Monica Mion

Postconditioning during coronary angioplasty in acute myocardial infarction: the POST-AMI trial

BACKGROUND Postconditioning (PC) has been suggested to reduce myocardial damage during primary percutaneous coronary intervention (PPCI), nevertheless clinical experience is limited. We aimed to explore the cardioprotective effect of PC using cardiac magnetic resonance (CMR) in ST-elevation myocardial infarction (STEMI) patients treated by PPCI. METHODS A total of 78 patients with first STEMI (aged 59±12 years) referred for PPCI, were stratified for STEMI location and randomly assigned to conventional PPCI or PPCI with PC. All patients, with occluded infarct related artery and no collateral circulation, received abciximab intravenously before PPCI. After reperfusion by effective direct stenting, control subjects underwent no further intervention, while in treated patients PC was performed within 1 min of reflow by 4 cycles of 1-minute inflation and 1-minute deflation of the angioplasty balloon. Primary end-point was infarct size (IS) reduction, expressed as percentage of left ventricle mass assessed by delayed enhancement on CMR at 30±10 days after index PPCI. RESULTS All baseline characteristics but diabetes (p=0.06) were balanced between groups. Postconditioning patients trended toward a larger IS compared to those treated by standard PPCI (20±12% vs 14±10%, p=0.054). After exclusion of diabetics, PC group still showed a trend to larger IS (p=0.116). Major adverse events seem to be more frequent in PC group irrespective to diabetic status (p=0.053 and p=0.080, respectively). CONCLUSIONS This prospective, randomized trial suggests that PC did not have the expected cardioprotective effect and on the contrary it might harm STEMI patients treated by PPCI plus abciximab. (Clinical Trial Registration-unique identifier: NCT01004289).

Widespread Increase in Myeloid Calcifying Cells Contributes to Ectopic Vascular Calcification in Type 2 Diabetes

Rationale: Acquisition of a procalcific phenotype by resident or circulating cells is important for calcification of atherosclerotic plaques, which is common in diabetes. Objective: We aim to identify and characterize circulating calcifying cells, and to delineate a pathophysiological role for these cells in type 2 diabetes. Methods and Results: We demonstrate for the first time that a distinct subpopulation of circulating cells expressing osteocalcin and bone alkaline phosphatase (OC+BAP+) has procalcific activity in vitro and in vivo. The study of naïve patients with chronic myeloid leukemia indicated that OC+BAP+ cells have a myeloid origin. Myeloid calcifying OC+BAP+ cells (MCCs) could be differentiated from peripheral blood mononuclear cells, and generation of MCCs was closely associated with expression of the osteogenic transcription factor Runx2. In gender-mismatched bone marrow–transplanted humans, circulating MCCs had a much longer half-life compared with OC−BAP− cells, suggesting they belong to a stable cell repertoire. The percentage of MCCs was higher in peripheral blood and bone marrow of type 2 diabetic patients compared with controls but was lowered toward normal levels by optimization of glycemic control. Furthermore, diabetic carotid endoarterectomy specimens showed higher degree of calcification and amounts of cells expressing OC and BAP in the &agr;-smooth muscle actin–negative areas surrounding calcified nodules, where CD68+ macrophages colocalize. High glucose increased calcification by MCCs in vitro, and hypoxia may regulate MCC generation in vitro and in vivo. Conclusions: These data identify a novel type of blood-derived procalcific cells potentially involved in atherosclerotic calcification of diabetic patients.

Point-of-care testing of cardiac markers: results from an experience in an Emergency Department.

AIM An experimental approach to the use of point-of-care testing for cardiac markers in the Emergency Department (ED) of our Institution has been carried out using two devices (SCS, Dade Behring and Triage Cardiac Panel, Biosite Diagnostics) for the measurement of cardiac markers. RESULTS (1) From the analytical point of view, a fundamental tool for an efficient management of patients was the agreement between results from point-of-care testing and from the instruments located in STAT lab and/or central laboratory: in about 5% of patients, a lack of comparability of data, resulted in an inappropriate admission of patients (medical vs. intensive care unit). (2) The actual total turnaround time (TAT) in the management of samples sent to STAT lab was estimated to be equal to 82.5 min (50th percentile). (3) In the same organizational setting, the use of a point-of-care device produced a turnaround time equal to 17 min (50th percentile). (4) The reduction in turnaround time resulted in a faster discharge for five patients who had normal ECG findings and cardiac marker values, the Delta time (POCT-STAT lab) ranging from -10 to -70 min. CONCLUSIONS The point-of-care option evaluated also in relation to personnel issues for staff working in the ED, brought some interesting questions about the characteristics of POCT devices (easy to use 100%, safety for operator 91%) and the obtained results (quantitative and correlated to STAT lab, 91%), as well as the need of other options such as the implementation of rapid tube sample delivery.

Evidence for Decreased Circulating Apelin beyond Heart Involvement in Uremic Cardiomyopathy

Background: Plasma apelin concentration in heart failure has been described in small studies reporting conflicting results. In hemodialysis (HD) patients, apelin decreased more in those with more severe heart involvement. It is unclear if uremia is connected to this reduction irrespective of heart failure. We compared apelin in two cardiomyopathies with different renal function. Methods: Observational study conducted in 30 adult Caucasian outpatients in class I NYHA not affected by diabetes or ischemic heart, 15 with idiopathic dilated cardiomyopathy (DCM) and 15 with uremic dilated cardiomyopathy undergoing HD. Plasma apelin, creatinine, high-sensitivity C-reactive protein, endothelin, NT proB-type natriuretic peptide (NT-proBNP), and Doppler echocardiogram were evaluated. Results: Heart involvement was more severe in the DCM patients (lower ejection fraction, greater diastolic volume index, and worse index of myocardial performance). Median value of apelin in HD patients (19.1 pg/ml) was one third of that in DCM patients (58.2 pg/ml) whereas creatinine, NT-proBNP, and C-reactive protein were 11, 80, and 9 times higher respectively in HD than in DCM patients. Median values of endothelin were comparable in both groups. Apelin was not significantly correlated with any variable. Conclusion: Uremic status was the determinant for decreased plasma apelin in HD patients regardless of the severity of heart involvement.

Precision performance at low levels and 99th percentile concentration of the Access AccuTnl assay on two different platforms.

Abstract Background: Cardiac troponins currently represent the preferred biomarkers for the detection of myocardial necrosis. The objective of the present study was to compare the performance of the Access® AccuTnI® assay (Beckman Coulter) measured on two different platforms, the UniCel® DxI 800 and the Access® 2 (Beckman Coulter). In particular, the serum cardiac troponin I (cTnI) concentration corresponding to 10% coefficient of variation (CV), the cTnI assay minimum detectable concentration (MDC), and the serum cTnI 99th percentile in healthy subjects were calculated. Methods: The Access® AccuTnI® is a paramagnetic particle chemiluminescent immunoassay. Imprecision profiles were determined according to the Clinical and Laboratory Standards Institute EP5-A protocol using serum pools. The MDC was calculated as mean+3 SD of 20 determinations of the zero calibrator during one run. The 99th percentile was determined analyzing serum samples from 679 healthy blood donors (523 males, 156 females; 18–71 years old). Results: cTnI concentrations are given in μg/L. 10% CV values (95% confidence interval, CI) were 0.0577 (0.0467–0.0750) (UniCel® DxI 800) and 0.0486 (0.0255–0.0596) (Access® 2). MDC values were 0.011 (UniCel® DxI 800) and 0.012 (Access® 2). The 99th percentile (95% CI) value was 0.0340 (0.0298–0.0410). Conclusions: Our data confirm the reliability of the evaluated cTnI assay and demonstrate the comparability of the cTnI values between the platforms studied. Clin Chem Lab Med 2009;47:367–71.

Analytical and clinical evaluation of a new heart-type fatty acid-binding protein automated assay

Abstract Background: The accurate and rapid recognition of myocardial injury in patients presenting in the emergency department (ED) with chest pain continues to be a clinical challenge. Heart-type fatty acid-binding protein (H-FABP) appears to be one of the best candidates among the new early cardiac markers studied. Methods: We evaluated the analytical characteristics of a new quantitative and fully automated H-FABP assay (Randox Laboratories Ltd., Crumlin, UK) and compared its clinical performance with respect to the myoglobin (Myo) assay (Dade Behring, Milan, Italy). A precision study was carried out by testing three levels of quality control (QC) material and two in-house pool (P) samples. To test the accuracy of H-FABP determinations in plasma (lithium-heparin) samples, H-FABP concentrations measured in a set of matched sera and plasma samples were compared. A total of 77 non-consecutive patients (51 males and 26 females; 62±16years) who presented to the ED with chest pain suggesting myocardial ischemia were enrolled. The patients were classified into two groups (acute myocardial infarction, n=22; non-acute myocardial infarction, n=55) on the basis of the discharge diagnosis. Results: The between-day imprecision for three levels of control material and serum pool samples was 6.26%–8.04% (range 2.32–44.03μg/L) and 9.03%–12.63% (range 11.85–65.13μg/L), respectively. In the serum vs. plasma study, bias was +0.178 (95% CI −0.033 to +0.389). The best cut-off and the associated diagnostic efficacy were 95μg/L and 89.47% for Myo and 5.09μg/L and 98.70% for H-FABP, respectively. Conclusions: H-FABP determination in patients with ischemic symptoms may be a more reliable early indication of cardiac damage than myoglobin. Clin Chem Lab Med 2006;44:1383–5.

Design and Methodologies of the POSTconditioning during Coronary Angioplasty in Acute Myocardial Infarction (POST-AMI) Trial

Background: Reperfusion remains the definitive treatment for acute myocardial infarction (AMI), but restoring blood flow carries the potential to exacerbate the ischemia-related injury. Postconditioning might modify reperfusion-induced adverse events. Study Design: The POSTconditioning during Coronary Angioplasty in Acute Myocardial Infarction (POST-AMI) trial is a single-center, prospective, randomized study, with a planned inclusion of 78 patients with ST-elevation AMI. Patients will be randomly assigned to the postconditioning arm [primary angioplasty (PA) and stenting followed by brief episodes of ischemia-reperfusion early after recanalization] or non-postconditioning arm. All patients will be treated medically according to current international guidelines, including glycoprotein IIb/IIIa inhibitors before PA. The primary end point is to evaluate whether postconditioning, compared to plain PA, reduces infarct size estimated by cardiac magnetic resonance (CMR) at 30 ± 10 days after the AMI. Secondary end points are microvascular obstruction observed at CMR, ST-segment resolution, angiographic myocardial blush grade <2, non-sustained/sustained ventricular tachycardia in the 48 h following PA, left ventricular remodeling and function at follow-up CMR, and the reduction of major adverse cardiac events at 30 days and 6 months. Conclusion: The POST-AMI trial will evaluate the usefulness of postconditioning in limiting infarct size during the early and late phases after AMI.

Copeptin decrease from admission to discharge has favorable prognostic value for 90-day events in patients admitted with dyspnea

Abstract Background: With patients referred to emergency departments (EDs) for acute dyspnea, emergency physicians should consider all possible diagnoses and assess patients’ risk stratification. Copeptin has been shown to have prognostic power for subsequent events, such as death and rehospitalization in patients admitted for dyspnea. The aim of this study was to investigate prognostic role of copeptin variations during hospitalization in patients admitted for dyspnea. Methods: We conducted a prospective, multicentric, observational study in acute dyspneic patients in three ED centers in Italy. Clinical data and copeptin assessments were performed at admission, and at discharge. A 90-day follow-up was performed. Results: A total of 336 patients were enrolled, and on the basis of final diagnosis distinguished into two groups: acute heart failure and no acute heart failure. Compared to a control group, in all studied population copeptin values at admission resulted in a significantly (p<0.001) higher median (maximum–minimum): 31 (0–905) versus 8 (0–13) pmol/L. Median copeptin value at admission was 42 (0–905) pmol/L in acute heart failure patients and 20 (0–887) pmol/L in no acute heart failure, respectively (p<0.001). In all studied patients and in each group copeptin at admission and discharge showed significant predictive value for 90-day events (p<0.001). Furthermore, in all patients population and in both groups Δ copeptin values from admission to discharge also showed significant predictive value for 90-day events (p<0.001). Conclusions: In patients admitted for acute dyspnea, admission, discharge and Δ copeptin variations have significant prognostic value from subsequent 90-day death and rehospitalization.

PATHFAST NT-proBNP (N-terminal-pro B type natriuretic peptide): a multicenter evaluation of a new point-of-care assay.

Abstract Background: The biochemical determination of cardiac natriuretic peptides, primarily brain natriuretic peptide (BNP) and the amino-terminal fragment of its pro-hormone proBNP (NT-proBNP), are reliable tools for diagnosing cardiac disease, establishing prognosis and evaluating the effectiveness of treatment. These biomarkers have proven to be of particular value in the management of chronic and acute heart failure patients, and in the outpatient and the emergency setting. Methods: A multicenter evaluation was performed to assess the practicability, and the analytical and clinical performance of a new point-of-care testing (POCT) PATHFAST™ NT-proBNP assay. This is an immunochemiluminescent assay using two polyclonal antibodies in a sandwich test format, and performed with a PATHFAST™ automated analyzer. Results: The limit of detection (mean+3 SD of the signal of 20 replicates of the zero calibrator obtained in one run) was 0.535 ng/L. An imprecision study, performed in accordance with the CLSI protocol, showed coefficients of variation of 4.0%–6.4% (within-run imprecision), 0.0%–3.4% (between-run imprecision), 5.5%–7.2% (between-day imprecision), 7.6%–8.9% (total imprecision). The method was linear to 28,755 ng/L. Slopes and intercepts ranged from 0.89 to 0.90 and from 10.96 to 22.85, respectively when lithium-heparin plasma samples (n=100) were used to compare the assay under evaluation with the routine laboratory methods (Dimension RxL®, Stratus® CS). When testing matched samples (n=52), a significant difference was found between the 50th percentile NT-proBNP concentration in K2EDTA whole blood, K2EDTA plasma, lithium-heparin plasma and serum. No significant interference was observed for NT-proBNP in lipemic (tryglicerides up to 28.54 mmol/L), icteric (total and conjugated bilirubin up to 513 and 13 μmol/L, respectively) or hemolyzed (hemoglobin up to 13.50 g/L) samples. The NT-proBNP concentration in a group of 180 healthy donors was significantly influenced by age and gender. In a selected population of patients (n=56) with acute dyspnea admitted to the emergency department, a marked reduction in cardiac natriuretic peptide concentrations was observed in hospitalized patients suffering from heart failure who had a better prognosis compared with those with a poorer prognosis (NT-proBNP mean Δ change, % from –22 to –71 vs. +9 to –11). Conclusions: The satisfactory analytical and clinical performance of the PATHFAST™ NT-proBNP assay, together with its excellent practicability, suggests that it would be a reliable tool in clinical practice, in the emergency setting for point-of-care testing, as well as in the central laboratory. Clin Chem Lab Med 2010;48:1029–34.

Interleukin-6 and tumor necrosis factor-alpha as biochemical markers of heart failure: a head-to-head clinical comparison with B-type natriuretic peptide.

Background The reliability of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) as biochemical markers of heart failure in comparison to B-type natriuretic peptide (BNP) has not been investigated in depth. Aim To compare the correlations between IL-6, TNF, BNP plasma concentrations and some clinical and instrumental variables and their prognostic value in heart failure patients. Methods In 79 patients with heart failure, the correlations between IL-6, TNF and BNP plasma concentrations and a series of 18 variables were studied. Outcome events were death from any cause and combined death and heart transplantation. Results At univariate analysis, BNP and IL-6 plasma concentrations correlated with each other (r = 0.4828; P < 0.0001), with New York Heart Association class, fluid retention, left ventricular ejection fraction, mean right atrial pressure, mean pulmonary pressure and cardiac index. All these correlations were stronger with BNP. TNF plasma concentration correlated only with New York Heart Association class and left ventricular ejection fraction. During follow-up, 1–32 months, 14 patients died and nine underwent heart transplantation. At univariate analysis, both BNP and IL-6 plasma concentrations were predictors of death and heart transplantation, but only BNP was a predictor of death; however, only creatinine plasma level was an independent predictor of prognosis. Conclusion IL-6 and TNF are less reliable biochemical markers than BNP in heart failure patients.