Initiation Of Ventricular Tachyarrhythmias Research Articles

Pathophysiology and Risk Stratification of Sudden Cardiac Death in Ischemic Heart Disease

Sudden cardiac death accounts for approximately 360,000 annually in the United States and is the cause of half of all cardiovascular deaths. Ischemic heart disease is the major cause of death in the general adult population. Sudden cardiac death can be due to arrhythmic or non-arrhythmic cardiac causes, for example, myocardial rupture. Arrhythmic sudden cardiac death may be caused by ventricular tachyarrhythmia (ventricular tachycardia/ventricular fibrillation) or pulseless electrical activity/asystole. The majority of research in risk stratification centers on ventricular tachyarrhythmias simply because of the availability of a successful management strategy, the implantable cardioverter/ defibrillator. Currently the main criterion of primary defibrillator prophylaxis is the presence of organic heart disease and depressed left ventricular systolic function assessed as left ventricular ejection fraction. However, only one third of eligible patients benefit from the implantable defibrillator, resulting in significant redundancy in the use of the device. The cost to the health care system of sustaining this approach is substantial. Further, the current low implantation rate among eligible population probably reflects a perceived low benefit-to-cost ratio of the device. Therefore, attempts to optimize the selection process for primary implantable defibrillator prophylaxis are paramount. The present report will review the most recent pathophysiology and risk stratification strategies for sudden cardiac death beyond the single criterion of depressed ejection fraction. Emphasis will be placed on electrophysiological surrogates of conduction disorder, dispersion of repolarization, and autonomic imbalance, which represent our current understanding of the electrophysiological mechanisms that underlie the initiation of ventricular tachyarrhythmias. Further, factors that modify arrhythmic death, including noninvasive risk variables, biomarkers, and genomics will be addressed. These factors may have great utility in predicting sudden cardiac arrhythmic death in the general public.

Inducibility of Atrial and Ventricular Arrhythmias Along the Ligament of Marshall: Role of Autonomic Factors

The mechanism(s) underlying atrial fibrillation (AF) initiation along the ligament of Marshall (LOM) remains controversial. We sought to examine the role of the autonomic nervous system in arrhythmogenesis along the LOM. In 31 anesthetized dogs, a left thoracotomy exposed the LOM. During atrial pacing, high-frequency stimulation (HFS: 200 Hz, 0.1 ms pulse width, 40 ms duration, 0.6-12 V) was delivered during atrial refractoriness to different sites of LOM (LOM(CS)= near coronary sinus; LOM(LIPV)= near left inferior pulmonary vein; LOM(LS-LIPV)= between LIPV and left superior pulmonary vein (LSPV); LOM(LSPV)= near LSPV). HFS was repeated after intravenous administration of esmolol (1 mg/kg; n = 9) or atropine (2 mg; n = 12). Norepinephrine (10(-7) M, 0.4 cc) was injected into LOM(LSPV) (n = 5). The median voltages for HFS to induce AF were 3.2 V, 3.2 V, 8.0 V*(,double dagger), and 12 V*(,double dagger) at LOM(CS), LOM(LIPV), LOM(LS-LIPV), and LOM(LSPV), respectively (*P < 0.01, compared with LOM(CS) and double dagger P < 0.01, compared with LOM(LIPV)). Esmolol or atropine markedly increased the threshold for AF induction. Ventricular tachycardias (VT) and accelerated junctional rhythm were induced in 8 of 12 and 6 of 12 dogs after atropine administration, respectively. Sustained VT occurred within minutes in 5 of 5 dogs receiving norepinephrine injection into the LOM(LSPV.) HFS induced AF along LOM with a gradient of stimulation thresholds from LOM(CS) (lowest) toward LOM(LSPV) (highest). This response was inhibited by esmolol or atropine. These data suggest an autonomic basis for AF initiation in LOM, and both sympathetic and parasympathetic neural elements play an important role in AF initiation. Hyperactivity of the sympathetic neural elements in LOM may be crucial in the initiation of ventricular tachyarrhythmias.

Pattern recognition and time-frequency representation of cardiac rhythm dynamics

86 14 14 22/73 Roelke et al, JACC 1994 92 7 – 59/1102 Anderson et al, JACC, 1995 – – 25 38/286 Meyerfeldt et al, EHJ, 1997 85 13 2 90/260 Taylor et al, JCE, 2000 56 – – 52/68 Saeed et al, AJC, 2000 – – 8 309/4973 Gronefeld et al, PACE 2002 complex and includes a multitude of time-varying components. Analysis of changes in these components has proven useful for analysis of the autonomic nervous system activity, as well as stress responses that might be related to clinically significant ischemic and arrhythmic events. However, because of the multicomponent structure of cardiac rhythm, tracking changes in this signal, in particular abrupt and irregular perturbations, is technically challenging. One important goal of the time-series analysis of cardiac rhythm is an identification of patterns and mechanisms predisposing to the initiation of ventricular tachyarrhythmias (VTA). Changes in cardiac rhythm have been consistently found before the onset of VTA in different patient populations. The predominant pattern of changes

Letter by Selvaraj and Chauhan Regarding Article, “Upsurge in T-Wave Alternans and Nonalternating Repolarization Instability Precedes Spontaneous Initiation of Ventricular Tachyarrhythmias in Humans”

HomeCirculationVol. 115, No. 1Letter by Selvaraj and Chauhan Regarding Article, “Upsurge in T-Wave Alternans and Nonalternating Repolarization Instability Precedes Spontaneous Initiation of Ventricular Tachyarrhythmias in Humans” Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBLetter by Selvaraj and Chauhan Regarding Article, “Upsurge in T-Wave Alternans and Nonalternating Repolarization Instability Precedes Spontaneous Initiation of Ventricular Tachyarrhythmias in Humans” Raja J. Selvaraj and Vijay S. Chauhan Raja J. SelvarajRaja J. Selvaraj Division of Cardiology, University Health Network, Toronto, Canada Search for more papers by this author and Vijay S. ChauhanVijay S. Chauhan Division of Cardiology, University Health Network, Toronto, Canada Search for more papers by this author Originally published2 Jan 2007https://doi.org/10.1161/CIRCULATIONAHA.106.650952Circulation. 2007;115:e9To the Editor:We read with interest the article by Shusterman et al1 concerning repolarization dynamics preceding spontaneous initiation of ventricular tachyarrhythmias in humans. Two related time-domain methods measured a larger magnitude of “alternans” at 30 minutes compared with 60 to 120 minutes preceding arrhythmia onset. Spectral analysis of T-wave amplitude showed a nonuniform increase in power in all frequency ranges. The authors interpret these findings as a surge in alternans and nonalternating repolarization complexity preceding the arrhythmia.An increase in sympathetic activity preceding the onset of ventricular arrhythmia was reported by the authors in the same population.2 This can lead to increased noise in the ECG recordings from perspiration and an increase in motion and respiratory artifact.3The modified moving average and, to a larger extent, the intrabeat average measurements are affected by noise that cannot be completely removed by preprocessing.3 Using these time-domain methods, the authors have previously emphasized the need to measure surrogate alternans in the isoelectric T end to P onset segment to show that an increase in T-wave alternans magnitude is not artifactually attributable to noise.3 It is unclear why the authors did not use a similar analysis of surrogate alternans in the present study1 to ensure that noise was not a confounder.Using the spectral method, white noise can spuriously increase the spectral power in the alternans frequency, and subtraction of the spectral power in a “noise band” is required to measure true alternans.4 Therefore, the increase in spectral power seen in all frequency ranges could be explained by an increase in noise rather than an increase in “nonalternating repolarization complexity.” The possibility of subharmonics influencing the measured power in the alternans range is another important confounder, particularly respiratory subharmonics (0.15 to 0.25 cpb), which increase in spectral power before the tachyarrhythmia. The authors feel the contribution of respiratory subharmonics is improbable because the increase in T-wave alternans magnitude has been confirmed by 3 independent methods. However, the concordant findings do not exclude the confounding effects of subharmonics, because these methods are all inherently influenced by subharmonics.3 Although the increase in alternans may not be accounted for entirely by respiratory subharmonics, this is likely an important contribution and is not unexpected, because respiratory excursions that influence T-wave amplitude can increase during sympathetic surges preceding tachyarrhythmia. Thus, we feel that white noise and respiratory oscillations may significantly contribute to the apparent increase in alternating and nonalternating repolarization instability.DisclosuresNone.1 Shusterman V, Goldberg A, London B. Upsurge in T-wave alternans and nonalternating repolarization instability precedes spontaneous initiation of ventricular tachyarrhythmias in humans. Circulation. 2006; 113: 2880–2887.LinkGoogle Scholar2 Shusterman V, Aysin B, Gottipaty V, Weiss R, Brode S, Schwartzman D, Anderson KP. Autonomic nervous system activity and the spontaneous initiation of ventricular tachycardia. ESVEM Investigators. Electrophysiologic Study Versus Electrocardiographic Monitoring Trial. J Am Coll Cardiol. 1998; 32: 1891–1899.CrossrefMedlineGoogle Scholar3 Shusterman V, Goldberg A. Tracking repolarization dynamics in real-life data. J Electrocardiol. 2004; 37 (suppl): 180–186.CrossrefMedlineGoogle Scholar4 Bloomfield DM, Hohnloser SH, Cohen RJ. Interpretation and classification of microvolt T wave alternans tests. J Cardiovasc Electrophysiol. 2002; 13: 502–512.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetails January 2, 2007Vol 115, Issue 1 Advertisement Article InformationMetrics https://doi.org/10.1161/CIRCULATIONAHA.106.650952PMID: 17200449 Originally publishedJanuary 2, 2007 PDF download Advertisement SubjectsArrhythmias

Response to Letter Regarding Article, “Upsurge in T-Wave Alternans and Nonalternating Repolarization Instability Precedes Spontaneous Initiation of Ventricular Tachyarrhythmias in Humans”

We thank Drs Selvaraj and Chauhan for their interest in our work1 and discussion of the possible impact of white noise and respiration. We do not feel that white noise is a significant problem, although respiration (along with other physiological factors) may play a role, as emphasized in our report. We used the “surrogate” analysis (ie, test of baseline stability) to control for white noise, respiration, movement, and other sources of artifacts. In addition, we removed noisy segments of data and used sectional (T-wave) averaging to …

Upsurge in T-Wave Alternans and Nonalternating Repolarization Instability Precedes Spontaneous Initiation of Ventricular Tachyarrhythmias in Humans

Analysis of repolarization instability, manifested by T-wave alternans (TWA), has proved useful for arrhythmia risk assessment. However, temporal relations between TWA and the spontaneous initiation of ventricular tachyarrhythmias (VTA) in humans are unknown. We examined continuous dynamics of repolarization in Holter electrocardiograms with spontaneous sustained (>30 seconds) VTA. Ambulatory electrocardiograms from 42 patients (79% with ischemic heart disease; left ventricular ejection fraction, 37+/-15%) were digitized, and the lead with the highest magnitude of the T wave was selected for analysis. TWA was examined by the modified moving average and intrabeat average analyses. To examine non-TWA (longer-period) oscillations in the repolarization segment, spectral energy of oscillations of consecutive T-wave amplitudes was calculated with the use of the short-time Fourier transform. Heart rate variability was assessed with the Fourier transform as well. TWA increased before the onset of VTA and reached a peak value of 23.6+/-11.7 microV 10 minutes before the event (P=0.0007). Spectral power of the oscillations of consecutive T-wave amplitudes increased nonuniformly, with the greatest increase in the respiratory range (2.6 microV2; P=0.005). In the TWA range, the change was smaller but highly pronounced relative to the 60- to 120-minute level (65%; P=0.003). The low-frequency and high-frequency heart rate variability power declined before the arrhythmia (P=0.04 and P=0.06, respectively). The magnitude of repolarization instability, manifested by TWA and beat-to-beat oscillations of T-wave amplitudes at other frequencies, increased before the onset of VTA. Tracking of these dynamics can facilitate timely detection of high-risk periods and may be useful for initiation of preventive treatments.

Detecting instabilities of cardiac rhythm

Diminished beat-to-beat variations in cardiac cycle lengths (CLs) are associated with poor prognosis after acute myocardial infarction and in patients with heart failure. Short-long-short sequences of cardiac cycles, or ultra-short rhythm instabilities, precede initiation of ventricular tachyarrhythmias in some patients. However, little is known about clinical or prognostic significance of abrupt short-term instabilities in CL (AICL) that occur minutes to hours before the event, in part because appropriate analytical methods are lacking. Although various techniques have been used to analyze CL changes, methods for analysis of AICL are limited. We compared performance of time domain, spectral, nonlinear, and pattern recognition techniques with respect to the detection and quantification of AICL. Because of high intra- and inter-subject variability of CL, pattern recognition techniques compared favorably to other studied methods. In continuous ambulatory ECG recordings, AICL occurred hours before spontaneous initiation of sustained atrial and ventricular arrhythmias in different patient populations. AICL were also found prior to the onset of spontaneous ventricular arrhythmias in a mouse model of congestive heart failure. To quantify AICL, we used the number of unstable orthogonal projection coefficients; this number gradually increased hours before the event. Removal of ectopic beats reduced but did not eliminate AICL. To illustrate potential physiological effects and temporal evolution of AICL, we used a simple, continuous, two-dimensional model of cardiac tissue governed by the Morris-Lecar equations. Computer simulations in this model showed that AICL may lead to gradual accumulation of spatial irregularities of the propagation wavefront giving rise to the initiation of reentry. Time-frequency analysis of the most significant eigenvectors of cardiac rhythm in subjects undergoing head-up tilt showed that AICL could indicate instabilities and unsuccessful adaptation of autonomic nervous system activity to physiological stimuli.

Ventricular tachyarrhythmias in a canine model of LQT3: arrhythmogenic effects of sympathetic activity and therapeutic effects of mexiletine.

The ventricular tachyarrhythmias associated with the LQT3 syndrome are typically bradycardia-dependent. However, some episodes can be associated with exercise or emotional stress, suggesting a different arrhythmogenic mechanism when sympathetic activity predominates. This study examined the potential arrhythmogenic mechanisms during periods of autonomically mediated transient heart rate acceleration in a canine anthopleurin-A model of LQT3 syndrome. Using plunge needle electrodes, transmural unipolar electrograms of the left ventricle were recorded from endocardial (Endo), mid-myocardial (Mid) and epicardial (Epi) sites. The activation-recovery interval (ARI) was measured to estimate local refractoriness. The cardiac cycle length was gradually shortened by cessation of vagal stimulation (vagal stimulation protocol (VSP)), and intramural electrograms and onset mode of ventricular tachyarrhythmias were analyzed in 7 experiments. The VSP was performed 8 times before and 5 times after administration of mexiletine in each experiment. Before mexiletine, vagal stimulation slowed the heart rate and created large transmural ARI dispersion because of a greater ARI prolongation at Mid rather than Epi/Endo sites. After cessation of vagal stimulation, unipolar electrograms started to show ARI alternans and ventricular premature beats developed sporadically. Sustained ventricular tachyarrhythmias were induced in 12 of the 56 trials of the VSP. Initiation of ventricular tachyarrhythmias was associated with delayed conduction at Mid/Endo sites. Mexiletine attenuated transmural ARI dispersion, and neither ARI alternans nor ventricular tachyarrhythmias was observed during all 35 trials of the VSP after mexiletine administration. Heart rate acceleration induced by an abrupt shift to a state of predominant sympathetic activity enhances arrhythmias in this LQT3 model. Mexiletine homogenizes ventricular repolarization, suppresses premature complexes and was antiarrhythmic during ventricular tachyarrhythmias induced by the VSP.

Circadian variation of malignant ventricular arrhythmias in patients with ischemic and nonischemic heart disease after cardioverter defibrillator implantation

OBJECTIVESThe purpose of this study was to examine the circadian variation of ventricular arrhythmias detected by an implantable cardioverter defibrillator in patients with and without ischemic heart disease.BACKGROUNDPrevious studies have shown a circadian variation of ventricular arrhythmias, sudden death and myocardial infarction with a peak occurrence in the morning hours. The circadian pattern, which is similar for both arrhythmic and ischemic events, suggests that ischemia may play a critical role in the genesis of ventricular arrhythmias and sudden death. We hypothesized that, if ischemia plays an important role in the triggering of ventricular arrhythmias, the circadian pattern should be different in patients with ischemic heart disease compared with patients with nonischemic heart disease.METHODSThe circadian variation of ventricular arrhythmias recorded by an implantable cardioverter defibrillator was studied in 310 patients during a mean follow-up of 181 ± 163 days. Two hundred four patients had a history of ischemic heart disease and 106 patients had nonischemic heart disease. The times of the episodes of ventricular arrhythmias were retrieved from the data log of each device during follow-up, and the circadian pattern was compared between the two groups.RESULTSDuring follow-up, 1,061 episodes of ventricular arrhythmias were recorded by the device in the 310 patients. Six hundred eighty-two episodes occurred in the group of patients with ischemic heart disease and 379 occurred in the nonischemic heart disease group. The circadian variation of the episodes showed a typical pattern with a morning and afternoon peak in both groups of patients with ischemic and nonischemic heart disease, but there was no significant difference between the two groups.CONCLUSIONSThe circadian rhythm of ventricular arrhythmias in patients with ischemic heart disease is similar to patients with nonischemic heart disease, suggesting that the trigger mechanisms of the initiation of ventricular tachyarrhythmias may be similar, irrespective of the underlying heart disease.

Antiarrhythmic actions of tocainide in canine models of previous myocardial infarction

The antiarrhythmic and antifibrillatory efficacies of the class IB antiarrhythmic agent tocainide were characterized in conscious dogs in the early subacute phase of anterior myocardial infarction (48 hours after infarction) and in anesthetized dogs with ventricular tachyarrhythmias that were inducible by programmed stimulation more chronically (10.8 ± 1.0 days) after anterior myocardial infarction. The frequency of spontaneous premature ventricular complexes in the early subacute postinfarction phase was reduced significantly from 48.4% ± 10.5% to 8.2% ± 5.0% of total complexes ( p < 0.01) by the cumulative intravenous administration of 10 mg/kg tocainide. In the late postinfarction setting, the intravenous administration of tocainide (6 mg/kg intravenous loading dose + 100 μg/kg/min intravenous maintenance infusion) suppressed the initiation of ventricular tachyarrhythmias by programmed stimulation in 5 of 12 animals that were tested and slowed the rate of tachycardia in 3 additional animals. However, the incidence of ventricular fibrillation and of the total number of arrhythmia-related deaths that resulted from the occurrence of a secondary ischemic insult in the presence of previous infarction did not differ significantly between tocainide (75% [9 of 12] incidence of both ventricular fibrillation and of total number of arrhythmia-related deaths) and saline-vehicle control groups (80% [12 of 15] incidence of ventricular fibrillation; 93,3% [14 of 15] incidence of total number of arrhythmia-related deaths). These findings suggest that although class I agents such as tocainide may be efficacious in the suppression of spontaneous premature ventricular complexes and ventricular arrhythmias immediately after myocardial infarction, they may be of limited value in the prevention of malignant ischemic arrhythmias that occur later after myocardial infarction.

Histopathologic Correlates of Inducible Ventricular Tachycardia in Two Experimental Canine Models of Myocardial Infarction

Ventricular tachyarrhythmias are the leading cause of sudden cardiac death. Determination of the substrates conducive to the initiation of ventricular tachyarrhythmias remains an important clinical goal. The purpose of this study was to correlate electrophysiologic and histopathologic parameters conducive to the initiation of sustained ventricular tachycardia using programmed electrical stimulation in two canine models of myocardial infarction. Histopathologic correlates included: infarct pattern (heterogeneous vs. homogeneous morphology), distribution (viable epicardial or endocardial rim), and size. Twenty-one adult dogs were randomly divided into two groups: (1) 12 dogs underwent two-stage, 2-hour occlusion of the proximal left anterior descending coronary artery (LAD); and (2) nine animals had permanent, complete occlusion of the LAD with latex embolization. Using programmed ventricular pacing with two premature ventricular extrastimuli, initiation of ventricular tachycardia was attempted at both 1 and 2 weeks after infarction with the chest closed and opened each time. Electrophysiologic evaluation of the infarct type correlated significantly with the histologic morphology of the infarction (p less than 0.001), the presence of a viable epicardial rim was an extremely important discriminating variable for ability to induce sustained ventricular tachycardia (p = 0.04). The presence of an endocardial rim was not significant (p = 1.0). Infarct size alone was only marginally related to ventricular tachycardia inducibility (p = 0.08). Non-uniform infarcts were more conducive to the initiation of sustained ventricular tachycardia than homogeneous infarcts (p = 0.025). The presence of a large, non-uniform infarct was the best overall discrimination variable for inducibility (p = 0.0002). Thus, in these experimental models, specific infarct morphologies correlate significantly with susceptibility to inducible sustained ventricular tachyarrhythmias.

Nonarrhythmogenicity of therapeutic cryothermic lesions of the myocardium

There is increasing interest in the application of surgical methods to the treatment of refractory ventricular tachyarrhythmias (VT). Cryothermic ablation is one of the more promising techniques. However, there is clinical concern that a cryothermic lesion may lead to later arrhythmias. Previous studies have shown that dogs with nonhomogeneous, transmural infarctions are susceptible to VT initiation using programmed electrical stimulation (PES). The purpose of this study was to compare the incidence of inducing VT in dogs with transepicardial cryothermic myocardial damage (Group A) versus dogs with nonhomogeneous transmural infarctions resulting from 2-hr occlusion of the left anterior descending coronary artery (LAD) and subsequent reperfusion (Group B). Twelve dogs in each group were studied 10–14 days later using PES with unipolar cathodal ventricular pacing and two ventricular extrastimuli. Initiation of VT was attempted from at least six normal intramyocardial sites in each dog along the distribution of the LAD and in close proximity (⩽1 cm) to areas of chronically cryoablated damaged tissue. All dogs survived the initial procedure. VT was not inducible in any dog in Group A. Histological as well as electrophysiological evaluation, including determination of regional excitability thresholds and refractory periods employing strength-interval curves, revealed that all of the Group A dogs had homogeneous transmural infarcts with variable subendocardial sparing. In conclusion (1) cryothermal injury produces homogeneous damage; and (2) the lesion produced is not arrhythmogenic at 7–14 days.

Limitations of failure of procainamide during electrophysiologic testing to predict response to other medical therapy

To determine whether failure of procainamide to prevent initiation of ventricular tachyarrhythmias during electrophysiologic testing predicted failure of other antiarrhythmic regimens, 81 consecutive patients with coronary artery disease whose ventricular tachyarrhythmias remained inducible during procainamide administration were studied. Overall, 26 (12%) of 216 subsequent drug studies were successful and at least one effective drug regimen was identified in 22 (27%) of the 81 patients. Drug success was significantly related to the arrhythmia induced at baseline study; 7% of drug studies were successful in patients with sustained ventricular tachycardia, 24% in patients with ventricular fibrillation, and 29% in patients with nonsustained ventricular tachycardia. An effective drug regimen was found in 11 (19%) of 59 patients with sustained ventricular tachycardia, 4 (50%) of 8 patients with ventricular fibrillation and 7 (50%) of 14 patients with nonsustained ventricular tachycardia. In patients with sustained ventricular tachycardia, failure of procainamide to suppress the arrhythmia correlated with failure of other agents used singly but not in combination. This study supports the view that when procainamide fails to prevent initiation of the arrhythmia in patients with inducible sustained ventricular tachycardia it is unlikely that other individual standard agents will be effective. However, combination regimens may suppress the arrhythmia and should be evaluated. In patients with nonsustained ventricular tachycardia, all agents should be evaluated because failure to respond to procainamide does not predict subsequent responses to other agents either alone or in combination.

Further electrophysiologic and anatomic correlates in a canine model of chronic myocardial infarction susceptible to the initiation of sustained ventricular tachyarrhythmias.

A canine model of chronic myocardial infarction has been studied in which animals are susceptible to the initiation of sustained ventricular tachyarrhythmias using routine methods of programmed stimulation. The pacing-induced arrhythmias in this model are similar to those observed in man in their mode of initiation and termination, as well as in their response to both pacing and pharmacologic interventions. Indirect evidence has suggested a localized protected reentrant mechanism for these arrhythmias. The susceptibility to arrhythmia initiation in this model has been related to both electrophysiologic and histopathologic findings. Consistently, animals have demonstrated a marked heterogeneity of local properties of excitability and refractoriness at sites within areas of infarction. Correspondingly, animals have shown a marked inhomogeneity of histopathologic findings within areas of infarction, with close interspersing of normal and abnormal myocardium. Remarkably, even animals with small mottled infarctions, often less than 1 cm x 2 cm and electrocardiographically silent, were highly susceptible to the initiation of ventricular tachyarrhythmias, and especially fibrillation. Thus, initial provocative studies in this model have suggested its potential importance both in studying arrhythmia mechanisms and in evaluating the efficiency of potential antiarrhythmic interventions. In addition, this should be an ideal model in which to correlate pathophysiologic and morphologic alterations in the setting of chronic myocardial infarction.

Ventricular extrastimulation in the mitral valve prolapse syndrome. Evidence for ventricular reentry

Fourteen patients with mitral valve prolapse and essentially normal coronary arteries were evaluated for ventricular arrhythmias, utilizing programmed ventricular extrastimulation. Three were symptomatic with ventricular tachyarrhythmias. Application of appropriately timed ventricular extrasystoles initiated the tachyarrhythmias in these three patients. The remaining eleven mitral prolapse patients were apparently free of tachycardias. Repetitive ectopic beats were not induced by extrastimulation in these eleven patients. The initiation of ventricular tachyarrhythmias by extrastimulation suggests a reentrant mechanism for the ventricular ectopy of mitral valve prolapse.