Multicentre evaluation of a second generation point-of-care assay with an extended range for the determination of N-terminal pro-brain natriuretic peptide.

BACKGROUND: In the second generation of the point-of-care (POC) assay Roche CARDIAC proBNP, the upper limit of the measuring range was extended from 3000 to 9000 ng/L. METHODS: A thirteen-site multicentre evaluation was carried out to assess the analytical performance of the POC NT-proBNP assay and to compare it with a laboratory N-terminal pro-brain natriuretic peptide (NT-proBNP) assay. RESULTS: In method comparisons of six lots of POC NT-proBNP with the lab reference method (Elecsys proBNP) mean bias ranged from -10 to +17%. In lot-to-lot comparisons all six investigated lots of POC NT-proBNP showed excellent agreement, with mean bias between -7% and +2%. The majority of all coefficients of variation obtained from ten-fold measurements using 56 native blood samples were below 8%. No interference was observed with hemolytic blood (hemoglobin concentrations up to 0.12 mmol/L), lipemic blood (triglyceride concentrations up to 14.0 mmol/L) nor icteric blood (bilirubin concentrations up to 63 micromol/L). Hematocrit values between 24% and 51% had no influence on the assay result. High NT-proBNP concentrations above the measuring range of POC NT-proBNP did not lead to false low results due to potential high-dose hook effect. Results with POC NT-proBNP were not influenced by different ambient temperatures (18 degrees C to 32 degrees C), the sample material used, nor by over- or underdosing by 15 microL compared to the regular sample volume of 150 microL. CONCLUSIONS: The POC NT-proBNP assay showed an excellent analytical performance including a good agreement with the laboratory method. The assay is therefore suitable for its intended use in point-of-care settings.

Continuous mechanical chest compression during in-hospital cardiopulmonary resuscitation of patients with pulseless electrical activity.

UNLABELLED: Survival after in-hospital pulseless electrical activity (PEA) cardiac arrest is poor and has not changed during the last 10 years. Effective chest compressions may improve survival after PEA. We investigated whether a mechanical device (LUCAS™-CPR) can ensure chest compressions during cardiac arrest according to guidelines and without interruption during transport, diagnostic procedures and in the catheter laboratory. METHODS: We studied mechanical chest compression in 28 patients with PEA (pulmonary embolism (PE) n=14; cardiogenic shock/acute myocardial infarction; n=9; severe hyperkalemia; n=2; sustained ventricular arrhythmias/electrical storm; n=3) in a university hospital setting. RESULTS: During or immediately after CPR, 21 patients underwent coronary angiography and or pulmonary angiography. Successful return of a spontaneous circulation (ROSC) was achieved in 27 out of the 28 patients. Ten patients died within the first hour and three patients died within 24h after CPR. A total of 14 patients survived and were discharged from hospital (13 without significant neurological deficit). Interestingly, six patients with PE did not have thrombolytic therapy due to contraindications. CT-angiography findings in these patients showed fragmentation of the thrombus suggesting thrombus breakdown as an additional effect of mechanical chest compressions. No patients exhibited any life-threatening device-related complications. CONCLUSION: Continuous chest compression with an automatic mechanical device is feasible, safe, and might improve outcomes after in-hospital-resuscitation of PEA. Patients with PE may benefit from effective continuous chest compression, probably due to thrombus fragmentation and increased pulmonary artery blood flow.

Differential heart rate dynamics in transient left ventricular apical and midventricular ballooning.

BACKGROUND: The aim of the present study was to assess potential differences in cardiac autonomic nervous modulation in patients with transient left ventricular apical ballooning syndrome (AB) and the midventricular variant (MB) of this syndrome. OBJECTIVE: We hypothesized that differences in regional distribution of cardiac autonomic innervation in AB and MB may induce alterations in autonomic modulation, and we tested this assumption by using a combination of traditional and novel nonlinear parameters of heart rate variability (HRV). METHODS: In a prospective single-center study, 49 consecutive patients with transient left ventricular dysfunction syndrome underwent Holter electrocardiographic recording on the third day after admission. A total of 27 recordings of patients with AB and 10 recordings of patients with MB were valid for analysis of HRV, nonlinear dynamic measures of HRV, detrended fluctuation analysis (DFA), and phase-rectified signal averaging (PRSA). RESULTS: There were no significant differences in baseline clinical characteristics between AB and MB patients. Patients with MB showed significantly lower values for mean RR interval (835 ± 104 ms vs. 908 ± 118 ms; P < .05), 1/f power law slope (-1.28 ± 0.2 vs. -1.13 ± 0.2; P < .01), and deceleration capacity (DC) (4.6 ± 1.4 ms vs. 6.0 ± 1.4 ms; P < .01), and significantly higher values for low-frequency (LF) spectral component (5.3 ± 0.5 ln ms(2)/Hz vs. 4.8 ± 0.5 ln ms(2)/Hz), LF/high-frequency (HF) (1.7 ± 0.9 ms vs. 1.3 ± 0.6 ms; P < .05), and DFA α1 (1.09 ± 0.1 vs. 0.99 ± 0.1; P < .01) than patients with AB. There were no significant correlations between parameters of HRV, DFA, 1/f power law slope, and PRSA. CONCLUSION: There are significant differences in heart rate dynamics between AB and MB syndromes. Patients with MB show stronger fractal correlations of heart rate dynamics. Thus, inhomogeneous efferent bilateral sympathetic coactivation and differences in reflex autonomic regulation may be underlying pathophysiological mechanisms for AB and MB syndromes.

Slowing the progression of chronic allograft nephropathy by conversion from cyclosporine to tacrolimus: a randomized controlled trial.

BACKGROUND: Chronic allograft nephropathy (CAN) is a multifactorial process with immunologic and nonimmunologic factors. Because tacrolimus (Tac) has been ascribed a beneficial effect on some of these factors when compared to cyclosporine A (CyA), a randomized controlled trial was conducted to investigate whether conversion from CyA to Tac can ameliorate the progression of renal dysfunction in kidney transplant recipients (KTR) with CAN. METHODS: Of the 46 patients with biopsy-proven CAN enrolled, 24 were converted from CyA to Tac, whereas 22 patients were maintained on CyA. Serum creatinine (SCrea), lipid profiles and an antihypertensive score (AHS) were determined after 3, 6 and 12 months. AHS is based on the total number and dosages of antihypertensive medications used. SCrea and AHS were additionally evaluated at 36 months. RESULTS: SCrea was decreased in the Tac group (Tac(baseline): 297 +/- 67 micromol/L; Tac(6): 261+/- 70 micromol/L, P < 0.001; Tac(12): 254 +/- 55 micromol/L, P < 0.001; Tac(36): 255 +/- 78 micromol/L, P = 0.235), whereas a significant increase of SCrea was detected in the CyA group (CyA(baseline): 279 +/- 77 micromol/L, CyA(12): 333 +/- 98 micromol/L, P < 0.001; CyA(36): 317 +/- 89 micromol/L, P < 0.001). Compared to CyA therapy, SCrea in the Tac group declined after 12 and 36 months (P = 0.011 and 0.048, respectively) as well as AHS (Tac(12): 59 +/- 13, CyA(12): 83 +/- 14, P < 0.001; Tac(36): 60 +/- 12, CyA(36): 84 +/- 14, P < 0.001). LDL cholesterol was lower in the Tac group after 12 months (Tac(12): 2.5 +/- 0.5 mmol/L, CyA(12): 3.5 +/- 0.6 mmol/L, P < 0.001). CONCLUSION: Conversion from CyA to Tac in KTR with CAN improves allograft function, lowers blood pressure, and reduces LDL cholesterol. This superior profile may translate into improved long-term graft survival.

Simvastatin acutely reduces myocardial reperfusion injury in vivo by activating the phosphatidylinositide 3-kinase/Akt pathway.

Long-term pretreatment with statins reduces myocardial injury after acute ischemia and reperfusion by increasing the expression of endothelial nitric oxide synthase (eNOS). We hypothesized that statins may act rapidly enough to protect the myocardium from ischemia/reperfusion injury when given right at the beginning of the reperfusion period and tried to delineate the role of PI 3-kinase/Akt pathway in early eNOS activation. Activated simvastatin was given intravenously 3 minutes before starting the reperfusion after temporary coronary artery occlusion (CAO) in anaesthetized rats. Simvastatin significantly increased myocardial PI 3-kinase activity, AktSer473, and eNOSSer1177 phosphorylation and reduced infarct size by 42%. Infarct size reduction as well as activation of PI 3-kinase/Akt/eNOS pathway were not observed in rats co-treated with the PI 3-kinase inhibitor wortmannin. Contribution of eNOS was further delineated using the NOS inhibitor L-NAME, which could completely block cardioprotection by the statin. In summary, simvastatin acutely reduces the extent of myocardial necrosis in normocholesterolemic rats in an NO- dependent manner by activating the PI 3-kinase/Akt pathway. This is the first study demonstrating short-term cardioprotective effects of simvastatin in an in vivo model of ischemia/reperfusion.