Stefania Vecchietti

Electrocardiographic Changes during Hemodiafiltration with Different Potassium Removal Rates

Background/Aims: Sudden K removal is thought to be implicated in ECG alterations observed during hemodialysis (HD). The effects of the K removal rate on ECG-derived parameters have been investigated. Methods: Two different hemodiafiltration (HDF) schedules were used for 10 HD patients: the dialysate K concentration was kept constant in HDFst, while in HDFK it was decreased during the session in order to maintain a uniform plasma-dialysate K gradient. A 12-lead Holter monitor was used to acquire the ECG in the course of the treatments. Classical ECG parameters and overall indices for quantifying ventricular repolarization abnormalities were evaluated. Results: Several ECG parameters were affected by both HD therapies (ST depression, QRS amplitude and QT dispersion), but only indices of the homogeneity of repolarization (PCA-T, E1-T) were significantly affected by the K removal rate. Conclusion: The present study confirms the large impact of HD therapy on ECG. The analysis of the spatial T wave complexity points out the intrinsic arrhythmogenic implications of the K removal rate.

Can paroxysmal atrial fibrillation be predicted

Atrial fibrillation is an ECG rhythm with a significant mortality due to stroke. The objective of this study was to detect those patients most likely to develop atrial fibrillation, and to identify ECGs closest to the onset of fibrillation. Our hypothesis was that patients with atrial fibrillation would have atrial ectopy, and the frequency of this activity would increase prior to onset of fibrillation. From a learning set of 100 30-minute ECGs from 50 patients, 25 without atrial fibrillation (normal) and 25 who subsequently developed atrial fibrillation, an algorithm was developed to detect the presence of ectopic beats using R-R interval data. In the learning set, 37/50 abnormal and 34/50 normal patients were identified, giving a potential screening accuracy of 71%. As a prediction test to detect the ECGs closest to atrial fibrillation, 19/25 were correctly identified. For the test set, a total of 29/50 were correctly assigned to the normal and fibrillation groups, and a 39/50 score obtained in predicting the onset of atrial fibrillation.

Computer simulation of wild-type and mutant human cardiac Na+ current

Long QT syndrome (LQTS) and Brugada syndrome (BrS) are inherited diseases predisposing to ventricular arrhythmias and sudden death. Genetic studies linked LQTS and BrS to mutations in genes encoding for cardiac ion channels. Recently, two novel missense mutations at the same codon in the gene encoding the cardiac Na+ channel (SCN5A) have been identified: Y1795C (causing the LQTS phenotype) and Y1795H (causing the BrS phenotype). Functional studies in HEK293 cells showed that both mutations alter the inactivation of Na+ current and cause a sustained Na+ current upon depolarisation. In this paper, a nine state Markov model was used to simulate the Na+ current in wild-type Na+ cardiac channel and the current alterations observed in Y1795C and Y1795H mutant channels. The model includes three distinct closed states, a conducting open state and five inactivation states (one fast-, two intermediate- and two closed-inactivation). Transition rates between these states were identified on the basis of previously published voltage-clamp experiments. The model was able to reproduce the experimental Na+ current in mutant channels just by altering the assignment of model parameters with respect to wild-type case. Parameter assignment was validated by performing action potential clamp experiments and comparing experimental and simulated INa current. The Markov model was subsequently introduced in the Luo–Rudy model of ventricular myocyte to investigate “in silico” the consequences on the ventricular cell action potential of the two mutations. Coherently with their phenotypes, the Y1795C mutation prolongs the action potential, while the Y1795H mutation causes only negligible changes in action potential morphology.

Action potential changes due to Y1795H mutation in Brugada syndrome patients: a simulation study

Several mutations of the gene encoding for the cardiac sodium channel (SCN5A) are associated with congenital Brugada syndrome (BrS), but the assessment of their functional consequences with the experimental models is biased by technical limitations. To overcome such limitations we used a novel approach combining in vitro data and computer modeling. The Y1795H mutation of SCN5A was evaluated. A Markovian model capable to reproduce the kinetics of both wild type (WT) and mutant channels was incorporated into the Luo-Rudy comprehensive model of ventricular cells. Here presented results highlight the high sensitivity of simulated AP of virtual transgenic cells to the maximum conductance assigned to the sodium current in mutant channel model. A value of about 10000 S/F allows the reproduction of coherent action potentials in WT and mutant cells.

Markovian model for wild-type and mutant (Y1795C and Y1795H) human cardiac Na/sup +/ channel

Long QT syndrome (LQTS) and Brugada syndrome (BrS) are inherited syndromes predisposing to ventricular arrhythmias and sudden death. Emerging evidences related LQTS and BrS to dysfunctions of cardiac ion channels. Recently, two novel missense mutations in gene encoding for the cardiac Na channel have been identified (Y1795C for LQTS and Y1795H for BrS). Both mutations alter inactivation, intermediate inactivation, onset of inactivation of Na current and cause a sustained Na current. In this study we present a Markovian model of wild type and mutant Na channels. Model includes three closed states, an open state, and five inactivated states. Transition rates between these states were identified on the basis of electrophysiological experiments. The model is able to reproduce the current alterations observed in mutant channels just by alter the transition rates with respect to wild type assignment.

Analysis of T wave complexity during arrhythmic phases caused by hemodialysis

The sensitivity of an index based on the principal component analysis (PCA) of the T-wave to the frequency of premature ventricular contractions (PVCs) caused by hemodialysis was investigated. The ECGs from 24 hemodialysis sessions were studied. From the 12-lead Holter recording, the first and the last hours were extracted. The sessions were classified on the basis of the trend of PVC occurrence in the last hour with respect to the first one: no change in PVC occurrence (group A), and increased PVCs (group B). PCA was applied to the T-wave extracted from each beat over leads I, II and VI to V6, so determining the degree of correlation between the eight T-waveforms. The index of complexity (PCA-T), defined as the ratio between the second and the first eigenvalue, was calculated. No difference was found in PCA-T in the first hour of hemodialysis between the two groups (A: 0.16/spl plusmn/0.11, B: 0.20/spl plusmn/0.08). Hemodialysis caused a significant increase in PCA-T in both group A (to 0.23/spl plusmn/0.13, p<0.001) and group B (to 0.33/spl plusmn/0.10, p<0.001). However, the increase in PCA-T was significantly higher in group B with respect to group A (0.13/spl plusmn/0.05 vs 0.07/spl plusmn/0.051 p<0.05). These results show that hemodialysis significantly increases the complexity of the T-wave. Such an increase is greater when a significant increase in the frequency of PVCs occurs.

Computer-model analysis of the effect of potassium changes on the sinus node pacemaking

It is well know that sinus node pacemaker activity is strictly related to the autonomic outflow, but the role of plasma potassium level on sinusal pacemaking is not yet well understood. A computer model of the sinus node cell was used to analyze heart rate data collected during purely diffusive hemodialysis, which allowed large changes in extracellular potassium concentration to be achieved without eliciting notable changes in the autonomic modulation. Model-based analysis revealed that changes of potassium concentration can cause large heart rate variations (from 60 to 90 bpm). According to experimental data, a significant heart rate increase was predicted by the model after potassium decrease and calcium and pH increase. A highly non-linear heart rate dependence on potassium was also recognized and its relationship with calcium and pH levels was disclosed. It was concluded that potassium changes in physiological range have an important, complex, impact on the pacemaking rhythm independently of autonomic outflow.