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Background: The multicenter ATTEST study recently assessed 1084 patients with ischemic stroke or transient ischemic attack (TIA) of undetermined cause and found that routine transthoracic echocardiography (TTE) detects abnormalities with treatment implications (i.e., major cardiac sources of embolism) in only 1% of patients, of whom most (91%) also had major electrocardiographic (ECG)-abnormalities. In this study, we performed a cost-effectiveness analysis of different TTE strategies., Methods: We compared the cost-effectiveness of three strategies of TTE assessment: (1) TTE in all patients; (2) TTE only in patients with major ECG-abnormalities; and (3) TTE not performed. Input data were derived from ATTEST and systematic literature reviews. A Markov model was developed that simulated recurrent ischemic stroke or TIA and intracranial and gastro-intestinal bleeding complications in patients with ischemic stroke or TIA of undetermined cause. Primary outcome was the additional costs per additional quality-adjusted life-year (QALY) from a Dutch societal perspective., Results: Performing TTE only in patients with major ECG-abnormalities led to 0.0083 additional QALYs and €108 additional costs per patient as compared with not performing TTE (€12,987/QALY). Performing TTE in all patients resulted in 0.0005 additional QALYs and €422 additional costs per patient as compared with performing TTE only in case of major ECG-abnormalities (€805,336/QALY)., Conclusions: In patients with ischemic stroke or TIA of undetermined cause, a strategy of performing TTE only in patients who also had major ECG-abnormalities resulted in the most favorable ratio of additional costs per additional QALY. This supports performing TTE only in patients, who also have major ECG-abnormalities., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Matthijs Meijs reports financial support was provided by ZonMw. Clemens von Birgelen reports a relationship with Abbott Vascular Inc that includes: funding grants. Clemens von Birgelen reports a relationship with BIOTRONIK Inc that includes: funding grants. Clemens von Birgelen reports a relationship with Boston Scientific Corporation that includes: funding grants. Clemens von Birgelen reports a relationship with Medtronic that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Aim: To determine the effectiveness of functional stress testing and computed tomography angiography (CTA) for diagnosis of obstructive coronary artery disease (CAD)., Methods and Results: Two-thousand nine-hundred twenty symptomatic stable chest pain patients were included in the international Collaborative Meta-Analysis of Cardiac CT consortium to compare CTA with exercise electrocardiography (exercise-ECG) and single-photon emission computed tomography (SPECT) for diagnosis of CAD defined as ≥ 50% diameter stenosis by invasive coronary angiography (ICA) as reference standard. Generalised linear mixed models were used for calculating the diagnostic accuracy of each diagnostic test including non-diagnostic results as dependent variables in a logistic regression model with random intercepts and slopes. Covariates were the reference standard ICA, the type of diagnostic method, and their interactions. CTA showed significantly better diagnostic performance (p < 0.0001) with a sensitivity of 94.6% (95% CI 92.7-96) and a specificity of 76.3% (72.2-80) compared to exercise-ECG with 54.9% (47.9-61.7) and 60.9% (53.4-66.3), SPECT with 72.9% (65-79.6) and 44.9% (36.8-53.4), respectively. The positive predictive value of CTA was ≥ 50% in patients with a clinical pretest probability of 10% or more while this was the case for ECG and SPECT at pretest probabilities of ≥ 40 and 28%. CTA reliably excluded obstructive CAD with a post-test probability of below 15% in patients with a pretest probability of up to 74%., Conclusion: In patients with stable chest pain, CTA is more effective than functional testing for the diagnosis as well as for reliable exclusion of obstructive CAD. CTA should become widely adopted in patients with intermediate pretest probability., Systematic Review Registration: PROSPERO Database for Systematic Reviews-CRD42012002780., Critical Relevance Statement: In symptomatic stable chest pain patients, coronary CTA is more effective than functional testing for diagnosis and reliable exclusion of obstructive CAD in intermediate pretest probability of CAD., Key Points: Coronary computed tomography angiography showed significantly better diagnostic performance (p < 0.0001) for diagnosis of coronary artery disease compared to exercise-ECG and SPECT. The positive predictive value of coronary computed tomography angiography was ≥ 50% in patients with a clinical pretest probability of at least 10%, for ECG ≥ 40%, and for SPECT 28%. Coronary computed tomography angiography reliably excluded obstructive coronary artery disease with a post-test probability of below 15% in patients with a pretest probability of up to 74%., (© 2024. The Author(s).)

Objectives: Coronary computed tomography angiography (CCTA) has higher diagnostic accuracy than coronary artery calcium (CAC) score for detecting obstructive coronary artery disease (CAD) in patients with stable chest pain, while the added diagnostic value of combining CCTA with CAC is unknown. We investigated whether combining coronary CCTA with CAC score can improve the diagnosis of obstructive CAD compared with CCTA alone., Methods: A total of 2315 patients (858 women, 37%) aged 61.1 ± 10.2 from 29 original studies were included to build two CAD prediction models based on either CCTA alone or CCTA combined with the CAC score. CAD was defined as at least 50% coronary diameter stenosis on invasive coronary angiography. Models were built by using generalized linear mixed-effects models with a random intercept set for the original study. The two CAD prediction models were compared by the likelihood ratio test, while their diagnostic performance was compared using the area under the receiver-operating-characteristic curve (AUC). Net benefit (benefit of true positive versus harm of false positive) was assessed by decision curve analysis., Results: CAD prevalence was 43.5% (1007/2315). Combining CCTA with CAC improved CAD diagnosis compared with CCTA alone (AUC: 87% [95% CI: 86 to 89%] vs. 80% [95% CI: 78 to 82%]; p < 0.001), likelihood ratio test 236.3, df: 1, p < 0.001, showing a higher net benefit across almost all threshold probabilities., Conclusion: Adding the CAC score to CCTA findings in patients with stable chest pain improves the diagnostic performance in detecting CAD and the net benefit compared with CCTA alone., Clinical Relevance Statement: CAC scoring CT performed before coronary CTA and included in the diagnostic model can improve obstructive CAD diagnosis, especially when CCTA is non-diagnostic., Key Points: • The combination of coronary artery calcium with coronary computed tomography angiography showed significantly higher AUC (87%, 95% confidence interval [CI]: 86 to 89%) for diagnosis of coronary artery disease compared to coronary computed tomography angiography alone (80%, 95% CI: 78 to 82%, p < 0.001). • Diagnostic improvement was mostly seen in patients with non-diagnostic C. • The improvement in diagnostic performance and the net benefit was consistent across age groups, chest pain types, and genders., (© 2023. The Author(s).)

Background: Guidelines recommend routine transthoracic echocardiography (TTE) after ischaemic stroke or transient ischaemic attack of undetermined cause; yet, only limited scientific evidence exists. Therefore, we aimed to determine in these patients the prevalence of TTE-detected major cardiac sources of embolism (CSE), which are abnormalities leading to therapeutic changes., Methods: Six Dutch hospitals conducted a prospective observational study that enrolled patients with ischaemic stroke or transient ischaemic attack of undetermined cause. Patients underwent TTE after comprehensive diagnostic evaluation on stroke units, including blood chemistry, 12-lead electrocardiogram (ECG), ≥ 24 h continuous ECG monitoring, brain imaging and cervical artery imaging. Primary outcome measure was the proportion of patients with TTE-detected major CSE., Results: From March 2018 to October 2020, 1084 patients, aged 66.6 ± 12.5 years, were enrolled; 456 (42.1%) patients were female and 869 (80.2%) had ischaemic stroke. TTE detected major CSE in only 11 (1.0%) patients. Ten (90.9%) of these patients also had major ECG abnormalities (previous infarction, major repolarisation abnormalities, or previously unknown left bundle branch block) that would have warranted TTE assessment regardless of stroke evaluation. Such ECG abnormalities were present in 11.1% of the total study population. A single patient (0.1%) showed a major CSE despite having no ECG abnormality., Conclusions: This multicentre cross-sectional study in patients who-after workup on contemporary stroke units-were diagnosed with ischaemic stroke or transient ischaemic attack of undetermined cause found TTE-detected major CSE in only 1% of all patients. Most of these patients also had major ECG abnormalities. These findings question the value of routine TTE assessment in this clinical setting., (© 2023. The Author(s).)

Objectives: Guidelines advise cardiac rhythm monitoring for 3 up to 30 days for detecting atrial fibrillation (AF) in patients with ischemic stroke of undetermined cause. However, the optimal monitoring duration is unknown. We aimed to determine the AF detection rate during 7-day outpatient cardiac rhythm monitoring in this patient group., Methods: Participants from a large tertiary hospital in a prospective observational study (ATTEST) underwent outpatient cardiac rhythm monitoring after a negative standard diagnostic evaluation (i.e., 12-lead electrocardiogram and in-hospital telemetry). Primary outcome was the rate of newly detected AF., Results: We examined 373 patients [age: 67.8±11.6 years; women: 166(44.5%); stroke: 278(74.5%)]. Median monitoring duration was 7 days (Inter Quartile Range (IQR) 7-7), performed after median of 36 days (IQR 27-47). AF was newly detected in 17(4.6%) patients, 5.4% of patients with ischemic stroke and 2.1% of patients with TIA. 53% of AF was detected on day-1, after day-3 73% of new AF was found. First AF episodes were detected up to day-7. Diabetes and increasing age were independent predictors of new AF., Conclusion: After ischemic stroke or TIA of undetermined cause, 7-day outpatient cardiac rhythm monitoring detected new AF in 4.6%. Patients with AF had significantly more cardiovascular risk factors. Although about 50% of first AF episodes occurred during the first day of monitoring, new AF was detected up to day-7, implying that the recommended minimum of 3 days cardiac rhythm monitoring after ischemic stroke of undetermined cause is insufficient. Subsequent long-term rhythm monitoring should be considered in selected patients., Competing Interests: Declaration of Competing Interest C. von Birgelen reports that the research department of Thoraxcentrum Twente has received institutional research grants provided by Abbott Vascular, Biotronik, Boston Scientific, and Medtronic, outside the present research. All other authors declared that they have no conflict of interest., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: There is conflicting evidence about the comparative diagnostic accuracy of the Agatston score versus computed tomography angiography (CTA) in patients with suspected obstructive coronary artery disease (CAD)., Purpose: To determine whether CTA is superior to the Agatston score in the diagnosis of CAD., Methods: In total 2452 patients with stable chest pain and a clinical indication for invasive coronary angiography (ICA) for suspected CAD were included by the Collaborative Meta-analysis of Cardiac CT (COME-CCT) Consortium. An Agatston score of > 400 was considered positive, and obstructive CAD defined as at least 50% coronary diameter stenosis on ICA was used as the reference standard., Results: Obstructive CAD was diagnosed in 44.9% of patients (1100/2452). The median Agatston score was 74. Diagnostic accuracy of CTA for the detection of obstructive CAD (81.1%, 95% confidence interval [CI]: 77.5 to 84.1%) was significantly higher than that of the Agatston score (68.8%, 95% CI: 64.2 to 73.1%, p < 0.001). Among patients with an Agatston score of zero, 17% (101/600) had obstructive CAD. Diagnostic accuracy of CTA was not significantly different in patients with low to intermediate (1 to < 100, 100-400) versus moderate to high Agatston scores (401-1000, > 1000)., Conclusions: Results in our international cohort show CTA to have significantly higher diagnostic accuracy than the Agatston score in patients with stable chest pain, suspected CAD, and a clinical indication for ICA. Diagnostic performance of CTA is not affected by a higher Agatston score while an Agatston score of zero does not reliably exclude obstructive CAD., Key Points: • CTA showed significantly higher diagnostic accuracy (81.1%, 95% confidence interval [CI]: 77.5 to 84.1%) for diagnosis of coronary artery disease when compared to the Agatston score (68.8%, 95% CI: 64.2 to 73.1%, p < 0.001). • Diagnostic performance of CTA was not affected by increased amount of calcium and was not significantly different in patients with low to intermediate (1 to <100, 100-400) versus moderate to high Agatston scores (401-1000, > 1000). • Seventeen percent of patients with an Agatston score of zero showed obstructive coronary artery disease by invasive angiography showing absence of coronary artery calcium cannot reliably exclude coronary artery disease., (© 2022. The Author(s).)

Background: Patients with ischemic stroke or transient ischemic attack (TIA) of undetermined cause often undergo cardiac imaging in search of a cardioembolic source. As the choice of the most appropriate imaging approach is controversial and therapeutic implications have changed over time, we aimed to identify in patients with "cryptogenic stroke or TIA" the yield of transthoracic or transesophageal echocardiography (TTE or TEE) and cardiac computed tomography (CT)., Methods and Results: We performed a systematic review and meta-analysis according to the PRISMA guidelines. Included were studies that assessed consecutive patients with ischemic stroke or TIA of undetermined cause to evaluate the yield of TTE, TEE, or cardiac CT for detecting cardioembolic sources. For each type of cardioembolic source the pooled prevalence was calculated. Only six out of 1458 studies fulfilled the inclusion criteria (1022 patients). One study reported the yield of TTE, four of TEE, and one of both TTE and TEE; no study assessed cardiac CT. Mean patient age ranged from 44.3-71.2 years, 49.2-59.7% were male. TTE detected 43 cardioembolic sources in 316 patients (4 (1.3%) major, 39 (12.3%) minor), and TEE 248 in 937 patients (55 (5.9%) major, 193 (20.6%) minor). The most prevalent major cardioembolic source was left atrial appendage thrombus, yet results were heterogeneous among studies., Conclusions: TTE and TEE infrequently detect major cardioembolic sources that require a change of therapy. Findings should be interpreted with caution due to the limited number of studies. A large-sized prospective clinical trial is warranted to support evidence-based decision-making., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background/aim: Current guidelines recommend transthoracic echocardiography (TTE) and ambulatory rhythm monitoring following ischemic stroke or transient ischemic attack (TIA) of undetermined cause for identifying cardioembolic sources (CES). Due to ongoing controversies about this routine strategy, we evaluated its yield in a real-world setting., Methods: In a tertiary medical center, we retrospectively evaluated consecutive patients with ischemic stroke or TIA of undetermined cause, who (after standard work-up) underwent TTE, ambulatory rhythm monitoring, or both. CES were classified as major if probably related to ischemic events and warranting a change of therapy., Results: Between January 2014 and December 2017, 674 patients had ischemic stroke or TIA of undetermined cause. Of all 484 patients (71.8%) who underwent TTE, 9 (1.9%) had a major CES. However, 7 of them had already been identified for cardiac evaluation due to new major electrocardiographic abnormalities or cardiac symptoms. Thus, only 2 patients (0.4%) truly benefitted from unselected TTE screening. Ambulatory rhythm monitoring was performed in 411 patients (61.0%) and revealed AF in 10 patients (2.4%)., Conclusion: Detecting a major CES is essential because appropriate treatment lowers the risk of recurrent stroke. Nonetheless, in this real-world study that aimed at routine use of TTE and ambulatory rhythm monitoring in patients with ischemic stroke or TIA of undetermined cause, the prevalence of major CES was low. Most patients with major CES on TTE already had an indication for referral to a cardiologist, suggesting that major CES might also have been identified with a much more selective use of TTE., (© 2021 The Author(s) Published by S. Karger AG, Basel.)

Background and Purpose: The rate of newly detected (paroxysmal) atrial fibrillation (AF) during inpatient cardiac telemetry is low. The objective of this study was to evaluate the additional diagnostic yield of an automated detection algorithm for AF on telemetric monitoring compared with routine detection by a stroke unit team in patients with recent ischemic stroke or TIA., Methods: Patients admitted to the stroke unit of Medisch Spectrum Twente with acute ischemic stroke or TIA and no history of AF were prospectively included. All patients had telemetry monitoring, routinely assessed by the stroke unit team. The ST segment and arrhythmia monitoring (ST/AR) algorithm was active, with deactivated AF alarms. After 24 h the detections were analyzed and compared with routine evaluation., Results: Five hundred and seven patients were included (52.5% male, mean age 70.2 ± 12.9 years). Median monitor duration was 24 (interquartile range 22-27) h. In 6 patients (1.2%) routine analysis by the stroke unit team concluded AF. In 24 patients (4.7%), the ST/AR Algorithm suggested AF. Interrater reliability was low (κ, 0.388, p < 0.001). Suggested AF by the algorithm turned out to be false positive in 11 patients. In 13 patients (2.6%) AF was correctly diagnosed by the algorithm. None of the cases detected by routine analysis were missed by the algorithm., Conclusions: Automated AF detection during 24-h telemetry in ischemic stroke patients is of additional value to detect paroxysmal AF compared with routine analysis by the stroke unit team alone. Automated detections need to be carefully evaluated., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

The original version of this article, published on 19 March 2018, unfortunately contained a mistake. The following correction has therefore been made in the original: The names of the authors Philipp A. Kaufmann, Ronny Ralf Buechel and Bernhard A. Herzog were presented incorrectly.

Objectives: To analyse the implementation, applicability and accuracy of the pretest probability calculation provided by NICE clinical guideline 95 for decision making about imaging in patients with chest pain of recent onset., Methods: The definitions for pretest probability calculation in the original Duke clinical score and the NICE guideline were compared. We also calculated the agreement and disagreement in pretest probability and the resulting imaging and management groups based on individual patient data from the Collaborative Meta-Analysis of Cardiac CT (CoMe-CCT)., Results: 4,673 individual patient data from the CoMe-CCT Consortium were analysed. Major differences in definitions in the Duke clinical score and NICE guideline were found for the predictors age and number of risk factors. Pretest probability calculation using guideline criteria was only possible for 30.8 % (1,439/4,673) of patients despite availability of all required data due to ambiguity in guideline definitions for risk factors and age groups. Agreement regarding patient management groups was found in only 70 % (366/523) of patients in whom pretest probability calculation was possible according to both models., Conclusions: Our results suggest that pretest probability calculation for clinical decision making about cardiac imaging as implemented in the NICE clinical guideline for patients has relevant limitations., Key Points: • Duke clinical score is not implemented correctly in NICE guideline 95. • Pretest probability assessment in NICE guideline 95 is impossible for most patients. • Improved clinical decision making requires accurate pretest probability calculation. • These refinements are essential for appropriate use of cardiac CT.