Intensive heart rhythm monitoring to decrease ischemic stroke and systemic embolism - the Find-AF 2 study - rationale and design

Background Atrial fibrillation (AF) is one of the most frequent causes of stroke. Several randomized trials have shown that prolonged monitoring increases the detection of AF, but the effect on reducing recurrent cardioembolism, i.e. ischemic stroke and systemic embolism, remains unknown. We aim to evaluate whether a risk-adapted, intensified heart rhythm monitoring with consequent guideline conform treatment, which implies initiation of oral anticoagulation (OAC), leads to a reduction of recurrent cardioembolism. Methods Find-AF 2 is a randomized, controlled, open-label parallel multicenter trial with blinded endpoint assessment. 5,200 patients ≥ 60 years of age with symptomatic ischemic stroke within the last 30 days and without known AF will be included at 52 study centers with a specialized stroke unit in Germany. Patients without AF in an additional 24-hour Holter ECG after the qualifying event will be randomized in a 1:1 fashion to either enhanced, prolonged and intensified ECG-monitoring (intervention arm) or standard of care monitoring (control arm). In the intervention arm, patients with a high risk of underlying AF will receive continuous rhythm monitoring using an implantable cardiac monitor (ICM) whereas those without high risk of underlying AF will receive repeated 7-day Holter ECGs. The duration of rhythm monitoring within the control arm is up to the discretion of the participating centers and is allowed for up to 7 days. Patients will be followed for at least 24 months. The primary efficacy endpoint is the time until recurrent ischemic stroke or systemic embolism occur. Conclusions The Find-AF 2 trial aims to demonstrate that enhanced, prolonged and intensified rhythm monitoring results in a more effective prevention of recurrent ischemic stroke and systemic embolism compared to usual care

Different impacts on the heart after COVID-19 infection and vaccination: insights from cardiovascular magnetic resonance

INTRODUCTION: Myocarditis-like findings after COVID-19 (coronavirus disease 2019) infection and vaccination were reported by applying cardiovascular magnetic resonance (CMR). These results are very heterogenous and dependent on several factors such as hospital admission or outpatient treatment, timing of CMR, and symptomatic load. This retrospective study aimed to identify differences in myocardial damage in patients with persistent symptoms both after COVID-19 infection and vaccine by applying CMR. MATERIALS AND METHODS: This study entails a retrospective analysis of consecutive patients referred for CMR between August 2020 and November 2021 with persistent symptoms after COVID-19 infection or vaccination. Patients were compared to healthy controls (HC). All patients underwent a CMR examination in a 1.5-T scanner with a scan protocol including: cine imaging for biventricular function and strain assessment using feature tracking, T2 mapping for the quantification of edema, and T1 mapping for diffuse fibrosis and late gadolinium enhancement (LGE) for the detection and quantification of focal fibrosis. Patients were divided into a subacute COVID-19 (sCov) group with symptoms lasting 12 weeks, and patients after COVID-19 vaccination (CovVac). RESULTS: A total of 162 patients were recruited of whom 141 were included for analysis. The median age in years (interquartile range (IQR)) of the entire cohort was 45 (37–56) which included 83 women and 58 men. Subgroups were as follows (total patients per subgroup, median age in years (IQR), main gender): 34 sCov, 43 (37–52), 19 women; 63 pCov, 52 (39–58), 43 women; 44 CovVac, 43 (32–56), 23 men; 44 HC (41 (28–52), 24 women). The biventricular function was preserved and revealed no differences between the groups. No active inflammation was detected by T2 mapping. Global T1 values were higher in pCov in comparison with HC (median (IQR) in ms: pCov 1002ms (981–1023) vs. HC 987ms (963–1009; p = 0.005) with other parings revealing no differences. In 49/141 (34.6%) of patients, focal fibrosis was detectable with the majority having a non-ischemic pattern (43/141; 30.4%; patients) with the subgroups after infection having more often a subepicardial pattern compared with CovVac (total (% of group): sCov: 7/34(21%); pCov 13/63(21%); CovVac 2/44(5%); p = 0.04). CONCLUSION: Patients after COVID-19 infection showed more focal fibrosis in comparison with patients after COVID-19 vaccination without alterations in the biventricular function

Comparison of manual and artificial intelligence based quantification of myocardial strain by feature tracking - a cardiovascular MR study in health and disease

OBJECTIVES: The analysis of myocardial deformation using feature tracking in cardiovascular MR allows for the assessment of global and segmental strain values. The aim of this study was to compare strain values derived from artificial intelligence (AI)-based contours with manually derived strain values in healthy volunteers and patients with cardiac pathologies. MATERIALS AND METHODS: A cohort of 136 subjects (60 healthy volunteers and 76 patients; of those including 46 cases with left ventricular hypertrophy (LVH) of varying etiology and 30 cases with chronic myocardial infarction) was analyzed. Comparisons were based on quantitative strain analysis and on a geometric level by the Dice similarity coefficient (DSC) of the segmentations. Strain quantification was performed in 3 long-axis slices and short-axis (SAX) stack with epi- and endocardial contours in end-diastole. AI contours were checked for plausibility and potential errors in the tracking algorithm. RESULTS: AI-derived strain values overestimated radial strain (+ 1.8 ± 1.7% (mean difference ± standard deviation); p = 0.03) and underestimated circumferential (- 0.8 ± 0.8%; p = 0.02) and longitudinal strain (- 0.1 ± 0.8%; p = 0.54). Pairwise group comparisons revealed no significant differences for global strain. The DSC showed good agreement for healthy volunteers (85.3 ± 10.3% for SAX) and patients (80.8 ± 9.6% for SAX). In 27 cases (27/76; 35.5%), a tracking error was found, predominantly (24/27; 88.9%) in the LVH group and 22 of those (22/27; 81.5%) at the insertion of the papillary muscle in lateral segments. CONCLUSIONS: Strain analysis based on AI-segmented images shows good results in healthy volunteers and in most of the patient groups. Hypertrophied ventricles remain a challenge for contouring and feature tracking. CLINICAL RELEVANCE STATEMENT: AI-based segmentations can help to streamline and standardize strain analysis by feature tracking. KEY POINTS: • Assessment of strain in cardiovascular magnetic resonance by feature tracking can generate global and segmental strain values. • Commercially available artificial intelligence algorithms provide segmentation for strain analysis comparable to manual segmentation. • Hypertrophied ventricles are challenging in regards of strain analysis by feature tracking

Fast acquisition of left and right ventricular function parameters applying cardiovascular magnetic resonance in clinical routine - validation of a 2-shot compressed sensing cine sequence

OBJECTIVES: To evaluate if cine sequences accelerated by compressed sensing (CS) are feasible in clinical routine and yield equivalent cardiac morphology in less time. DESIGN: We evaluated 155 consecutive patients with various cardiac diseases scanned during our clinical routine. LV and RV short axis (SAX) cine images were acquired by conventional and prototype 2-shot CS sequences on a 1.5 T CMR. The 2-shot prototype captures the entire heart over a period of 3 beats making the acquisition potentially even faster. Both scans were performed with identical slice parameters and positions. We compared LV and RV morphology with Bland-Altmann plots and weighted the results in relation to pre-defined tolerance intervals. Subjective and objective image quality was evaluated using a 4-point score and adapted standardized criteria. Scan times were evaluated for each sequence. RESULTS: In total, no acquisitions were lost due to non-diagnostic image quality in the subjective image score. Objective image quality analysis showed no statistically significant differences. The scan time of the CS cines was significantly shorter (p < .001) with mean scan times of 178 ± 36 s compared to 313 ± 65 s for the conventional cine. All cardiac function parameters showed excellent correlation (r 0.978-0.996). Both sequences were considered equivalent for the assessment of LV and RV morphology. CONCLUSIONS: The 2-shot CS SAX cines can be used in clinical routine to acquire cardiac morphology in less time compared to the conventional method, with no total loss of acquisitions due to nondiagnostic quality. Trial registration: ISRCTN12344380. Registered 20 November 2020, retrospectively registered

Lazy Luna: extendible software for multilevel reader comparison in cardiovascular magnetic resonance imaging

BACKGROUND AND OBJECTIVES: Cardiovascular Magnetic Resonance (CMR) imaging is a growing field with increasing diagnostic utility in clinical routine. Quantitative diagnostic parameters are typically calculated based on contours or points provided by readers, e.g. natural intelligences (NI) such as clinicians or researchers, and artificial intelligences (AI). As clinical applications multiply, evaluating the precision and reproducibility of quantitative parameters becomes increasingly important. Although segmentation challenges for AIs and guidelines for clinicians provide quality assessments and regulation, the methods ought to be combined and streamlined for clinical applications. The goal of the developed software, Lazy Luna (LL), is to offer a flexible evaluation tool that is readily extendible to new sequences and scientific endeavours. METHODS: An interface was designed for LL, which allows for comparing annotated CMR images. Geometric objects ensure precise calculations of metric values and clinical results regardless of whether annotations originate from AIs or NIs. A graphical user interface (GUI) is provided to make the software available to non-programmers. The GUI allows for an interactive inspection of image datasets as well as implementing tracing procedures, which follow statistical reader differences in clinical results to their origins in individual image contours. The backend software builds on a set of meta-classes, which can be extended to new imaging sequences and clinical parameters. Following an agile development procedure with clinical feedback allows for a quick implementation of new classes, figures and tables for evaluation. RESULTS: Two application cases present LL's extendibility to clinical evaluation and AI development contexts. The first concerns T1 parametric mapping images segmented by two expert readers. Quantitative result differences are traced to reveal typical segmentation dissimilarities from which these differences originate. The meta-classes are extended to this new application scenario. The second applies to the open source Late Gadolinium Enhancement (LGE) quantification challenge for AI developers “Emidec”, which illustrates LL's usability as open source software. CONCLUSION: The presented software Lazy Luna allows for an automated multilevel comparison of readers as well as identifying qualitative reasons for statistical reader differences. The open source software LL can be extended to new application cases in the future

Factors associated with time delay to carotid stenting in patients with a symptomatic carotid artery stenosis

Treatment of a symptomatic stenosis is known to be most beneficial within 14 days after the presenting event but this can frequently not be achieved in daily practice. The aim of this study was the assessment of factors responsible for this time delay to treatment. A retrospective analysis of a prospective two-center CAS database was carried out to investigate the potential factors that influence a delayed CAS treatment. Of 374 patients with a symptomatic carotid stenosis, 59.1% were treated beyond ≥14 days. A retinal TIA event (OR = 3.59, 95% CI 1.47–8.74, p < 0.01) was found to be a predictor for a delayed treatment, whereas the year of the intervention (OR = 0.32, 95% CI 0.20–0.50, p < 0.01) and a contralateral carotid occlusion (OR = 0.42, 95% CI 0.21–0.86, p = 0.02) were predictive of an early treatment. Similarly, within the subgroup of patients with transient symptoms, the year of the intervention (OR = 0.28, 95% CI 0.14–0.59, p < 0.01) was associated with an early treatment, whereas a retinal TIA as the qualifying event (OR = 6.96, 95% CI 2.37–20.47, p < 0.01) was associated with a delayed treatment. Treatment delay was most pronounced in patients with an amaurosis fugax, whereas a contralateral carotid occlusion led to an early intervention. Although CAS is increasingly performed faster in the last years, there is still scope for an even more accelerated treatment strategy, which might prevent future recurrent strokes prior to treatment

When TADs go bad: chromatin structure and nuclear organisation in human disease

Chromatin in the interphase nucleus is organised as a hierarchical series of structural domains, including self-interacting domains called topologically associating domains (TADs). This arrangement is thought to bring enhancers into closer physical proximity with their target genes, which often are located hundreds of kilobases away in linear genomic distance. TADs are demarcated by boundary regions bound by architectural proteins, such as CTCF and cohesin, although much remains to be discovered about the structure and function of these domains. Recent studies of TAD boundaries disrupted in engineered mouse models show that boundary mutations can recapitulate human developmental disorders as a result of aberrant promoter-enhancer interactions in the affected TADs. Similar boundary disruptions in certain cancers can result in oncogene overexpression, and CTCF binding sites at boundaries appear to be hyper-mutated across cancers. Further insights into chromatin organisation, in parallel with accumulating whole genome sequence data for disease cohorts, are likely to yield additional valuable insights into the roles of noncoding sequence variation in human disease

Vector assembly of colloids on monolayer substrates

The key to spontaneous and directed assembly is to encode the desired assembly information to building blocks in a programmable and efficient way. In computer graphics, raster graphics encodes images on a single-pixel level, conferring fine details at the expense of large file sizes, whereas vector graphics encrypts shape information into vectors that allow small file sizes and operational transformations. Here, we adapt this raster/vector concept to a 2D colloidal system and realize &apos;vector assembly&apos; by manipulating particles on a colloidal monolayer substrate with optical tweezers. In contrast to raster assembly that assigns optical tweezers to each particle, vector assembly requires a minimal number of optical tweezers that allow operations like chain elongation and shortening. This vector approach enables simple uniform particles to form a vast collection of colloidal arenes and colloidenes, the spontaneous dissociation of which is achieved with precision and stage-by-stage complexity by simply removing the optical tweezers