Spatiotemporal correlation analyses: a new procedure for standardisation of DC magnetocardiograms

There is a lack of standard methods for the analysis of magnetocardiograms (MCGs). MCG signals have a shape similar to the ECG (P wave, QRS complex, T wave). High-quality multichannel recordings can indicate even slight disturbances of de- and repolarisation. The purpose of our study was to apply a new approach in the analysis of signal-averaged DC-MCGs. DC-MCGs (31-channel) were recorded in 182 subjects: 110 patients after myocardial infarction and 72 controls. Spatiotemporal correlation analysis of the QRS complex and T wave patterns throughout the entire heart cycle was used to analyse homogeneity of de- and repolarisation. These plots were compared to standard ECG analyses (electrical axis, Q wave, ST deviation, T polarity and shape). Spatiotemporal correlation analyses seem to be applicable in assessing the course of electrical repolarisation with respect to homogeneity. MCG provided all diagnostic information contained in common ECG recordings at high significance levels. The ECG patterns were included in 5/8 of our parameters for electrical axis, 6/8 for Qwave, 7/8 for ST deviation and 5/8 for T-polarity based on two time series of correlation coefficients. We conclude that our spatiotemporal correlation approach provides a new tool for standardised analysis of cardiac mapping data such as MCG

Low HRV entropy is strongly associated with myocardial infarction

Heart rate variability (HRV) is a marker of autonomous activity in the heart. An important application of HRV measures is the stratification of mortality risk after myocardial infarction. Our hypothesis is that the information entropy of HRV, a non-linear approach, is a suitable measure for this assessment. As a first step, to evaluate the effect of myocardial infarction on the entropy, we compared the entropy to standard HRV parameters. The entropy was estimated by compressing the tachogram with Bzip2. For univariate comparison, statistical tests were used. Multivariate analysis was carried out using automatically generated decision trees. The classification rate and the simplicity of the decision trees were the two evaluation criteria. The findings support our hypothesis. The meanNN-normalized entropy is reduced in patients with myocardial infarction with very high significance. One entropy parameter alone exceeds the discrimination strength of multivariate standards-based trees

Postextrasystolic regulation patterns of blood pressure and heart rate in patients with idiopathic dilated cardiomyopathy

Assessment of fluctuations in heart rate (HR) following a premature ventricular complex (PVC) is valuable for identifying patients at high risk of sudden cardiac death. We hypothesised that postextrasystolic potentiation is the main determinant of the regulation patterns of blood pressure (BP) and HR following a PVC. Twelve patients with idiopathic dilated cardiomyopathy (IDC) and 13 control subjects with single PVCs (comparable coupling intervals) were investigated. Non-invasive finger arterial BP and ECGs were analysed. Regulation patterns following a single PVC were quantified using the indices postextrasystolic amplitude potentiation (PEAP) and maximum turbulence slope of five consecutive mean BP values (MBP-TS), and compared with the HR turbulence parameters turbulence slope (HR-TS) and turbulence onset (HR-TO). PEAP was significantly higher in IDC patients compared to controls (48.7 ± 32.6 vs. 9.8 ± 5.4 %, P < 0.01), whereas MBP-TS was lower (0.97 ± 0.60 vs. 2.07 ± 1.04 mmHg BBI−1 (BBI, beat-to-beat interval), P < 0.05), as was HR-TS (8.46 ± 7.90 vs. 30.73 ± 22.90 ms BBI−1, P < 0.01). HR-TO was significantly higher in IDC patients (−0.56 ± 2.19 vs. −5.52 ± 4.13 %, P < 0.01). In addition, the regulation patterns of BP and HR following a single PVC differed significantly between IDC patients and controls. Specifically, we observed pronounced PEAPs in IDC patients. The baroreflex response initiated by the low pressure amplitude of the PVC was suppressed in IDC patients due to the augmented potentiation of the first postextrasystolic blood pressure. Furthermore, IDC patients displayed impressive postextrasystolic pulsus alternans phenomena, whereas healthy subjects exhibited a typical baroreflex pattern. The pulsus alternans phenomenon seems to be triggered by a PVC

Gremlin-1 is an inhibitor of macrophage migration inhibitory factor and attenuates atherosclerotic plaque growth in ApoE-/- Mice

Monocyte infiltration and macrophage formation are pivotal steps in atherosclerosis and plaque vulnerability. Gremlin-1/Drm is crucial in embryo-/organogenesis and has been shown to be expressed in the adult organism at sites of arterial injury and to inhibit monocyte migration. The purpose of the present study was to evaluate and characterize the role of Gremlin-1 in atherosclerosis. Here we report that Gremlin-1 is highly expressed primarily by monocytes/macrophages in aortic atherosclerotic lesions of ApoE(-/-) mice and is secreted from activated monocytes and during macrophage development in vitro. Gremlin-1 reduces macrophage formation by inhibiting macrophage migration inhibitory factor (MIF), a cytokine critically involved in atherosclerotic plaque progression and vulnerability. Gremlin-1 binds with high affinity to MIF (K-D = 54 nM), as evidenced by surface plasmon resonance analysis and co-immunoprecipitation, and reduces MIF-induced release of TNF-alpha from macrophages. Treatment of ApoE(-/-) mice with a dimeric recombinant fusion protein, (m)Gremlin1-Fc, but not with equimolar control Fc or inactivated (m)Gremlin1-Fc, reduced TNF-alpha expression, the content of monocytes/macrophages of atherosclerotic lesions, and attenuated atheroprogression. The present data disclose that Gremlin-1 is an endogenous antagonist of MIF and define a role for Gremlin-1/MIF interaction in atherosclerosis

Genetic Risk Score for Intracranial Aneurysms: Prediction of Subarachnoid Hemorrhage and Role in Clinical Heterogeneity

Background: Recently, common genetic risk factors for intracranial aneurysm (IA) and aneurysmal subarachnoid hemorrhage (ASAH) were found to explain a large amount of disease heritability and therefore have potential to be used for genetic risk prediction. We constructed a genetic risk score to (1) predict ASAH incidence and IA presence (combined set of unruptured IA and ASAH) and (2) assess its association with patient characteristics. Methods: A genetic risk score incorporating genetic association data for IA and 17 traits related to IA (so-called metaGRS) was created using 1161 IA cases and 407 392 controls from the UK Biobank population study. The metaGRS was validated in combination with risk factors blood pressure, sex, and smoking in 828 IA cases and 68 568 controls from the Nordic HUNT population study. Furthermore, we assessed association between the metaGRS and patient characteristics in a cohort of 5560 IA patients. Results: Per SD increase of metaGRS, the hazard ratio for ASAH incidence was 1.34 (95% CI, 1.20-1.51) and the odds ratio for IA presence 1.09 (95% CI, 1.01-1.18). Upon including the metaGRS on top of clinical risk factors, the concordance index to predict ASAH hazard increased from 0.63 (95% CI, 0.59-0.67) to 0.65 (95% CI, 0.62-0.69), while prediction of IA presence did not improve. The metaGRS was statistically significantly associated with age at ASAH (β=-4.82×10-3per year [95% CI, -6.49×10-3to -3.14×10-3]; P=1.82×10-8), and location of IA at the internal carotid artery (odds ratio=0.92 [95% CI, 0.86-0.98]; P=0.0041). Conclusions: The metaGRS was predictive of ASAH incidence, although with limited added value over clinical risk factors. The metaGRS was not predictive of IA presence. Therefore, we do not recommend using this metaGRS in daily clinical care. Genetic risk does partly explain the clinical heterogeneity of IA warranting prioritization of clinical heterogeneity in future genetic prediction studies of IA and ASAH