Ventricular response during lungeing exercise in horses with lone atrial fibrillation

Reasons for performing the study Atrial fibrillation (AF) is the most important dysrhythmia affecting performance in horses and has been associated with incoordination, collapse and sudden death. Limited information is available on ventricular response during exercise in horses with lone AF. Objectives To investigate ventricular response in horses with lone AF during a standardised lungeing exercise test. Methods A modified base-apex electrocardiogram was recorded at rest and during a standardised lungeing exercise test from 43 horses diagnosed with lone AF. During the test horses walked for 7min, trotted for 10min, cantered for 4min, galloped for 1min and recovered for 7min. Results Individual average heart rate during walk ranged from 42 to 175beats/min, during trot from 89 to 207 beats/min, during canter from 141 to 269 beats/min, and during gallop from 191 to 311 beats/min. Individual beat-to-beat maximal heart rate ranged from 248 to 492 beats/min. Ventricular premature depolarisations were present in 81% of the horses: at rest (16%), during exercise (69%), and during recovery (2%). In 33% of the horses, broad QRS complexes with R-on-T morphology were found. Conclusions Exercising horses with lone AF frequently develop disproportionate tachycardia. In addition, QRS broadening and even R-on-T morphology is frequently found. QRS broadening may originate from ventricular ectopic foci or from aberrant intraventricular conduction, for example due to bundle branch block. This might explain the high number of complexes currently classified as ventricular premature depolarisations. Potential relevance Prevalence of QRS broadening and especially R-on-T was very high in horses with AF and was found at low levels of exercise. These dysrhythmias are considered risk factors for the development of ventricular tachycardia and fibrillation and they might explain signs of weakness, collapse or sudden death that have been reported in horses with AF

Pacemaker Prevention Therapy in Drug–refractory Paroxysmal Atrial Fibrillation: Reliability of Diagnostics and Effectiveness of Prevention Pacing Therapy in Vitatron™ Selection® device

Introduction. Atrial fibrillation (AF), the most common and rising disorder of cardiac rhythm, is quite difficult to control and/or to treat. Non pharmacological therapies for AF may involve the use of dedicated pacing algorithms to detect and prevent atrial arrhythmia that could be a trigger for AF onset. Selection 900E/AF2.0 Vitatron DDDRP pacemaker (1) keeps an atrial arrhythmia diary thus providing detailed onset reports of arrhythmias of interest, (2) provides us data about the number of premature atrial contractions (PACs) and (3) plots heart rate in the 5 minutes preceding the detection of an atrial arrhythmia. Moreover, this device applies four dedicated pacing therapies to reduce the incidence of atrial arrhythmia and AF events. Aim of the Study. To analyze the reliability to record atrial arrhythmias and evaluate effectiveness of its AF preventive pacing therapies. Material and Methods. We enrolled 15 patients (9 males and 6 females, mean age of 71±5 years, NYHA class I–II), with a DDDRP pacemaker implanted for a “bradycardia–tachycardia” syndrome, with advanced atrioventricular conduction disturbances. We compared the number and duration of AF episodes’ stored in the device with a contemporaneous 24h Holter monitoring. After that, we switched on the atrial arrhythmias detecting algorithms, starting from an atrial rate over 180 beats per minute for at least 6 ventricular cycles, and ending with at least 10 ventricular cycles in sinus rhythm. Thereafter, in order to evaluate the possible reduction in PACs number and in number and duration of AF episodes, we tailored all the four pacing preventive algorithms. Patients were followed for 24±8 months (from 20 to 32 months). Results. All 59 atrial arrhythmia episodes occurred in the first part of this trial, were correctly recorded by both systems, with a correlation coefficient (r) of 0.96. During the follow–up, we observed a significant reduction not only in PACs number (from 83±12/day to 2.3±0.8/day) but also in AF episodes (from 46±7/day to 0.12±0.03/day) and AF burden (from 93%±6% to 0.3%±0.06%). An increase in atrial pacing percentages (from 3%±0.5% to 97%±3%) was also contemporaneously observed. Conclusion. In this pacemaker, detection of atrial arrhythmia episodes is highly reliable, thus making available an appropriate monitoring of heart rhythm, mainly suitable in AF asymptomatic patients. Moreover, the significant reduction of atrial arrhythmia episodes indicates that this might represent a suitable therapeutic option for an effective preventive therapy of AF in paced brady–tachy patients

Shortening of the Short Refractory Periods in Short QT Syndrome.

BACKGROUND: Diagnosis of short QT syndrome (SQTS) remains difficult in case of borderline QT values as often found in normal populations. Whether some shortening of refractory periods (RP) may help in differentiating SQTS from normal subjects is unknown. METHODS AND RESULTS: Atrial and right ventricular RP at the apex and right ventricular outflow tract as determined during standard electrophysiological study were compared between 16 SQTS patients (QTc 324±24 ms) and 15 controls with similar clinical characteristics (QTc 417±32 ms). Atrial RP were significantly shorter in SQTS compared with controls at 600- and 500-ms basic cycle lengths. Baseline ventricular RP were significantly shorter in SQTS patients than in controls, both at the apex and right ventricular outflow tract and for any cycle length. Differences remained significant for RP of any subsequent extrastimulus at any cycle length and any pacing site. A cut-off value of baseline RP <200 ms at the right ventricular outflow tract either at 600- or 500-ms cycle length had a sensitivity of 86% and a specificity of 100% for the diagnosis of SQTS. CONCLUSIONS: Patients with SQTS have shorter ventricular RP than controls, both at baseline during various cycle lengths and after premature extrastimuli. A cut-off value of 200 ms at the right ventricular outflow tract during 600- and 500-ms basic cycle length may help in detecting true SQTS from normal subjects with borderline QT values

Frequency Analysis of Atrial Fibrillation From the Surface Electrocardiogram

Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice. Neither the natural history of AF nor its response to therapy are sufficiently predictable by clinical and echocardiographic parameters. Atrial fibrillatory frequency (or rate) can reliably be assessed from the surface electrocardiogram (ECG) using digital signal processing (filtering, subtraction of averaged QRST complexes, and power spectral analysis) and shows large inter-individual variability. This measurement correlates well with intraatrial cycle length, a parameter which appears to have primary importance in AF domestication and response to therapy. AF with a low fibrillatory rate is more likely to terminate spontaneously, and responds better to antiarrhythmic drugs or cardioversion while high rate AF is more often persistent and refractory to therapy. In conclusion, frequency analysis of AF seems to be useful for non-invasive assessment of electrical remodeling in AF and may subsequently be helpful for guiding AF therapy

Automatic Mode Switching in Atrial Fibrillation

Automatic mode switching (AMS) algorithms were designed to prevent tracking of atrial tachyarrhythmias (ATA) or other rapidly occurring signals sensed by atrial channels, thereby reducing the adverse hemodynamic and symptomatic consequences of a rapid ventricular response. The inclusion of an AMS function in most dual chamber pacemaker now provides optimal management of atrial arrhythmias and allows the benefit of atrioventricular synchrony to be extended to a population with existing atrial fibrillation. Appropriate AMS depends on several parameters: a) the programmed parameters; b) the characteristics of the arrhythmia; c) the characteristics of the AMS algorithm. Three qualifying aspects constitute an AMS algorithm: onset, AMS response, and resynchronization. Since AMS programs also provide data on the time of onset and duration of AMS episodes, AMS data may be interpreted as a surrogate marker of ATAs recurrence. Recently, stored electrograms corresponding to episodes of ATAs have been introduced, thus clarifying the accuracy of AMS in detecting ATAs Clinically this information may be used to assess the efficacy of an antiarrhythmic intervention or the risk of thromboembolic events, and it may serve as a valuable research tool for evaluating the natural history and burden of ATAs

Chronic beta-adrenoceptor blockade and human atrial cell electrophysiology: evidence of pharmacological remodelling

&lt;b&gt;Objective:&lt;/b&gt; Chronic beta-adrenoceptor antagonist (&#946;-blocker) treatment reduces the incidence of reversion to AF in patients, possibly via an adaptive myocardial response. However, the underlying electrophysiological mechanisms are presently unclear. We aimed to investigate electrophysiological changes in human atrial cells associated with chronic treatment with &#946;-blockers and other cardiovascular-acting drugs. &lt;b&gt;Methods:&lt;/b&gt; Myocytes were isolated enzymatically from the right atrial appendage of 40 consenting patients who were in sinus rhythm. The cellular action potential duration (APD), effective refractory period (ERP), L-type Ca&lt;sup&gt;2+&lt;/sup&gt; current (&lt;i&gt;I&lt;/i&gt;&lt;sub&gt;CaL&lt;/sub&gt;), transient (&lt;i&gt;I&lt;/i&gt;&lt;sub&gt;TO&lt;/sub&gt;) and sustained (&lt;i&gt;I&lt;/i&gt;&lt;sub&gt;KSUS&lt;/sub&gt;) outward K&lt;sup&gt;+&lt;/sup&gt; currents, and input resistance (&lt;i&gt;R&lt;/i&gt;&lt;sub&gt;i&lt;/sub&gt;) were recorded using the whole cell patch clamp. Drug treatments and clinical characteristics were compared with electrophysiological measurements using simple and multiple regression analyses. P&#60;0.05 was taken as statistically significant. &lt;b&gt;Results:&lt;/b&gt; In atrial cells from patients treated chronically with &#946;-blockers, the APD&lt;sub&gt;90&lt;/sub&gt; and ERP (75 beats/min stimulation) were significantly longer, at 213&#177;11 and 233&#177;11 ms, respectively (&lt;i&gt;n&lt;/i&gt; = 15 patients), than in cells from non-&#946;-blocked patients, at 176&#177;12 and 184&#177;12 ms (n = 11). These cells also displayed a significantly reduced action potential phase 1 velocity (22&#177;3 vs. 34&#177;3 V/s). Chronic &#946;-blockade was also associated with a significant reduction in the heart rate (58&#177;3 vs. 69&#177;5 beats/min) and in the density of ITO (8.7&#177;1.3 vs. 13.7&#177;2.1 pA/pF), an increase in the Ri (214&#177;24 vs. 132&#177;14 M&#937;), but no significant change in &lt;i&gt;I&lt;/i&gt;&lt;sub&gt;CaL&lt;/sub&gt; or &lt;i&gt;I&lt;/i&gt;&lt;sub&gt;KSUS&lt;/sub&gt;. The &lt;i&gt;I&lt;/i&gt;&lt;sub&gt;TO&lt;/sub&gt; blocker 4-aminopyridine largely mimicked the changes in phase 1 and ERP associated with chronic &#946;-blockade, in cells from non-&#946;-blocked patients. Chronic treatment of patients with calcium channel blockers or angiotensin converting enzyme inhibitors (&lt;i&gt;n&lt;/i&gt; = 11–13 patients) was not associated with any significant changes in atrial cell electrophysiology. &lt;b&gt;Conclusion:&lt;/b&gt; The observed atrial cellular electrophysiological changes associated with chronic &#946;-blockade are consistent with a long-term adaptive response, a type of ‘pharmacological remodelling’, and provide mechanistic evidence supportive of the anti-arrhythmic actions of &#946;-blockade

Adverse reactions of amiodarone

Adverse drug reaction is defined by the World Health Organization as any response to a drug that is noxious and unintended and occurs at a dose normally used in man. Older people are at elevated risk of adverse drug reactions-because of changes in pharmacodynamics, concurrent use of multiple medications and the related drug interactions. However, adverse drug reactions are significantly underestimated in the elderly population that is also exposed to inappropriate drugs. Amiodarone is an antiarrhythmic drug used commonly for the treatment of atrial fibrillation and is increasingly prescribed in older people. While amiodarone is an efficient drug for rhythm control, it's a carrier of different adverse reactions, and pro and cons must be carefully evaluated before its use especially in older people

A comparative study of early afterdepolarization-mediated fibrillation in two mathematical models for human ventricular cells

Early afterdepolarizations (EADs), which are abnormal oscillations of the membrane potential at the plateau phase of an action potential, are implicated in the development of cardiac arrhythmias like Torsade de Pointes. We carry out extensive numerical simulations of the TP06 and ORd mathematical models for human ventricular cells with EADs. We investigate the different regimes in both these models, namely, the parameter regimes where they exhibit (1) a normal action potential (AP) with no EADs, (2) an AP with EADs, and (3) an AP with EADs that does not go back to the resting potential. We also study the dependence of EADs on the rate of at which we pace a cell, with the specific goal of elucidating EADs that are induced by slow or fast rate pacing. In our simulations in two-and three-dimensional domains, in the presence of EADs, we find the following wave types: (A) waves driven by the fast sodium current and the L-type calcium current (Na-Ca-mediated waves); (B) waves driven only by the L-type calcium current (Ca-mediated waves); (C) phase waves, which are pseudo-travelling waves. Furthermore, we compare the wave patterns of the various wave-types (Na-Ca-mediated, Ca-mediated, and phase waves) in both these models. We find that the two models produce qualitatively similar results in terms of exhibiting Na-Ca-mediated wave patterns that are more chaotic than those for the Ca-mediated and phase waves. However, there are quantitative differences in the wave patterns of each wave type. The Na-Ca-mediated waves in the ORd model show short-lived spirals but the TP06 model does not. The TP06 model supports more Ca-mediated spirals than those in the ORd model, and the TP06 model exhibits more phase-wave patterns than does the ORd model

Characterisation of the Na, K pump current in atrial cells from patients with and without chronic atrial fibrillation

&lt;b&gt;Objective:&lt;/b&gt; To assess the contribution of the Na, K pump current (&lt;i&gt;I&lt;/i&gt;&lt;sub&gt;p&lt;/sub&gt;) to the action potential duration (APD) and effective refractory period (ERP) in human atrial cells, and to investigate whether &lt;i&gt;I&lt;/i&gt;&lt;sub&gt;p&lt;/sub&gt; contributes to the changes in APD and ERP associated with chronic atrial fibrillation (AF). &lt;b&gt;Methods:&lt;/b&gt; Action potentials and ion currents were recorded by whole-cell patch clamp in atrial myocytes isolated from consenting patients undergoing cardiac surgery, who were in sinus rhythm (SR) or AF (&#62;3 months). &lt;b&gt;Results:&lt;/b&gt; In cells from patients in SR, the &lt;i&gt;I&lt;/i&gt;&lt;sub&gt;p&lt;/sub&gt; blocker, ouabain (10 &#956;M) significantly depolarised the membrane potential, Vm, from -80&#177;2 (mean&#177;S.E.) to -73&#177;2 mV, and lengthened both the APD (174&#177;17 vs. 197&#177;23 ms at 90% repolarisation) and ERP (198&#177;22 vs. 266&#177;14 ms; P&#60;0.05 for each, Student's t-test, &lt;i&gt;n&lt;/i&gt;=7 cells, 5 patients). With an elevated pipette [Na&lt;sup&gt;+&lt;/sup&gt;] of 30 mM, &lt;i&gt;I&lt;/i&gt;&lt;sub&gt;p&lt;/sub&gt; was measured by increasing extracellular [K&lt;sup&gt;+&lt;/sup&gt;] ([K&lt;sup&gt;+&lt;/sup&gt;]o) from 0 to 5.4 mM. This produced an outward shift in holding current at -40 mV, abolished by 10 muM ouabain. K&#177; and ouabain-sensitive current densities were similar, at 0.99&#177;0.13 and 1.12&#177;0.11 pA/pF, respectively (P&#62;0.05; &lt;i&gt;n&lt;/i&gt;=9 cells), confirming the K&#177;induced current as &lt;i&gt;I&lt;/i&gt;&lt;sub&gt;p&lt;/sub&gt;. &lt;i&gt;I&lt;/i&gt;&lt;sub&gt;p&lt;/sub&gt; increased linearly with increasing Vm between -120 and +60 mV (&lt;i&gt;n&lt;/i&gt;=25 cells). Stepwise increments in [K&lt;sup&gt;+&lt;/sup&gt;]&lt;sub&gt;o&lt;/sub&gt; (between 0 and 10 mM) increased Ip in a concentration-dependent manner (maximum response, &lt;i&gt;E&lt;/i&gt;&lt;sub&gt;max&lt;/sub&gt;=1.19&#177;0.09 pA/pF; EC50=1.71&#177;0.15 mM; n=27 cells, 9 patients). In cells from patients in AF, the sensitivity of Ip to both Vm and [K+]o (&lt;i&gt;E&lt;/i&gt;&lt;sub&gt;max&lt;/sub&gt;=1.02&#177;0.05 pA/pF, EC50=1.54&#177;0.11 mM; &lt;i&gt;n&lt;/i&gt;=44 cells, 9 patients) was not significantly different from that in cells from patients in SR. Within the group of patients in AF, long-term digoxin therapy (&lt;i&gt;n&lt;/i&gt;=5 patients) was associated with a small, but significant, reduction in &lt;i&gt;E&lt;/i&gt;&lt;sub&gt;max&lt;/sub&gt; (0.92&#177;0.07 pA/pF) and EC&lt;sub&gt;50&lt;/sub&gt; (1.35&#177;0.15 mM) compared with non-treatment (&lt;i&gt;E&lt;/i&gt;&lt;sub&gt;max&lt;/sub&gt;=1.13&#177;0.08 pA/pF, EC&lt;sub&gt;50&lt;/sub&gt;=1.76&#177;0.14 mM; P&#60;0.05 for each, &lt;i&gt;n&lt;/i&gt;=4 patients). In cells from non-digoxin-treated patients in AF, the voltage- and [K&lt;sup&gt;+&lt;/sup&gt;]&lt;sub&gt;o&lt;/sub&gt;-sensitivity (&lt;i&gt;E&lt;/i&gt;&lt;sub&gt;max&lt;/sub&gt; and EC&lt;sub&gt;50&lt;/sub&gt;) were similar to those in cells from patients in SR. &lt;b&gt;Conclusions:&lt;/b&gt; The Na, K pump current contributes to the human atrial cell Vm, action potential shape and ERP. However, the similarity in Ip sensitivity to both [K&lt;sup&gt;+&lt;/sup&gt;]&lt;sub&gt;o&lt;/sub&gt; and &lt;i&gt;V&lt;/i&gt;&lt;sub&gt;m&lt;/sub&gt; between atrial cells from patients with and without chronic AF indicates that &lt;i&gt;I&lt;/i&gt;&lt;sub&gt;p&lt;/sub&gt; is not involved in AF-induced electrophysiological remodelling in patients