Reentrant Ventricular Tachyarrhythmias Research Articles

Melatonin pretreatment does not modify extrasystolic burden in the rat ischemia-reperfusion model.

The mechanism of reentrant ventricular tachyarrhythmias complicating acute myocardial ischemia is largely based on the interaction between an arrhythmogenic substrate and triggers. Melatonin was proposed as an antiarrhythmic medication and was shown to ameliorate the arrhythmogenic substrate. Also, melatonin provides a sympatholytic effect in different settings and might attenuate ectopic activity, which provides reentry triggers. In the present study, we aimed at evaluating the melatonin effects on cardiac sympathetic activity and the incidence of premature ventricular beats during the episode of ischemia-reperfusion. Experiments were done in a total of 26 control and 28 melatonin-treated (10 mg/kg, daily, for 7 days) male rats. Sympathetic fibers density was assessed by glyoxylic acid-induced fluorescence. Continuous electrocardiograms recording was performed during ischemia-reperfusion episodes (5 min/5 min, respectively) induced by reversible coronary occlusion. Myocardial expression of tyrosine hydroxylase, a rate-limiting enzyme of catecholamine biosynthesis was assessed by Western blotting. No differences in the state of sympathetic innervation were observed in histochemical analysis. However, Western blotting analysis demonstrated that melatonin treatment suppressed tyrosine hydroxylase expression in the non-ischemic (p < 0.05 versus control) but not ischemic regions of myocardium. The melatonin-treated animals had longer RR-intervals in the baseline state than the control animals (264 ± 48 ms versus 237 ± 33 ms, p = 0.044, respectively), but this difference decayed during the period of ischemia due to the increase of heart rate in the treated group. The number of premature ventricular beats did not differ between the control and treated groups during the ischemic and reperfusion periods. One-week melatonin pretreatment caused a slight peripheral sympatholytic effect that attenuated during ischemia and completely disappeared by the onset of reperfusion. The slight expression of sympathetic downregulation was associated with the lack of any effect of melatonin on extrasystolic burden. Collectively, the data suggest that melatonin cannot target the triggers of reentrant arrhythmias.

The Classically Cardioprotective Agent Diazoxide Elicits Arrhythmias in Type 2 Diabetes Mellitus

BackgroundType 2 diabetes mellitus (T2DM) is associated with an enhanced propensity for ventricular tachyarrhythmias (VTs) under conditions of metabolic demand. Activation of mitochondrial adenosine triphosphate-sensitive potassium (KATP) channels by low-dose diazoxide (DZX) improves hypoglycemia-related complications, metabolic function, and triglyceride and free fatty acid levels and reverses weight gain in T2DM. ObjectivesIn this study, we hypothesized that DZX prevents ischemia-mediated arrhythmias in T2DM via its putative cardioprotective and antidiabetic property. MethodsZucker obese diabetic fatty (ZO) rats (n = 43) with T2DM were studied. Controls consisted of Zucker lean (ZL; n = 13) and normal Sprague-Dawley (SprD; n = 30) rats. High-resolution optical action potential mapping was performed before and during challenge with no-flow ischemia for 12 min. ResultsElectrophysiological properties were relatively stable in T2DM hearts at baseline. In contrast, ischemia uncovered major differences between groups, because action potential duration (APD) in T2DM failed to undergo progressive adaptation to ischemic challenge. DZX promoted the incidence of arrhythmias, because all DZX-treated T2DM hearts exhibited ischemia-induced VTs that persisted on reperfusion. In contrast, untreated T2DM and controls did not exhibit VT during ischemia. Unlike DZX, pinacidil promoted ischemia-mediated arrhythmias in both control and T2DM hearts. Rapid and spatially heterogeneous shortening of APD preceded the onset of arrhythmias in T2DM. DZX-mediated proarrhythmia in T2DM was not related to changes in the messenger ribonucleic acid expression of Kir6.1, Kir6.2, SUR1A, SUR1B, SUR2A, SUR2B, or ROMK (renal outer medullary potassium channel). ConclusionsIschemia uncovers a paradoxical resistance of T2DM hearts to APD adaptation. DZX reverses this property, resulting in rapid and heterogeneous APD shortening. This promotes reentrant VT during ischemia. DZX should be avoided in diabetic patients at risk of ischemic events.

Ventricular arrhythmias induced by long-term use of ephedrine in two competitive athletes

Ephedrine is a sympathomimetic substance used by sportsmen as a doping substance because of its stimulating and slimming effects. We report two cases of ventricular arrhythmias induced by abuse of ephedrine in two competitive athletes. Endomyocardial biopsies guided by electroanatomic mapping revealed contraction-band necrosis, a myocardial injury frequently observed in cases of catecholamine excess. Our cases suggest that long-term abuse of ephedrine may result in myocardial damage, and that these structural alterations may promote areas of slow conduction favoring re-entrant ventricular tachyarrhythmias and a long-lasting risk of ventricular arrhythmias.

Electrophysiologic characteristics and catheter ablation of ventricular tachyarrhythmias among patients with heart failure on ventricular assist device support

Ventricular tachyarrhythmias (VT) are common among ventricular assist device (VAD) recipients, yet electrophysiologic (EP) characteristics and catheter ablation outcomes remain uncharacterized. To evaluate the EP characteristics and catheter ablation outcomes for VTs among heart failure patients on VAD support. The Cleveland Clinic registry of consecutive patients undergoing VAD placement in 1991-2010 with medically refractory, symptomatic VT referred for EP study and catheter ablation. Among 611 recipients of VAD (mean age 53.3 ± 12.4 years, 80% men), 21 patients (3.4%) were referred for 32 EP procedures, including 11 patients (52%) presenting with implantable cardioverter-defibrillator therapy (13 shocks, 26 antitachycardia pacing). Data from 44 inducible tachycardias (mean cycle length 339 ± 59 ms) demonstrated monomorphic VT (n = 40, 91%; superior axis 52%, right bundle branch block morphology 41%) and polymorphic ventricular tachycardia (PMVT)/ventricular fibrillation (n = 4, 8%). Electroanatomic mapping of 28 tachycardias in 20 patients demonstrated reentrant VT related to intrinsic scar (n = 21 of 28, 75%) more commonly than the apical inflow cannulation site (n = 4 of 28, 14%), focal/microreentry VT (n = 2 of 28, 7%), or bundle branch reentry (n = 1 of 28, 3.5%). Catheter ablation succeeded in 18 of 21 patients (86%). VT recurred in 7 of 21 patients (33%) at a mean of 133 ± 98 days, and 6 patients (29%) required repeat procedures, with subsequent recurrence in 4 of 21 patients (19%). Catheter ablation of VT is effective among recipients of VAD. Intrinsic myocardial scar, rather than the apical device cannulation site, appears to be the dominant substrate.

Risk Stratification and Prevention of Sudden Death in Patients with Heart Failure

For almost the past decade, recommendations for the use of implantable cardioverter defibrillators (ICDs) for primary prevention of sudden cardiac death have been based upon the left ventricular ejection fraction (LVEF). Current guidelines recommend an ICD for heart failure patients with LVEF ≤35% and NYHA functional class of II or III; however, because the majority of heart failure patients who qualify for ICD implantation based on these criteria will never have an event requiring ICD therapy over several years of follow-up, additional methods of risk stratification for sudden death are clearly needed. Additionally, most of the nearly 300,000 cardiac arrests that occur each year occur in patients without heart failure or significant left ventricular dysfunction. To improve the identification of patients at risk for sudden death, several criteria other than ejection fraction have been proposed and studied. Markers of autonomic tone, including heart rate turbulence and QT dynamicity, have shown some ability to predict total mortality but not arrhythmic events. Microvolt T-wave alternans testing was initially thought to be highly predictive of life-threatening arrhythmias, but prospective large sub-studies of the MADIT II and SCD-HeFT trials have failed to show a predictive value for T-wave alternans testing. Newer markers for risk are based upon the detection of myocardial fibrosis, which forms the substrate for re-entrant and malignant ventricular tachyarrhythmias. Markers of collagen turnover or quantification of myocardial scar by MRI may hold the best promise for identifying patients at highest risk for sudden cardiac death and may also identify patients at high risk but with an ejection fraction above 35%, who are not currently recommended for ICD implantation.

Arrhythmogenic Right Ventricular Cardiomyopathy in an Octogenarian Presenting with Ventricular Tachycardia

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is one of the major causes of sudden death. Myocardial atrophy with subsequent fibro-fatty replacement predominantly affects right ventricular myocardium and results in global and regional dysfunction as well as areas of slow conduction and dispersion of refractoriness, which are prerequisites for reentrant ventricular tachyarrhythmias. ARVC is commonly presented in patients <65 years old. However, few cases of elderly people suffering from this cardiomyopathy have been reported in the literature. We present a case of an 82-year-old woman with sustained ventricular tachycardia due to first diagnosed ARVC.

Electrophysiological basis of arrhythmogenicity of QT/T alternans in the long-QT syndrome: tridimensional analysis of the kinetics of cardiac repolarization.

Tachycardia-dependent QT/T alternans occurs in patients with the congenital or idiopathic form of long-QT syndrome (LQTS) and may presage the onset of polymorphic ventricular tachyarrhythmias. To examine the electrophysiological basis of arrhythmogenicity of QT/T alternans in LQTS, the tridimensional repolarization pattern of QT/T alternans was studied in the anthopleurin-A model of LQTS, a surrogate for LQT3. In 11 anesthetized mongrel puppies, tridimensional repolarization and activation patterns were analyzed from 256 to 384 unipolar electrograms. Cardiac repolarization was evaluated as the activation-recovery interval (ARI) of local electrograms. To induce QT/T alternans, the pacing cycle length (CL) was abruptly shortened in steps of 50 ms from a basic drive of 1000 ms. ARIs were calculated at epicardial (Epi), midmyocardial (Mid), and endocardial (End) sites. ARI restitution at each site was assessed by using a single premature stimulation delivered after the basic drive. ARI alternans occurred at longer CLs at Mid sites compared with End and Epi sites, and the magnitude of alternans at Mid sites was greater. Two factors contributed to the modulation of ARI during QT/T alternans: (1) differences in restitution kinetics at Mid sites, characterized by larger DeltaARI and a slower time constant (tau), and (2) differences in diastolic intervals resulting in different input to restitution at the same constant CL. These 2 factors could explain not only the onset of alternans at Mid sites at longer CLs but also the critical observation that ARI dispersion between Epi and Mid sites during alternans was greater than during the slower basic CL. Marked ARI alternans could be present in local electrograms without manifest alternation of the QT/T segment in the surface ECG. The latter was seen at critically short CLs associated with reversal of the gradient of ARI between Epi and Mid sites, with a consequent reversal of polarity of the intramyocardial QT wave in alternate cycles. The arrhythmogenicity of QT/T alternans was primarily due to the greater degree of spatial dispersion of repolarization during alternans than during slower rates not associated with alternans. This could result in functional conduction block and reentrant ventricular tachyarrhythmias during the fixed drive associated with alternans.

Dispersion of QT interval in patients with and without susceptibility to ventricular tachyarrhythmias after previous myocardial infarction

The aim of this study was to estimate the value of QT dispersion measurement from the standard 12-lead electrocardiogram (ECG) in identifying patients susceptible to reentrant ventricular tachyarrhythmias after a previous myocardial infarction. Variability in QT interval duration on the different leads of the 12-lead ECG has been proposed as an indicator of risk for ventricular arrhythmias in different clinical settings, but the value of QT dispersion measurement in identifying patients at risk for reentrant ventricular tachyarrhythmias after myocardial infarction is not known. The QT interval duration, QT dispersion and clinical and angiographic variables were compared between 30 healthy subjects; 40 patients with a previous myocardial infarction but no history of arrhythmic events or inducible ventricular tachycardia during programmed electrical stimulation; and 30 postinfarction patients with a history of cardiac arrest (n = 12) or sustained ventricular tachycardia (n = 18) and inducible, sustained monomorphic ventricular tachycardia by electrical stimulation. Dispersion of the corrected QT interval (QTc) differed significantly between the study groups and was significantly increased in patients with susceptibility to ventricular tachyarrhythmias ([mean +/- SD] 104 +/- 41 ms) compared with that in both healthy subjects (38 +/- 14 ms, p < 0.001) and postinfarction patients with no susceptibility to arrhythmias (65 +/- 31 ms, p < 0.001). Maximal QT interval duration was also prolonged in the group with arrhythmias compared with that in the other groups (p < 0.001). Multivariate analysis, including clinical and angiographic variables, QT dispersion and maximal QT interval, showed that QT dispersion was the independent factor that most effectively identified the patient groups with and without susceptibility to ventricular tachyarrhythmias (p < 0.001). Increased QT dispersion is related to susceptibility to reentrant ventricular tachyarrhythmias, independent of degree of left ventricular dysfunction or clinical characteristics of the patient, suggesting that the simple, noninvasive measurement of this interval from a standard 12-lead ECG makes a significant contribution to identifying patients at risk for life-threatening arrhythmias after a previous myocardial infarction.

Signal-Averaged Electrocardiographic Detection of Terminal QRS Deflection Suggesting Late Potentials

A terminal QRS deflection on a 12-lead electrocardiogram (previously described as peri-infarction block) most likely represents slowed conduction in a large area of myocardium near the infarct zone. We have described a patient with peri-infarction block, abnormal findings on signal-averaged electrocardiogram, and reentrant ventricular tachyarrhythmias. Our observation underscores the need to recognize the importance of terminal QRS deflections in the appropriate clinical situation.

Lack of correlation between transient myocardial ischemia and late potentials on the signal-averaged electrocardiogram

The relation between transient myocardial ischemia and late potentials was investigated in 100 patients with coronary artery disease who underwent serial recordings of the signal-averaged electrocardiogram before, during and after dipyridamole infusion. During this test, 47 patients (group 1) developed transient myocardial ischemia (with ST elevation in 14 cases and ST depression in 33), whereas 53 patients (group 2) did not. Baseline signal-averaged electrocardiogram was abnormal in 20 patients (20%): a QRS duration >115 ms was seen in 6 patients, a late potential (root mean square voltage of last 40 ms of QRS [RMS40] <25 μV) in 9, both abnormalities in 5, with no significant differences between groups 1 and 2 (26 vs 15%, respectively). In both groups, comparison of recordings obtained before, during and after dipyridamole test revealed no significant changes in QRS duration and RMS40. Absence of significant differences was also observed when patients with transient ischemic ST elevation or ST depression were examined separately. During the test, 100% of abnormal basal recordings remained abnormal and 98% of normal recordings remained within normal limits. In only 2 patients (from group 1) RMS40, which showed borderline values at baseline, decreased to abnormal values during dipyridamole test. These data suggest that electrophysiologic abnormalities induced by transient myocardial ischemia may not bear any relation with the substrate for chronic reentrant ventricular tachyarrhythmias, as reflected by late potentials on the signal-averaged electrocardiogram.

The antiarrhythmic actions of intravenous and oral UM424 in postinfarction canine myocardium.

The electrophysiologic and antiarrhythmic effects of oral and intravenous UM424 were studied in canine models of acute and chronic myocardial injury. In the first phase of this study, reentrant ventricular tachyarrhythmias and/or ventricular fibrillation were initiated by programmed electrical stimulation techniques in seven dogs 48-120 h after myocardial infarction. The cycle length of these reentrant ventricular beats was 176 +/- 16 ms, and they were accompanied by fractionated asynchronous epicardial electrical activity in the injured region that bridged the diastolic interval, i.e., 143 +/- 37 ms. When this prolonged, diastolic electrical activity ceased, the ventricular tachyarrhythmias ceased. UM424 5 mg/kg i.v. increased the effective refractory period of the normal myocardium by 21 ms (p less than 0.05), depressed cardiac conduction in the injured, infarcted myocardium and suppressed these reentrant tachyarrhythmias. Ventricular fibrillation could not be initiated after UM424. In the second phase of this study, a canine model of coronary artery thrombosis was used to produce spontaneous ventricular arrhythmias. UM424 60 mg/kg p.o. converted these ventricular arrhythmias to normal sinus rhythm. This pharmacologic action was not associated with deleterious hemodynamic side effects and lasted for 3 h, the duration of each experiment. These results demonstrate that after oral or intravenous administration, UM424 possess antiarrhythmic and antifibrillatory actions in canine models of acute and chronic myocardial injury.

Actions of disopyramide on potential reentrant pathways and ventricular tachyarrhythmias in conscious dogs during the late post-myocardial infarction phase

The effect of intravenous disopyramide (plasma level 3.7 ± 1.6 μg/ml, mean ± standard deviation) on reentrant ventricular tachyarrhythmias was studied by programmed ventricular stimulation in 11 conscious dogs 3 to 8 days after experimental myocardial infarction. Sustained ventricular tachycardia (VT) was induced in 4 dogs (mean cycle length 173 ± 14 ms) and nonsustained VT in 7 (8 ± 4 beats, mean cycle length 136 ± 18 ms). Disopyramide prevented induction of VT in 1 of 4 dogs with sustained VT and 3 of 7 with nonsustained VT, and increased VT cycle length by more than 30 % in 2 dogs with sustained VT and 2 of 7 with nonsustained VT. Disopyramide prolonged refractoriness in the infarct zone, measured by analysis of electrograms from an implanted “composite” electrode, by 38 to 53%, depending on the mode of pacing. These values were significantly greater than the increase produced by disopyramide in ventricular effective refractory period (13 ± 12%), QRS duration and QT interval. Disopyramide has a selective effect on potential reentry circuits in ischemic myocardium, and prolongs refractoriness in abnormal myocardium to a greater extent than its effect on the normal ventricle.

Comparative study of the effect of slow channel inhibiting agents on ischemia-induced conduction delay as relevant to the genesis of ventricular fibrillation

Conduction delay has been shown to be an important factor in the genesis of ventricular fibrillation (VF). We evaluated the relationship between conduction delay and (1) initiation of VF and (2) the effects of Ca ++ blockers on conduction delay in 41 dogs: eight control (nontreated, non-VF); nine ischemic VF; eight verapamil-treated (0.15 mg/kg bolus followed by 7.5 μg/kg/min); eight diltiazem-treated (20 μg/kg/min); and eight nifedipine-treated (0.1 mg/kg bolus). Propagation of electrically-induced premature impulses from the midmyocardial bipole of one transmural electrode was recorded at epicardial and endocardial bipoles of other electrodes before and 5, 15, and 30 minutes after coronary ligation. Conduction delay (i.e., conduction times compared to preligation levels) of VF, verapamil, diltiazem, and nifedipine groups were compared to control group in normal and in the center and border of ischemic zones in both base to apex (anterograde) and apex to base (retrograde) directions. Results showed that there was no change in conduction delay in the normal zone between control and VF groups or the treated groups, but both in the center and border of ischemic zone VF was quantitatively related to conduction delay and Ca ++ blockers, except that nifedipine significantly reduced conduction delay. We conclude that our model provides a new approach to the assessment of anti-VF intervention. Further, verapamil and diltiazem appear to be useful agents in reducing the risk of ischemia-induced reentrant ventricular tachyarrhythmias.

When is myocardial mapping clinically valuable?

All cardiac arrhythmias are either automatic or reentrant. Automatic arrhythmias occur in the periinfarction or perioperative period. Chronic, recurrent arrhythmias are typically reentrant. By definition, reentrant arrhythmias are inducible with programmed electrical stimulation. When a malignant cardiac arrhythmia is identified, the patient is taken to the electrophysiologic laboratory for study. Reentrant ventricular tachyarrhythmias are induced with programmed electrical stimulation. Pharmacologic suppression is guided by electrophysiologic testing. When antiarrhythmic suppression fails, surgical intervention may be an effective alternative. Endocardial catheter mapping before surgery may serve as an important guide to the surgeon. Myocardial mapping is clinically valuable only when all antiarrhythmic therapy has failed, and the patient is considered to be a candidate for surgical intervention. When surgical intervention is planned, we consider preoperative catheter mapping desirable and intraoperative electrophysiologic localization mandatory.

Increased normoxic-to-ischemic tissue borderzone as the cause for reentrant ventricular tachyarrhythmias

Reentrant ventricular tachyarrhythmias (VT) are potential sequelae of ischemic myocardial damage. Ventricular tachyarrhythmias induced by programmed stimulation correlate well with spontaneously occurring clinical arrhythmias. The purpose of this study was to assess the potential of provoking VT in homogeneous and heterogeneous (mottled) models of canine myocardial infarction. Twenty-two mongrel dogs were evaluated with programmed stimulation open chest under barbiturate anesthesia. Dogs were divided into four groups: (A) Seven dogs were studied acutely (nonoperated controls); (B) five dogs were studied 7–14 days after the pericardium had been opened and a pursestring suture placed in the left atrium (sham-operated controls); (C) five dogs were studied 7–14 days after the mid-left anterior descending coronary artery (LAD) was infused with vinyl latex (homogeneous infarcts); and (D) five dogs were studied 7–14 days after the LAD was two-stage occluded and then reperfused after 2 hr (heterogeneous infarcts). Using unipolar cathodal ventricular pacing with two premature ventricular extrastimuli, initiation of a VT was attempted in each dog at 10 sites. Three (43%) of the acute dogs (Group A) and three (60%) of the sham-operated dogs (Group B) exhibited VT, but at only one site in each dog, 6 100 or 6.0% of the sites attempted in these 10 dogs. Similarly, in the dogs with homogeneous latex infarctions, VT was reproducibly induced from one site in each of four (80%) dogs, but at only 4 50 , or 8.0% of sites. In comparison, VT was initiated in all five dogs with chronic heterogeneous infarctions (Group D) at 46 50 or 92% ( P < 0.001) of the sites stimulated. These results confirm that heterogeneous ischemic injury predisposes to reentrant VT.

Electrophysiologic and anatomic correlates of sustained ventricular tachyarrhythmias in a model of chronic myocardial infarction

Ten healthy adult mongrel dogs were subjected to two stage occlusions of the mid or distal left anterior descending coronary artery modified by a reperfusion stage. In 9 of 10 animals studied at 3 or more days after coronary occlusion, sustained reentrant ventricular tachyarrhythmias could be reproducibly initiated or terminated, or both, using routine methods of programmed electric stimulation. Plunge electrodes were inserted at multiple subepicardial, intramyocardial and subendocardial sites from areas of normal and infarcted myocardium to evaluate electrophysiologic properties of excitability and refractoriness. With use of constant current unipolar cathodal stimulation, strength-interval curves were measured at these sites and correlated with regional histopathologic findings. In this model, infarcts were mottled, with close interspersing of normal and abnormal myocardium. Although excitability thresholds and refractoriness tended to increase within areas of infarction, marked disparities in excitability thresholds, effective and relative refractory periods and duration of relative refractory periods (relative minus effective refractory period) were observed within areas of infarction at sites only 1 to 2 mm apart anatomically. This milieu of anatomic and electrophysiologic heterogeneity is apparently sufficient to predispose to the initiation of sustained reentrant ventricular tachyarrhythmias.