Boekholdt, S. Matthijs

BACKGROUND: Cardiac computed tomography (CT) acquired during the acute stroke imaging protocol is an emerging modality to detect cardiac thrombi. We determined its yield in patients with acute ischemic stroke. METHODS: We performed a 1-stage individual patient data meta-analysis of 4 prospective observational cohorts (AIS of HEARTS [Acute Ischemic Stroke of Heart-Related Embolic Sources Detected on Acute Cardiac CT Scans]), including patients with acute ischemic stroke who underwent ECG-gated or non–ECG-gated cardiac CT between May 2018 and June 2024. We excluded patients with transient ischemic attack or stroke mimics. The primary outcome was the proportion of patients with a thrombus on cardiac CT. Secondary outcomes were additional scan time, radiation dose, comparison with echocardiography, and 90-day outcomes. We performed logistic regression analyses to compare 90-day outcomes between patients with and without thrombus, adjusting for age, sex, history of atrial fibrillation, ischemic heart disease, chronic heart failure, stroke or transient ischemic attack, anticoagulant use, prestroke modified Rankin Scale score, National Institutes of Health Stroke Scale score, large vessel occlusions, and intravenous thrombolysis, as appropriate for each outcome. RESULTS: We included 3919 patients (median age, 74 [interquartile range (IQR), 63–82], 58% male, median National Institutes of Health Stroke Scale score 6 [IQR, 3–12]). Cardiac CT detected a thrombus in 243 (6.2%) patients. Among 1323 patients that underwent both cardiac CT and transthoracic echocardiography, cardiac CT had a higher yield than transthoracic echocardiography (odds ratio, 7.4 [95% CI, 4.0–15.1]; P <0.001). Median additional scan time was 6 minutes (IQR, 5–7) for ECG-gated and 13 seconds (IQR, 12–61) for non–ECG-gated cardiac CT. Median additional radiation dose was 2.9 mSv (IQR, 1.6–4.1). Patients with thrombi had higher 90-day mortality (33% versus 15%, adjusted odds ratio, 1.6 [95% CI, 1.1–2.3]) and worse modified Rankin Scale scores (median modified Rankin Scale score 3 versus 2, adjusted odds ratio, 1.6 [95% CI, 1.2–2.0]), but similar recurrent stroke rates (5% versus 4%, adjusted odds ratio, 1.4 [95% CI, 0.7–2.5]). CONCLUSIONS: Implementing cardiac CT into the acute stroke imaging protocol is feasible, detects thrombi in ≈6% of patients, and has a higher yield than transthoracic echocardiography. Cardiac thrombi were associated with higher mortality, but not higher stroke recurrence. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT07165093.

Abstract Background Increased QRS voltages in athletes’ ECGs are attributed to electrophysiological cellular adaptations, complicating the detection of left ventricular hypertrophy (LVH). Conversely, higher extracellular volume (ECV), indicative of diffuse fibrosis, reduces QRS voltages – so-called ‘relative voltage deficiency’– and can mask true LVH on ECG. Purpose To investigate sex-specific associations between QRS voltages and myocardial ECV and assess the impact of ECV on false-positive and negative ECG-LVH detection in elite athletes. Methods We conducted a cross-sectional, sex-specific, contrast-enhanced CMR study in healthy, elite athletes with normal ECGs and no complete right bundle branch blocks. Myocardial ECV (%) was measured from pre- and post-contrast T1 mapping. LVH on CMR was defined as an indexed LVM &gt;75 g/m² (men) or &gt;59 g/m² (women). Primary analyses evaluated correlations between ECV, LVM, and summed 12-lead ECG voltages (including voltage/LVM to assess independence), as well as Sokolow-Lyon and Cornell voltages. Secondary multivariable logistic regression examined the association of ECV on false-positive and false-negative ECG-LVH rates using Sokolow-Lyon (≥3.5 mV) and sex-specific Cornell (≥2.8 mV in men; ≥2.3 mV in women) criteria for CMR-LVH. Results In 162 elite athletes (median age 25 years, 44% female, 45% endurance, 96% Caucasian), 23% met Sokolow-Lyon criteria, 6% met Cornell criteria, and 17% had LVH on CMR. The median myocardial ECV was 23% (range 19–31%), which was lower in male compared to female athletes (22% [Q1-Q3: 21–23%] vs 25% [23–26%]; p&lt;0.001). In both sexes, summed 12-lead voltages were inversely correlated with ECV (ρ=–0.36 to –0.37; p=0.001), independent of LVM (voltage/LVM: ρ=–0.33; p=0.004). Only in female athletes did 12-lead voltages correlate with LVM (ρ=0.37; p=0.001). Logistic regression confirmed that lower ECV was associated with an increased likelihood of false-positive Sokolow-Lyon (OR: 0.64 per 1% ECV increment; p=0.011), independent of body mass index (OR: 0.77 per kg/m²; p=0.039) male sex (OR: 2.7; p=0.123) and age (OR: 0.93 per year; p=0.075; AUROC 0.82). Higher ECV conferred greater odds of a false-negative (OR 3.98 per %; p=0.041), though this was limited by small LVH-positive sample size. In Cornell-based models, lower ECV was not statistically significantly associated with increased false-positive rate (OR 0.59; p=0.059). Conclusion In elite athletes, lower ECV ("denser" myocardium) is associated with increased QRS voltages and higher false-positive ECG-LVH rate, particularly for Sokolow-Lyon, while higher ECV may dampen voltages and can mask true LVH on the ECG. Although sex-specific criteria partly mitigate ECV-related effects, these findings demonstrate inherent limitations of voltage-based LVH criteria in athletes. Unexpectedly low QRS voltages in athletes with otherwise high LVM may imply increased ECV, though further research is warranted.Figure:Likelihood of False Pos SL rate Table:Population characteristics

Background: Cardiac CT acquired during the acute stroke imaging protocol is an emerging diagnostic modality to detect cardiac thrombi. We aimed to determine its diagnostic yield in a large, international, multicenter study. Methods: We performed an individual patient data meta-analysis by pooling prospective and retrospective observational data of patients with acute ischemic stroke (AIS) who underwent cardiac CT (ECG-gated or non-ECG-gated) as part of the acute imaging protocol between May 2018 and June 2024. We excluded patients with a TIA or stroke mimic. The primary outcome was the proportion of patients with a cardiac thrombus detected on cardiac CT. Secondary outcomes were additional scan time and radiation dose, comparison of yield with echocardiography, and 90-day mortality and recurrent ischemic stroke rates. Results: We included 3940 patients from 4 hospitals (median age 74 [IQR 63-82], 58.0% male, median NIHSS 6 [IQR 3-12], median time onset to hospital arrival 100 minutes [IQR 62-185]). Atrial fibrillation at baseline was present in 23.1% patients, and 29.6% had a large vessel occlusion. Cardiac CT was non-diagnostic in 17 (0.4%) patients. In total, cardiac CT detected 254 cardiac thrombi in 243/3923 (6.2%) patients. Thrombi were located in the left atrial appendage (n=193), left atrium (n=19), and left ventricle (n=42). Of 95/243 (39.1%) patients with a cardiac thrombus that underwent echocardiography (median interval cardiac CT-echocardiography: 2 days), transthoracic echocardiography detected a thrombus in 18/92 (19.6%) patients and transesophageal echocardiography in 2/5 (40.0%) patients. The diagnostic yield in patients that underwent both modalities was higher for cardiac CT (OR 7.5 [CI 4.0-15.3], p<0.001). Median additional scan time was 6 minutes (IQR 5-7) for ECG-gated and 17 seconds (IQR 15-63) for non-ECG-gated cardiac CT. Median additional radiation dose was 5.4mSv (IQR 3.0-7.6). Patients with a cardiac thrombus on cardiac CT had higher 90-day mortality than those without a thrombus (33.3% vs 14.6%, p<0.001). We found no difference in 90-day recurrent stroke rate (5.4% vs 4.4%, p=0.50). Conclusion: Routine cardiac CT performed during the acute stroke imaging protocol detects a cardiac thrombus in 1 out of 16 patients with AIS, with a 7-times higher yield than routine echocardiography. Mortality rate was doubled in patients with a cardiac thrombus, but 90-day stroke recurrence risk did not differ.

Background: The rate of intracardiac thrombus detection in the hyperacute phase of stroke varies from 5% to 12% between studies. Our aim was to compare the thrombus detection rate between ECG-gated and non-ECG-gated cardiac CT protocols in acute stroke patients, using data from a large, international, multicentre registry. Methods: We conducted an individual patient data meta-analysis by pooling prospective and retrospective observational data from stroke patients assessed at four comprehensive stroke centres who underwent either ECG-gated or non-ECG-gated cardiac CT (extended CT angiography or two-phase non-ECG-gated cardiac CT) as part of the acute stroke imaging protocol between May 2018 and June 2024. The primary outcome was the proportion of patients with a cardiac thrombus in gated vs non gated techniques. Results: Of 3,940 patients, 1,474 (37.4%) underwent ECG-gated and 2,466 (62.6%) non-ECG-gated cardiac CT. Patients in the ECG-gated group were younger (median age 72 [IQR 62–81] vs. 74 [IQR 64–82] years, p = 0.000) and had a lower NIHSS at baseline (median 5 [IQR 2–12] vs. 6 [IQR 3–13], p < 0.00). There was a higher rate of thrombus detection with ECG-gated CT compared to non-gated CT (7.5% vs. 5.5%, p = 0.011. The association remained significant after adjusting for age, sex, baseline NIHSS score, and baseline atrial fibrillation (adjusted OR 1.87, 95% CI 1.42–2.47, p = 0.000). ECG-gated CT was associated with lower radiation dose (3.6 vs. 6.3 mSv, p = 0.000) but longer acquisition time (5.8 vs. 0.28 min, p = 0.000). Conclusion: ECG-gated cardiac CT has a higher detection rate for intracardiac thrombus detection compared to non-ECG-gated CT in patients with acute ischemic stroke.

Abstract Introduction Cardiac CT is increasingly used to screen for cardioembolism in stroke patients. We assessed the frequency and management of non-cardiac incidental findings on prospective ECG-gated cardiac CT in patients with a suspected stroke. Patients and methods This was a post-hoc analysis of the Mind the Heart study, a prospective single-centre cohort study including consecutive adult patients with acute ischaemic stroke (AIS), transient ischaemic attack (TIA), or a stroke mimic who underwent cardiac CT as part of an acute stroke imaging protocol. Endpoints were pre-defined non-cardiac incidental findings that were detected on cardiac CT: pulmonary embolism (PE), potential malignant lesions, pulmonary consolidations or ground-glass densities, bone fractures, lymphadenopathy, focal liver lesions, and ascending aortic or pulmonary artery dilatation. Change of management was defined as additional treatment or follow-up. Results We included 654 patients (57% men, median age 71 [IQR 59–80] years) of whom 451 (69%) had AIS, 48 had TIA (7%), and 155 had a stroke mimic (24%). Overall, 58 non-cardiac incidental findings were found in 55 (8%; 95%CI, 6–11) patients. The most frequent incidental findings were consolidations or ground-glass densities (n = 17, 3%), liver cysts or non-specific hypodensities (n = 14, 2%), pulmonary nodules or masses (n = 9, 1%), and PEs (n = 8, 1%). Incidental findings led to a change of management in 17/55 (31%) patients of whom 13/55 (24%) had additional follow-up and 9/55 (16%) received treatment (anticoagulation n = 8, chemotherapy n = 1). Discussion & Conclusion Non-cardiac incidental findings were observed on cardiac CT in 8% of patients with a suspected stroke. These findings changed management in 31% of these patients.

BACKGROUND: Left atrial (LA) diverticula are focal outpouchings of the LA wall and may increase ischemic stroke risk. We studied recurrent ischemic stroke in patients with acute ischemic stroke and LA diverticula detected on cardiac computed tomography. METHODS: We used data from a prospective cohort study of patients with acute ischemic stroke undergoing cardiac computed tomography acquired during the acute stroke imaging protocol. Cardiac radiologists systematically assessed the presence and characteristics of LA diverticula, defined as LA wall outpouchings with a length/ostium width ratio >0.5 and length ≥3 mm. We compared recurrent ischemic stroke and functional outcome (modified Rankin Scale) after 2 years between patients with and without LA diverticula, adjusting for age, history of atrial fibrillation and ischemic stroke, and anticoagulation use. RESULTS: Of 447 included patients (median age 72 [interquartile range (IQR), 62–81], 59% male), 126 (28%) had LA diverticula: median length 6 mm (IQR, 4–8), width 5 mm (IQR, 4–7), and volume 113 mm 3 (IQR, 52–254). There was no statistically significant difference in age (median 70 [IQR, 58–79] versus 73 [IQR, 63–81]; P =0.06), sex (64% versus 57% male; P =0.28), history of ischemic stroke (21% versus 17%; P =0.48), atrial fibrillation (11% versus 19%; P =0.09), or baseline National Institutes of Health Stroke Scale score (median 5 [IQR, 2–14] versus 5 [IQR, 3–14]; P =0.54) between patients with and without LA diverticula, respectively. Recurrent ischemic stroke was more common in patients with LA diverticula (18/124 [15%] versus 24/314 [8%], adjusted hazard ratio, 2.01 [95% CI, 1.08–3.77]), and recurrence risk increased with diverticulum volume (adjusted hazard ratio, 1.02 [95% CI, 1.01–1.03] per 10 mm 3 ). Functional outcome was better in patients with diverticula (median modified Rankin Scale score of 2 [IQR, 1–3] versus 3 [IQR, 1–6], adjusted common odds ratio, 0.62, [95% CI, 0.42–0.92]). CONCLUSIONS: LA diverticula are a common finding on cardiac computed tomography in patients with acute ischemic stroke, and the risk of recurrent ischemic stroke was increased in these patients, particularly in those with larger diverticula. Atrial diverticula may be a risk factor for recurrent ischemic stroke. REGISTRATION: URL: https://www.onderzoekmetmensen.nl/nl/trial/50352 ; Unique identifier: NL6413901818.