Initiation Of Tachycardia Research Articles

Dynamic sympathetic control of atrioventricular conduction time and heart period.

Although power spectra of R-R and P-R intervals in response to random respiration show similar frequency distributions, the way in which dynamic sympathetic regulation contributes to such similarity remains unknown. We estimated the transfer function from sympathetic stimulation to the atrioventricular interval (AV conduction time; T(AV)) with and without constant atrial pacing in seven anesthetized cats. The transfer function from sympathetic stimulation to T(AV), except for absolute gain values, approximated a low-pass filter similar to that from sympathetic stimulation to the A-A interval (heart period; T(AA)). The 90%-rise times did not differ between the T(AA) and T(AV) step responses (32.3 +/- 1.8 vs. 29.6 +/- 3.2 s). Constant pacing augmented the T(AV) step response (-0.58 +/- 0.10 vs. -0.86 +/- 0.12 ms/Hz, P < 0.05) without affecting the 90%-rise time. These findings suggest that the dynamic characteristics of sympathetic control are similar between T(AA) and T(AV) despite the different electrophysiological mechanisms determining T(AA) and T(AV). A numerical simulation indicated that if the dynamic characteristics of the sympathetic control do not match between T(AA) and T(AV), a critical condition for initiation of reentrant tachycardia would be encountered.

Electrophysiological characteristics and radiofrequency ablation of focal atrial tachycardia originating from the superior vena cava.

The initiation of focal atrial tachycardia (AT) from the superior vena cava (SVC) remains unclear. In 3 patients (2 females, 1 male; aged 57, 66 and 50 years, respectively) with focal AT arising from different parts of the SVC, the AT occurred spontaneously, rather than being induced by electrical stimulation. The cycle length of the tachycardia was highly variable, ranging between 190 and 300 ms in patient 1, 180 and 320ms in patient 2, and 200 and 300ms in patient 3. The clinical or associated arrhythmias were atrial fibrillation (AF) (patients 1, 3) and atrial flutter (AFL) (patients 2, 3). A presumed SVC potential that was earlier than the activation of all the other mapping sites was recorded during AT at the lower anterior (15-mm above the atriocaval junction), the mid-anterior (25-mm above the atriocaval junction) and the lower posterior aspect of the SVC (17-mm above the atriocaval junction. Radiofrequency (RF) ablation targeting the SVC focus with the SVC potential promptly eliminated the focal AT in all 3 patients. The coexistent typical AFL was ablated, but the AF was not. The follow-up period was 6, 6, and 3 months, respectively, for each of the patients under no antiarrhythmic medication; there has not been a recurrence of symptomatic palpitation. In conclusion, focal electrical firing in the SVC can initiate AT and this type of focal AT is always associated with AFL or AF. RF ablation guided by the presumed SVC potential is safe and highly effective in eliminating the tachycardia.

Role of structural barriers in the mechanism of alternans-induced reentry.

Previously, using an animal model of T-wave alternans in structurally normal myocardium, we demonstrated that repolarization can alternate with opposite phase between neighboring myocytes (ie, discordant alternans), causing spatial dispersions of repolarization that form the substrate for functional block and reentrant ventricular fibrillation (VF). However, the mechanisms responsible for cellular discordant alternans and its electrocardiographic manifestation (ie, T-wave alternans) in patients with structural heart disease are unknown. We hypothesize that electrotonic uncoupling between neighboring regions of cells by a structural barrier (SB) is a mechanism for discordant alternans. Using voltage-sensitive dyes, ventricular action potentials were recorded from 26 Langendorff-perfused guinea pig hearts in the absence (ie, control) and presence of an insulating SB produced by an epicardial laser lesion. Quantitative analysis of magnitude and phase of cellular alternans revealed that in controls, action potential duration alternated in phase at all ventricular sites above a critical heart rate (269+/-17 bpm), ie, concordant alternans. Also, above a faster critical heart rate threshold (335+/-24 bpm), action potential duration alternated with opposite phase between sites, ie, discordant alternans. In contrast, only discordant but not concordant alternans was observed in 80% of hearts with the SB, and discordant alternans always occurred at a significantly slower heart rate (by 68+/-28 bpm) compared with controls. Therefore, the SB had a major effect on the alternans-heart rate relation, which served to facilitate the development of discordant alternans. Whether a SB was present or not, discordant alternans produced considerable increases (by approximately 170%) in the maximum spatial gradient of repolarization, which in turn formed the substrate for unidirectional block and reentry. However, by providing a structural anchor for stable reentry, discordant alternans in the presence of a SB led most often to sustained monomorphic ventricular tachycardia rather than to VF, whereas in the absence of a SB discordant alternans caused VF. SBs facilitate development of discordant alternans between cells with different ionic properties by electrotonically uncoupling neighboring regions of myocardium. This may explain why arrhythmia-prone patients with structural heart disease exhibit T-wave alternans at lower heart rates. These data also suggest a singular mechanism by which T-wave alternans forms a substrate for initiation of both VF and sustained monomorphic ventricular tachycardia.

New mechanism of antiarrhythmic drug action: increasing L-type calcium current prevents reentrant ventricular tachycardia in the infarcted canine heart.

We studied whether increasing L-type calcium current has antiarrhythmic effects. Reentrant circuits in the epicardial border zone (EBZ) of healing canine infarcts were mapped during sustained ventricular tachycardia. The cardiac-specific L-type calcium current enhancer Bay Y5959 prevented initiation of sustained ventricular tachycardia in 7 of 14 experiments. Bay Y5959 caused slowing of conduction in areas of slow nonuniform conduction in reentrant circuits; block eventually occurred. Conduction was not affected in other regions of the circuits or in more normal areas of the EBZ, nor was the EBZ effective refractory period changed. Bay Y5959 also improved conduction of premature impulses so that lines of unidirectional block necessary for VT initiation were not formed, an effect not related to a change in the effective refractory period at the site of block. Block of conduction caused by enhanced L-type calcium current in reentrant circuits may result from a decreased gap junctional conductance consequent to an increase in intracellular calcium. An increase in L-type calcium current may improve conduction of premature impulses.

Analysis of intracardiac electrograms showing monomorphic ventricular tachycardia in patients with implantable cardioverter-defibrillators

Ventricular tachycardia (VT) initiation and its relation to various clinical factors was studied by reviewing intracardiac electrograms from patients with implantable cardioverter-defibrillators. Events were divided into (1) sudden onset without preceding ventricular premature complexes (VPCs), (2) extrasystolic onset with VPCs, or (3) paced, depending on the type and morphology of the last 5 beats before initiation of VT. Prematurity index, sinus rate, cycle length, and presence of short-long-short sequence for each episode was noted. A total of 268 episodes of VT among 52 patients were analyzed. Extrasystolic initiation was the most frequent pattern (177; 66%) followed by sudden onset (75; 28%) and paced (16; 6%). Among extrasystolic onset, 99 episodes (56%) were due to multiple VPCs and 149 episodes (84%) had different VPC morphology than the subsequent VT. Among pacing-induced VT, 13 of 16 episodes were due to inappropriate pacing due to undersensing of prior R waves. Sudden-onset episodes were slower (mean cycle length 383 ± 97 ms) than extrasystolic (mean cycle length 336 ± 88 ms, p = 0.002) and paced (mean cycle length 313 ± 85 ms, p = 0.01) onset. Patients in the sudden-onset group had better left ventricular ejection fraction (33 ± 15%) than the extrasystolic (29 ± 11%, p <0.001) and paced (28 ± 14%, p <0.01) groups. Extrasystolic onset with multiple, late coupled VPCs was the most common pattern of VT initiation and was associated with lower ejection fraction. Sudden-onset initiation was more common with better preserved systolic function.

John B. Barlow: master clinician and compleat cardiologist.

This paper reports the case of a 76-year-old man in whom atrial flutter with varying atrioventricular block and intermittent right bundle-branch block was found. This is the first report on tachycardia-dependent right bundle-branch block associated with supernormal conduction in a case of atrial flutter. When an impulse is conducted to the ventricles beyond 0.72 s after a QRS complex of right bundle-branch block configuration, the impulse falls after the abnormally long effective refractory period of the right bundle branch and passes through the right bundle branch. When the conducted impulse occurs within 0.72 s after a QRS complex of right bundle-branch block configuration, the impulse usually falls in the refractory period and is blocked in the right bundle branch; however, only when the impulse occurs 0.48 or 0.49 s after that does it fall in the supernormal period and passes through the right bundle branch. The findings in the present report strengthen our previous suggestion that the presence of supernormal conduction plays an important role in the initiation of reentrant ventricular tachycardia.

Radiofrequency application to the posteroseptal region alters retrograde accessory pathway activation.

Radiofrequency applications to the posteroseptal region can ablate the atrioventricular accessory pathway residing in this area. In conjunction with the adjacent anatomic structures, however, ablative lesions which do not effectively ablate the accessory pathway could markedly alter retrograde atrial activation sequence and confound interpretation of further mapping of an accessory pathway. Electrophysiologic studies, endocardial activation mapping and radiofrequency catheter ablation were undertaken in three patients with recurrent supraventricular tachycardia. Patients were initially thought to have a single posteroseptal accessory pathway; earliest ventrioatrial activation during tachycardias and during ventricular pacing was at the coronary sinus ostium, but initial radiofrequency applications were unsuccessful to ablate the pathway. After initial radiofrequency applications to the posteroseptal region, the earliest retrograde atrial activation changed to the right atrial free wall in two patients. Additional radiofrequency application to the posteroseptal area was able to ablate the single posteroseptal accessory pathway in one patient. Radiofrequency application to the right atrial free wall was required to stop tachycardia initiation in other patient. The third patient was suspected of having a slow-slow atrioventricular nodal reentry tachycardia. Radiofrequency application to the posteroseptal area changed the earliest retrograde atrial activation to the distal coronary sinus recording site, mimicking an accessory pathway at the left atrial free wall. Radiofrequency application to the anteroseptum was able to ablate the concealed accessory pathway. Radiofrequency applications to the posteroseptal region can markedly alter retrograde atrial activation, thereby confounding further mapping of the accessory pathway.

Upregulation of Na(+)/Ca(2+) exchanger expression and function in an arrhythmogenic rabbit model of heart failure.

Three-dimensional cardiac mapping in rabbits with nonischemic cardiomyopathy has shown that ventricular arrhythmias initiate by a nonreentrant mechanism that may be due to triggered activity from delayed afterdepolarizations. Delayed afterdepolarizations are thought to be due to spontaneous release of Ca(2+) from the sarcoplasmic reticulum (SR) and consequent activation of an inward Na(+)/Ca(2+) exchange (NaCaX) current. The goal of this study was to determine whether there is enhanced NaCaX gene expression and functional activity that may contribute to nonreentrant activation. Heart failure (HF) was induced in rabbits by combined aortic insufficiency and aortic constriction. HF rabbits had left ventricular enlargement (left ventricular end-diastolic dimension increased from 1.43+/-0.03 to 1.97+/-0.05 cm) and severely depressed function (fractional shortening reduced from 37% to 26%, P<0.02). Heart-to-body weight was increased by 79% in HF. Western blots showed a 93% increase in NaCaX protein in HF (P<0.04). NaCaX mRNA (7-kb transcript) was increased by 104% relative to the 18S rRNA in HF. A 14-kb NaCaX transcript was also seen in the HF rabbits, raising total NaCaX mRNA to 2.7-fold compared with controls. The amplitude of caffeine-induced contractures, used to assess SR Ca(2+) load, was not significantly different in HF. Relaxation and [Ca(2+)](i) decline during caffeine-induced contractures is attributable to Ca(2+) transport by NaCaX and was 61% and 45% faster in HF (P<0.05), respectively. NaCaX current measured under controlled voltage clamp conditions was also 2-fold higher in HF cells. SR Ca(2+)-ATPase mRNA and protein levels and Ca(2+) current density were not significantly altered in HF. Twitch amplitudes from HF myocytes were 26% smaller compared with control (P<0.02), but twitch relaxation and [Ca(2+)](i) decline (due largely to SR Ca(2+)-ATPase) were not altered. Thus myocytes and myocardium from HF rabbits exhibit enhanced NaCaX expression and function. The enhanced NaCaX activity may contribute to depressed contractions, increased transient inward current (for a given SR Ca(2+) release), delayed afterdepolarizations, and nonreentrant initiation of ventricular tachycardia in this arrhythmogenic model of HF.

Discontinuous propagation of the cardiac impulse and arrhythmogenesis.

SummaryThe complex discontinuous architecture of cardiac tissue induces a number of interactions between the cellular properties of the myocardium that affect impulse propagation:1. Slow (&lt; 10 cm/sec) conduction velocities in the myocardium can only be achieved by discontinuous conduction. In the more continuous type of conduction, as occurring during inhibition of INa, conduction block occurs at velocities of approximately 20 cm/sec.2. If the discontinuity reaches a critical degree, Ica, L is needed to propagate the cardiac impulse. This situation may occur during cell‐to‐cell uncoupling and at sites of local tissue discontinuities.3. The conduction phenomena occurring at tissue discontinuities, such as pivoting points, isthmus, and abrupt tissue expansions are markedly influenced by the underlying properties of the cellular network. Electrical uncoupling at the cellular level can reduce the effect of the discontinuities to produce conduction block and reverse unidirectional block to bidirectional conduction. By contrast, reduction of INa increases the probability of unidirectional block at such sites. Since activation of INa may become rate‐dependent at high rates and in depolarized tissue, this predicts an instability in activation patterns during a tachycardia.Do the above considerations really predict arrhythmogensis? It is obvious that increasing the degree of structural discontinuity creates a substrate for reentrant arrhythmias. However, with the exception of the demonstration of spiral wave initation in vitro,5 no direct effects of tissue discontinuities on arrhythmia initiation have been demonstrated so far. Furthermore, pathologies associated with an increased degree of structural discontinuities, such as a hypertrophy and failure, also show an increased propensity to triggered arrhythmias, and initiation of ventricular tachcardias from small foci has been observed in whole hearts. These complexities make it difficult to extrapolate findings of experimental and theoretical work at the cellular level directly to whole hearts and human pathologies where several mechanisms for initiation and maintenance of tachycardias may coexist.

Chaos and the Transition to Ventricular Fibrillation

Sudden cardiac death resulting from ventricular fibrillation can be separated into 2 components: initiation of tachycardia and degeneration of tachycardia to fibrillation. Clinical drug studies such as CAST and SWORD demonstrated that focusing exclusively on the first component is inadequate as a therapeutic modality. The hope for developing effective pharmacological therapy rests on a comprehensive understanding of the second component, the transition from tachycardia to fibrillation. We summarize evidence that the transition from tachycardia to fibrillation is a transition to spatiotemporal chaos, with similarities to the quasiperiodic transition to chaos seen in fluid turbulence. In this scenario, chaos results from the interaction of multiple causally independent oscillatory motions. Simulations in 2-dimensional cardiac tissue suggest that the destabilizing oscillatory motions during spiral-wave reentry arise from restitution properties of action potential duration and conduction velocity. The process of spiral-wave breakup in simulated cardiac tissue predicts remarkably well the sequence by which tachycardia degenerates to fibrillation in real cardiac tissue. Modifying action potential duration and conduction velocity restitution characteristics can prevent spiral-wave breakup in simulated cardiac tissue, suggesting that drugs with similar effects in real cardiac tissue may have antifibrillatory efficacy (the Restitution Hypothesis). If valid for the real heart, the Restitution Hypothesis will support a new paradigm for antiarrhythmic drug classification, incorporating an antifibrillatory profile based on effects on cardiac restitution and the traditional antitachycardia profile (classes 1 through 4).

Factors affecting epicardial dispersion of repolarization: a mapping study in the isolated porcine heart.

Non-uniform drug-induced prolongation of repolarization predominating in the midmyocardial (M) cell layers has been shown to be responsible for perpetuation of reentry, giving rise to torsade de pointes. However, the absence of M cells in immature animals, especially the pig, suggests other possible underlying mechanisms. We sought to examine, in this species, the effects of predisposing factors to torsade de pointes on the dispersion of epicardial repolarization and their contribution to arrhythmogenesis. Computerized mapping of repolarization and activation was conducted on the epicardial surface in 29 Langendorff-perfused hearts of eight-week-old pigs. Activation-recovery intervals were measured simultaneously from 128 unipolar electrograms. Baseline iso-interval maps were dipolar (41%) or multipolar (59%). Dispersion of repolarization was reverse frequency-dependent but was unaffected by lowering [K+]o. DL-Sotalol (0.1 mmol/l) reinforced local gradients and thus increased epicardial dispersion, whereas intramural recordings did not demonstrate any predominant effect in midmyocardial layers. Phenylephrine (1 mumol/l) notably augmented DL-sotalol effects. After [Mg++]o lowering, although dispersion was not significantly increased, DL-sotalol was associated with the spontaneous occurrence of polymorphic ventricular tachycardia in seven out of nine experiments. When maps of repolarization of escape beats were compared with activation maps of first arrhythmic beats, an arc of functional dissociation was observed in the vicinity of a steep gradient of repolarization in two out of nine tachycardias. Epicardial dispersion of repolarization is increased by slow rates, DL-sotalol and phenylephrine but is not the only requirement for initiation of polymorphic ventricular tachycardia. In combination with other factors, it helps continuation of the arrhythmia in this model.

Dispersion-based reentry: mechanism of initiation of ventricular tachycardia in isolated rabbit hearts.

The aim of the study was to determine whether facilitation of reentry by potassium-channel openers is related to dispersion of refractoriness and/or modification of anisotropic properties of ventricular myocardium. The dispersion of ventricular effective refractory period (VERP), longitudinal and transverse ventricular conduction velocities (thetaL and thetaT, respectively), and wavelength [lambda = VERP x theta(L or T)] were studied in Langendorff-perfused left ventricular epicardium in 20 rabbits during infusion of incremental doses of levcromakalim or nicorandil. Dispersion of refractoriness was assessed using standard deviation of VERP mean (SD-VERP), dispersion index (DI; SD-VERP/mean VERP), and maximum dispersion (Dmax = VERPmax - VERPmin). Ventricular conduction velocities and anisotropic ratio were not modified, whatever the dose used. VERP and lambda were significantly shortened at high concentrations of levcromakalim and nicorandil. At these doses, SD-VERP, DI, and Dmax were increased significantly. Analysis of ventricular tachycardia induction, performed using a high-resolution ventricular mapping system, confirmed that heterogeneity and shortening of VERP were factors inducing functional conduction block. Our data suggest that, in rabbit left ventricular epicardium, functional conduction block facilitating the occurrence of reentry could be initiated by shortening and, especially, by dispersion of refractoriness during infusion of potassium-channel openers.

Modulation of the hyperpolarization-activated inward current (If) by antiarrhythmic agents in isolated human atrial myocytes.

The hyperpolarization-activated inward current (If) has been discussed to contribute to arrhythmias in human atrial myocardium. If was found to be increased by beta-adrenergic stimulation. In the present study, we evaluate the modulation of If by carbachol, adenosine and by class Ic, III and IV antiarrhythmic drugs in isolated human atrial myocytes. The whole-cell patch-clamp technique was used to record If in isolated myocytes from 18 human right atrial appendages. A typical time- and voltage-dependent hyperpolarization-activated inward current could be recorded in all cells investigated (n=56). Mean current density recorded at -130 mV was -2.8+/-1.2 pApF(-1). Both adenosine and carbachol were found to directly inhibit If in human atrial myocytes by shifting the activation curves to more negative potentials. Adenosine 10(-5) mol/l shifted the potential of half-maximal activation by -5.9+/-0.4 mV from -99.4+/-0.6 mV to -105.3+/-0.4 mV (n=8; P<0.05), and carbachol 10(-5) mol/l by -5.7+/-0.5 mV from -99.2+/-0.5 mV to -104.9+/-0.6 mV (n=6; P<0.05). The concentration-response curve of adenosine calculated by a Hill function yielded a half-maximal effect of adenosine (EC50) at a concentration of 3.6+/-0.5 micromol/l, a maximal shift of -6.5+/-0.3 mV, and a Hill coefficient (h) of 2.40. We did not observe any effect of flecainide (10(-5) mol/l; n=8), sotalol (10(-5) mol/l; n=6), amiodarone (10(-5) mol/l; n=6) or verapamil (10(-5) mol/l; n=5) on If in human atrial myocytes. However, propafenone (10(-5) mol/l) was found to reversibly reduce If current size (9/13 cells) by shifting the activation curve by -5.2+/-0.4 mV (P<0.05). In human atria adenosine- and muscarinic receptor stimulation might function as endogenous protective mechanisms inhibiting the initiation of ectopic tachycardia by reducing If current size. Propafenone may be more effective in some patients with atrial tachycardias that do not respond to other class Ic, III and IV antiarrhythmic drugs. However, it has yet to be defined whether these agents suppress atrial tachycardias via an inhibition of If in vivo.

Autonomic nervous system activity and the spontaneous initiation of ventricular tachycardia. ESVEM Investigators. Electrophysiologic Study Versus Electrocardiographic Monitoring Trial.

We hypothesized that neurohormonal activity contributes to the initiation of sustained ventricular tachycardia (VT) as reflected in indices of heart rate variability (HRV). Autonomic nervous system activity participates in experimental arrhythmias but clinical studies have been inconsistent. Holter electrocardiograms from 53 patients with VT were analyzed. Heart rate variability indices were determined over 5 and 15 min and 24 h and examined for changes before the onset of VT. Heart rate variability indices in the frequency domain included ultra low frequency power (FP) (ULFP): 0-0.0033 Hz; very low FP (VLFP): 0.0033-0.04 Hz; low FP (LFP): 0.04-0.15 Hz; high FP (HFP): 0.15-0.4 Hz; total power (TP); normalized LFP (LFPn); normalized HFP (HFPn), and the ratio: LFP/HFP. Heart rate variability indices were severely diminished: TP: 12,009+/-11,076 ms2; ULFP: 10,087+/-9,565 ms2; VLFP: 1,416+/-1,571 ms2; LFP: 544+/-620 ms2; HFP: 161+/-176 ms2, and LFP/HFP: 3.68+/-2.83. Heart rate increased before VT (80.4+/-17.3 to 85.3+/-17.4 bpm, p < 0.001). Several HRV variables declined 30 min before VT compared to 24-h values (VLFP: -5.89+/-17.81%, p = 0.031; LFP: -5.23+/-14.3%, p = 0.003; HFP: -4.35+/-13.7%, p = 0.04). LFPn and the LFP/HFP ratio decreased significantly before the onset of VT (-17.7+/-46.9%, p = 0.035 and -8.24+/-38.8%, p = 0.037, respectively), whereas HFPn increased slightly (4.29+/-29.9%, p = 0.097). Heart rate rose, whereas LFP, LFPn and LFP/HFP fell before the onset of VT. This pattern of changes could be explained by a rise in sympathetic activity and saturation of the HRV signal resulting in dissociation of the average and rhythmical effects of sympathetic activity. These findings suggest that alterations in autonomic activity contributed to arrhythmogenesis in this group of patients.

Angiotensin-converting enzyme inhibition produces electrophysiologic but not antiarrhythmic effects in the intact heart.

Although angiotensin-converting enzyme (ACE) inhibitors are known to influence favorably the structural remodeling of the heart after myocardial infarction, the mechanisms by which ACE inhibitors improve survival are not well understood. The hypothesis that ACE inhibitors may possess antiarrhythmic activity has been studied in various isolated tissue preparations. However, the electrophysiologic effects of ACE inhibitors in the intact heart are not well understood. The effect of the ACE inhibitor enalaprilat on intact heart electrophysiology was studied by using multisite optical action-potential recordings with voltage-sensitive dyes. Action potentials were recorded simultaneously from 128 left ventricular epicardial sites in 15 Langendorff perfused hearts subjected to an endocardial cryoablation procedure, which was used to restrict propagation to a thin viable rim of epicardium. Action-potential duration (APD) was significantly prolonged in 67% of preparations perfused with 5 mg/L enalaprilat. Higher concentration of enalaprilat (50 mg/L) prolonged APD in all preparations tested. This APD-prolonging effect persisted over a broad range of stimulus rates, indicating the absence of reverse use-dependent properties. Enalaprilat did not modify conduction velocity, nor did it affect spatial dispersion of repolarization times. In addition, enalaprilat had no effect on ventricular fibrillation threshold and failed to suppress the initiation of ventricular tachycardia using an anatomically defined reentrant circuit. These findings indicate that in the intact heart, enalaprilat does indeed have electrophysiologic effects that cause APD prolongation, particularly at high drug concentrations. However, this effect was not of sufficient magnitude in the guinea pig to suppress the initiation of ventricular fibrillation or reentrant ventricular tachycardia.

Induction of Atrioventricular Node Reentrant Tachycardia With Adenosine: Differential Effect of Adenosine on Fast and Slow Atrioventricular Node Pathways

Objectives. This study sought to evaluate the sensitivity of fast and slow atrioventricular (AV) node pathways to incremental doses of adenosine in patients with typical AV node reentrant tachycardia.Background. Although adenosine is known to depress conduction through the AV node, the relative sensitivity to adenosine of the anterograde fast and slow pathways in patients with dual AV node pathways and typical AV node reentrant tachycardia has not previously been studied.Methods. Sixteen patients with dual AV node physiology and typical AV node reentrant tachycardia and 10 control patients were given incremental doses of adenosine during atrial pacing.Results. In 14 of 16 patients with dual-AV node physiology, administration of small doses of adenosine during atrial pacing led consistently to transient block of impulse conduction in the fast pathway before block in the slow pathway, resulting in abrupt prolongation of the AH interval with continued 1:1 AV conduction. The mean (±SD) doses of adenosine required to cause conduction block in the fast and slow pathways were 2.7 ± 3.0 and 7.2 ± 4.7 mg, respectively (p = 0.004). In 9 of 16 patients, administration of low dose adenosine led to initiation of AV node reentrant tachycardia. The control patients showed no abrupt increases in AH interval with administration of adenosine during atrial pacing.Conclusions. In most patients with dual AV node pathways and typical AV node reentrant tachycardia, the fast pathway is more sensitive than the slow pathway to the effects of adenosine.

Mechanisms for absence of inverse relationship between coupling intervals of premature impulses initiating reentrant ventricular tachycardia and intervals between premature and first tachycardia impulses.

During initiation of tachycardias by programmed stimulation (PES), an inverse relationship between the coupling interval of the premature impulse (V1V2) and the interval between the premature impulse and the first impulse of tachycardia (V2T1) has been proposed to be a specific indicator of reentry. However, an inverse relationship has not always been observed during initiation of clinical reentrant ventricular tachycardias (VTs). Reentrant VT was initiated by PES in twelve 4-day-old infarcted dog hearts. The relationship between V1V2 and V2T1 was always direct. Mapping of the epicardial border zone (EBZ) indicated that initiation of VT was secondary to functional orthodromic block of V2, propagation of V2 around the line of block, and antidromic propagation through the original location of the block. In 7 dogs, the line of orthodromic block and the pathway of orthodromic propagation were similar for different V1V2 coupling intervals. Orthodromic conduction time around the line to its distal side was longer at shorter V1V2 intervals, but a shorter antidromic delay in the area of unidirectional block for shorter V1V2 intervals, possibly reflecting small changes in the conduction pathway involving deeper layers of the EBZ, resulted in shorter V2T1 intervals. In the other 5 dogs, the orthodromic conduction pathway of V2 around the line of block changed markedly, with a shorter pathway for shorter V1V2 intervals resulting in shorter V2T1 intervals. An inverse relationship between V1V2 and V2T1 is not a specific indicator of functional reentry.

ELECTROPHYSIOLOGIC EVALUATION OF SUPRAVENTRICULAR TACHYCARDIA

The evolution of intracardiac recording and programmed stimulation has allowed a better definition of the mechanisms and types of a variety of supraventricular tachyarrhythmias . This article describes the evaluation of supraventricular tachycardias resulting from atrioventricular (AV) nodal reentry, circus movement tachycardia using a concealed accessory pathway , and atrial tachycardia. The appropriate interpretation of intracardiac recordings and programmed stimulation to assess the mechanism of arrhythmia is based on understanding of the characteristic responses of known mechanisms of arrhythmias to programmed stimulation as well as response to drugs. 8 , 19 The mechanisms of all paroxysmal tachycardias are due to either abnormalities of impulse formation or abnormalities of conduction leading to reentry. Enhanced impulse formation may be due to abnormal automaticity or triggered activity as a result of either delayed afterdepolarizations or early afterdepolarizations. In the atrium and in particular for supraventricular arrhythmias , early afterdepolarizations probably do not play a role. The characteristics of automatic rhythms are that they can neither be initiated nor terminated in a reproducible way by programmed stimulation. Although annihilation of an automatic focus may be possible in experimental models, it is not predictable and has not yet been described in humans. The most common response of automatic rhythms to overdrive pacing is overdrive suppression or, in mildly depolarized tissue, no effect or, rarely, acceleration. Triggered rhythms caused by delayed afterdepolarizations are characterized by their ability to be initiated by programmed stimulation; however, such tachycardias are more readily induced by overdrive pacing rather than timed extrastimuli and do not require conduction delay or block for initiation. A direct relationship between the coupling interval or paced cycle length initiating rhythm and the interval to the onset of the rhythm and early cycle lengths of the rhythm as well as overdrive acceleration in response to rapid pacing are typical of arrhythmias related to delayed afterdepolarizations. Reentrant arrhythmias are most well understood and constitute the vast majority of clinical arrhythmias. The requirements for reentry include the presence of at least functional or anatomically distinct potential pathways that are linked proximally and distally to form a closed circuit of conduction, unidirectional block in one of these pathways, and slow conduction over the unblocked pathway allowing the previous blocked pathway time to recover. Reentrant arrhythmias can be reproducibly initiated and terminated by timed extrastimuli (usually in association with conduction delay or block) or rapid pacing. Frequently the conduction delay can be seen as an inverse relationship between the coupling interval of the initiating extrastimulus and the interval to the onset of the first complex of the tachycardia. In addition, during reentrant arrhythmias, continuous resetting of the tachycardia with fusion (i.e., entrainment) is diagnostic of reentry because fusion represents the presence of wavefronts, orthodromic and antidromic , occurring at the same time. This cannot happen in a focal tachycardia. Thus, the electrophysiologic evaluation of supraventricular tachycardia should include analysis of (1) mode of initiation of tachycardia, (2) atrial activation sequence during the tachycardia, (3) effect of atrial or ventricular stimulation during the tachycardia, (4) requirement of the atrium or ventricles to initiate and sustain the tachycardia, (5) influence of bundle-branch block on conduction and cycle length of the tachycardia, and (6) effect of drugs or physiologic perturbation of the autonomic nervous system on the tachycardia. 8 , 19

Role of sympathovagal balance in the initiation of idiopathic ventricular tachycardia originating from right ventricular outflow tract.

VT originating from the right ventricular outflow tract (RVOT) is prone to occur when sympathetic nervous activity is increased. beta-Blockade is, therefore, effective in suppressing this VT. The purpose of this study was to determine the role of sympathovagal balance assessed by heart rate variability (HRV) in the spontaneous initiation of repetitive premature ventricular contractions (PVCs) and VT (five or more consecutive PVCs) arising from RVOT in seven patients without structural heart diseases. Frequency-domain measures of HRV were determined by analyzing 24-hour Holter electrocardiographic recording with the maximum entropy method over a 1,280-second period immediately before the onset of 35 single PVCs, 26 episodes of 2-4 consecutive PVCs, and 21 episodes of VT. High frequency component (HF: 0.15-0.40 Hz) was used as an index of parasympathetic activity, and the ratio of low frequency component (LF: 0.04-0.15 Hz) to HF (LF/HF ratio), as an index of sympathovagal balance. NN50(%), a time-domain variable of parasympathetic activity, was also determined. Mean RR interval and any measures of HRV did not change significantly before single PVCs. Mean RR interval shortened and HF decreased prior to repetitive PVCs and VT. The LF/HF ratio, however, increased only before the onset of VT. NN50(%) tended to decrease before repetitive PVCs and decreased significantly before VT. With propranolol (30-60 mg/day), frequency of repetitive PVCs was suppressed from 2,048 +/- 1,201 to 746 +/- 658/day and VT was totally abolished, but frequency of single PVCs did not change significantly. In conclusion, sympathetic predominance plays an important role in the initiation of repetitive PVCs and VT originating from RVOT in patients without structural heart diseases.

Programmed stimulation of the ventricles--back to the future.

In the inaugural issue of this journal appeared two articles describing programmed electrical stimulation of the ventricles. Fisher et al. evaluated a new method for induction of ventricular tachycardia, in “Ultrarapid Train Stimulation versus Conventional Programmed Electrical Stimulation for Induction of Ventricular Arrhythmias in Patients with Coronary Artery Disease”[1]. Wyse et al. describe the effects of a conventional programmed stimulation protocol on QT dispersion, in “Divergence of Endocardial QT Interval Components during Programmed Electrical Stimulation Including Observations during Induction of Sustained Ventricular Tachyarrhythmias”[2]. The publication of these articles, 25 years after Wellens ~rst described programmed stimulation of the ventricles in humans [3], offers an opportunity to re_ect on the status of programmed electrical stimulation in clinical electrophysiology, its utility and limitations. In order to interpret appropriately the signi~cance of these two studies, it may be useful to consider how we use programmed ventricular stimulation in practice. While programmed stimulation was initially applied to elucidate the mechanisms responsible for monomorphic sustained ventricular tachycardia, and to aid in its diagnosis [3], later investigators applied the technique to patients who had experienced syncope or survived cardiac arrest (without documentation of the initiating arrhythmia), for similar reasons that it had been utilized in patients with spontaneous sustained ventricular tachycardia [4,5]. It has been used more recently in patients who have never experienced any symptomatic arrhythmia, in order to assess their risk for sudden cardiac death [6]. Further complicating these matters, is the fact that the technique has been applied to patients with the above arrhythmias occurring in association with a variety of anatomic substrates, including coronary artery disease, cardiomyopathies, etc. Why are these factors important? It is very likely that not only are the mechanisms responsible for ventricular tachyarrhythmias dependent on the type of associated heart disease, but even within the subset of patients with coronary artery disease for example, the characteristics of tachycardias are dependent in many respects on the clinical presentation [7]. There is also evidence that within the group of patients with coronary artery disease, the site of previous myocardial infarction can in_uence the arrhythmia substrate [8,9]. In this light, I would like to review brie_y the highlights of the studies by Fisher and Wyse. Fisher and his colleagues extended their earlier studies of the termination of ventricular tachycardia by ultrarapid stimulation trains, to the potential of this technique for initiation of ventricular tachycardia [10]. By coupling ultrarapid trains (at cycle lengths of 10, 20, or 30 msec) of progressively increasing duration to a standard “drive” of seven or eight beats, they were able to deliver 1, 2, or 3 extrastimuli with the greatest possible degree of prematurity relatively quickly. Their results show a high degree of concordance for inducible ventricular tachyarrhythmias between their standard stimulation protocol, and the ultrarapid train protocol, but the train protocol reached one of the predetermined endpoints in signi~cantly less time (5.25 versus 16.1 minutes). Unfortunately, the reproducibility of tachycardia induction was evaluated in only 3 patients. Wyse and his colleagues examined the effect of programmed ventricular stimulation on the difference between the endocardial QT intervals of the last extrastimulus, recorded at the right ventricular apex and out_ow tract. By using unique and original recording technology, the investigators were able to achieve very high ~delity measures of local QT intervals. The duration of the initial portion of the QT interval bore a linear relationship to the prematurity of the extrastimulus in the control group of patients without structural heart disease. As expected, this interval shortened as the extrastimulus prematurity increased. Of interest, the terminal portions of the QT interval did not exhibit the expected rate adaptation, but rather remained constant or increased with increasing extrastimulus prematurity. In contrast, the experimental patient group, consisting of patients with prior myocardial infarction undergoing electrophysiologic studies for evaluation of spontaneous ventricular tachyarrhythmias, showed a blunting of the adaptation of the initial and total QT interval to extrastimulus prematurity. The terminal component of the QT interval in the study patients behaved in a manner similar to that of the control group. The control patients showed minimal “dispersion” of the QT intervals that displayed a _at relationship to extrastimulus prematurity. The QT “dispersion” of patients with ventricular arrhythmias Journal of Interventional Cardiac Electrophysiology 1997;1:281–285 © Kluwer Academic Publishers. Boston. Printed in U.S.A.