to 2007, including MEDLINE, EMBASE, CINAHL, AMED, Cochrane and ZETOC, were searched systematically. We identified 475 published papers relating to blood pressure, oxygen saturation and positioning, blood glucose and body temperature. Review methods. Titles and abstracts were reviewed independently by two reviewers and 61 relevant studies were read in full. The quality of included studies was assessed and proformas were used to record detailed data. A narrative synthesis described how the evidence from the papers could inform our understanding of physiological parameters and their association with outcome. Results. Current evidence suggests that patient outcome is worse when physiological parameters deviate from 'normal' in the acute phase of stroke. Conclusions. The evidence supports the need for monitoring and recording of blood pressure, oxygen saturation (including consideration of positioning), blood glucose and body temperature in the acute phase of stroke. This review has reinforced the importance of monitoring physiological parameters in the acute phase of stroke and adds support to the recommendation that monitoring should play a key role within nursing care

Global Effect of the COVID-19 Pandemic on Stroke Volumes and Cerebrovascular Events A 1-Year Follow-up

Background and Objectives Declines in stroke admission, IV thrombolysis (IVT), and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the effect of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), IVT, and mechanical thrombectomy over a 1-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year (March 1, 2019, to February 29, 2020). Methods We conducted a longitudinal retrospective study across 6 continents, 56 countries, and 275 stroke centers. We collected volume data for COVID-19 admissions and 4 stroke metrics: ischemic stroke admissions, ICH admissions, IVT treatments, and mechanical thrombectomy procedures. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases. Results There were 148,895 stroke admissions in the 1 year immediately before compared with 138,453 admissions during the 1-year pandemic, representing a 7% decline (95% CI [95% CI 7.1-6.9]; p &lt; 0.0001). ICH volumes declined from 29,585 to 28,156 (4.8% [5.1-4.6]; p &lt; 0.0001) and IVT volume from 24,584 to 23,077 (6.1% [6.4-5.8]; p &lt; 0.0001). Larger declines were observed at high-volume compared with low-volume centers (all p &lt; 0.0001). There was no significant change in mechanical thrombectomy volumes (0.7% [0.6-0.9]; p = 0.49). Stroke was diagnosed in 1.3% [1.31-1.38] of 406,792 COVID-19 hospitalizations. SARS-CoV-2 infection was present in 2.9% ([2.82-2.97], 5,656/195,539) of all stroke hospitalizations. Discussion There was a global decline and shift to lower-volume centers of stroke admission volumes, ICH volumes, and IVT volumes during the 1st year of the COVID-19 pandemic compared with the prior year. Mechanical thrombectomy volumes were preserved. These results suggest preservation in the stroke care of higher severity of disease through the first pandemic year. © 2023 Lippincott Williams and Wilkins. All rights reserved

Global Impact of the COVID-19 Pandemic on Stroke Volumes and Cerebrovascular Events: One-Year Follow-up.

Declines in stroke admission, intravenous thrombolysis, and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the impact of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), intravenous thrombolysis (IVT), and mechanical thrombectomy over a one-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year (March 1, 2019, to February 29, 2020). We conducted a longitudinal retrospective study across 6 continents, 56 countries, and 275 stroke centers. We collected volume data for COVID-19 admissions and 4 stroke metrics: ischemic stroke admissions, ICH admissions, intravenous thrombolysis treatments, and mechanical thrombectomy procedures. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases. There were 148,895 stroke admissions in the one-year immediately before compared to 138,453 admissions during the one-year pandemic, representing a 7% decline (95% confidence interval [95% CI 7.1, 6.9]; p&lt;0.0001). ICH volumes declined from 29,585 to 28,156 (4.8%, [5.1, 4.6]; p&lt;0.0001) and IVT volume from 24,584 to 23,077 (6.1%, [6.4, 5.8]; p&lt;0.0001). Larger declines were observed at high volume compared to low volume centers (all p&lt;0.0001). There was no significant change in mechanical thrombectomy volumes (0.7%, [0.6,0.9]; p=0.49). Stroke was diagnosed in 1.3% [1.31,1.38] of 406,792 COVID-19 hospitalizations. SARS-CoV-2 infection was present in 2.9% ([2.82,2.97], 5,656/195,539) of all stroke hospitalizations. There was a global decline and shift to lower volume centers of stroke admission volumes, ICH volumes, and IVT volumes during the 1st year of the COVID-19 pandemic compared to the prior year. Mechanical thrombectomy volumes were preserved. These results suggest preservation in the stroke care of higher severity of disease through the first pandemic year. This study is registered under NCT04934020