Intracardiac Conduction Times Research Articles

Electrical remodelling post cardiac resynchronization therapy in patients with ischemic and non-ischemic heart failure

BackgroundThe beneficial effects of cardiac resynchronization therapy (CRT) in heart failure are largely considered to be due to improved mechanical contractility. The contributory role of electrical remodelling is less clear. We sought to evaluate the impact of electrical remodelling in these patients. Methods33 patients with conventional indications for CRT and with ischemic (ICM) (n = 17) and non-ischemic (NICM) (n = 16) aetiologies for heart failure were prospectively recruited. Functional parameters of peak exercise oxygen consumption (VO2max) and Minnesota quality of life (QOL) score, echocardiographic measures of LV functions and parameters of electrical remodelling, e.g. intrinsic QRS duration (iQRSD), intracardiac conduction times of LV pacing to RV electrocardiogram (LVp-RVegm), were measured at CRT implant and after 6 months. ResultsOnly two electrical parameters predicted functional or symptomatic improvement. LVp-RVegm reduction significantly correlated with improvement in VO2max (r = −0.42, p = 0.03 while reduction in iQRSD significantly correlated with improvement in QOL score (r = 0.39, p = 0.04). The extent of changes in LVp-RVegm and iQRSD was significantly greater in NICM than in ICM patients (p = 0.017 and p = 0.042 for heterogeneity). There was also significant differential impact on QOL score in the NICM relative to the ICM group (p = 0.003) but none with VO2max. On multivariate analysis, only non-ischemic aetiology was a significant determinant of reduction in iQRSD. ConclusionCRT induces potentially beneficial reduction in LVp-RVegm and iQRSD, which are seen selectively in NICM rather than ICM patients. The extent of improvement in these markers is associated with some functional and symptomatic measures of CRT efficacy.

Surface and intracardiac ECG for discriminating conduction disorders after CoreValve implantation

BackgroundTranscatheter aortic valve implantation (TAVI) has been developed to minimize operative morbidity and mortality in high-risk symptomatic patients unfit for open surgery. With the proximity of the aortic valve annulus to the conduction system there is, however, an unknown risk of conduction disturbances necessitating monitoring and often cardiac pacing.Materials and methodsWe enrolled 50 consecutive patients from January 2007 to 2008 in our prospective evaluation of conduction disturbances measured by surface and intracardiac ECG recordings. Baseline parameters, procedural characteristics as well as twelve-lead surface ECG and intracardiac conduction times were revealed pre-interventionally, after TAVI and at 7-day follow-up.ResultsTAVI was performed successfully in all patients. During 7 days of follow-up the rate for first-degree AV block raised from 14% at baseline to 44% at day 7 (p < 0.001), while rates for type II second- and third-degree were 0 versus 8% (p < 0.001) and 0 versus 12% (p < 0.001), respectively. Similarly, the prevalence of new left bundle branch block (LBBB) rose from 2 to 54% (p < 0.001). Intracardiac measurements revealed a prolongation of both AH and HV interval from 123.7 ± 41.6 to 136.6 ± 40.5 ms (p < 0.001) and from 54.8 ± 11.7 to 71.4 ± 20.0 ms (p < 0.001), respectively. Pacemaker implantation at a mean follow-up of 4.8 ± 1.2 days was subsequently performed in 23 patients (46%) due to complete AV block (12%) and type II second-degree AV block (8%) while another 13 patients (26%) received a pacemaker for the combination of new LBBB with marked HV prolongation. The high rate of first-degree AV block was primarily driven by an increase in HV interval.ConclusionCardiac conduction disturbances were common in the early experience with CoreValve implantation necessitating close surveillance for at least 1 week.

Electrophysiological effects of MS-551 in humans: a class III antiarrhythmic agent.

To investigate the clinical effects of MS-551, a Class III antiarrhythmic agent, 11 patients underwent electrophysiological study. MS-551 was given intravenously as an initial dose of 0.2 or 0.3 mg/kg for 5 minutes followed by the continuous infusion at 0.2 or 0.3 mg/kg for 30 minutes, respectively, in all patients. The rate corrected QT interval increased significantly from 3 minutes after the beginning of MS-551 infusion. The sinus heart rate decreased significantly by 8% at 10 minutes after the drug administration (P < 0.025). Mean PR and QRS intervals, and blood pressure were not significantly affected by the drug. Mean PA, AH, and HV intervals during sinus rhythm were also not affected. The effective refractory periods (ERPs) of the atrium and ventricle were significantly prolonged by 13% from 202 +/- 24 ms to 231 +/- 26 ms (P < 0.0005), and by 7% from 238 +/- 11 ms to 257 +/- 13 ms (P < 0.002), respectively, by MS-551. The ERP of the atrioventricular node and sinoatrial nodal recovery time were not changed significantly by the drug. This is a report of the effects of MS-551 in humans. This agent could be useful for treatment of tachyarrhythmias by prolongation of ERPs of the atrium and ventricle without significant variations of blood pressure and intracardiac conduction times. It is noteworthy that MS-551 slightly but significantly decreased heart rate.

Positive inotropy linked with class III antiarrhythmic action: electrophysiological effects of the cardiotonic agent DPI 201-106 in the dog heart in vivo

The aim was to investigate whether the positive inotrope DPI 201-106 prolongs ventricular monophasic action potential duration and refractoriness in vivo without affecting conduction, thus possessing class III antiarrhythmic characteristics in vivo. Electrophysiological and haemodynamic effects of DPI 201-106 (0.5, 1.0, and 2.0 mg.kg-1 intravenously) were studied at spontaneous heart rate and at three different paced cycle lengths (353, 300, and 261 ms). The following were recorded: monophasic action potentials from right ventricular endocardium; intracardiac conduction times by His bundle electrocardiography; refractoriness by programmed electrical stimulation; and left ventricular (LV) pressures. Seven mongrel dogs of either sex, weighing 14-24 kg, were studied under sodium pentobarbitone anaesthesia. DPI 201-106 prolonged ventricular monophasic action potential duration and refractoriness dose dependently and most effectively at long cycle lengths, with no effect on intracardiac conduction times. DPI 201-106 increased LV dP/dtmax, while LV systolic and end diastolic pressures were unchanged both during spontaneous and paced heart rate. DPI 201-106 decreased spontaneous heart rate. Prolonged monophasic action potential duration and increased refractoriness, with no effect on conduction, indicate class III antiarrhythmic action of DPI 201-106 in vivo.

Antiarrhythmic efficacy, clinical electrophysiology, and pharmacokinetics of 3-methoxy-O-desmethyl encainide (MODE) in patients with inducible ventricular tachycardia or fibrillation.

In most patients, the clinical effects of therapy with encainide are mediated by the generation of the active metabolites O-desmethyl encainide and 3-methoxy-O-desmethyl encainide (MODE). Data from in vitro and animal studies have indicated that MODE has electrophysiologic and pharmacokinetic features that make its further evaluation desirable; in earlier studies, we found that MODE suppressed chronic high-frequency nonsustained ventricular arrhythmias at plasma concentrations of 50-160 ng/ml. We now report the clinical electrophysiology, antiarrhythmic activity, and pharmacokinetics of MODE in 17 patients with inducible ventricular tachyarrhythmias (VTs) in whom programmed electrical stimulation was performed before drug administration and after one or two sequences of loading and maintenance infusions of MODE. Because the relation between plasma concentration and effect had been incompletely defined, a dose-titration approach was adopted: available pharmacokinetic data were used to construct loading and maintenance infusion regimens that were predicted to attain low plasma concentrations in initial patients while higher infusion rates were evaluated in subsequent patients. MODE prevented VT induction in three of 17 patients and VT cycle length was increased by greater than or equal to 100 msec in a further seven of 17; most responses to MODE occurred at plasma concentrations greater than 556 ng/ml (greater than 1 SD above mean plasma MODE during encainide therapy). Response to MODE did not predict subsequent response to oral therapy with encainide. MODE increased intracardiac conduction times, QT intervals during atrial and ventricular pacing, and right ventricular effective refractory periods (RVERP); changes in RVERP were most prominent at rapid pacing rates, while changes in intracardiac conduction were rate-independent at cycle lengths between 400 and 600 msec. Plasma MODE concentrations measured during electrophysiology study correlated well with those predicted by the pharmacokinetic simulations (r = 0.91, p less than 0.001). Serial plasma sampling after programmed electrical stimulation indicated a minimum MODE elimination half-life of 8.2 +/- 5.4 hours. Side effects were confined to three instances of asymptomatic conduction system depression in subjects with latent conduction system disturbances. We conclude that MODE slows intracardiac conduction, delays repolarization, and can suppress or substantially modify inducible VT. Moreover, it was only with the adoption of the dose-titration strategy that we were able to safely demonstrate that plasma MODE concentrations higher than those routinely observed during encainide therapy were required to substantially alter cardiac electrophysiology.

Effects of halothane with and without histamine and/or epinephrine on automaticity, intracardiac conduction times, and development of dysrhythmias in the isolated guinea pig heart.

Histamine is released during allergic reactions, and is known to produce cardiac dysrhythmias. The authors compared the cardiac effects of histamine and epinephrine during exposure to halothane in the isolated perfused guinea pig heart. Responses studied were spontaneous sinus rate, intra-atrial conduction time, atrial-septal conduction time (ASCT), intraventricular conduction time (IVCT), and left ventricular pressure (LVP). The incidence and type of dysrhythmias with histamine and halothane and with epinephrine and halothane were analyzed from electrograms. The authors found that halothane alone (0.7 to 2.1 vol%) causes dose-dependent depressions of sinus rate and LVP, prolongs ASCT and IVCT, and produces atrioventricular (AV) block with junctional bradycardia. Histamine alone (.01-10 microM) increases sinus rate and LVP but, like halothane, prolongs ASCT. Halothane antagonizes the inotropic and chronotropic effects of histamine, but enhances ASCT compared with histamine alone. Histamine with halothane greatly increases the incidence of junctional tachycardia with AV dissociation from 0% with histamine alone up to 48%. Epinephrine alone (0.1-5 microM), like histamine, increases sinus rate and LVP, but does not cause a relative increase in ASCT. Halothane antagonizes the inotropic and chronotropic effects of epinephrine, but increases the incidence of ventricular tachycardia from 6% to 28%, and the incidence of premature ventricular excitations from 0% to 40%, compared with epinephrine alone. The authors' in vitro findings show that histamine and halothane, like epinephrine and halothane, can cause dysrhythmias, but that the genesis and type of dysrhythmias induced by these agents are dissimilar. Consequently, the release of histamine with an anaphylactoid reaction during halothane anesthesia, and the treatment of the reaction with epinephrine, could result in dangerous ventricular tachydysrhythmias.

Cardiac effects of thoracic epidural morphine caused by increased vagal activity in the dog.

This study was carried out in order to investigate possible side-effects of thoracic epidural morphine on cardiac electrophysiology, haemodynamics and metabolism. In pentobarbital-anaesthetized dogs, intracardiac conduction times were determined by His bundle electrography, and refractoriness by programmed electrical stimulation; monophasic action potential recordings were obtained from the right ventricle by the suction electrode technique. Cardiac output, left ventricular and aortic blood pressures were measured, as well as plasma concentrations of morphine, free fatty acids, glycerol, glucose and lactate. Thoracic epidural morphine (0.12 mg X kg-1) reduced spontaneous heart rate, prolonged atrioventricular nodal conduction time and refractoriness, and reduced left ventricular dP/dt max. Bilateral vagotomy reversed these effects. Intra-atrial, His Purkinje and intraventricular conduction times, atrial and ventricular refractoriness and action potential duration, stroke volume and mean aortic blood pressure, as well as the metabolic variables, were not significantly influenced by thoracic epidural morphine with or without vagotomy. Peak plasma morphine levels of 12-25 ng X ml-1 were measured 10 min after morphine injection. In conclusion, this study demonstrates depressive side-effects of epidural morphine on cardiac function, mediated by an increased vagal activity.

Electrophysiological effects of thoracic epidural analgesia in the dog heart in situ.

To investigate cardiac electrophysiological effects of thoracic epidural analgesia, a local anaesthetic solution, 0.5% bupivacaine, was administered into the thoracic epidural space in twelve pentobarbital anaesthetised dogs. Intracardiac conduction times were measured by His bundle electrography and refractoriness was determined by programmed electrical stimulation. Monophasic action potentials were recorded from the right ventricle by a suction electrode technique. Thoracic epidural analgesia increased the ventricular effective and functional refractory period, as well as the duration of the monophasic action potential. The intra-atrial and His-Purkinje conduction times and the QRS-width were not significantly influenced. AV nodal conduction time and AV nodal functional refractory period were markedly prolonged by thoracic epidural analgesia. Thoracic epidural analgesia induced AV block of the second degree in most experiments after a second dose of bupivacaine during pacing at higher frequencies. We conclude that thoracic epidural analgesia has significant cardiac electrophysiological effects which may be both antiarrhythmic and arrhythmogenic. Thoracic epidural analgesia should be used with care in patients with atrioventricular conduction disturbances.

Carotid sinus hypersensitivity in patients presenting with syncope.

In 23 patients (ages 44 to 81) presenting with syncope, vertigo, or transient amnesia, carotid sinus massage produced a significant bradycardia in association with symptoms. The 10 most severely symptomatic patients were studied electrophysiologically, including measurement of intracardiac conduction times and corrected sinus node recovery times, as well as with carotid sinus massage before and after atropine. The only detectable abnormality in five of this group was asystole produced by carotid sinus massage; the other five had, in addition, evidence of either sinuatrial disease or an intracardiac conduction defect. Cardiac pacing in these 10 patients completely abolished their symptoms. In a control group of 52 asymptomatic patients (ages 36 to 87), an abnormal response to carotid sinus massage was uncommon (2%).

Electrophysiologic properties of perhexiline

Perhexiline maleate (Pexid), a promising clinical antiarrhythmic and antianginal drug, was evaluated for its electrophysiologic effects on the entire conduction system of the intact canine heart throughout a wide range of therapeutic and potentially toxic doses. Intracardiac conduction times were measured by bipolar intramyocardial and transvenous endocardial electrodes before and following the intravenous administration of each dose of perhexiline maleate, 3 mg/kg every 30 min for a total of 4 doses in 7 open-chest anesthetized dogs. Eight animals served as controls in which similar operative technique and electrophysiologic variables were recorded after infusion of the maleate diluent. In addition, the effects of perhexiline on atrial and ventricular thresholds to electrical stimulation were recorded, as well as the QRS and QT intervals, sinus rate, and rhythm disorders. It was observed that perhexiline did not significantly (p greater than .05) alter sinus rate, QT interval, QRS duration, PR interval, intra-atrial conduction time, atrioventricular nodal conduction time, and His-Purkinje conduction velocity. The drug did not affect the cardiac threshold to electrical stimulation of less than 0.1 ma. No ectopic atrial or ventricular activity emerged during the accumulated influence of the agent. From this study, it is concluded that perhexiline does not exert deleterious actions on the conduction system of the intact canine heart. In view of the negligible toxic effects and its efficacy in treating ventricular tachyarrhythmias in patients, the drug deserves further clinical evaluation.