Cardiolipin, α-d-glucopyranosyl, and l-lysylcardiolipin from Gram-positive bacteria: FAB MS, monofilm and X-ray powder diffraction studies

AbstractCardiolipin preparations from Streptococcus B, Listeria welshimeri, Staphylococcus aureus, and a glucosyl and lysyl derivative of cardiolipin were analysed for fatty acid composition and fatty acid combinations. Three different fatty acid patterns are described and up to 17 molecular species were identified in Streptococcus B lipids by high resolution FAB MS. The physicochemical properties of these lipids were characterised in the sodium salt form by monofilm experiments and X-ray powder diffraction. All lipids formed stable monofilms. The minimal space requirement of unsubstituted cardiolipin was dictated by the fatty acid pattern. Substitution with l-lysine led to a decrease of the molecular area, substitution with d-glucopyranosyl to an increase. On self assembly at 100% relative humidity, all preparations adopted lamellar structures. They showed a high degree of order, in spite of the heterogeneous fatty acid compositions and numerous fatty acid combinations. The repeat distances in lamellar fluid phase varied between 4.99 and 5.52 nm, the bilayer thickness between 3.70 and 4.46 nm. Surprising were the low values of sorbed water per molecule of the glucosyl and lysyl derivatives which were 58 and 60%, compared with those of the respective cardiolipin. When Na+ was replaced as counterion by Ba2+, the bilayer structure was retained, but the lipids were in the lamellar gel phase and the fatty acids were tilted between 32 and 53° away from the bilayer normal. Wide angle X-ray diffraction studies and electron density profiles are also reported. Particular properties of glucosyl cardiolipin are discussed

Magnetic Proximity Effect in Perovskite Superconductor/Ferromagnet Multilayers

$\mathrm{YBa_2Cu_3O_7/La_{2/3}Ca_{1/3}MnO_3}$ superconducting/ferromagnetic (SC/FM) multilayers have been studied by neutron reflectometry. Evidence for a characteristic difference between the structural and magnetic depth profiles is obtained from the occurrence of a structurally forbidden Bragg peak in the FM state. The comparison with simulated reflectivity curves allows us to identify two possible magnetization profiles: a sizable magnetic moment within the SC layer antiparallel to the one in the FM layer (inverse proximity effect), or a ``dead'' region in the FM layer with zero net magnetic moment. The former scenario is supported by an anomalous SC-induced enhancement of the off-specular reflection, which testifies to a strong mutual interaction of SC and FM order parameters.Comment: 4 pages, 2 figures, submitted to PR

Alteration of Multiple Leukocyte Gene Expression Networks is Linked with Magnetic Resonance Markers of Prognosis After Acute ST-Elevation Myocardial Infarction

Prognostic relevant pathways of leukocyte involvement in human myocardial ischemic-reperfusion injury are largely unknown. We enrolled 136 patients with ST-elevation myocardial infarction (STEMI) after primary angioplasty within 12 h after onset of symptoms. Following reperfusion, whole blood was collected within a median time interval of 20 h (interquartile range: 15-25 h) for genome-wide gene expression analysis. Subsequent CMR scans were performed using a standard protocol to determine infarct size (IS), area at risk (AAR), myocardial salvage index (MSI) and the extent of late microvascular obstruction (lateMO). We found 398 genes associated with lateMO and two genes with IS. Neither AAR, nor MSI showed significant correlations with gene expression. Genes correlating with lateMO were strongly related to several canonical pathways, including positive regulation of T-cell activation (p = 3.44 x 10(-5)), and regulation of inflammatory response (p = 1.86 x 10(-3)). Network analysis of multiple gene expression alterations associated with larger lateMO identified the following functional consequences: facilitated utilisation and decreased concentration of free fatty acid, repressed cell differentiation, enhanced phagocyte movement, increased cell death, vascular disease and compensatory vasculogenesis. In conclusion, the extent of lateMO after acute, reperfused STEMI correlated with altered activation of multiple genes related to fatty acid utilisation, lymphocyte differentiation, phagocyte mobilisation, cell survival, and vascular dysfunction

Cardiac magnetic resonance assessment of central and peripheral vascular function in patients undergoing renal sympathetic denervation as predictor for blood pressure response

Background: Most trials regarding catheter-based renal sympathetic denervation (RDN) describe a proportion of patients without blood pressure response. Recently, we were able to show arterial stiffness, measured by invasive pulse wave velocity (IPWV), seems to be an excellent predictor for blood pressure response. However, given the invasiveness, IPWV is less suitable as a selection criterion for patients undergoing RDN. Consequently, we aimed to investigate the value of cardiac magnetic resonance (CMR) based measures of arterial stiffness in predicting the outcome of RDN compared to IPWV as reference. Methods: Patients underwent CMR prior to RDN to assess ascending aortic distensibility (AAD), total arterial compliance (TAC), and systemic vascular resistance (SVR). In a second step, central aortic blood pressure was estimated from ascending aortic area change and flow sequences and used to re-calculate total arterial compliance (cTAC). Additionally, IPWV was acquired. Results: Thirty-two patients (24 responders and 8 non-responders) were available for analysis. AAD, TAC and cTAC were higher in responders, IPWV was higher in non-responders. SVR was not different between the groups. Patients with AAD, cTAC or TAC above median and IPWV below median had significantly better BP response. Receiver operating characteristic (ROC) curves predicting blood pressure response for IPWV, AAD, cTAC and TAC revealed areas under the curve of 0.849, 0.828, 0.776 and 0.753 (p = 0.004, 0.006, 0.021 and 0.035). Conclusions: Beyond IPWV, AAD, cTAC and TAC appear as useful outcome predictors for RDN in patients with hypertension. CMR-derived markers of arterial stiffness might serve as non-invasive selection criteria for RDN

Rising utilization of coronary CT angiography across Europe over the last decade: insights from a large prospective European registry

Abstract Background/Introduction The recently updated 2019 ESC guidelines for the diagnosis and management of chronic coronary syndromes endorse the use of coronary computed tomography angiography (CCTA) for exclusion of obstructive coronary artery disease in patients with a low clinical likelihood (Class I, LOE B). Higher demand for CCTA requires broad availability, inevitably involving smaller healthcare providers, such as non-academic hospitals and private practices. Nevertheless, most published data on CCTA image quality and safety rely on exams performed in high-volume academic centers, and little is known about CCTA in non-academic settings. Purpose To investigate the utilization of CCTA across Europe over the last decade, focusing on differences between academic and non-academic centers. Methods We included patients with stable chest pain and suspected coronary artery disease (CAD) who received CCTA and were included in the European Society of Cardiovascular Radiology MR/CT registry 01/2010–01/2020. We compared CT equipment, image quality, radiation dose, the incidence of periprocedural adverse events, patient characteristics, and CCTA findings between academic (high volume university hospitals) and non-academic centers (non-academic hospitals and private practices). Results Overall, 64,317 patients (41.2% women; age 60±13 years) from 212 sites across 19 European countries were included. Academic centers submitted most cases in 2010—2014 (51.6%), whereas non-academic centers accounted for 71.3% of records in 2015–2020. While non-academic centers used less advanced technology, radiation dose remained low (4.54 [interquartile range (IQR) 2.28–6.76] mSv) with a 30% decline of high-dose scans (>7 mSv) over time. Diagnostic image quality was reported in 97.7% of cases, and the rate of acute scan-related events was low (0.4%) (Figure 1). From 2010–2014 to 2015–2020, CCTA nearly doubled in patients with low to intermediate pretest-probability, women >50, and 40–60 years old men (Figure 2). CAD presence and extent decreased slightly over time (prevalence: 2010–2014: 41.5% vs. 2015–2020: 40.6%), (multi-vessel disease in those with CAD: 2010–2014: 61.9% vs. 2015–2020: 55.9%; all p<0.01). Conclusion CCTA expands rapidly to non-academic centers across Europe, increasing availability while maintaining relatively low radiation dose, high diagnostic image quality, and safety. Broad availability of high-quality CCTA is essential for a successfully implementation of the recently updated guidelines for the diagnosis and management of chronic coronary syndromes. Funding Acknowledgement Type of funding sources: None. Changes in CCTA utilizationChanges in patient characteristic

Clinical characteristics and role of early cardiac magnetic resonance imaging in patients with suspected ST-elevation myocardial infarction and normal coronary arteries

A variety of conditions other than acute myocardial infarction may cause ST-elevation. Our objective was to evaluate the impact of cardiac magnetic resonance (CMR) on differential diagnosis from a prospective series of patients with suspected ST-elevation myocardial infarction (STEMI) and completely normal coronary arteries. Among 1,145 patients with suspected STEMI, 49 patients had completely normal coronary arteries and entered a prospective registry. CMR was done within 24 h, if possible, and included function analyses, T2-weighted imaging (T2 ratio), T1-weighted imaging before and after gadolineum administration (global relative enhancement; gRE), and late gadolineum enhancement (LGE). All patients were asked for a follow-up CMR after approximately 3 months. The incidence of patients with suspected STEMI and normal coronary arteries was 4.3% and mean age was 45 ± 14 years (STEMI group 64 ± 13 years; P < 0.001). 55% had a recent history of infection. Cardiac biomarkers showed a moderate elevation on admission. There was a significant change from baseline to follow-up for LV end-diastolic volumes (EDV) (P < 0.001), LV mass (P < 0.05), mean T2 ratio (P < 0.05), and LGE volume (P < 0.05). Major diagnostic groups were myocarditis (29%), pericarditis (27%), and takotsubo cardiomyopathy (10%). 18% were regarded as non-diagnostic. The study showed an incidence of 4.3% of patients with suspected STEMI and completely normal coronary arteries. Early CMR was valuable in the evaluation of the differential diagnoses and to exclude myocardial abnormalities in patients with uncertain aetiology. Further studies are needed for the assessment of long-term outcome