Analysis of factors affecting the accuracy of 18F-fluorodeoxyglucose positron emission tomography combined with computed tomography in case of suspected prosthetic valve infective endocarditis

Aim. To analyze the factors affecting the accuracy of 18F-fluorodeoxyglucose positron emission tomography combined with computed tomography (PET/CT) in case of suspected prosthetic valve endocarditis (PVE).Material and methods. The results of PET/CT performed in 66 patients after heart valve replacement were analyzed: 55 patients with suspected PVE (≥3 months after surgery) and 11 comparison groups without PVE (2 months after surgery). In the group with suspected PVE (n=55) at the time of the study, 27% (15/55) had a normal body temperature, 85% (47/55) — no leukocytosis. In 16% (9/55), the examination was performed from 3 to 6 months after surgery and in 67% (37/55)  — against the background of long-term antibiotic therapy (ABT). The final diagnosis of PVE was made on the basis of clinical (including 6±3 followup), laboratory, instrumental, and intraoperative (n=40) data: confirmed  — in 37 patients; ruled out — in 29 patients. In order to determine the influence of factors on obtaining false PET/CT results, the odds ratio was calculated.Results. In the group with suspected PVE (n=55), the PET/CT results made it possible to establish and rule out PVE in 92% (34/37) and 67% (12/18) of patients, respectively. In 16% (9/55) of patients, false positive (n=6) and false negative (n=3) results. Thus, the sensitivity, specificity and diagnostic accuracy of PET/CT in the diagnosis of PVE were 92%, 67% and 84%, respectively; positive and negative predictive values — 85% and 80%. The analysis of the odds ratio did not reveal the relationship of low inflammatory activity, the interval between surgery and PET/CT from 3 to 6 months, and long-term ABT before PET/CT with false PET/CT results (p>0,05). In the comparison group without PVE (n=11), 91% (10/11) received false positive PET/CT results, and one patient received a true negative result.Conclusion. The data obtained indicate the high informative value of PET/CT in the diagnosis of PVE. Interval >2 months between surgery and PET/CT significantly reduces the accuracy of PET/CT results. Other factors analyzed in the presented group did not affect the accuracy of PET/CT results

Atrial arrhythmogenicity of KCNJ2 mutations in short QT syndrome: Insights from virtual human atria

Gain-of-function mutations in KCNJ2-encoded Kir2.1 channels underlie variant 3 (SQT3) of the short QT syndrome, which is associated with atrial fibrillation (AF). Using biophysically-detailed human atria computer models, this study investigated the mechanistic link between SQT3 mutations and atrial arrhythmogenesis, and potential ion channel targets for treatment of SQT3. A contemporary model of the human atrial action potential (AP) was modified to recapitulate functional changes in IK1 due to heterozygous and homozygous forms of the D172N and E299V Kir2.1 mutations. Wild-type (WT) and mutant formulations were incorporated into multi-scale homogeneous and heterogeneous tissue models. Effects of mutations on AP duration (APD), conduction velocity (CV), effective refractory period (ERP), tissue excitation threshold and their rate-dependence, as well as the wavelength of re-entry (WL) were quantified. The D172N and E299V Kir2.1 mutations produced distinct effects on IK1 and APD shortening. Both mutations decreased WL for re-entry through a reduction in ERP and CV. Stability of re-entrant excitation waves in 2D and 3D tissue models was mediated by changes to tissue excitability and dispersion of APD in mutation conditions. Combined block of IK1 and IKr was effective in terminating re-entry associated with heterozygous D172N conditions, whereas IKr block alone may be a safer alternative for the E299V mutation. Combined inhibition of IKr and IKur produced a synergistic anti-arrhythmic effect in both forms of SQT3. In conclusion, this study provides mechanistic insights into atrial proarrhythmia with SQT3 Kir2.1 mutations and highlights possible pharmacological strategies for management of SQT3-linked AF

Novel non-invasive algorithm to identify the origins of re-entry and ectopic foci in the atria from 64-lead ECGs: A computational study.

Atrial tachy-arrhytmias, such as atrial fibrillation (AF), are characterised by irregular electrical activity in the atria, generally associated with erratic excitation underlain by re-entrant scroll waves, fibrillatory conduction of multiple wavelets or rapid focal activity. Epidemiological studies have shown an increase in AF prevalence in the developed world associated with an ageing society, highlighting the need for effective treatment options. Catheter ablation therapy, commonly used in the treatment of AF, requires spatial information on atrial electrical excitation. The standard 12-lead electrocardiogram (ECG) provides a method for non-invasive identification of the presence of arrhythmia, due to irregularity in the ECG signal associated with atrial activation compared to sinus rhythm, but has limitations in providing specific spatial information. There is therefore a pressing need to develop novel methods to identify and locate the origin of arrhythmic excitation. Invasive methods provide direct information on atrial activity, but may induce clinical complications. Non-invasive methods avoid such complications, but their development presents a greater challenge due to the non-direct nature of monitoring. Algorithms based on the ECG signals in multiple leads (e.g. a 64-lead vest) may provide a viable approach. In this study, we used a biophysically detailed model of the human atria and torso to investigate the correlation between the morphology of the ECG signals from a 64-lead vest and the location of the origin of rapid atrial excitation arising from rapid focal activity and/or re-entrant scroll waves. A focus-location algorithm was then constructed from this correlation. The algorithm had success rates of 93% and 76% for correctly identifying the origin of focal and re-entrant excitation with a spatial resolution of 40 mm, respectively. The general approach allows its application to any multi-lead ECG system. This represents a significant extension to our previously developed algorithms to predict the AF origins in association with focal activities

Current status of nuclear cardiology in the Russian Federation

The article is devoted to the analysis of the current status of nuclear cardiology in the Russian Federation. The data on the number of facilities performing radionuclide investigations for the diagnosis and monitoring of the treatment of cardiovascular diseases, their staffing and equipment are given. The statistics of the conducted nuclear cardiology tests for 2018-2020 are given, as well as their methods, features and diagnostic significance are described

Wnt signalling and cancer stem cells

[Abstract] Intracellular signalling mediated by secreted Wnt proteins is essential for the establishment of cell fates and proper tissue patterning during embryo development and for the regulation of tissue homeostasis and stem cell function in adult tissues. Aberrant activation of Wnt signalling pathways has been directly linked to the genesis of different tumours. Here, the components and molecular mechanisms implicated in the transduction of Wnt signal, along with important results supporting a central role for this signalling pathway in stem cell function regulation and carcinogenesis will be briefly reviewed.Ministerio de Ciencia e Innovación; SAF2008-0060

In silico assessment of the effects of quinidine, disopyramide and E-4031 on short QT syndrome variant 1 in the human ventricles.

Aims Short QT syndrome (SQTS) is an inherited disorder associated with abnormally abbreviated QT intervals and an increased incidence of atrial and ventricular arrhythmias. SQT1 variant (linked to the rapid delayed rectifier potassium channel current, IKr) of SQTS, results from an inactivation-attenuated, gain-of-function mutation (N588K) in the KCNH2-encoded potassium channels. Pro-arrhythmogenic effects of SQT1 have been well characterized, but less is known about the possible pharmacological antiarrhythmic treatment of SQT1. Therefore, this study aimed to assess the potential effects of E-4031, disopyramide and quinidine on SQT1 using a mathematical model of human ventricular electrophysiology. Methods The ten Tusscher et al. biophysically detailed model of the human ventricular action potential (AP) was modified to incorporate IKr Markov chain (MC) formulations based on experimental data of the kinetics of the N588K mutation of the KCNH2-encoded subunit of the IKr channels. The modified ventricular cell model was then integrated into one-dimensional (1D) strand, 2D regular and realistic tissues with transmural heterogeneities. The channel-blocking effect of the drugs on ion currents in healthy and SQT1 cells was modeled using half-maximal inhibitory concentration (IC50) and Hill coefficient (nH) values from literatures. Effects of drugs on cell AP duration (APD), effective refractory period (ERP) and pseudo-ECG traces were calculated. Effects of drugs on the ventricular temporal and spatial vulnerability to re-entrant excitation waves were measured. Re-entry was simulated in both 2D regular and realistic ventricular tissue. Results At the single cell level, the drugs E-4031 and disopyramide had hardly noticeable effects on the ventricular cell APD at 90% repolarization (APD90), whereas quinidine caused a significant prolongation of APD90. Quinidine prolonged and decreased the maximal transmural AP heterogeneity (δV); this led to the decreased transmural heterogeneity of APD across the 1D strand. Quinidine caused QT prolongation and a decrease in the T-wave amplitude, and increased ERP and decreased temporal susceptibility of the tissue to the initiation of re-entry and increased the minimum substrate size necessary to prevent re-entry in the 2D regular model, and further terminated re-entrant waves in the 2D realistic model. Quinidine exhibited significantly better therapeutic effects on SQT1 than E-4031 and disopyramide. Conclusions The simulated pharmacological actions of quinidine exhibited antiarrhythmic effects on SQT1. This study substantiates a causal link between quinidine and QT interval prolongation in SQT1 and suggests that quinidine may be a potential pharmacological agent for treating SQT1 patients

Effects of temperature in juvenile seabass (Dicentrarchus labrax L.) biomarker responses and behaviour: implications for environmental monitoring

The effects of temperature on European seabass (Dicentrarchus labrax L.) juveniles were investigated using a 30-day bioassay carried out at 18 and 25 °C in laboratory conditions. A multiparameter approach was applied including fish swimming velocity and several biochemical parameters involved in important physiological functions. Fish exposed for four weeks to 25 °C showed a decreased swimming capacity, concomitant with increased oxidative stress (increased catalase and glutathione peroxidase activities) and damage (increased lipid peroxidation levels), increased activity of an enzyme involved in energy production through the aerobic pathway (isocitrate dehydrogenase) and increased activities of brain and muscle cholinesterases (neurotransmission) compared to fish kept at 18 °C. Globally, these findings indicate that basic functions, essential for juvenile seabass surviving and well performing in the wild, such as predation, predator avoidance, neurofunction and ability to face chemical stress may be compromised with increasing water temperature. This may be of particular concern if D. labrax recruitment phase in northwest European estuaries and coastal areas happens gradually inmore warm environments as a consequence of global warming. Considering that the selected endpoints are generally applied in monitoring studies with different species, these findings also highlight the need of more research, including interdisciplinary and multiparameter approaches, on the impacts of temperature on marine species, and stress the importance of considering scenarios of temperature increase in environmental monitoring and in marine ecological risk assessment

A three-dimensional human atrial model with fiber orientation. Electrograms and arrhythmic activation patterns relationship

The most common sustained cardiac arrhythmias in humans are atrial tachyarrhythmias, mainly atrial fibrillation. Areas of complex fractionated atrial electrograms and high dominant frequency have been proposed as critical regions for maintaining atrial fibrillation; however, there is a paucity of data on the relationship between the characteristics of electrograms and the propagation pattern underlying them. In this study, a realistic 3D computer model of the human atria has been developed to investigate this relationship. The model includes a realistic geometry with fiber orientation, anisotropic conductivity and electrophysiological heterogeneity. We simulated different tachyarrhythmic episodes applying both transient and continuous ectopic activity. Electrograms and their dominant frequency and organization index values were calculated over the entire atrial surface. Our simulations show electrograms with simple potentials, with little or no cycle length variations, narrow frequency peaks and high organization index values during stable and regular activity as the observed in atrial flutter, atrial tachycardia (except in areas of conduction block) and in areas closer to ectopic activity during focal atrial fibrillation. By contrast, cycle length variations and polymorphic electrograms with single, double and fragmented potentials were observed in areas of irregular and unstable activity during atrial fibrillation episodes. Our results also show: 1) electrograms with potentials without negative deflection related to spiral or curved wavefronts that pass over the recording point and move away, 2) potentials with a much greater proportion of positive deflection than negative in areas of wave collisions, 3) double potentials related with wave fragmentations or blocking lines and 4) fragmented electrograms associated with pivot points. Our model is the first human atrial model with realistic fiber orientation used to investigate the relationship between different atrial arrhythmic propagation patterns and the electrograms observed at more than 43000 points on the atrial surface.This work was partially supported by the Plan Nacional de Investigacion Cientifica, Desarrollo e Innovacion Tecnologica, Ministerio de Ciencia e Innovacion of Spain (TEC2008-02090), by the Plan Avanza (Accion Estrategica de Telecomunicaciones y Sociedad de la Informacion), Ministerio de Industria Turismo y Comercio of Spain (TSI-020100-2010-469), by the Programa Prometeo 2012 of the Generalitat Valenciana and by the Programa de Apoyo a la Investigacion y Desarrollo de la Universitat Politecnica de Valencia (PAID-06-11-2002). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Tobón Zuluaga, C.; Ruiz Villa, CA.; Heidenreich, E.; Romero Pérez, L.; Hornero, F.; Saiz Rodríguez, FJ. (2013). A three-dimensional human atrial model with fiber orientation. Electrograms and arrhythmic activation patterns relationship. PLoS ONE. 8(2):1-13. https://doi.org/10.1371/journal.pone.0050883S11382Ho SY, Sanchez-Quintana D, Anderson RH (1998) Can anatomy define electric pathways? In: International Workshop on Computer Simulation and Experimental Assessment of Electrical Cardiac Function, Lausanne, Switzerland. 77–86.Tobón C (2009) Evaluación de factores que provocan fibrilación auricular y de su tratamiento mediante técnicas quirúrgicas. Estudio de simulación. Master Thesis Universitat Politècnica de València.Ruiz C (2010) Estudio de la vulnerabilidad a reentradas a través de modelos matemáticos y simulación de la aurícula humana. Doctoral Thesis Universitat Politècnica de València.Tobón C (2010) Modelización y evaluación de factores que favorecen las arritmias auriculares y su tratamiento mediante técnicas quirúrgicas. Estudio de simulación. Doctoral Thesis Universitat Politècnica de València.Henriquez, C. S., & Papazoglou, A. A. (1996). Using computer models to understand the roles of tissue structure and membrane dynamics in arrhythmogenesis. Proceedings of the IEEE, 84(3), 334-354. doi:10.1109/5.486738Grimm, R. A., Chandra, S., Klein, A. L., Stewart, W. J., Black, I. W., Kidwell, G. A., & Thomas, J. D. (1996). Characterization of left atrial appendage Doppler flow in atrial fibrillation and flutter by Fourier analysis. American Heart Journal, 132(2), 286-296. doi:10.1016/s0002-8703(96)90424-xMaleckar, M. M., Greenstein, J. L., Giles, W. R., & Trayanova, N. A. (2009). K+ current changes account for the rate dependence of the action potential in the human atrial myocyte. American Journal of Physiology-Heart and Circulatory Physiology, 297(4), H1398-H1410. doi:10.1152/ajpheart.00411.200