Planken, R Nils

Background Homozygous familial hypercholesterolemia (HoFH), characterized by extremely elevated low‐density lipoprotein cholesterol (LDL‐C) due to severely impaired LDL‐C clearance from circulation, remains challenging to treat. Here, we investigated clinical benefits of monoclonal antibody, evinacumab, inhibiting angiopoietin‐like 3, recently approved in children with homozygous familial hypercholesterolemia. Methods This retrospective, observational study included 13 children with homozygous familial hypercholesterolemia on oral lipid‐lowering therapy and assessed their attainment of LDL‐C goal, need for lipoprotein apheresis (LA), and cardiac plaque formation at initiation of evinacumab and at follow‐up of 2.0 (1.3–3.0) years. Results Evinacumab, initiated at age 11 (8.5–13.5) years, increased number of patients reaching LDL‐C goal from none before initiation to 9 of 13 (69%; P =0.004) at follow‐up. Mean±SD LDL‐C at follow‐up was 111 (44) mg/dL, compared with 206 (61) mg/dL before evinacumab (mean difference, −95 mg/dL [95% CI, −142 to −47]; P <0.001). Before initiation of evinacumab, 11 of 13 children received LA with average interval of 7.8 days. At follow‐up, LA frequency decreased in 7 of 11 children with average interval of 18.9 days; increase between LA sessions was 11.0 days (3.5–18.5; P =0.008), 42% longer session interval. For 3 (15%) children, due to evinacumab initiation, LA remained dispensable over the course of treatment. Coronary computed tomography angiography showed plaque stabilization (n=5), regression (n=3), and no formation (n=2), in 10 of 13 (77%) children, and plaque progression in 3 (23%) children. Conclusions Add‐on evinacumab increased number of children with homozygous familial hypercholesterolemia reaching and maintaining LDL‐C goal, concomitant reduction in LA frequency, and in most patients, stabilization or improvement in coronary computed tomography angiography findings.

Abstract The persistent global rise in atherosclerotic cardiovascular disease (ASCVD) challenges the effectiveness of current risk factor-based algorithms in primary prevention. Most myocardial infarctions occur in individuals without prior symptoms or recognized standard modifiable risk factors, underscoring the need to improve risk stratification. Coronary CT imaging, including coronary artery calcium scoring (CACS) and coronary computed tomography angiography (CCTA), enables direct non-invasive visualization of coronary atherosclerosis, supporting a shift from population-based prevention towards personalized, disease-based risk assessment and targeted preventive treatment. CCTA provides comprehensive evaluation of plaque burden, composition, stenosis severity, and high-risk plaque (HRP) features, thereby refining risk stratification and guiding personalized treatment decisions. The presence and total burden of coronary atherosclerotic plaque are considered the primary CCTA-derived markers for guiding preventive therapy, while noncalcified plaque burden and HRP features may support treatment intensification. Advances in CT technology, including photon-counting CT, and the application of artificial intelligence-based tools may further refine risk assessment by enabling accurate and reproducible plaque quantification and characterization. Although no randomized trials have yet demonstrated that CCTA-based screening improves clinical outcomes in asymptomatic individuals compared with standard care, the same is true of traditional cardiovascular risk scores. Three large ongoing randomized trials are currently evaluating whether CCTA-guided, personalized prevention strategies can reduce ASCVD events. The results are eagerly awaited and may redefine the role of CCTA in asymptomatic individuals.

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 Aims Lipoprotein(a) [Lp(a)] is a causal risk factor for cardiovascular events. However, the effect of Lp(a) on coronary plaque composition and high-risk plaque features has not been fully characterized. This study aimed to investigate the association between Lp(a) and coronary atherosclerotic plaque phenotype at the plaque level. Methods and results This study included 710 patients who underwent coronary computed tomography angiography (CCTA) and had Lp(a) measured between 2008 and 2024. CCTA scans were analysed with a previously validated artificial intelligence-based algorithm (AI-QCT, Cleerly Inc.). The association of Lp(a) with non-calcified and calcified plaque volumes and HRP features was evaluated at the plaque level using generalized estimating equation models adjusted for traditional cardiovascular risk factors. Among the 710 patients, the mean age was 56 ± 10 years and 379 (53%) were male. In total, 3642 plaques were identified. In the adjusted plaque-level analysis, elevated Lp(a) (≥150 nmol/L) was associated with an increase in non-calcified plaque volume per plaque (P = 0.009), but not with an increase in calcified plaque volume (P = 0.81). Furthermore, elevated Lp(a) (≥150 nmol/L) was strongly associated with the presence of high-risk plaque at the plaque level (adjusted odds ratio: 1.78, 95% CI: 1.25–2.54, P = 0.001), whereas low-density lipoprotein-cholesterol and high-sensitivity C-reactive protein were not (P &gt; 0.05). Conclusion In this plaque-level CCTA study of 3642 individual plaques, elevated Lp(a) levels were independently associated with increased non-calcified plaque volume and with the presence of high-risk plaque, but not with calcified plaque volume. These findings elucidate the impact of Lp(a) on unstable plaque phenotypes, even in patients without prior cardiovascular events.

Increased epicardial adipose tissue attenuation on CT images was associated with the presence and recurrence of atrial fibrillation in studies using consistent or corrected tube voltage settings, suggesting its potential as a prognostic marker.

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.