República: Año III Número 387 - (14/11/33)

PURPOSE OF REVIEW: The purpose of this study was to investigate the association of 26 inflammatory biomarkers (acute phase proteins, cytokines, chemokines) and renal markers with coronary lipid core burden index (LCBI) assessed by near-infrared spectroscopy (NIRS) imaging, as well as the association of these biomarkers with long-term cardiovascular outcome. RECENT FINDINGS: NIRS-derived LCBI has recently been shown to be an independent predictor of major adverse cardiac events (MACE). However, studies on the association between circulating biomarkers and NIRS-derived characteristics have not yet been performed. Between 2008 and 2011, 581 patients underwent diagnostic coronary angiography or percutaneous coronary intervention for stable angina pectoris or acute coronary syndrome (ACS). NIRS of a non-culprit vessel was performed in a subset of 203 patients. In multivariable analyses, TNF-alpha tended to be associated with higher LCBI (beta 0.088 ln (pg/ml) increase per unit LCBI; 95% CI 0.000-0.177, p = 0.05) after adjustment for clinical characteristics. However, this association did not persist after Bonferroni correction (statistical threshold 0.0019). Major adverse cardiac events (MACE) were registered in 581 patients during a median follow-up time of 4.7 years (IQR: [4.2-5.6] years). After adjustment for clinical characteristics and Bonferroni correction, IL-8 (HR 1.60; 95% CI [1.18-2.17] per ln (pg/ml), p = 0.002) was borderline associated with MACE and significantly associated with all-cause mortality or ACS (HR 1.75; 95% CI [1.24-2.48] per ln (pg/ml), p = 0.0015). In conclusion, we found that IL-8 was independently associated with clinical outcome, but altogether, the multiplex panel we investigated here did not render a useful blood biomarker of high LCBI

In search of an efficient strategy to monitor disease status of chronic heart failure outpatients

_Introduction_ Blood biomarkers have the potential to monitor the severity of chronic heart failure (CHF). Studies correlating repeated measurements of blood biomarkers with repeatedly assessed New York Heart Association (NYHA) class over a prolonged follow-up period, and concomitantly investigating their associations with clinical endpoints, have not yet been performed. _Methods_ Between 2011–2013, 263 CHF patients were included. At inclusion and subsequently every 3 months, we measured N-terminal pro-B-type natriuretic (NT-proBNP), high-sensitivity troponin T (Hs-TnT) and C-reactive protein (CRP), and assessed NYHA class. The primary endpoint comprised heart failure hospitalisation, cardiovascular mortality, cardiac transplantation or left ventricular assist device implantation. Time-dependent Cox models were used. _Results_ Mean age was 67 ± 13 years, 72% were men and 27% were in NYHA class III–IV. We obtained 886 repeated measures (median 3 [IQR 2–5] per patient). The primary endpoint was reached in 41 patients during a median follow-up of 1.0 [0.6–1.4] year. Repeatedly measured NT-proBNP and Hs-TnT were significantly associated with repeatedly assessed NYHA class, whereas CRP was not (NT-proBNP: β [95% CI]: 1.56 [1.17–2.06]ln(ng/l) increase per point increase in NYHA class, p = 0.002; HsTNT: β [95% CI]: 1.58 [1.21–2.07]). Serially measured NT-proBNP (HR [95% CI]:2.86 [1.73–4.73]), CRP (1.69 [1.21–2.34]) and NYHA class (2.33 [1.51–3.62]) were positively and independently associated with the primary endpoint, whereas Hs-TnT lost statistical significance after multivariable adjustment. A model containing serially measured NYHA class and NT-proBNP displayed a C-index of 0.84, while serially measured NYHA class and CRP showed a C-index of 0.82. _Conclusion_ Temporal NT-proBNP, CRP and NYHA class patterns are independently associated with adverse clinical outcome. Serially measured NT-proBNP and NYHA class are best suited for monitoring CHF outpatients

e-Transmission of ECGs for expert consultation results in improved triage and treatment of patients with acute ischaemic chest pain by ambulance paramedics

Aims: In pre-hospital settings handled by paramedics, identification of patients with myocardial infarction (MI) remains challenging when automated electrocardiogram (ECG) interpretation is inconclusive. We aimed to identify those patients and to get them on the right track to primary percutaneous coronary intervention (PCI). Methods and results: In the Rotterdam-Rijnmond region, automated ECG devices on all ambulances were supplemented with a modem, enabling transmission of ECGs for online expert interpretation. The diagnostic protocol for acute chest pain was modified and monitored for 1 year. Patients with an ECG that met the criteria for ST-elevation myocardial infarction (STEMI) were immediately transported to a PCI hospital. ECGs that did not meet the STEMI criteria, but showed total ST deviation ≥800 µv were transmitted for online interpretation by the ECG expert. Online supervision was offered as a service if ECGs showed conduction disorders, or had an otherwise ‘suspicious’ pattern according to the ambulance paramedics. We enrolled 1,076 patients with acute ischaemic chest pain who did not meet the automated STEMI criteria. Their mean age was 63 years; 64% were men. After online consultation, 735 (68%) patients were directly transported to a PCI hospital for further treatment. PCI within 90 min was performed in 115 patients. Conclusion: During a 1-year evaluation of the modified pre-hospital triage protocol for patients with acute ischaemic chest pain, over 100 acute MI patients with an initially inconclusive ECG received primary PCI within 90 min. Because of these results, we decided to continue the operation of the modified protocol

Plasma concentrations of molecular lipid species predict long-term clinical outcome in coronary artery disease patients

We investigated the associations of ten previously identified high risk molecular lipid species and three ceramide ratios with the occurrence of major adverse cardiac events (MACEs) during a median follow-up of 4.7 years in patients with coronary artery disease (CAD). Between 2008 and 2011, 581 patients underwent diagnostic coronary angiography or percutaneous coronary intervention for stable angina pectoris (SAP) or acute coronary syndrome (ACS). Blood was drawn prior to the index procedure and lipid species were determined. The primary endpoint was the occurrence of a MACE, comprising all-cause mortality, nonfatal ACS, or unplanned coronary revascularization. The secondary endpoint comprised all-cause mortality or nonfatal ACS. During a median follow-up of 4.7 [IQR: 4.2-5.6] years, 155 patients (27%) had MACEs. In multivariable analyses, Cer(d18:1/16:0) concentration was associated with MACEs (hazard ratio 2.32; 95% CI [1.09-4.96] per natural logarithm (ln) (pmol/ml) P = 0.

Associations of 26 Circulating Inflammatory and Renal Biomarkers with Near-Infrared Spectroscopy and Long-term Cardiovascular Outcome in Patients Undergoing Coronary Angiography (ATHEROREMO-NIRS Substudy)

Purpose of Review: The purpose of this study was to investigate the association of 26 inflammatory biomarkers (acute phase proteins, cytokines, chemokines) and renal markers with coronary lipid core burden index (LCBI) assessed by near-infrared spectroscopy (NIRS) imaging, as well as the association of these biomarkers with long-term cardiovascular outcome. Recent Findings: NIRS-derived LCBI has recently been shown to be an independent predictor of major adverse cardiac events (MACE). However, studies on the association between circulating biomarkers and NIRS-derived characteristics have not yet been performed. Summary: Between 2008 and 2011, 581 patients underwent diagnostic coronary angiography or percutaneous coronary intervention for stable angina pectoris or acute coronary syndrome (ACS)

Blood Biomarkers and Novel Imaging Techniques in Acquired Heart Disease

The main conclusions of the thesis can be summarized as follows: Part 1, coronary artery disease - Higher SXscore is associated with higher atherosclerotic burden as assessed by NIRS and RF-IVUS in a single non-stenotic coronary artery segment in patients with CAD. - A multiplex panel of 26 inflammatory biomarkers (acute phase proteins, cytokines, and chemokines) and renal markers did not render a useful blood biomarker of high NIRS-derived LCBI. Conversely, circulating serum PCSK9 levels were positively associated with LCBI. This association was independent of established cardiac risk factors, statin use and serum LDL-C. - Plasma IL-8, plasma Cer(d18:1/16:0) and serum PCSK9 levels were independently associated with adverse cardiovascular outcomes during a median follow-up period of 4.7 years in patients with CAD. - After 1 year intensive rosuvastatin therapy clinically relevant reductions in CRP levels were observed in a series of patients with established CAD. The observed CRP changes were correlated with changes in IVUS-derived plaque characteristics in ACS patients, but not in SAP. CRP changes were uncorrelated with changes in LDL-C levels. Part II, heart failure: - Serially assessments NT-proBNP and Hs-TnT were positively associated with serially assessed NYHA class in patients with stable CHF. Repeatedly measured NT-proBNP and CRP both add individually to serial NYHA-class assessments for monitoring CHF patients in terms of discriminative ability compared to a model with only serial NYHA class measurements. - The dynamic, temporal patterns of serially measured NT-proBNP and CRP are strong and independent predictors of adverse clinical events in patients with stable CHF. Not only the evolution of biomarkers level, but also their instantaneous rate of change in NT-proBNP and CRP levels as well as the area under the curve of the trajectory of NT-proBNP, were associated with adverse outcome. - The temporal pattern of circulating miR-22-3p is a strong and independent predictor of prognosis in CHF patients. - Repeatedly assessed glomerular function (creatinine, eGFR and CysC), and tubular function (NAG and KIM-1) independently predicts adverse clinical outcomes in CHF patients. Both renal compartments chronically deteriorate, but not in parallel, during clinically silent progression of CH

Retention time prediction in temperature-​programmed, comprehensive two-​dimensional gas chromatography: Modeling and error assessment

In this paper we present a model relating exptl. factors (column lengths, diams. and thickness, modulation times, pressures and temp. programs) with retention times. Unfortunately, an anal. soln. to calc. the retention in temp. programmed GC×GC is impossible, making thus necessary to perform a numerical integration. In this paper we present a computational phys. model of GC×GC, capable of predicting with a high accuracy retention times in both dimensions.Once fitted (e.g., calibrated)​, the model is used to make predictions, which are always subject to error. In this way, the prediction can result rather in a probability distribution of (predicted) retention times than in a fixed (most likely) value. One of the most common problems that can occur when fitting unknown parameters using exptl. data is overfitting. In order to detect overfitting situations and assess the error, the K-​fold cross-​validation technique was applied. Another technique of error assessment proposed in this article is the use of error propagation using Jacobians. This method is based on estn. of the accuracy of the model by the partial derivs. of the retention time prediction with respect to the fitted parameters (in this case entropy and enthalpy for each component) in a set of given conditions. By treating the predictions of the model in terms of intervals rather than as precise values, it is possible to considerably increase the robustness of any optimization algorithm