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Purpose: During incremental atrial pacing in patients with atrioventricular nodal reentrant tachycardia, the PR interval often exceeds the RR interval (PR > RR) during stable 1:1 AV conduction. However, the PR/RR ratio has never been evaluated in a large group of patients with pacing from the proximal coronary sinus and after isoproterenol challenge. Our study validates new site of pacing and easier method of identification of PR > RR., Material and Methods: A prospective protocol of incremental atrial pacing from the proximal coronary sinus was carried out in 398 patients (AVNRT-228 and control-170). The maximum stimulus to the Q wave interval (S-Q = PR), SS interval (S-S), and Q-Q (RR) interval were measured at baseline and 10 min after successful slow pathway ablation and after isoproterenol challenge (obligatory)., Results: The mean maximum PR/RR ratios at baseline were 1.17 ± 0.24 and 0.82 ± 0.13 (p < 0.00001) in the AVNRT and controls respectively. There were no PR/RR ratios ≥1 at baseline and after isoproterenol challenge in 12.3% of the AVNRT group and in 95.9% of the control group (p < 0.0001). PR/RR ratios ≥1 were absent in 98% of AVNRT cases after slow pathway ablation/modification in children and 99% of such cases in adults (P = NS). The diagnostic performance of PR/RR ratio evaluation before and after isoproterenol challenge had the highest diagnostic performance for AVNRT with PR/RR > = 1 (sensitivity: 88%, specificity: 96%, PPV-97%, NPV-85%)., Conclusions: The PR/RR ratio is a simple tool for slow pathway substrate and AVNRT evaluation. Eliminating PR/RR ratios ≥1 may serve as a surrogate endpoint for slow pathway ablation in children and adults with AVNRT., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Given the increasing popularity of aliskiren, particularly in combination with angiotensin converting enzyme inhibitor (e.g. enalapril), it is important to determine whether its use in combination with these agents is associated with potentially life threatening safety events. Analytical methods for the simultaneous determination of both drugs in plasma and urine utilized in clinical studies on efficacy and safety have not been fully described in the literature. In this work, a new, fast and reliable method using a digitally controlled microextraction by packed sorbent (eVol(®)-MEPS) followed by ultra-high performance liquid chromatography (UHPLC) coupled with tandem mass spectrometry (MS/MS) was developed and validated to quantify an aliskiren, enalapril and its active metabolite in both human plasma and urine. Chromatographic separation was accomplished on a Poroshell 120 EC-C18 column with a gradient elution system consisting of 0.1% formic acid in water and acetonitrile (1.5min of total analysis). Detection was performed by multiple reaction monitoring (MRM) mode using electrospray ionization in the positive ion mode. This assay method has been fully validated in terms of selectivity, linearity, accuracy, precision, stability, recovery and matrix effect. The developed method can be applied to the routine determination of selected compounds in human plasma and urine and can be useful to elucidate the mechanisms of the potential risks triggered by the combination of aliskiren and enalapril as well as its active metabolite enalaprilat., (Copyright © 2014 Elsevier B.V. All rights reserved.)

A simple, accurate and sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantitation of α-ketoglutaric acid (α-KG), L-carnitine (L-CAR) and acetyl-L-carnitine (acetyl-L-CAR) in human urine as potential biomarkers of cardiovascular disease. The separation was performed using an isocratic elution of 0.1% formic acid in water and acetonitrile (97:3, v/v) on an Acclaim 120 C8 column (150 mm × 4.6 mm, 3.0 μm). The flow rate of the mobile phase was 1.2 mL/min and the total assay run time was 3 min. Detection was performed on a triple-quadrupole mass spectrometer in selected reaction monitoring (SRM) mode via an electrospray ionization (ESI) source in positive and negative ion modes. This method covered a linearity range of 0.1-500 ng/mL for L-CAR and acetyl-L-CAR and 1-1000 ng/mL for α-KG with lower limits of quantification (LLOQ) of 0.08 ng/mL for L-CAR, 0.04 ng/mL for acetyl-L-CAR and 0.8 ng/mL for α-KG. The intra-day and inter-day precision and accuracy of the quality control samples exhibited relative standard deviations of less than 5.54% and relative error values from -5.95% to 3.11%. Analyte stability was evaluated under various sample preparation, analysis and storage conditions and varied from -9.89% to -0.47%. A two-step solid-phase extraction (SPE) procedure using silica gel and quaternary amine cartridges was used for urine sample cleanup. The average recoveries for all analyzed compounds were better than 86.64% at three concentrations. The method was successfully applied for the quantitation of α-KG, L-CAR and acetyl-L-CAR in human urine samples., (Copyright © 2012 Elsevier B.V. All rights reserved.)

A sensitive ultra-performance liquid chromatography tandem mass spectrometry method with electrospray ionisation (UHPLC-ESI-MS/MS) was developed for the simultaneous determination of 52 compounds: β-blockers, polyphenols (antioxidants) and their metabolites in mixture of standards and after addition the 52 standard solutions to human urine samples. The analyses of urine samples obtained from patients treated with β-blockers were also carried out. The separation of analytes was performed on a Hypersil GOLD™ column (100 mm × 2.1mm, 1.9 μm) using a gradient elution profile for 10 min and mobile phase consisting of 0.1% formic acid in water and acetonitrile. In these conditions, some of the tested compounds were not separated, but this was compensated by the use of MS/MS detection. The drugs, polyphenols and their metabolites were detected with a tandem mass spectrometer after being ionised positively or negatively (depending on the molecule) using an electrospray ionisation (ESI) source. The MS system was operated in the selected reaction monitoring (SRM) mode, where one quantitation and one confirmation transition was done for each analyte. The quantitative method was validated for selectivity, linearity, low limits of quantitation, accuracy, precision, recovery, matrix effect and analyte stability. The LLOQ varied from 0.01 to 0.40 ng mL(-1) for β-blockers and from 0.05 to 40.0 ng mL(-1) for polyphenols. The linear range was 0.08-1000 ng mL(-1) for the drugs and 0.10-2300 ng mL(-1) for the polyphenols. Intra-day and inter-day precision was less than 8%, and the accuracy ranged from -4.40 to 2.23% for all analytes. The average recoveries for all compounds analysed were better than 90%. The developed method can be successfully used to monitor cardiovascular drugs and their metabolites in urine samples of patients treated with β-blockers and can also be used to study the effect of polyphenols on the metabolism of drugs., (Copyright © 2011 Elsevier B.V. All rights reserved.)