Natural History of late Potentials in the First Ten Days After Acute Myocardial Infarction and Relation

to Early Ventricular Arrhythmias

MARK McGUIRE, MB, DENNIS KUCHAR, MD, JAMES GANIS, BSc, NEVILLE SAMMEL, MB, and CHARLES THORBURN, MB

Serial signal-averaged etectrocardkgrams (ECGs) were performed every 48 hours in 50 patients ad- mitted to the coronary care unit with acute myocar- dial infarction. The prevalence of late potentials was 32% at presentation (mean time to recordin 12.4 f 8.6 hours after onset of chest pain) and in- creased progressively throughout the hospital stay. New late potentfafs were recorded in patients with no prior acute myocardlal infarction as early as 3 hours after the onset of chest pain and as late as 8 days. Late potentlats appeared transiently in only 3 patients. The detectton of late potenttats In the initial dgnabavera9ed ECG ktentified patients with cllni-

tally si9ntflcant early ventricular atiythmtas with a sensitivity of 80% and speciffty of 72 % . The pre- dktive accuracy was 38% for a posftive test and 84% for a negative test. Pattents with early ventrk- ular arrhythmias had signtfkantly tower vdtage tn the terminal 40 ms of the filtered QFtS complex (18 f 8 vs 32 f 19 pV, p <O.Ol) than those wfthout arrhythmias. The dgnal-avera@ ECG may be use- ful in tdentifyiq patients at hi9h rtsk of devebpkrg clinically sigtfftcant early ventricular arrhythmias af- ter acute myocardtal infarction.

(Am J Cardiol 1988;61:1187-1190)

I n recent years, several groups of investigators using high-gain electrocardiography and signal-averaging techniques have detected abnormal low amplitude signals in the electrocardiograms of patients with chronic recurrent ventricular tachycardia.1-4 These signals, termed late potentials, are found in the termi- nal region of the QRS complex and extend into the ST segment. Late potentials are thought to arise in areas of abnormal myocardium exhibiting slow conduction (an essential requirement for reentrant ventricular tachy- cardia).

Several groups have investigated the natural histo- ry of late potentials detected in survivors of acute myo- cardial infarction (AMI) and their relation to subse- quent ventricular arrhythmias.s-8 However, with few exceptionsg*10 these studies have been confined to the period following hospital discharge. Ventricular ar-

From the Cardiovascular Unit, St, Vincent’s Hospital, Victoria Street, Darlinghurst, New South Wales, Australia. Manuscript received October 21.1987; revised manuscript received and ac- cepted February 25,1988.

Address for reprints: Mark McGuire, MB, Coronary Care Unit, St. Vincent’s Hospital, Victoria Street, Darlinghurst, New South Wales 2010, Australia.

rhythmias occurring within the first 48 hours after AM1 may have mechanisms different from those of late arrhythmias11v12 and it is unknown if they are also associated with late potentials. This prospective study examines the natural history of late potentials during the period of hospitalization for AM1 and the relation between late potentials and early ventricular arrhyth- mias.

Methods Definitions: Acute myocardial infarction was de-

fined as the development of chest pain plus either the appearance of new Q waves on the ECG or elevation of the MB fraction of creatine kinase to twice the upper limit of the normal range. The definition of early ven- tricular arrhythmia was ventricular fibrillation or sus- tained ventricular tachycardia occurring within 24 hours of the onset of chest pain. Sustained ventricular tachycardia was defined as that lasting >8O seconds with a rate of >l8O beats/min or causing cardiovascu- lar collapse.

Patients: Our study group consisted of 56 consecu- tive patients with AM1 (45 males, 11 females, mean age 60 f 11 years), admitted to the coronary care unit be- tween July and October 1986. Nine patients had a prior

118% LATE POTENTIALS IN AMI

AMI. Only 1 patient was receiving antiarrhythmic therapy before hospital admission (quinidine sulfate for recurrent atria1 arrhythmias]. Patients were ex- cluded from the study if the admission ECG revealed bundle branch block or if the signal-averaged ECG could not be performed within 24 hours of the onset of chest pain. Fifty patients completed the study protocol. The reasons for failure to complete the protocol in- cluded 3 deaths, 1 from cardiogenic shock, 1 from in- tractable ventricular fibrillation and 1 from an unwit- nessed arrhythmia, 2 patients who elected to withdraw and 1 patient who required temporary pacing, thus invalidating the signal-averaged ECG technique. Al- though serial signal-averaged ECGs could not be performed in these 6 patients, all had a recording per- formed on admission and all were monitored for ar- rhythmias for at least 24 hours; thus, the initial signal- averaged ECG could be correlated with the develop- ment of cardiac arrhythmias.

Signal-averaged electrocardiogram: Signal-aver- aged ECGs were performed on all patients as soon as possible after admission and thenceforth every 48 hours until discharge or day 10. The mean time to the initial recording was 12.4 f 6.6 hours after the onset of chest pain. Signal-averaged ECGs were performed with an Arrhythmia Research Technology high-reso- lution electrocardiograph (model 1011 using methods previously described by Simson and Denes et a1.13 The signal-averaged ECG was recorded by means of the standard bipolar orthogonal leads X, Y and Z. Sig- nals from 200 to 300 beats were amplified, digitized, averaged and then filtered with a bidirectional high band pass filter of 40 Hz. Such a filter was chosen because of previous work by Denes et a1,13 which sug- gested that the use of a 40-Hz high pass filter may result in more reproducible recordings. Signals from the 3 leads were combined into a vector magnitude, calculated for each point in the QRS as: Vector magni- tude = ,/(X2 + Y2 + Zz). The root mean square voltage of the terminal 40 ms of the filtered QRS complex

a 60

G I- 3

50

E 40 LLI 5 30

g 20

10

0 1 3 5 7-10

TIME(DAY S)

FIGURE 1. Prevalence of late potentials In the study populatlon during hospltal stay and at discharge (day 7 through 10). LP = late potential.

(V40), the duration of the filtered QRS complex and the duration of low amplitude signals in the terminal (IRS were determined by computer algorithm. A late potential was defined as total filtered QRS duration >12O ms or V4O <2O pV. Previous work has demon- strated that the use of these definitions confers high specificity and sensitivity for the prediction of ventric- ular tachycardia.3J3

Arrhythmia detection: On arrival at the coronary care unit, all patients were monitored by a central electrocardiographic monitoring system. Arrhythmias were detected visually and by an automated detection system that alerted the staff to the presence of ventric- ular fibrillation or heart rates >13O beats/min. Patients were monitored electrocardiographically for at least 48 hours.

Statistical methods: Results are expressed as mean f standard deviation and were compared using chi- square analysis with continuity correction or Student t test where appropriate.

Results Natural history: The following data refer only to

the 50 patients who completed the study protocol. Late potentials were recorded in 29 patients (58% of total) during the hospital stay. Late potentials appeared as early as 3 hours after the onset of chest pain in patients with no prior infarction and as late as 8 days. Late potentials were present in 16 patients (32%) on the initial signal-averaged ECG and 26 patients (52%) on discharge. If patients with known prior AM1 were to be excluded from analysis the prevalence of late po- tentials would be similar (29 and 51%, respective- ly). The number of patients with late potentials at vari- ous times during the hospital stay is shown in Figure 1. Late potentials were present transiently in only 3 patients (6%). In 2 of the cases in which late poten- tials “disappeared,” low amplitude signals were still visible at the offset of the QRS but the V40 exceeded 20 WV.

Clinical characteristics: Table I lists the clinical differences between those patients who developed late potentials during the hospital stay (group 1) and those who did not (group 2). These data refer only to the 50 patients who completed the study protocol. There were no statistically significant differences be- tween the 2 groups with respect to age, sex, peak cre- atine kinase activity, infarct site or history of prior infarction. Late potentials were not more common in those with Q-wave as compared with non-Q-wave in- farction or in those receiving thrombolytic or lidocaine therapy. Lidocaine was not administered routinely or for “warning arrhythmias” but only after clinically ‘significant arrhythmias or nonsustained ventricular tachycardia had developed.

Cardiac arrhythmias: Early ventricular arrhyth- mias developed in 10 (18%) of the 56 patients. Only 1 of them had received thrombolytic therapy. The arrhyth- mia was ventricular fibrillation in 6 cases (11%) and sustained ventricular tachycardia in 4 (7%). Late po- tentials were present in the initial recording in 8 of the 10 patients with early ventricular arrhythmia (80%).

June 1. 1988 THE AMERICAN JOURNAL OF CARDIOLOGY Volume 81 1189

The initial signal-averaged ECG was performed be- fore the arrhythmic event in 4 patients and afterwards in 6 (<I2 hours after the arrhythmia, mean 7.8 f 5.2 hours). Eight of the 21 patients who had late potentials in the initial recording developed early ventricular arrhythmias. Only 2 of the 35 patients without late potentials developed early ventricular arrhythmias. The association between a late potential present in the initial signal-averaged ECG and early ventricular ar- rhythmias was statistically significant (chi-square test with continuity correction, p CO.01).

Signal-averaged electrocardiographic parame- ters: These findings are listed in Table II. The V40 differed significantly between the group that devel- oped early ventricular arrhythmia and the group that did not (17 f 8 vs 32 f 19 pV, p <O.lO). Although the duration of the filtered QRS complex tended to be longer in the group with arrhythmias, this difference was not statistically significant. The duration of low amplitude signals in the region of the terminal QRS was longer in patients with early ventricular arrhyth- mias (p <0.005).

Discussion The most important findings in this study include:

(1) late potentials appear within hours or days of AMI; (2) the prevalence of late potentials increases progres- sively in the early postinfarction period; (3) transient late potentials are uncommon: (4) late potentials are associated with clinically significant ventricular ar- rhythmias occurring within 24 hours of onset of AMI.

Natural history of late potentials: In our study, late potentials were detected in 5870 of patients during their hospital stay. The prevalence of late potentials was 5270 at the time of hospital discharge. This figure is in agreement with the findings of investigators who have used similar methods7s8 but is higher than the figures of those who have used other techniques.6,9

Of particular interest is the time of appearance of new late potentials. Late potentials were detected in patients with no history of prior AM1 as early as 3 hours after the onset of chest pain. In the group of patients with no history of prior AMI, 29% had late potentials when the initial signal-averaged ECG was recorded. Thus, in many patients late potentials ap- peared within hours of the onset of infarction. These “early” late potentials must clearly have a different pathophysiological basis from that proposed for late potentials associated with chronic recurrent ventricu- lar tachycardia. The latter are thought to arise from areas of myocardium in which surviving muscle fibers are separated by intervening areas of fibrosis resulting in slowed and asynchronous electric conduction.14 Gardner et all5 have demonstrated that directly re- corded fractionated electrograms arise from these areas of abnormal myocardium and Simson et a116 have shown that late potentials correspond temporally to this delayed, fractionated, electric activity. We have shown that late potentials may appear before fibrosis could have developed, in which case the anatomic substrate is probably a region of ischemic and partially depolarized cells resulting in slow and fractionated

TABLE I Clinical Characteristics of 50 Patients and Relation to Presence of Late Potential

Age W Sex (M/F) Peak CK-MB (IU/liter) Site of AMI

Group 1 Group 2 (n = 29) (n = 21)

60f 10 59f 12 2316 1813

172 f 140 146 f 124

p Value

NS NS NS

Anterior 10 11 NS Inferior 17 7 NS Indeterminate 2 3 NS

Q wave 24 16 NS Prior AMI 5 4 NS Thrombolytic therapy 7 6 NS Lidocaine therapy 1 IO 6 NS

AMI = acute myocardial infarction; CK-MB = activity of MB fraction of creatine kinase; NS = not significant; 7 refers to those receiving lidocaine during the first 48 hours after AMI.

TABLE II Parameters of lnltlal Signal-Averaged Electrocardiogram In 56 Patients

Ventricular Arrhythmia Within 24 Hours of AMI

+ 0 p Value

v 40 W) 17 f 8 32 f 19 <O.Ol QRSD (ms) 108 f 7 101 f 14 <O.lO LAS (ms) 43 f 9 33f 11 <0.005

AMI = acute myocardial infarction: LAS = duration of low amplitude signals (<40 r.rV) in terminal QRS; QFtSD = duration of filtered QRS complex; V 40 = mean voltage of terminal 40 ms of QRS.

conduction. This finding supports work performed in experimental animals in which delayed, fractionated electric activity extending into the ST segment has been detected within minutes of coronary artery liga- tion.17

In most patients, once late potentials had appeared they tended to remain. Transient late potentials were detected in only 3 patients (670). In 1 patient the late potential resolved with no visible trace of low ampli- tude signals in the region of the terminal QRS, while in the other 2 patients low amplitude signals were still visible but the V4O exceeded the arbitrarily defined limit of 20 /*V.

The steady increase in the prevalence of late poten- tials throughout the hospital stay has implications for the assessment of risk of late ventricular arrhythmias. When recording signal-averaged ECGs for this pur- pose, we recommend that the recording be made as close as possible to the time of discharge to maximize the chance of detecting late potentials.

Clinical characteristics of patients with late poten- tials: No clinical characteristics were found to corre- late with the development of late potentials. This find- ing agrees with those of Gomes et al’” but differs from those of Kuchar et al8 and Denniss et al6 who have demonstrated an association between late potentials and anterior wall site of infarction and between late potentials and peak creatine kinase activity. The rea-

1190 LATE POTENTIALS IN AMI

son for this discrenancv is not obvious but mav be 1978;41:697-702.

related to differendes in” the size of the study po~.&la- tions.

Late potentials and early ventricular arrhythmias: Late potentials detected in signal-averaged ECGs re- corded soon after admission were found to be associ- ated with early ventricular arrhythmias. The presence of a late potential identified those patients who de- veloped clinically significant ventricular arrhythmias with a sensitivity of 80% and specificity of 72%. The predictive accuracy was 38% for a positive test and 94% for a negative test. Kertes et a19 found no such relation in a similar study. The reason for this discrep- ancy is uncertain but possibly relates to the different methods used for late potential detection. Because these workers found late potentials in only 16% of survivors of myocardial infarction, their method ap- pears to be less sensitive than the method used by Simson a modification of which was used in our study.

In 6 of the 10 patients with early ventricular ar- rhythmias the initial signal-averaged ECG recording was made after the arrhythmic event, and it is possible that the late potentials appeared as the result of some intervention such as electrical cardioversion or antiar- rhythmic drug therapy. Nevertheless, we think this unlikely for several reasons. First, there is evidence that neither cardioversion nor antiarrhythmic drug therapy can induce late potentials.l*J9 Second, these late potentials remained after the cessation of anti- arrhythmic therapy. Finally, there was no statistical- ly significant difference between groups 1 and 2 in the proportion of patients undergoing antiarrhythmic therapy.

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