Quantitative assessment of angioplasty-induced vascular inflammation with 19F cardiovascular magnetic resonance imaging.

BACKGROUND: Macrophages play a pivotal role in vascular inflammation and predict cardiovascular complications. Fluorine-19 magnetic resonance imaging (19F MRI) with intravenously applied perfluorocarbon allows a background-free direct quantification of macrophage abundance in experimental vascular disease models in mice. Recently, perfluorooctyl bromide-nanoemulsion (PFOB-NE) was applied to effectively image macrophage infiltration in a pig model of myocardial infarction using clinical MRI scanners. In the present proof-of-concept approach, we aimed to non-invasively image monocyte/macrophage infiltration in response to carotid artery angioplasty in pigs using 19F MRI to assess early inflammatory response to mechanical injury. METHODS: In eight minipigs, two different types of vascular injury were conducted: a mild injury employing balloon oversize angioplasty only (BA, n = 4) and a severe injury provoked by BA in combination with endothelial denudation (BA + ECDN, n = 4). PFOB-NE was administered intravenously three days after injury followed by 1H and 19F MRI to assess vascular inflammatory burden at day six. Vascular response to mechanical injury was validated using X-ray angiography, intravascular ultrasound and immunohistology in at least 10 segments per carotid artery. RESULTS: Angioplasty was successfully induced in all eight pigs. Response to injury was characterized by positive remodeling with predominantly adventitial wall thickening and concomitant infiltration of monocytes/macrophages. No severe adverse reactions were observed following PFOB-NE administration. In vivo 19F signals were only detected in the four pigs following BA + ECDN with a robust signal-to-noise ratio (SNR) of 14.7 ± 4.8. Ex vivo analysis revealed a linear correlation of 19F SNR to local monocyte/macrophage cell density. Minimum detection limit of infiltrated monocytes/macrophages was estimated at approximately 410 cells/mm2. CONCLUSIONS: In this proof-of-concept study, 19F MRI enabled quantification of monocyte/macrophage infiltration after vascular injury with sufficient sensitivity. This may provide the opportunity to non-invasively monitor vascular inflammation with MRI in patients after angioplasty or even in atherosclerotic plaques.

SYSTEMI - systemic organ communication in STEMI: design and rationale of a cohort study of patients with ST-segment elevation myocardial infarction.

BACKGROUND: ST-segment elevation myocardial infarction (STEMI) still causes significant mortality and morbidity despite best-practice revascularization and adjunct medical strategies. Within the STEMI population, there is a spectrum of higher and lower risk patients with respect to major adverse cardiovascular and cerebral events (MACCE) or re-hospitalization due to heart failure. Myocardial and systemic metabolic disorders modulate patient risk in STEMI. Systematic cardiocirculatory and metabolic phenotyping to assess the bidirectional interaction of cardiac and systemic metabolism in myocardial ischemia is lacking. METHODS: Systemic organ communication in STEMI (SYSTEMI) is an all-comer open-end prospective study in STEMI patients > 18 years of age to assess the interaction of cardiac and systemic metabolism in STEMI by systematically collecting data on a regional and systemic level. Primary endpoint will be myocardial function, left ventricular remodelling, myocardial texture and coronary patency at 6 month after STEMI. Secondary endpoint will be all-cause death, MACCE, and re-hospitalisation due to heart failure or revascularisation assessed 12 month after STEMI. The objective of SYSTEMI is to identify metabolic systemic and myocardial master switches that determine primary and secondary endpoints. In SYSTEMI 150-200 patients are expected to be recruited per year. Patient data will be collected at the index event, within 24 h, 5 days as well as 6 and 12 months after STEMI. Data acquisition will be performed in multilayer approaches. Myocardial function will be assessed by using serial cardiac imaging with cineventriculography, echocardiography and cardiovascular magnetic resonance. Myocardial metabolism will be analysed by multi-nuclei magnetic resonance spectroscopy. Systemic metabolism will be approached by serial liquid biopsies and analysed with respect to glucose and lipid metabolism as well as oxygen transport. In summary, SYSTEMI enables a comprehensive data analysis on the levels of organ structure and function alongside hemodynamic, genomic and transcriptomic information to assess cardiac and systemic metabolism. DISCUSSION: SYSTEMI aims to identify novel metabolic patterns and master-switches in the interaction of cardiac and systemic metabolism to improve diagnostic and therapeutic algorithms in myocardial ischemia for patient-risk assessment and tailored therapy. TRIAL REGISTRATION: Trial Registration Number: NCT03539133.

Revealing concealed cardioprotection by platelet Mfsd2b-released S1P in human and murine myocardial infarction.

Antiplatelet medication is standard of care in acute myocardial infarction (AMI). However, it may have obscured beneficial properties of the activated platelet secretome. We identify platelets as major source of a sphingosine-1-phosphate (S1P) burst during AMI, and find its magnitude to favorably associate with cardiovascular mortality and infarct size in STEMI patients over 12 months. Experimentally, administration of supernatant from activated platelets reduces infarct size in murine AMI, which is blunted in platelets deficient for S1P export (Mfsd2b) or production (Sphk1) and in mice deficient for cardiomyocyte S1P receptor 1 (S1P1). Our study reveals an exploitable therapeutic window in antiplatelet therapy in AMI as the GPIIb/IIIa antagonist tirofiban preserves S1P release and cardioprotection, whereas the P2Y12 antagonist cangrelor does not. Here, we report that platelet-mediated intrinsic cardioprotection is an exciting therapeutic paradigm reaching beyond AMI, the benefits of which may need to be considered in all antiplatelet therapies.

Relevance of pre-existing anaemia for patients admitted for acute coronary syndrome to an intensive care unit: a retrospective cohort analysis of 7418 patients.

Aims: Patients with acute coronary syndrome (ACS) frequently suffer from anaemia, but its role in patients admitted to an intensive care unit (ICU) is unclear. This analysis evaluates the prognostic relevance of different degrees of anaemia and their specific impact on disease severity and the outcome in critically ill ACS patients. Methods and results: and results The multi-centre electronic Intensive Care Unit Collaborative Research Database was used, and all patients admitted with ACS were included in a retrospective analysis. Anaemia and its degrees were defined according to the criteria by the World Health Organization. A multi-level logistic regression analysis was used to fit three sequential regression models for the binary primary outcome of hospital mortality. A total of 7418 patients were included; 3437 patients (46%) had anaemia on admission. Patients with anaemia were significantly older [61 (53-70) vs. 70 (61-78) years, P < 0.001], more often female (P < 0.001), and required an increased rate of vasopressor use (P < 0.001) and mechanical ventilation (P < 0.001). With the higher Sequential organ failure assessment score (1 vs. 2; P < 0.001) and Acute Physiology And Chronic Health Evaluation (35 vs. 47; P < 0.001) scores, a higher degree of anaemia was associated with prolonged ICU stay (2 vs. 5 days, P < 0.001). Even patients with mild anaemia needed significantly from more intensive treatment and suffered worse outcome. Intensive care unit and hospital mortality were inversely associated with haemoglobin levels. Conclusion: Nearly half of critically ill patients with ACS suffer from anaemia, which is associated with increased illness severity, complex ICU procedures, and mortality-even in mild anaemia. Haemoglobin on admission is an independent factor for adverse outcome.

Current and Future Aspects of Multimodal Imaging, Diagnostic, and Treatment Strategies in Bicuspid Aortic Valve and Associated Aortopathies.

Bicuspid aortic valve (BAV) is the most frequent congenital cardiac abnormality leading to premature aortic valve apparatus dysfunction and is often associated with aortopathy. Therefore, current guidelines recommend a surgical aortic valve replacement (SAVR), even if many patients are deemed inoperable owing to their comorbidities and require alternatives such as transcatheter aortic valve replacement (TAVR). However, BAV variations remain challenging for procedural success. Therefore, the latest development in different imaging modalities (echocardiography, multislice-computertomographie, cardiovascular magnetic resonance) allows in-depth analysis for preprocedural risk stratification, follow up, and patient selection. Furthermore, we shed light on the latest developments in pre- and periprocedural fusion imaging as well as on current and future treatment options.