Standards for analysis of ventricular late potentials using high-resolution or signal-averaged electrocardiography: a statement by a task force committee of the European Society of Cardiology, the American Heart Association, and the American College of Cardiology.

Sufficient data are available to recommend the use of the high-resolution or signal-averaged electrocardiogram in patients recovering from myocardial infarction without bundle branch block to help determine their risk for developing sustained ventricular tachyarrhythmias. However, no data are available about the extent to which pharmacological or nonpharmacological interventions in patients with late potentials have an impact on the incidence of sudden cardiac death. Therefore, controlled, prospective studies are required before this issue can be resolved. As refinements in techniques evolve, it is anticipated that the clinical value of high-resolution or signal-averaged electrocardiography will continue to increase.

Alterations in the initial portion of the signal-averaged QRS complex in acute myocardial infarction with ventricular tachycardia.

This study was designed to examine 2 hypotheses: that acute myocardial infarction (AMI) alters early cardiac activation measured by signal-averaging; and that the magnitude of abnormality of early activation may be greater in patients with post-AMI ventricular tachycardia (VT). We examined the root-mean square voltage amplitude in 10-ms intervals over the first 80-ms of the signal-averaged QRS complex. Data from 42 healthy volunteers were compared with those from 52 patients with previous AMI (24 anterior) but no VT and 46 post-AMI patients (33 anterior AMI) with recurrent sustained VT. Patients with VT differed from other post-AMI patients because of lower left ventricular ejection fraction, more frequent aneurysm formation and higher levels of ventricular ectopic activity. A significant decrease in initial voltage amplitude occurred at 30 to 40 ms after the beginning of the QRS in both anterior and inferior AMI patients compared with the normal group. A further significant decrease in initial amplitude occurred in VT patients both after anterior and inferior AMI. These differences persisted for the remainder of the 80-ms interval. These changes were weakly related to QRS duration (r = 0.45), ejection fraction (r = 0.50) and poorly correlated with the presence of Q waves on 12-lead electrocardiogram (r = 0.21). Direct endocardial catheter recordings performed in VT patients confirmed abnormalities of local septal activation after anterior and inferior AMI.(ABSTRACT TRUNCATED AT 250 WORDS)

Electrophysiologic studies on atrioventricular nodal Wenckebach cycles.

Wenckebach cycles with a 4:3 ratio, produced by rapid atrial pacing, were studied in 27 anesthetized denervated dogs using programmed stimulation. A test stimulus (S') could be inserted after any preselected beat of the Wenckebach cycle. An on-line computer measured the atrial (A) to His bundle (H) intervals. In all dogs a progressive increase in atrioventricular (A-V) nodal refractoriness was seen in the effective refractory period for each beat and a rightward shift of the A'-H' relative to the A-A' refractory curves. Atypical Wenckebach cycles could be produced by small changes in the basic cycle length. No evidence for reentry was found from the refractory curves of Wenckebach cycles and by interruption of stimulation after the third stimulus of a 4:3 Wenckebach cycle. Analysis of the A'-H' relative to the H-A' refractory curves did not confirm a positive feedback mechanism. In order to mimic a Wenckebach cycle, a blocked premature beat was inserted during stressed 1:1 conduction. The changes in the refractory curves for successive beats after the premature beat were rate-dependent and similar to those in Wenckebach cycles but smaller in magnitude. In Wenckebach cycles there is a progressive increase in refractoriness, caused by cumulative effect similar to that seen after a blocked beat during stressed 1:1 conduction, until block occurs and the cycle resets.

Temporal relation between onset of cell anoxia and ischemic contractile failure. Myocardial ischemia and left ventricular failure in the isolated, perfused rabbit heart.

Contractile dysfunction is characteristic of the acutely ischemic myocardium. This study was undertaken to assess the temporal relations between the onset of cell anoxia and ischemic contractile failure in isolated, isovolumetric contracting rabbit hearts. High speed epicardial fluorescence photography using reduced nicotinamide adenosine nucleotide (NADH) was used to identify areas of cell anoxia. The onset of ischemia was correlated with deterioration of pressure generation over the course of sequential 60 second coronary arterial occlusions. In the isovolumetric contracting rabbit heart, areas of ischemia were detected 2 seconds after coronary occlusion. Significant reduction in peak systolic pressure occurred at 6 seconds of ischemic time and pressure continued to decrease throughout the 60 second period of coronary occlusion. NADH accumulation indicates imbalance of myocardial oxygen supply and demand and the cessation of oxygen utilization by the mitochondria. The results of this study indicate that ischemia is detectable within 1 to 2 seconds after coronary occlusion and that ischemic ventricular dysfunction occurs several seconds thereafter. Myocardial oxygen reserve is negligible.

Epicardial ischemia as delineated with epicardial S-T segment mapping andnicotinamide adenine dinucleotide (NADH) fluorescence photography.

In isolated rabbit hearts with an experimental coronary arterial occlusion, epicardial ischemia was identified by reduced nicotinamide adenine dinucleotide (NADH) fluorescence photography, a technique that detects areas of myocardial anoxia. Epicardial S-T segment mapping was performed to evaluate the S-T segment changes across an ischemic border defined by NADH fluorescence. After S-T segment mapping and perfusion with a fluorescein dye, serial selections of the hearts revealed that the ischemic area was transmural and and the border was nearly perpendicular to the epicardial surface. As the epicardial ischemic border was approached, S-T segment elevation was first detected 3.3 mm outside the ischemic border, and increased over a transition zone 7 mm wide. S-T segment negativity was not detected immediately outside the ischemic border. It is concluded from these studies that S-T segment changes give relatively imprecise definition of an ischemic border, and that S-T segment changes across an ischemic border are not consistent with those predicted by solid angle analysis.

Results of signal-averaged electrocardiography and electrophysiologic study in patients with nonsustained ventricular tachycardia after healing of acute myocardial infarction.

Programmed stimulation and signal-averaged electrocardiography were performed in 43 consecutive patients with nonsustained ventricular tachycardia (VT) after healing of inferior (29 patients) or anterior wall (14 patients) acute myocardial infarction. Twenty-two patients had inducible sustained VT. Patients with inferior infarction and inducible sustained VT had significantly longer filtered QRS durations (125 +/- 19 vs 112 +/- 15 ms, p less than 0.01) and significantly lower voltage in the last 40 ms of the filtered QRS complex (19 +/- 5 vs 30 +/- 14 microV, p less than 0.05) than those without inducible sustained VT. In contrast, the signal-averaged electrocardiographic measurements in patients with anterior infarction and inducible sustained VT did not differ significantly from those without inducible sustained VT. The results of these studies were compared with those of 2 control groups: 45 patients without ventricular arrhythmias after myocardial infarction and 95 patients with spontaneous and inducible sustained VT after myocardial infarction. The signal-averaged electrocardiographic measurements in patients with spontaneous nonsustained VT after inferior infarction were intermediate between the control group without arrhythmias and the control group with sustained VT. The signal-averaged electrocardiograms in patients with nonsustained VT after anterior infarction were not significantly different from those in patients without ventricular arrhythmias. The study shows that the site of infarction influences the signal-averaged electrocardiogram in patients with VT after myocardial infarction. The signal-averaged electrocardiogram may be useful in identifying patients with nonsustained VT after a remote inferior myocardial infarction who have inducible sustained VT.

Relation between late potentials on the body surface and directly recorded fragmented electrograms in patients with ventricular tachycardia.

The relation between low-amplitude, late potentials on the body surface and directly recorded electrograms in 8 patients with and 11 patients without ventricular tachycardia (VT) was studied. Bipolar X,Y,Z leads were signal-averaged and filtered with a digital technique. All patients had catheter endocardial left ventricular maps. The VT group had medically intractable VT and an endocardial excision was performed for control of VT. Before bypass, epicardial maps were obtained in the operating room. All studies were performed during normal sinus rhythm. Four patients without VT, each with a previous myocardial infarction, had fragmented endocardial electrograms recorded at 2.0 +/- 1.2 sites. The latest electrogram for each patient ended 87 +/- 8 ms after QRS onset, within the high-amplitude portion of the filtered QRS complex. All patients with VT had fragmented electrograms recorded at 6.1 +/- 3.1 sites/patient. Eighty-eight percent of the fragmented electrograms were endocardial. The latest fragmented electrogram for each patient ended 161 +/- 43 ms after QRS onset, significantly later than the fragmented electrograms from the patients without VT (p = 0.002). Six VT patients had low-amplitude, late potentials at the end of the filtered QRS complex. In these patients, the last 40 ms of the filtered QRS complex contained a higher proportion of fragmented electrograms compared with earlier segments of the QRS complex (68% versus 27%, p less than 0.001). Two patients with VT did not have late potentials. One patient with left bundle branch block had delayed left ventricular epicardial activation which masked the fragmented electrograms. The other had fragmented electrograms of brief duration which ended 80 +/- 12 ms after QRS onset, during the time of normal ventricular activation. It is concluded that the late potential corresponds to delayed, fragmented electrographic activity. Failure to record a late potential may arise from delayed ventricular activation at other sites from bundle branch block or fragmented electrograms of a brief duration.

Relation of late potentials to site of origin of ventricular tachycardia associated with coronary heart disease.

Signal-averaged electrocardiograms and endocardial catheter mapping were performed in 41 patients with coronary artery disease and sustained ventricular tachycardia (VT) to determine the relation between signal-averaged late potentials (SA-LPs) and catheter-mapped late activity (CM-LA) to the site of origin of VT. The 41 patients had 79 morphologically distinct VTs. Either CM-LA or SA-LP was present during sinus rhythm in 37 of 41 patients (90%). Twenty-two out of 30 patients (73%) had CM-LA corresponding to SA-LP during normal sinus rhythm. Patients with SA-LP had a significantly greater number of sites of CM-LA, which were later and longer in duration than patients without SA-LP present during sinus rhythm. In a select group of patients, those with both SA-LP and CM-LA, the site of origin of VT was located at or adjacent to a site of CM-LA during sinus rhythm in 38 of 44 (86%); however, 36 of 78 sites (46%) of CM-LA were clearly distant from the site of origin of VT. In conclusion, CM-LA corresponding to SA-LP in patients with VT is sensitive but not specific for the site of origin of VT.

Changes in cardiac excitability and vulnerability in NMR fields.

Alterations in ventricular excitability and vulnerability were assessed in nine isolated perfused rabbit hearts in and out of static external magnetic fields (4.7 tesla) associated with radiofrequency pulsing (5 gauss). Ventricular refractoriness was assessed with the strength interval relationship in and out of the NMR magnet. Strength interval curves were measured at threshold, at the midpoint of the strength interval relationship, and at 10 mA. The refractory period measured at threshold was 193 +/- 24 mS outside the magnet and 195 +/- 24 mS inside the magnet (P = ns). Ventricular refractoriness measured at the midpoint of the strength interval curve was 169 +/- 16 mS outside and 167 +/- 17 mS in the magnet (P = ns). At 10 mA the refractory period outside of the magnet was 162 +/- 16 mS and 161 +/- 17 mS in the magnet (P = ns). To assess ventricular vulnerability the repetitive response threshold and the ventricular fibrillation threshold were also determined in and out of the NMR magnet. The repetitive response threshold was 61 +/- 16 mA out of the magnet and 75 +/- 24 mA inside the magnet. This was significant at the P = 0.04 level. The ventricular fibrillation threshold was 71 +/- 14 mA out of the magnet and 81 +/- 20 mA in the magnet (P = ns). In summary, static magnetic fields associated with radiofrequency pulsing have no measureable effect on the strength interval relationship. There is no increase in ventricular vulnerability as assessed by the repetitive response threshold and the ventricular fibrillation threshold.

Display of epicardial ischemia by reduced nicotamide adenine dinucleotide fluorescence photography, electron microscopy, and ST segment mapping.

Reduced nicotinamide adenine dinucleotide (NADH) fluorescence photography, a technique of assessing myocardial ischemia, was correlated with ischemia as identified by ST segment mapping and electron microscopy (EM) in 25 Langdneorff perfused rabbit hearts following coronary occlusion. Nicotinamide adenine dinucleotide (NAD), a component of the intramitochondrial electron transport chain, becomes reduced during periods of ischemia (NADH). NADH fluoresces when excited by ultraviolet light. NAD does not. All three techniques were compared to assess their resolution of the "border zone" between ischemia and nonischemic myocardium. The border zone defined by NADH fluorescence is 0.1 mm or less. Areas of high NADH fluorescence invariably revealed ST segment elevation, whereas minimally fluorescent areas did not. St segment mapping yields a border zone of approximately 7 mm. Areas of high NADH fluorescence following 1 hour of ischemia displayed severe damage on EM as compared to matched controls. A zone of intermediate ultrastructural damage is identified in a 1 mm biopsy taken between fluorescent and nonfluorescent myocardium. This evidence confirms epicardial NADH fluorescence photography as an assay of myocardial ischemia. This high resolution technique delineates a border zone of narrow dimensions as compared with ST segment mapping.

Initiation of ventricular tachyarrhythmia with programmed stimulation: sensitivity and specificity in an experimental canine model.

Programmed stimulation (PS) is used in the catheterization laboratory and operating room to initiate and study malignant ventricular tachyarrhythmia (VT). The purpose of this study was to evaluate the specificity and sensitivity of PS in short-term studies of 10 normal animals (group A), 10 sham-operated controls (group B), and 10 dogs with chronic myocardial infarction susceptible to inducible VT by an occlusion-reperfusion method (group C). Groups B and C were studied 7 to 14 days after the initial procedure. the pH, PaO2, and PaCO2 were determined and corrected every 30 minutes during the procedure. When bipolar ventricular pacing with three ventricular extrastimuli was used, VT initiation was attempted at 10 normal intramyocardial sites in groups A and B and in close proximity (less than or equal to 1 cm) to areas of infarction in group C. When one ventricular extrastimulus was used during ventricular pacing, VT was induced in dogs with chronic infarctions (3 of 10, 30%, group C). Using two extrastimuli, however, VT was inducible in 4 of 10 (40%) of group A, 6 of 10 60%) of group B, and all 10 (100%) of group C. With three extrastimuli, all 30 dogs had inducible VT. Overall, PS with one extrastimulus was highly specific in 100% but insensitive in 30%. With two extrastimuli the sensitivity increased to 100%, but the specificity fell to 50%. Finally, with three extrastimuli the sensitivity was also 100%, but the specificity decreased to 0%. PS remains an invaluable technique in diagnosing and assessing therapy for patients with VT. The diagnostic implications of this test await more precise pathophysiologic elucidation of arrhythmic mechanisms.

Recovery of left ventricular function after graded cardiac ischemia as predicted by myocardial P-31 nuclear magnetic resonance.

The purpose of this study was to determine noninvasively some critical level of high-energy phosphate stores that relates to the recovery of ventricular contractile function after graded cardiac ischemia. Rabbit hearts (n = 30) were equipped with an intraventricular balloon to monitor developed pressure and +/- dp/dt and placed in a nuclear magnetic resonance magnet (Bruker, 4.7 Tesla). Each heart underwent 10, 20, 40, or 60 minutes of global ischemia followed by 1 hour of reperfusion. The pH as determined by nuclear magnetic resonance dropped from 7.14 +/- 0.04 to 7.07 +/- 0.07 (p less than 0.02) at 1 minute and to 6.19 +/- 0.08 at 30 minutes of ischemia; pH ceased to fall thereafter. Phosphocreatine was depleted to 10% +/- 7% of its preischemic control in 10 minutes. Adenosine triphosphate (ATP) concentrations were 71% +/- 14% and 1% +/- 2% at 10 and 60 minutes. Regression analysis of recovered developed pressure on end-ischemic ATP (EIATP) revealed: developed pressure = 0.93 (EIATP) + 23 (r2 = 0.99). We conclude that: anaerobic metabolism as evidenced by a fall in pH appears to be active for 30 minutes after normothermic ischemia and then ceases; phosphocreatine buffers the fall in ATP during early ischemia; there is a tight correlation between EIATP and recovery of left ventricular contractile function with a threshold content of approximately 80% below which recovery of function will not be complete.

Late potentials in an ovine model of acute transmural myocardial infarction.

The development of slow conduction during the first hours of acute transmural myocardial infarction (ATMI) was studied by signal-averaged electrocardiograms (SAE) in 19 adult anesthetized sheep. SAEs were recorded before and after intravenous infusions of lidocaine and bretylium were begun and 10, 30, and 60 min after ATMI produced by ligation of the left anterior descending and second diagonal coronary arteries. Four sheep died promptly of ventricular tachyarrhythmias; two others developed sustained ventricular arrhythmias, which precluded additional data. Biphasic changes in QRS duration, root mean square voltage of the terminal 40 ms of the QRS complex, and duration of terminal low-amplitude (less than 30 microV) signal were observed. Peak changes in conduction occurred 30 min after infarction and regressed toward baseline thereafter. At 30 min, all animals developed late potentials, which were defined as signals that exceeded both after-drug QRS duration and duration of terminal low-amplitude signal less than 30 microV by more than two standard deviations. At 60 min, only 3 of 13 (23%) animals had late potentials. Conduction is slowest 30 min after ATMI in sheep but may not be related to development of ventricular arrhythmias. In five of six sheep (83%), ventricular arrhythmias occurred within 15 min of infarction before peak slowing was observed by SAE.

Clinical application of signal averaging.

The signal averaging technique is used to reduce the level of noise contaminating the recording of a periodic signal like the electrocardiogram. The detection of ventricular late potentials and the surface activity of the His bundle and sinus node, as recorded by this technique, are discussed in this article.

Noninvasive identification of patients at high risk for sudden cardiac death. Signal-averaged electrocardiography.

Signal-averaged electrocardiography allows the detection of late potentials, which have been associated with delayed and disorganized ventricular activation. This article reviews the technique, describes the findings recorded from patients with ventricular tachyarrhythmias, and assesses the prognostic value of late potentials for ventricular tachyarrhythmias and sudden cardiac death in patients after an acute myocardial infarction. The role of signal-averaged electrocardiography in the evaluation of patients with syncope and cardiomyopathies is also briefly discussed.

Use of signals in the terminal QRS complex to identify patients with ventricular tachycardia after myocardial infarction.

Small, high-frequency electrocardiographic signals were recorded from the body surface in 39 patients with and 27 patients without ventricular tachycardia (VT). All patients were in normal sinus rhythm, had a previous myocardial infarction, were not taking antiarrhythmic drugs, and did not have bundle branch block. Bipolar X, Y, Z leads were signal averaged and processed by a bidirectional digital filter that allowed low-amplitude signals to be detected in the terminal QRS complex and ST segment. The high-pass filter frequency was 25 Hz. Patients with VT had a lower amplitude of high-frequency signal in the late QRS complex. In the last 40 msec of the filtered QRS complex, the patients with VT had 14.9 +/- 14.4 microV of high-frequency signal; patients without VT had 73.8 +/- 47.7 microV (p less than 0.0001). Ninety-two percent of the patients with VT had less than 25 microV of high-frequency voltage; only 7% of patients without VT had less than 25 microV (p less than 0.0001). Patients with VT had a longer QRS duration than those without VT, 139 +/- 26 vs 95 +/- 10 msec (p less than 0.0001). The QRS duration was longer than 120 msec in 72% of the patients with VT but in none of the patients without VT (p less than 0.0001). In all patients there was no separate and discrete high-frequency signal in the ST segment. Advanced signal processing of the ECG accurately identified the patients in the study with VT after myocardial infarction.

Oscillations of conduction, action potential duration, and refractoriness. A mechanism for spontaneous termination of reentrant tachycardias.

The mechanism of cycle length oscillation and its role in spontaneous termination of reentry was studied in an in vitro preparation of canine atrial tissue surrounding the tricuspid orifice. Reentry occurred around a fixed path with incomplete recovery of excitability. Among 18 experiments, there was complete concordance between the occurrence of spontaneous cycle length oscillation and spontaneous terminations; both were observed in 10 experiments and neither in the other eight (p less than 0.001). Local changes in conduction during oscillations resulted from the dependence of both conduction velocity and action potential duration on the preceding local diastolic interval. Interval-dependent changes in action potential duration contributed to the oscillation by altering the next diastolic interval. Because of changes in action potential duration, changes in cycle length were poorly correlated with changes in diastolic interval and, therefore, with local conduction velocity. Complex oscillations resulted from variations in conduction time at multiple sites in the circuit. Oscillations caused most spontaneous terminations. The critical event was an exceptionally long diastolic interval preceding the next-to-last cycle that accelerated local conduction (which tended to shorten the last cycle) and prolonged action potential duration and refractoriness at the site of block. Ninety-two of 99 recordings of spontaneous termination showed evidence of oscillation of conduction and refractoriness causing block.

Prognostic value of an abnormal signal-averaged electrocardiogram in patients with nonischemic congestive cardiomyopathy.

BACKGROUND: An abnormal signal-averaged ECG (SAECG) has predictive value for arrhythmic events in patients with coronary artery disease. The purpose of this study was to investigate whether an abnormal SAECG could provide prognostic information in patients with nonischemic dilated cardiomyopathy. METHODS AND RESULTS: We prospectively obtained SAECGs in 114 patients with dilated nonischemic cardiomyopathy. Twelve-lead ECGs, left ventricular ejection fractions, hemodynamic measurements, and peak exercise oxygen consumption (VO2) also were measured. An SAECG was defined as abnormal by any one of the three following criteria: filtered QRS duration > 120 msec, root-mean-square voltage in the last 40 msec < 20 microV, or duration < 40 microV > 38 msec at 40 Hz. Sixty-six patients had a normal SAECG, 20 patients had an abnormal SAECG, and 28 patients had bundle branch block (BBB). Mean follow-up was 10 +/- 5 months. Age, ejection fraction, peak VO2, pulmonary capillary wedge pressure, and cardiac index were not statistically different among the three groups. Use of antiarrhythmic drugs was similar among the three groups, although patients with BBB had more implantable defibrillators (p < 0.05). The incidence of previous atrial arrhythmias was similar for the three groups. Patients with abnormal SAECG or BBB had more past episodes of sustained ventricular tachycardia and/or sudden death episodes (n = 9) than patients with normal SAECG (n = 1) (p < 0.01). Prospectively, none of the 66 patients with normal SAECG died suddenly or had sustained ventricular arrhythmias. Two deaths occurred from progressive heart failure, and three patients required urgent transplant. In the 20 patients with an abnormal SAECG, four patients had sustained ventricular tachycardia, five patients died suddenly, two patients died from progressive heart failure, and one patient required urgent transplant. In the patients with BBB, four patients had sustained ventricular tachycardia, and four patients required urgent transplant. One-year event-free survival, i.e., absence of ventricular tachycardia and/or death, was 95% in patients with normal SAECG, 88% in patients with BBB, and only 39% in patients with an abnormal SAECG (p < 0.001). Multivariate analysis demonstrated that SAECG and New York Heart Association classification were independent predictors of survival. CONCLUSIONS: Patients with an abnormal SAECG had a statistically significant increase in sustained ventricular arrhythmias and/or death than did patients with a normal SAECG or BBB. This study demonstrates that an abnormal SAECG is a marker of past and future arrhythmic events in patients with nonischemic dilated cardiomyopathy. In contrast, patients with a dilated cardiomyopathy with a normal SAECG have an excellent prognosis with adverse outcome only from progressive heart failure.

A computer model of the electrogram: what causes fractionation?

Fractionated electrograms are frequently recorded during mapping studies in patients with coronary artery disease and ventricular tachycardia. The authors developed a computer model of electrogram generation based on the biophysics of volume conductor fields. They show that fractionated electrograms can be produced as otherwise uniform wavefronts of activation encounter regions of increased cellular coupling resistance. Because of this, local activation may not correspond to the largest or most rapid deflection in a polyphasic, fractionated electrogram.

A model of conduction through the N region of the AV node.

A computer model of the AV node was developed in order to study mechanisms of conduction delay in the AV node. Three cells were used corresponding to the AN, N, and NH region. The basic mechanisms for delay were a high intercellular resistance and a delayed, time dependent recovery of excitability in the center cell. The action potentials for all cells were held constant. The model reproduces antegrade conduction characteristics of the AV node and the waveform of the center cell resemble the two component action potentials of N cells. The model suggests that the conduction properties of the AV node may be due to subthreshold phenomenon.