Performance of highly sensitive cardiac troponin T assay to detect ischaemia at PET-CT in low-risk patients with acute coronary syndrome: a prospective observational study.

Highly sensitive troponin T (hs-TnT) assay has improved clinical decision-making for patients admitted with chest pain. However, this assay's performance in detecting myocardial ischaemia in a lowrisk population has been poorly documented. To assess hs-TnT assay's performance to detect myocardial ischaemia at positron emission tomography/CT (PET-CT) in low-risk patients admitted with chest pain. Patients admitted for chest pain with a nonconclusive ECG and negative standard cardiac troponin T results at admission and after 6 hours were prospectively enrolled. Their hs-TnT samples were at T0, T2 and T6. Physicians were blinded to hs-TnT results. All patients underwent a PET-CT at rest and during adenosine-induced stress. All patients with a positive PET-CT result underwent a coronary angiography. Forty-eight patients were included. Six had ischaemia at PET-CT. All of them had ≥1 significant stenosis at coronary angiography. Areas under the curve (95% CI) for predicting significant ischaemia at PET-CT using hs-TnT were 0.764 (0.515 to 1.000) at T0, 0.812(0.616 to 1.000) at T2 and 0.813(0.638 to 0.989) at T6. The receiver operating characteristicbased optimal cut-off value for hs-TnT at T0, T2 and T6 needed to exclude significant ischaemia at PET-CT was <4 ng/L. Using this value, sensitivity, specificity, positive and negative predictive values of hs-TnT to predict significant ischaemia were 83%/38%/16%/94% at T0, 100%/40%/19%/100% at T2 and 100%/43%/20%/100% at T6, respectively. Our findings suggest that in low-risk patients, using the hs-TnT assay with a cut-off value of 4 ng/L demonstrates excellent negative predictive value to exclude myocardial ischaemia detection at PET-CT, at the expense of weak specificity and positive predictive value. ClinicalTrials.gov Identifier: NCT01374607

The global distribution of known and undiscovered ant biodiversity

Invertebrates constitute the majority of animal species and are critical for ecosystem functioning and services. Nonetheless, global invertebrate biodiversity patterns and their congruences with vertebrates remain largely unknown. We resolve the first high-resolution (~20-km) global diversity map for a major invertebrate clade, ants, using biodiversity informatics, range modeling, and machine learning to synthesize existing knowledge and predict the distribution of undiscovered diversity. We find that ants and different vertebrate groups have distinct features in their patterns of richness and rarity, underscoring the need to consider a diversity of taxa in conservation. However, despite their phylogenetic and physiological divergence, ant distributions are not highly anomalous relative to variation among vertebrate clades. Furthermore, our models predict that rarity centers largely overlap (78%), suggesting that general forces shape endemism patterns across taxa. This raises confidence that conservation of areas important for small-ranged vertebrates will benefit invertebrates while providing a “treasure map” to guide future discovery.The Okinawa Institute of Science and Technology Graduate University, the Japan Society for the Promotion of Science, Japan Society for the Promotion of Science Postdoctoral Fellowships for Foreign Researchers Program, Japan Ministry of the Environment, Environment Research, and Technology Development Fund no. 4-1904, the Leverhulme Trust, the National Science Foundation, Australian Research Discovery Grant, Foundational Biodiversity Information Programme (South Africa), and the USDA and NIFA support of the Mississippi Entomological Museum.https://www.science.org/journal/sciadvam2023Zoology and Entomolog

Influence of socioeconomic factors on delays, management and outcome amongst patients with acute myocardial infarction undergoing primary percutaneous coronary intervention.

The outcome after primary percutaneous coronary intervention (pPCI) for ST-elevation myocardial infarction (STEMI) is strongly affected by time delays. In this study, we sought to identify the impact of specific socioeconomic factors on time delays, subsequent STEMI management and outcomes in STEMI patients undergoing pPCI, who came from a well-defined region of the French part of Switzerland. A total of 402 consecutive patients undergoing pPCI for STEMI in a large tertiary hospital were retrospectively studied. Symptom-to-first-medical-contact time was analysed for the following socioeconomic factors: level of education, origin and marital status. Main exclusion criteria were: time delay beyond 12 hours, previous treatment with fibrinolytic agents or patients immediately referred for coronary artery bypass graft surgery. Therefore, 222 patients were finally included. At 1 year, there was no difference in mortality between the different socioeconomic groups. Furthermore, there was no difference in management characteristics between them. Symptom-to-first-medical-contact time was significantly longer for patients with a low level of education, Swiss citizens and unmarried patients, with median differences of 23 minutes, 18 minutes and 13 minutes, respectively (p <0.05). Nevertheless, no difference was found regarding in-hospital management and clinical outcome. This study demonstrates that symptom-to-first-medical-contact time is longer amongst people with a lower educational level, Swiss citizens and unmarried people. Because of the low mortality rate in general, these differences in delays did not affect clinical outcomes. Still, tertiary prevention measures should particularly focus on these vulnerable populations

Comparative effects of fentanyl versus morphine on platelet inhibition induced by ticagrelor in patients with ST-segment elevation myocardial infarction: Full results of the PERSEUS randomized trial.

Morphine reduces absorption and delays action onset of potent oral P2Y₁₂ receptor inhibitors in patients with ST-segment elevation myocardial infarction (STEMI). We sought to determine the differential effects of fentanyl compared to morphine on the pharmacodynamics and pharmacokinetics of ticagrelor in STEMI patients undergoing primary percutaneous coronary intervention (PCI). PERSEUS (NCT02531165) was a prospective, single-center, open-label, randomized controlled study. Patients with STEMI who required analgesia were randomly assigned in a 1:1 ratio to treatment with intravenous fentanyl or morphine after ticagrelor loading dose (LD) administration. The primary endpoint was platelet reactivity at 2 hours after ticagrelor LD assessed by P2Y₁₂ reaction units (PRU). The study was prematurely stopped in June 2017 after enrolment of 38 out of 56 planned patients. PRU at 2 hours following ticagrelor LD was 173.3 ± 89.7 in the fentanyl group and 210.3 ± 76.4 in the morphine group (p = 0.179). At 4 hours, PRU was significantly lower among patients treated with fentanyl as compared to those treated with morphine (90.1 ± 97.4 vs. 168.0 ± 72.2; p = 0.011). Maximal plasma concentrations of ticagrelor and its active metabolite AR-C124910XX tended to be delayed and numerically lower among patients treated with morphine compared to fentanyl. Total exposures to ticagrelor and AR-C124910XX within 6 hours after ticagrelor LD were numerically greater among patients treated with fentanyl compared to those treated with morphine. In patients with STEMI undergoing primary PCI, fentanyl did not improve platelet inhibition at 2 hours after ticagrelor pre-treatment compared with morphine. Fentanyl may, however, accelerate ticagrelor absorption and increase platelet inhibition at 4 hours compared to morphine

Influence of intravenous fentanyl compared with morphine on ticagrelor absorption and platelet inhibition in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: rationale and design of the PERSEUS randomized trial.

Recent evidence demonstrates that intravenous morphine significantly reduces absorption and delays onset of action of oral P2Y12 receptor inhibitors in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI). We aimed to assess the influence of intravenous fentanyl compared with morphine on pharmacokinetics and pharmacodynamics of ticagrelor and its active metabolite (AR-C124910XX) in patients undergoing pPCI for STEMI. Single-centre, prospective, open-label, randomized controlled study that will randomly assign in a 1:1 ratio patients with STEMI undergoing pPCI to receive intravenous fentanyl or morphine following a pre-hospital 180-mg loading dose of ticagrelor (ClinicalTrials.gov Identifier: NCT02531165). Pharmacokinetic and pharmacodynamic analyses will be performed at baseline and 1, 2, 4, 6, and 12 h post-loading dose. Pharmacodynamic assessments will include P2Y12 reaction units (PRU) measured by VerifyNow P2Y12. Pharmacokinetic assessments include determination of maximal observed plasma concentrations, time for maximal plasma concentration, and area under the plasma concentration vs. time curve from time 0 to the last measurable concentration (AUC0-t) for ticagrelor and AR-C124910XX. The primary endpoint is platelet reactivity assessed by PRU at 2 h post ticagrelor loading dose. PERSEUS will provide randomized data regarding the impact of fentanyl administration, in patients with STEMI undergoing pPCI, on platelet inhibition and ticagrelor absorption and total exposure

Quantification of myocardial interstitial fibrosis and extracellular volume for the detection of cardiac allograft vasculopathy.

In search of a non-invasive alternative detection of early-stage cardiac allograft vasculopathy (CAV), in this preliminary study we tested the hypothesis that interstitial fibrosis quantified with cardiac magnetic resonance (CMR) can serve as a biomarker for the detection of CAV. Late-stage CAV was detected with routine X-ray coronary angiography (XRCA), while a coronary intima-media thickness ratio (IMTR) > 1 on optical coherence tomography (OCT) was used to detect early-stage CAV. Interstitial fibrosis was quantified in the endomyocardial biopsy (EMB) and indirectly with CMR as the T <sub>1</sub> relaxation time and extracellular volume (ECV). CMR was performed within 48 h of a single invasive procedure with XRCA, OCT, and EMB procurement in stable HTx recipients (n = 27; age 54 ± 13 years, 5.4 ± 3.7 years post-transplant). XRCA-CAV and IMTR > 1 were present in 15% and 75% of study patients, respectively. The T <sub>1</sub> relaxation times and ECV were increased in patients with XRCA-CAV (p = 0.03 each), while IMTR and EMB interstitial fibrosis were not significantly different (both p > 0.05). ECV (ρ = 0.46, p = 0.02) and IMTR (ρ = 0.58; p = 0.01) correlated with the histological quantity of interstitial fibrosis, while the T <sub>1</sub> relaxation time (p = 0.06) did not. The correlation of the IMTR with the EMB interstitial fibrosis tentatively validates the hypothesis that interstitial fibrosis may serve as an early indicator of CAV. Moreover, the significant association of CMR-based ECV with the magnitude of interstitial fibrosis in the biopsy suggests ECV as a potential biomarker for interstitial fibrosis due to early-stage CAV. The measurement of ECV may therefore have a role for non-invasive detection and follow-up of early-stage CAV

Quality assessment of cardiovascular magnetic resonance in the setting of the European CMR registry: description and validation of standardized criteria.

BACKGROUND: Cardiovascular magnetic resonance (CMR) has become an important diagnostic imaging modality in cardiovascular medicine. However, insufficient image quality may compromise its diagnostic accuracy. We aimed to describe and validate standardized criteria to evaluate a) cine steady-state free precession (SSFP), b) late gadolinium enhancement (LGE), and c) stress first-pass perfusion images. These criteria will serve for quality assessment in the setting of the Euro-CMR registry. METHODS: Thirty-five qualitative criteria were defined (scores 0-3) with lower scores indicating better image quality. In addition, quantitative parameters were measured yielding 2 additional quality criteria, i.e. signal-to-noise ratio (SNR) of non-infarcted myocardium (as a measure of correct signal nulling of healthy myocardium) for LGE and % signal increase during contrast medium first-pass for perfusion images. These qualitative and quantitative criteria were assessed in a total of 90 patients (60 patients scanned at our own institution at 1.5T (n=30) and 3T (n=30) and in 30 patients randomly chosen from the Euro-CMR registry examined at 1.5T). Analyses were performed by 2 SCMR level-3 experts, 1 trained study nurse, and 1 trained medical student. RESULTS: The global quality score was 6.7±4.6 (n=90, mean of 4 observers, maximum possible score 64), range 6.4-6.9 (p=0.76 between observers). It ranged from 4.0-4.3 for 1.5T (p=0.96 between observers), from 5.9-6.9 for 3T (p=0.33 between observers), and from 8.6-10.3 for the Euro-CMR cases (p=0.40 between observers). The inter- (n=4) and intra-observer (n=2) agreement for the global quality score, i.e. the percentage of assignments to the same quality tertile ranged from 80% to 88% and from 90% to 98%, respectively. The agreement for the quantitative assessment for LGE images (scores 0-2 for SNR <2, 2-5, >5, respectively) ranged from 78-84% for the entire population, and 70-93% at 1.5T, 64-88% at 3T, and 72-90% for the Euro-CMR cases. The agreement for perfusion images (scores 0-2 for %SI increase >200%, 100%-200%,<100%, respectively) ranged from 81-91% for the entire population, and 76-100% at 1.5T, 67-96% at 3T, and 62-90% for the Euro-CMR registry cases. The intra-class correlation coefficient for the global quality score was 0.83. CONCLUSIONS: The described criteria for the assessment of CMR image quality are robust with a good inter- and intra-observer agreement. Further research is needed to define the impact of image quality on the diagnostic and prognostic yield of CMR studies

Quality Assessment of Cardiac Magnetic Resonance Images at 1.5/3.0 T: Description and Validation of Standardized Criteria

PURPOSE: Cardiovascular magnetic resonance (CMR) has become a robust and important diagnostic imaging modality in cardiovascular medicine. However,insufficient image quality may compromise its diagnostic accuracy. No standardized criteria are available to assess the quality of CMR studies. We aimed todescribe and validate standardized criteria to evaluate the quality of CMR studies including: a) cine steady-state free precession, b) delayed gadoliniumenhancement, and c) adenosine stress first-pass perfusion. These criteria will serve for the assessment of the image quality in the setting of the Euro-CMR registry.METHOD AND MATERIALS: First, a total of 45 quality criteria were defined (35 qualitative criteria with a score from 0-3, and 10 quantitative criteria). Thequalitative score ranged from 0 to 105. The lower the qualitative score, the better the quality. The quantitative criteria were based on the absolute signal intensity (delayed enhancement) and on the signal increase (perfusion) of the anterior/posterior left ventricular wall after gadolinium injection. These criteria were then applied in 30 patients scanned with a 1.5T system and in 15 patients scanned with a 3.0T system. The examinations were jointly interpreted by 3 CMR experts and 1 study nurse. In these 45 patients the correlation between the results of the quality assessment obtained by the different readers was calculated.RESULTS: On the 1.5T machine, the mean quality score was 3.5. The mean difference between each pair of observers was 0.2 (5.7%) with a mean standarddeviation of 1.4. On the 3.0T machine, the mean quality score was 4.4. The mean difference between each pair of onservers was 0.3 (6.4%) with a meanstandard deviation of 1.6. The quantitative quality assessments between observers were well correlated for the 1.5T machine: R was between 0.78 and 0.99 (pCONCLUSION: The described criteria for the assessment of CMR image quality are robust and have a low inter-observer variability, especially on 1.5T systems.CLINICAL RELEVANCE/APPLICATION: These criteria will allow the standardization of CMR examinations. They will help to improve the overall quality ofexaminations and the comparison between clinical studies