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Background: The presence and clinical significance of hepatic tissue alterations as assessed by cardiac magnetic resonance imaging in patients with ST-segment-elevation myocardial infarction (STEMI), are unclear. This study aimed to investigate associations of hepatic T1 patterns with myocardial tissue damage and clinical outcomes in patients suffering from STEMI., Methods: We analyzed 485 patients with STEMI treated with percutaneous coronary intervention who were enrolled in the prospective magnetic resonance imaging in acute ST-elevation myocardial infarction study (MARINA STEMI). Myocardial function and left and right ventricular (RV) infarct characteristics were assessed by cardiac magnetic resonance within the first week after STEMI. Native hepatic T1 times and extracellular volume were evaluated from standard cardiac T1 maps at baseline and 4 months thereafter., Results: Median hepatic T1 times were 559 ms (interquartile range, 514-605) at baseline and decreased to 542 ms (interquartile range, 507-577) at 4 months ( P <0.001). Hepatic T1 times at baseline were independently associated with female sex (β 0.116; P =0.008), hyperlipidemia (β -0.116; P =0.008), and myocardial tissue damage (infarct size: β 0.178; P <0.001; microvascular obstruction: β 0.193; P <0.001; RV infarction: β 0.161; P <0.001). Determinants of hepatic T1 times at 4 months were female sex (β 0.123; P =0.002), multivessel disease (β 0.121; P =0.002), N-terminal pro-B-type natriuretic peptide (β 0.101; P =0.010), RV infarction (β 0.501; P <0.001), and RV end-systolic volume index (β 0.087; P =0.031). Patients without a decrease exhibited a higher frequency of major adverse cardiovascular events (13% versus 5%; P =0.003). Hepatic T1 times at baseline (hazard ratio, 1.87 [95% CI, 1.40-2.50]; P <0.001), 4 months (hazard ratio, 2.69 [95% CI, 2.15-3.36]; P <0.001), and hepatic extracellular volume at 4 months (hazard ratio, 1.59 [95% CI, 1.33-1.90]; P <0.001) were associated with major adverse cardiovascular events. After adjustment for univariable associates, only hepatic T1 times at 4 months were independently associated with adverse outcomes (hazard ratio, 2.86 [95% CI, 1.99-4.12]; P <0.001)., Conclusions: Hepatic tissue alterations determined by T1 mapping were associated with female sex, hyperlipidemia, multivessel disease, N-terminal pro-B-type natriuretic peptide, and left and RV myocardial tissue damage. These alterations can persist into the chronic phase after STEMI and indicate a worse clinical outcome., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04113356.

Background: Beyond therapeutic implications, PCSK9 (proprotein convertase subtilisin/kexin 9) has emerged as a promising cardiovascular biomarker. The exact role of PCSK9 in the setting of acute ST-elevation myocardial infarction (STEMI) is incompletely understood. We aimed to investigate the association of PCSK9 with ischemia-reperfusion injury, visualized by cardiac magnetic resonance imaging, in patients with STEMI revascularized by primary percutaneous coronary intervention (PCI)., Methods: In this prespecified substudy from the prospective MARINA-STEMI (NCT04113356) registry, we included 205 patients with STEMI. PCSK9 concentrations were measured from venous blood samples by an immunoassay 24 and 48 hours after PCI. The primary end point was defined as presence of intramyocardial hemorrhage according to cardiac magnetic resonance T2* mapping. Secondary imaging end points were the presence of microvascular obstruction (MVO) and infarct size. The clinical end point was the occurrence of major adverse cardiac events., Results: We observed a significant increase in PCSK9 levels from 24 to 48 hours (268-304 ng/mL; P <0.001) after PCI. PCSK9 24 hours after PCI did not show any relation to intramyocardial hemorrhage, MVO, and infarct size (all P >0.05). PCSK9 concentrations 48 hours post-STEMI were higher in patients with intramyocardial hemorrhage (333 versus 287 ng/mL; P =0.004), MVO (320 versus 292 ng/mL; P =0.020), and large infarct size (323 versus 296 ng/mL; P =0.013). Furthermore, patients with increased PCSK9 levels >361 ng/mL at 48 hours were more likely to experience major adverse cardiac events (15% versus 8%; P =0.002) during a median follow-up of 12 months., Conclusions: In patients with STEMI, a significant increase in PCSK9 was observed from 24 to 48 hours after PCI. While PCSK9 levels after 24 hours were not related to myocardial or microvascular injury, PCSK9 after 48 hours was significantly associated with intramyocardial hemorrhage, MVO, and infarct size as well as worse subsequent clinical outcomes., Registration: URL: https://www.clinicaltrials.gov; Unique identifier; NCT04113356., Competing Interests: None.

Existing research integrity (RI) guideline development methods are limited in including various perspectives. While co-creation methods could help to address this, there is little information available to researchers and practitioners on how, why and when to use co-creation for developing RI guidelines, nor what the outcomes of co-creation methods are. In this paper, we aim to address this gap. First, we discuss how co-creation methods can be used for RI guideline development, based on our experience of developing RI guidelines. We elaborate on steps including preparation of the aims and design; participant sensitization; organizing and facilitating workshops; and analyzing data and translating them into guidelines. Secondly, we present the resulting RI guidelines, to show what the outcome of co-creation methods are. Thirdly, we reflect on why and when researchers might want to use co-creation methods for developing RI guidelines. We discuss that stakeholder engagement and inclusion of diverse perspectives are key strengths of co-creation methods. We also reflect that co-creation methods have the potential to make guidelines implementable if followed by additional steps such as revision working groups. We conclude that co-creation methods are a valuable approach to creating new RI guidelines when used together with additional methods.

Background: Acute myocardial infarction is associated with the release of the co-transmitter neuropeptide-Y (NPY). NPY acts as a potent vasoconstrictor and is associated with microvascular dysfunction after ST-elevation myocardial infarction (STEMI). This study comprehensively evaluated the association of plasma NPY with myocardial function and infarct severity, visualized by cardiac magnetic resonance (CMR) imaging, in STEMI patients revascularized by primary percutaneous coronary intervention (PCI)., Methods: In this observational study, we included 260 STEMI patients enrolled in the prospective MARINA-STEMI (NCT04113356) study. Plasma NPY concentrations were measured by an immunoassay 24h after PCI from peripheral venous blood samples. Left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), infarct size (IS) and microvascular obstruction (MVO) were determined using CMR imaging., Results: Median plasma concentrations of NPY were 70 [interquartile range (IQR):35-115] pg/ml. NPY levels above median were significantly associated with lower LVEF (48%vs.52%, p=0.004), decreased GLS (-8.8%vs.-12.6%, p<0.001) and larger IS (17%vs.13%, p=0.041) in the acute phase after infarction as well as after 4 months (LVEF:50%vs.52%, p=0.030, GLS:-10.5vs.-12.9,p<0.001,IS:13%vs.10%,p=0.011). In addition, NPY levels were significantly related to presence of MVO (58%vs.52%, p=0.041). Moreover, in multivariable linear regression analysis, NPY remained significantly associated with all investigated CMR parameters (LVEF:p<0.001,GLS:p<0.001,IS:p=0.003,MVO:p=0.042) independent of other established clinical variables including high-sensitivity cardiac troponin T, pre-interventional TIMI flow 0 and left anterior descending artery as culprit lesion location., Conclusion: High plasma levels of NPY, measured 24h after STEMI, were independently associated with lower LVEF, decreased GLS, larger IS as well as presence of MVO, indicating plasma NPY as a novel clinical risk marker post STEMI., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Bovine paratuberculosis (PTB) is a chronic enteric disease caused by Mycobacterium avium subsp. paratuberculosis (MAP). Control of PTB is important given its negative economic consequences and the potential zoonotic role of MAP in Crohn's disease in humans., Methods: To determine the seroprevalence of MAP in Swiss dairy herds and to identify risk factors associated with seropositive herd status and high within-herd seroprevalence, 10,063 serum samples collected from cattle over 12 months of age in 171 Swiss dairy farms were analyzed using a commercial ELISA test. Eight herds were excluded due to non-interpretable ELISA results. Risk factors associated with seropositive herd status and high within-herd seroprevalence were investigated with regression models using results from a questionnaire on management practices possibly associated with the introduction or spread of MAP in the remaining 163 herds. Univariable logistic regression was performed, carrying forward for multivariable regression analysis when p  < 0.2., Results: The calculated between-herd true seroprevalence was 3.6% (95% CI, 0.96-8.4%). Due to the low within-herd seroprevalence, it was not possible to calculate the true seroprevalence at animal level; the apparent within-herd seroprevalence ranged from 2.3 to 5.5% with a median of 3.6% in nine positive farms. Herd size ( p  = 0.037) and the common grazing of lactating cows with cows from other herds ( p  = 0.014) were associated with seropositive herd status, while heifers sharing alpine pasture with dairy cattle from other herds were associated with a decreased probability of the herd to test seropositive ( p  = 0.042). Reliable identification of significant risk factors associated with MAP spread and high seroprevalence of PTB within seropositive herds was not possible due to low observed seroprevalence within herds and low sensitivity of the ELISA test., Discussion: These results highlight the limitation of serology for MAP diagnosis in small herds with low infection prevalence., Competing Interests: IL and JW were employed by SAFOSO AG. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ottardi, Lechner, Wang, Schmitt, Schneeberger, Schmid, Stephan and Meylan.)

Particle passage from the reticulorumen (RR) depends on particle density and size. A classic way of assessing these effects is the use of plastic markers of varying density and size that are recovered in the faeces. Here, we report results of an experiment where four fistulated reindeer (Rangifer tarandus, 96 ± 12 kg) were fed two different diets (browse, voluntary dry matter intake [DMI] 70 ± 10 g/kg 0.75 /d; or a pelleted diet, DMI 124 ± 52 g/kg 0.75 /d) and dosed via fistula with 8 different particle types combining densities of 1.03, 1.22 and 1.44 g/ml and sizes of 1, 10 and 20 mm. Generally, particles that passed the digestive tract intact (not ruminated) did so relatively early after marker dosing, and therefore had shorter mean retention times (MRT) than ruminated particles. On the higher intake, the overall mean retention time (MRT) of particles was shorter, but this was not an effect of shorter MRT for either intact or ruminated particles, but due to a higher proportion of intact particles at the higher intake. This supports the concept that ruminants do not adjust chewing behaviour depending on intake, but that a lower proportion of digesta is submitted to rumination due to pressure-driven escape from the forestomach at higher gut fills. Compared to cattle (Bos primigenius taurus), muskoxen (Ovibos moschatus) and moose (Alces alces) that had received the same markers, reindeer had a lower proportion of 1 mm particles that passed intact. Our results support the concept that the critical size threshold for particles leaving the ruminant forestomach is dependent on body size. While the results likely do not represent findings peculiar for reindeer, they indicate fundamental mechanisms operating in the forestomach of ruminants., Competing Interests: Declaration of competing interest The authors 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Dysglycaemia increases the risk of myocardial infarction and subsequent recurrent cardiovascular events. However, the role of dysglycaemia in ischemia/reperfusion injury with development of irreversible myocardial tissue alterations remains poorly understood. In this study we aimed to investigate the association of ongoing dysglycaemia with persistence of infarct core iron and their longitudinal changes over time in patients undergoing primary percutaneous coronary intervention (PCI) for acute ST-segment elevation myocardial infarction (STEMI)., Methods: We analyzed 348 STEMI patients treated with primary PCI between 2016 and 2021 that were included in the prospective MARINA-STEMI study (NCT04113356). Peripheral venous blood samples for glucose and glycated hemoglobin (HbA1c) measurements were drawn on admission and 4 months after STEMI. Cardiac magnetic resonance (CMR) imaging including T2 * mapping for infarct core iron assessment was performed at both time points. Associations of dysglycaemia with persistent infarct core iron and iron resolution at 4 months were calculated using multivariable regression analysis., Results: Intramyocardial hemorrhage was observed in 147 (42%) patients at baseline. Of these, 89 (61%) had persistent infarct core iron 4 months after infarction with increasing rates across HbA1c levels (<5.7%: 33%, ≥5.7: 79%). Persistent infarct core iron was independently associated with ongoing dysglycaemia defined by HbA1c at 4 months (OR: 7.87 [95% CI: 2.60-23.78]; p < 0.001), after adjustment for patient characteristics and CMR parameters. The independent association was present even after exclusion of patients with diabetes (pre- and newly diagnosed, n = 16)., Conclusions: In STEMI patients treated with primary PCI, ongoing dysglycaemia defined by HbA1c is independently associated with persistent infarct core iron and a lower likelihood of iron resolution. These findings suggest a potential association between ongoing dysglycaemia and persistent infarct core iron, which warrants further investigation for therapeutic implications., Competing Interests: Declaration of Competing Interest The authors 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 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The prognostic significance of various microvascular injury (MVI) patterns after ST-segment elevation myocardial infarction (STEMI) is not well known., Objectives: This study sought to investigate the prognostic implications of different MVI patterns in STEMI patients., Methods: The authors analyzed 1,109 STEMI patients included in 3 prospective studies. Cardiac magnetic resonance (CMR) was performed 3 days (Q1-Q3: 2-5 days) after percutaneous coronary intervention (PCI) and included late gadolinium enhancement imaging for microvascular obstruction (MVO) and T2∗ mapping for intramyocardial hemorrhage (IMH). Patients were categorized into those without MVI (MVO-/IMH-), those with MVO but no IMH (MVO+/IMH-), and those with IMH (IMH+)., Results: MVI occurred in 633 (57%) patients, of whom 274 (25%) had an MVO+/IMH- pattern and 359 (32%) had an IMH+ pattern. Infarct size was larger and ejection fraction lower in IMH+ than in MVO+/IMH- and MVO-/IMH- (infarct size: 27% vs 19% vs 18% [P < 0.001]; ejection fraction: 45% vs 50% vs 54% [P < 0.001]). During a median follow-up of 12 months (Q1-Q3: 12-35 months), a clinical outcome event occurred more frequently in IMH+ than in MVO+/IMH- and MVO-/IMH- subgroups (19.5% vs 3.6% vs 4.4%; P < 0.001). IMH+ was the sole independent MVI parameter predicting major adverse cardiovascular events (HR: 3.88; 95% CI: 1.93-7.80; P < 0.001)., Conclusions: MVI is associated with future adverse outcomes only in patients with a hemorrhagic phenotype (IMH+). Patients with only MVO (MVO+/IMH-) had a prognosis similar to patients without MVI (MVO-/IMH-). This highlights the independent prognostic importance of IMH in assessing and managing risk after STEMI., Competing Interests: Funding Support and Author Disclosures This work was supported by grants from the Austrian Science Fund (KLI 772-B), the Tiroler Wissenschaftsfonds, the Austrian Society of Cardiology, the Society for the Promotion of Cardiovascular Research, “Lilly” Germany, the University of Leipzig Heart Centre, and the British Heart Foundation (RE/18/6134217). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Mitral annular disjunction (MAD), defined as defective attachment of the mitral annulus to the ventricular myocardium, has recently been linked to malignant arrhythmias. However, its role and prognostic significance in patients requiring cardiopulmonary resuscitation (CPR) remain unknown. This retrospective analysis aimed to describe the prevalence and significance of MAD by cardiac magnetic resonance (CMR) imaging in out-of-hospital cardiac arrest (OHCA) patients., Methods: Eighty-six patients with OHCA and a CMR scan 5 days after CPR (interquartile range (IQR): 49 days before - 9 days after) were included. MAD was defined as disjunction-extent ≥ 1 mm in CMR long-axis cine-images. Medical records were screened for laboratory parameters, comorbidities, and a history of arrhythmia., Results: In 34 patients (40%), no underlying cause for OHCA was found during hospitalization despite profound diagnostics. Unknown-cause OHCA patients showed a higher prevalence of MAD compared to definite-cause patients (56% vs. 10%, p < 0.001) and had a MAD-extent of 6.3 mm (IQR: 4.4-10.3); moreover, these patients were significantly younger (43 years vs. 61 years, p < 0.001), more often female (74% vs. 21%, p < 0.001) and had fewer comorbidities (hypertension, hypercholesterolemia, coronary artery disease, all p < 0.005). By logistic regression analysis, the presence of MAD remained significantly associated with OHCA of unknown cause (odds ratio: 8.49, 95% confidence interval: 2.37-30.41, p = 0.001) after adjustment for age, presence of hypertension, and hypercholesterolemia., Conclusions: MAD is rather common in OHCA patients without definitive aetiology undergoing CMR. The presence of MAD was independently associated to OHCA without an identifiable trigger. Further research is needed to understand the exact role of MAD in OHCA patients., (© 2024. The Author(s).)

Background: Microvascular obstruction (MVO) and intramyocardial hemorrhage (IMH) are well-established imaging biomarkers of failed myocardial tissue reperfusion in patients with ST-segment elevation-myocardial infarction treated with percutaneous coronary intervention. MVO and IMH are associated with an increased risk of adverse outcome independent of infarct size, but whether the size of the culprit lesion vessel plays a role in the occurrence and severity of reperfusion injury is currently unknown. This study aimed to evaluate the association between culprit lesion vessel size and the occurrence and severity of reperfusion injury as determined by cardiac magnetic resonance imaging., Methods and Results: Patients (n=516) with first-time ST-segment-elevation myocardial infarction underwent evaluation with cardiac magnetic resonance at 4 (3-5) days after infarction. MVO was assessed with late gadolinium enhancement imaging and IMH with T2* mapping. Vessel dimensions were determined using catheter-based reference. Median culprit lesion vessel size was 3.1 (2.7-3.6) mm. MVO and IMH were found in 299 (58%) and 182 (35%) patients. Culprit lesion vessel size was associated with body surface area, diabetes, total ischemic time, postinterventional thrombolysis in myocardial infarction flow, and infarct size. There was no association between vessel size and MVO or IMH in univariable and multivariable analysis ( P >0.05). These findings were consistent across patient subgroups with left anterior descending artery and non-left anterior descending artery infarctions and those with thrombolysis in myocardial infarction 3 flow post-percutaneous coronary intervention., Conclusions: Comprehensive characterization of myocardial tissue reperfusion injury by cardiac magnetic resonance revealed no association between culprit lesion vessel size and the occurrence of MVO and IMH in patients treated with primary percutaneous coronary intervention for ST-segment-elevation myocardial infarction.

Background: Standard modifiable cardiovascular risk factors (SMuRFs) are well-established players in the pathogenesis of ST-elevation myocardial infarction (STEMI). However, in a significant proportion of STEMI patients, no SMuRFs can be identified, and the outcomes of this subgroup are not well described., Objectives: To assess the infarct characteristics at myocardial-tissue level and subsequent clinical outcomes in SMuRF-less STEMIs., Methods: This multicenter, individual patient-data analysis included 2012 STEMI patients enrolled in four cardiac magnetic resonance (CMR) imaging studies conducted in Austria, Germany, Scotland, and the Netherlands. Unstable patients at time of CMR (e.g. cardiogenic shock/after cardiac arrest) were excluded. SMuRF-less was defined as absence of hypertension, smoking, hypercholesterolemia, and diabetes mellitus. All patients underwent CMR 3(interquartile range [IQR]:2-4) days after infarction to assess left ventricular (LV) volumes and ejection fraction, infarct size and microvascular obstruction (MVO). Clinical endpoints were defined as major adverse cardiovascular events (MACE), including all-cause mortality, re-infarction and heart failure., Results: No SMuRF was identified in 185 patients (9%). These SMuRF-less patients were older, more often male, had lower TIMI risk score and pre-interventional TIMI flow, and less frequently multivessel-disease. SMuRF-less patients did not show significant differences in CMR markers compared to patients with SMuRFs (all p > 0.10). During a median follow-up of 12 (IQR:12-27) months, 199 patients (10%) experienced a MACE. No significant difference in MACE rates was observed between SMuRF-less patients and patients with SMuRFs (8vs.10%, p = 0.39)., Conclusions: In this large individual patient-data pooled analysis of low-risk STEMI patients, infarct characteristics and clinical outcomes were not different according to SMuRF status., Competing Interests: Declaration of Competing Interest The Authors declare that there is no conflict of interest., (Copyright © 2023 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)