Late potentials on signal-averaged electrocardiograms and patency of the infarct-related artery in survivors of acute myocardial infarction

330

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Late Potentials on Signal-Averaged Electrocardiograms and Patency Of the Infarct-Related Artery in Survivors of Acute Myocardial Infarction PIERCE J. VATTEROTT, MD, FACC,*t STEPHEN C. HAMMILL, MD, FACC,* KENT R. BAILEY, PHD,:j: CHRISTINE M. WILTGEN, BS,:j: BERNARD J. GERSH, MB,CHB, DPHIL, FACC* Rochester, Minnesota This study evaluated the relation between patency of the infarct· related artery and the presence of late potentials on the signal. averaged electrocardiogram (ECG) in 124 consecutive patients (98 men, 26 women; mean age 59 years) with acute myocardial infarction receiving thrombolytic therapy, acute percutaneous transluminal coronary angioplasty or standard care. All patients were studied by coronary angiography, measurement of ejection fraction and signal-averaged ECG. The infarct·related artery was closed in 51 patients and open in 73. Among patients with no prior myocardial infarction undergo· ing early attempted reperfusion therapy, a patent artery was associated with a decreased incidence of late potentials (20% versus 71 %; no significant difference in ejection fraction). In the 48 patients receiving thrombolytic agents within 4 h of symptom onset, the incidence of late potentials was 24% and 83% among

patients with an open or closed artery, respectively (p < 0.04). The most powerful predictors of late potentials were the presence of a closed infarct-related artery, followed by prior infarction and patient age. Among patients receiving thrombolytic agents within 4 h of symptom onset, the only variable that was predictive of the presence of late potentials was a closed infarct·related artery. These data imply that reperfusion of an infarct·related artery has a beneficial effect on the electrophysiologic substrate for serious ventricular arrhythmias that is independent of change in left ventricular ejection fraction as an index of infarct size. These findings might explain, in part, the low late mortality rate in survivors of myocardial infarction with documented reperfusion of the infarct-related artery. (J Am Coli CardioI1991,'17:330-7)

The prognosis after acute myocardial infarction has substantially improved over the last 20 years (1,2). Initial expectations that the mortality rate would be decreased by the use of thrombolytic agents appear to have been met (3-8). Accumulating evidence suggests that some of the salutary effects of reperfusion on the incidence of death may be related in part to mechanisms other than a decrease in infarct size (1) because although use of thrombolytic agents has resulted in improved ventricular function, in most trials (1,3,9,10), the changes have been modest at best. Potential mechanisms by which restoration of patency of the infarctrelated artery could improve survival include modification of the processes of infarct expansion, healing and remodeling (1,2,11-14), provision of collateral flow to other diseased

vessels (1) and alteration of the electrophysiologic substrate for life-threatening ventricular arrhythmias (15-17). Nonetheless. the greatest benefit is still obtained in patients treated early, implying an effect on myocardial salvage (18,19). Signal averaging and high-pass filtering of the surface electrocardiogram (ECG), a noninvasive computerized method of analyzing standard ECGs, identifies patients at risk for ventricular tachycardia (18,20-30). This high resolution ECG technique exposes microvolt signals at the end of the QRS complex (20). These "late potentials" are generated by conduction through abnormal myocardial tissue that can support a reentrant ventricular arrhythmia (18,21,23-30) and have been found to be predictive of subsequent ventricular tachycardia and sudden death in patients after an acute myocardial infarction (21.22,3 1-33). The present study evaluated the relation between patency of the infarct-related artery and the presence of signalaveraged late potentials (marker of a potentially arrhythmogenic substrate) in a consecutive series of patients with acute myocardial infarction. All patients either received thrombolytic therapy or underwent percutaneous transluminal coronary angioplasty in the acute stage of infarction.

From the 'Division of Cardiovascular Diseases and Internal Medicine and tSection of Biostatistics, Mayo Clinic and Mayo Foundation, Rochester. Minnesota. This study was presented in part at the 62nd Annual Scientific Sessions of the American Heart Association. New Orleans. November 1989. tPresent address: St. Paul Heart Clinic, 255 North Smith Avenue. Suite 100, St. Paul. Minnesota 55102. Manuscript received January 8. 1990: revised manuscript received August 29. 1990. accepted September II. 1990. Address for reprints: Bernard J. Gersh. MB. ChB. DPhil. Mayo Clinic. 200 First Street SW. Rochester, Minnesota 55905. © 1991

by the American College of Cardiology

0735-]097/91/$3.50

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Methods Study patients. The study group consisted of 124 patients who had an acute myocardial infarction and were hospitalized between January 24, 1986 and February 9, 1988. In all patients, the diagnosis of acute myocardial infarction was confirmed by both serial ECG and serum enzyme changes. For entry into the study, coronary angiography, measurement of ejection fraction and a signal-averaged ECG during hospitalization were required. All patients underwent cardiac catheterization and coronary and left ventricular angiography during the hospital stay. Forty-eight patients had received thrombolytic therapy within 4 h of symptom onset (recombinant tissue-type plasminogen activator in 45, streptokinase in 3), and 49 patients underwent percutaneous transluminal coronary angioplasty (as sole treatment in 23, with thrombolytic therapy in 26) during the hospital stay (performed within 24 h in 28 patients). Data collection. Cardiac catheterization data included identification of the infarct-related artery, presence or absence of coronary reperfusion, severity of the residual stenosis in the infarct-related artery after treatment, extent of coronary artery disease (number of coronary arteries with a diameter stenosis >70%) and time from onset of pain to first coronary angiogram. For 44 patients, more than one coronary angiogram was available. The arteriogram used to evaluate the infarct-related artery was recorded within 48 h of symptom onset in 63 patients, between 2 and 5 days in 31 patients and after 5 days in 30 patients. The coronary angiogram obtained closest in time to the predischarge signal-averaged ECG was used for the assessment of patency of the infarct-related artery. Other recorded data consisted of peak serum creatine kinase values and time from onset of pain to peak enzyme release and start of thrombolytic therapy. Ejection fraction was measured at discharge by radionuclide angiography in 99 patients and left ventricular angiography in 25 patients. Definitions. A closed infarct-related artery was defined as a complete occlusion. A patent infarct-related artery was defined as one with stenosis but not complete occlusion. The infarct-related artery was identified by the presence of angiographically visible thrombus or the correlation between wall motion abnormalities in the region subserved by the vessel and the distribution of the ECG changes of acute infarction. Identification of the infarct-related artery was done in a blinded manner. Occlusion of branch vessels of a major coronary artery was coded as occlusion of the parent vessel. The location of Q wave myocardial infarction by ECG criteria was determined as follows: anterior wall = new and diagnostic Q waves in any precordial lead VI through V6; inferior wall = new and diagnostic Q waves in leads II, III and aVF; lateral wall = new and diagnostic Q waves in leads I and aVL; and posterior wall = new and diagnostic increase in R wave voltage in lead V1 such that the R/S ratio was> 1.

331

A non-Q wave myocardial infarction was coded in the same distribution (except posterior wall myocardial infarction) with the requirement that the new repolarization changes persisted for ?:24 h. ECG signal averaging. Signal-averaged ECGs were obtained on the day of hospital discharge or 1 day earlier. Patients with bundle branch block or pre-excitation were excluded from the study. A Corazonix's Corporation Predictor was used to obtain average values. The signal-averaged ECG variables were defined as follows: signal-averaged QRS duration = computer-determined total QRS duration of the signal-averaged complex; root mean square voltage = last 40 ms of the vector magnitude QRS; and low amplitude signal = amount (in time) of the terminal vector magnitude QRS complex <40 /-LV. The averaged QRS complexes were filtered with fourthorder bidirectional high pass filters at 25, 40 and 80 Hz. After filtering, the total QRS duration was determined by computer algorithm as described previously (34). After determination of QRS onset and offset, the computer-calculated root mean square voltage and low amplitude signal were recorded. Each of these measurements was made after 25,40 and 80 Hz high pass filtering (21). Late potentials were defined as being present if two of the following criteria were met: root mean square voltage <20 /-LV, low amplitude signal >38 ms and QRS duration > 114 ms with 40 Hz filtering (21,22). Statistical analyses. All continuous clinical and coronary angiographic variables and nine signal-averaged ECG variables were examined with an unequal variance two-sample t test for their univariate significance in predicting patency versus occlusion of the infarct-related artery. Discrete clinical variables were analyzed by chi-square analysis. Stepwise logistic regression was then used to evaluate independently significant variables in predicting the presence of late potentials. After analysis in the total group, patients were separated into subgroups for further analysis. Subgroups consisted of patients with Q wave myocardial infarction, non-Q wave myocardial infarction, attempted acute reperfusion therapy, history of prior infarction, ECG infarct location and infarctrelated artery location.

Results Patient characteristics (Table 1). The 98 men and 26 women had a mean age of 59 years (range 29 to 87). Twenty-two patients had had a prior myocardial infarction, and 49 patients had had prior angina. At the time of coronary angiography, 51 patients had a closed infarct-related artery and 73 patients had a patent infarct-related artery. Myocardial infarction was Q wave in type in 83 patients and non-Q wave in 40 (the ECG for 1 patient was not available for analysis). The infarct location based on the ECG was anterior in 46 patients, inferior in 65 and lateral in 13.

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Table 1. Clinical Data in 124 Patients Variable Age (yr)* Gender (no. F/M) Prior angina (no.) Prior MI (no.) Ejection fraction (%)*t QRS duration (ms)*:j: Extent of coronary artery disease (no. of vessels) No disease Single vessel Two vessel Three vessel ECG location of MI (no.) Anterior Inferior Lateral MI type (no.) Q wave Non-Q wave Indeterminate Infarct-related artery (no.) LAD RCA LCx Graft§ Primary success after PTCA (no.) Time from onset of pain to thrombolytic therapy (min)* Peak CK (V/liter)* Time to peak CK (min)*

Total (n = 124)

Open Artery (n = 73)

Closed Artery (n = 51)

59 ± 12.5 26/98 49 22 46 ± 15 97 ± 12

15/58 27 9 47 ± 14.6 95 ± II

11/40 22 13 44 ± 15.6 99 ± 12

4 37 47 36

4 23 32 14

0 14 15 22

46 65 13

29 37 7

17 28 6

83 40

47 25

I

I

36 15 0

48 48 24 4 49

31 27 14 I 46

17 21 10 3 3

164 ± 52

163 ± 52

166 ± 57

995 ± 1,175 1.112 ± 648

1,098 ± 1J82 895 ± 460

847 ± 780 1,432 ± 750

p Value

0.06

}

0.014

<0.0001

*Mean ± SD. tEjection fraction was measured by radionuclide angiography in 99 patients (62 with an open infarct-related artery and 37 with a closed infarct-related artery) and left ventricular angiography in 25 patients (II with an open infarct-related artery and 14 with a closed infarct-related artery). :j:QRS duration measured by the Mayo Clinic ECG computer from a standard 15 lead recording. §Left circumflex coronary artery in two patients, left anterior descending coronary artery in one patient and right coronary artery in one. CK = creatine kinase; ECG = electrocardiographic; F = female; LAD = left anterior descending; LCx = left circumflex; M = male; MI = myocardial infarction; PTCA = percutaneous transluminal coronary angioplasty; RCA = right coronary artery.

Signal-averaged ECG variables versus clinical variables by status of the infarct-related artery (Table 2). Filtering at 40 Hz provided the widest discrimination by QRS duration and root mean square voltage associated with the most highly significant p values. The only other clinical variables achieving significance were time to peak serum creatine kinase value (p = 0.(001), number of diseased vessels (p = 0.014), prior myocardial infarction (p = 0.06) and duration of the QRS complex on the surface ECG (p = 0.05). Ejection fraction values were similar in both groups (Table I). Signal-averaged ECG, site and type of infarction and patency of the infarct-related artery (Table 3). There was a statistically significant difference in the presence of late potentials only with Q wave and inferior infarction, but a clear trend was present in patients with anterior infarction. The relation between vessel patency and late potentials was strongest when the infarct-related artery was the right coronary or left circumflex artery.

Table 2. Signal-Averaged Electrocardiographic Variables by Status of Infarct-Related Artery*

25 Hz filter QRS duration (ms) RMSV (/LV) LAS (ms) 40 Hz filter QRS duration (ms) RMSV (/LV) LAS (ms) 80 Hz filter QRS duration (ms) RMSV (/LV) LAS (ms) Late potentials present (%)

Open Artery (n = 73)

Closed Artery (n = 51)

P Value

107.5 ± 15.4 45.1 ± 33.0 29.5 ± 9.7

119.4 ± 19.9 29.1 ± 27.1 38.5 ± 15.8

0.0006 0.0038 0.0005

104.1 ± 14.3 31.4 ± 22.8 34.7 ± 10.7

118.8 ± 22.2 18.5 ± 14.2 44.5 ± 17.5

0.0001 0.0001 0.0006

%.3 ± 10.9 12.7 ± 8.0 47.5 ± 21.5 34

106.0 ± 18.2 9.9 ± 6.6 52.5 ± 21.6 65

0.001 0.03 NS 0.001*

*By chi-square analysis. Data are mean ± SD; p value calculated by unequal variance two-sample t test for continuous variables. LAS = low amplitude signal; RMSV = root mean square voltage.

Vol. 17, No.2 February 1991 :330-7

lACC

Table 3. Incidence of Late Potentials by Site and Type of Infarction and Infarct-Related Artery

100

Pts. With Late Potentials (%) No. of Pts. Type of infarction Qwave Non-Q wave Anterior Inferior Lateral Infarct-related artery LAD RCA LCx Graft

Open Artery


,,;

48 48 24 4

34 32 38 30 43

pValue 0.001

69 53 65 71 33

42 33 21 0

NS

0.079 0.001

NS

NS

59 76 60 33

0.003 0.054

NS

1.

Among patients with non-Q wave infarction, there was no significant difference in the incidence of late potentials in patients with an open or closed vessel, but the mean QRS duration at 40 Hz filtering was shorter when the vessel was open 002.3 ± 11.6 versus 115.3 ± 20.5 ms; p = 0.036). The presence or absence of collateral blood flow to the infarcted segment did not appear to influence whether late potentials were present. Cardiac catheterization information on collateral vessels was available in 49 of the 51 patients with an occluded infarct-related artery. Thirty of the 49 patients had collateral vessels and 20 (67%) of these 30 patients had late potentials. In the 19 patients without collateral vessels, 12 (63%) had late potentials (p = NS). Information on collateral vessels was available in 70 of the 73 patients with an open infarct-related artery; 11 had collateral vessels and 4 (36%) had late potentials. Among the 59 patients without collateral vessels, 20 (34%) had late potentials (p = NS). Figures 1 and 2 illustrate the effect of prior myocardial Figure 1. Incidence of late potentials on the signal-averaged electrocardiogram by patency of the infarct-related artery and the pre~ence (right) or absence (left) of prior infarction. Open bar mdlcates an open infarct-related artery; stippled bar indicates a closed infarct-related artery. Ejection fraction (EF) data are shown as mean values ± standard deviation. Numbers within the bars indicate the number of patients (Pts). No prior infarction

't!-

~

75

i

50

,,;

c: CD

Prior infarction P=NS 78

P=O.0013

""'--r-...

...!!.- ....

!i! .s=

'i III

&:

25

0 EF. %

9 47.3:!: 14.2

45.7:!:15.1

42.9:!: 18.0

Prior MI Reperfusion attempted P-NS

71

50

I--

~

~

42.3: 15.4

42.8:24.5

1ij

'E Q)

'0

a.

83 40 46 65 13

No prior MI Reperfusion attempted P=O.OO5

Closed Artery

Pts. = patients: other abbreviations as in Table

100

333

VATTEROTT ET AL. LATE POTENTIALS IN INFARCT-RELATED ARTERIES

13 38.8:!: 16.6

!§ .s=

0

EF,%

100

j

fIl

a:

45.7:!:".6

51.1:!:20.1

Reperfusion not attempted

Reperfusion not attempted 100

P-NS 50

rr:

P=NS 78

't

I-

0 EF.%

50.6:!:18.5

44.5: 13.9

44.0:26.5

37.1:!: 13.3

Figure 2. Incidence of late potentials with (upper) and without (lower) attempted acute reperfusion therapy in patients (Pts) with (right) or without (left) prior myocardial infarction (MI). Open bar indicates an open infarct-related artery; stippled bar indicates a closed infarct-related artery. Ejection fraction (EF) data are shown as mean values ± standard deviation. Numbers within the bars indicate the number of patients. infarction on the relation between vessel patency and late potentials. Only among patients without prior infarction was there a statistically significant difference in the incidence of late potentials between patients with an open or closed vessel. However, ejection fraction did not differ between these groups. Role of reperfusion therapy. Patients who underwent coronary angioplasty >24 h after the onset of symptoms were not included among the 61 patients categorized as receiving acute reperfusion therapy. In the absence of prior myocardial infarction (Fig. 2) among the 61 patients undergoing early attempted reperfusion therapy, a patent infarct-related artery was associated with a striking reduction in the incidence of late potentials (20% versus 71%). There was no significant difference in ejection fraction between the two groups. In patients who had no attempted reperfusion therapy, the incidence of late potentials was similar among patients with a closed or an open vessel. Among the 63 patients who did not receive reperfusion therapy, however, those with an open infarctrelated artery had a shorter QRS duration at 40 Hz filtering than did those with a closed infarct-related artery (l08 ± 19 versus 119 ± 22 ms, respectively; p = 0.047). When the analysis was confined to the 48 patients receiving thrombolytic therapy (all within 4 h of symptom onset), the incidence of late potentials was 24% and 83% among patients with an open or closed infarct-related artery, respectively (p < 0.004). Between groups, there was no significant difference in ejection fraction (measured by radionuclide angiography in 47 and ventricular angiography in I). Only II patients without prior myocardial infarction underwent coronary angioplasty alone within 24 h of symptom onset and only 1 of the 10 patients with an open vessel had late potentials.

334

VATTEROTT ET AL. LATE POTENTIALS IN INFARCT-RELATED ARTERIES

Table 4. Results of Stepwise Logistic Regression Analyses (dependent variable: presence of late potentials) Variable

Beta Coefficient

Chi-Square

All patients Closed IRA 1.16 8.4 Prior MI 1.33 5.4 Age 0.04 4.9 With attempted acute reperfusion therapy Closed IRA 2.18 6.4 5.6 Prior MI 2.24 -1.41 Prior angina 3.\ Acute reperfusion therapy not attempted Age 0.043 3.5 1.44 Prior MI 2.8 Qwave infarction 0.87 2.6 Receiving thrombolytic agents Closed IRA 2.42 7.7 IRA = infarct-related artery; MI = myocardial infarction.

pValue 0.003 0.021 0.027

0.011 0.018 0.08

0.059 0.093 0.11 0.0056

Stepwise logistic regression analyses (Table 4). The most poweIful predictor of late potentials was the presence of a closed infarct-related artery; the next most poweIful were a history of a prior infarction and age. Among patients undergoing attempted repeIfusion therapy in the acute stage of infarction, vessel patency and a history of prior infarction were the most poweIful predictors of late potentials; the absence of a history of prior angina was an additional predictor (this could be related to the presence of collateral vessels or multivessel disease). Among the 44 patients receiving thrombolytic therapy within 4 h of symptoms onset, the only variable that was predictive of the presence oflate potentials was a closed infarct-related artery.

Discussion Previous studies. Boineau and Cox (23) originally described endocardial recordings in the dog infarct model that showed both delay and fragmentation of the depolarization waveform in myocardium distal toa subacutely occluded coronary artery. Using a similar model, other investigators (18,24-30) described the relation between these "late potentials" and reentrant ventricular arrhythmias. Berbari et al. (20) developed the signal-averaged ECG, which made possible the recording of late potentials from the body surface. The signal-averaged ECG in survivors of infarction has been shown to be a powerful predictor of sudden death and late ventricular tachycardia (21,3l,33,35,36). Using the Cox proportional hazards model, Gomes et al. (22) found the signal-averaged ECG to be the most powerful of the 27 variables evaluated for the prediction of subsequent sudden death or ventricular tachycardia. The absence of late potentials correlates strongly with an absence of subsequent arrhythmic events (21,22,31-33,35,36).

lACC Vol. 17. No.2 February 1991:330-7

Effect of reperfusion therapy on late potentials. Our data imply that reperfusion of an infarct-related artery has a beneficial effect on the electrophysiologic substrate for serious ventricular arrhythmias, independent of any change in left ventricular ejection fraction, which is one of many imprecise clinical indicators of infarct size. This finding is consistent with recent data reported by Gang et al. (17) from patients receiving recombinant tissue-type plasminogen activator: late potentials in 8% of 44 patients so treated and 23% among a comparison group. Our data extend these observations and emphasize that the relation between vessel patency and late potentials appears to be a function of the timing of reperfusion, because in the absence of reperfusion therapy in the acute stage of infarction a patent vessel was not associated with a statistically significant reduction in late potentials. Nonetheless, even among patients not undergoing early therapy directed toward achieving reperfusion there was a favorable trend toward a decrease in late potentials, and other determinants of the signal-averaged ECG were affected favorably. The most striking difference in the incidence of late potentials was noted among patients receiving thrombolytic therapy within 4 h of symptom onset and in the relatively few patients undergoing successful coronary angioplasty within 24 h of symptom onset. Our data also illustrate the importance of prior infarction in the genesis of late potentials. Among patients with non-Q wave infarction, the association was weak (only the QRS duration differed among patients with an open or closed vessel). Effect of successful reperfusion therapy on mortality versus ventricular function. These findings might explain, in part, the low late mortality rate in infarct survivors with documented reperfusion of the infarct-related artery. The extremely low late mortality rate in some series (1,2,10) contrasts strikingly with the relatively modest changes in left ventricular function in patients with or without reperfusion. Our data highlight this discrepancy in that the difference between ejection fraction in patients with or without reperfusion was small; yet the incidence of late potentials in the two groups was markedly different. The overall incidence of late potentials in our series is higher than that reported by Gang et al. (17) in patients with or without a patent infarctrelated vessel. This difference in incidence is particularly notable because the criteria used in our study for the presence of late potentials were more strict than those used by Gang et al. (17). Previous studies (31-33,37) in conventionally treated patients found a 26% to 44% incidence rate of late potentials, which is consistent with our overall incidence rate of 47%. Turitto et al. (38) recently concluded that patency of the infarct-related artery did not significantly alter the incidence of late potentials. Although at first this observation appears to disagree with our findings and those of Gang et al. (17), all three studies display similar trends. In the study by Turitto et al. (38), 8% of the patients with a patent infarct-related artery had late potentials, which shows a trend even though it is not statistically significantly less than the 25% incidence

lACC Vol. 17, No.2 February 1991:330-7

in patients without successful thrombolysis. Moreover, the quantitative signal-averaged root mean square voltage of the last 40 ms was significantly (p < 0.05) more abnormal in patients with a closed infarct-related artery (38). Effect of timing of reperfusion therapy. Differences in results may be due to many factors. The timing of the administration of the thrombolytic agents could influence the heterogeneity of myocardial injury and the subsequent recording of late potentials (39). Thrombolytic therapy was administered within 4 h of symptom onset in our study as opposed to 6 h in previous studies (38,39). Furthermore the use of different thrombolytic agents that vary in their effectiveness in achieving early patency also could influence the development of late potentials (38,39). Most of the patients in the study of Turitto et a1. (38) received urokinase; our study used recombinant tissue-type plasminogen activator. In a recent study (40) of patients who underwent cardiac catheterization within 24 months after an acute myocardial infarction in which only a minority had had thrombolytic therapy, the incidence of late potentials was 8% and 40%, respectively, among patients with or without patency of the infarct-related artery. These data raise several issues with regard to the timing of reperfusion therapy. In many of our patients, the precise onset of reperfusion was unknown, and among patients undergoing coronary angioplasty, we defined the window for early reperfusion therapy as 24 h. In some patients who did not receive lytic therapy, spontaneous reperfusion may well have been a late phenomenon beyond the conventionally accepted period during which reperfusion can modify infarct size. Whether or not late reperfusion affects the incidence of late potentials cannot be answered from our data, but it appears that the major benefit occurred in patients in whom reperfusion was achieved relatively early after symptom onset. This supports the concept of the salutary effects of myocardial salvage, even though left ventricular ejection fraction may not be a sensitive indicator of infarct size (19). Pathophysiology of late potentials. It appears surprising that late potentials on the signal-averaged ECG were more frequent in patients with a closed infarct-related artery. It has been hypothesized (18,26,27,41) that restoration of patency could create a border zone of necrotic and live tissue, thus producing the substrate for ventricular reentry. In contrast, it has been suggested that the substrate created by the well demarcated transmural infarction that one would expect with a closed vessel and an absence of collateral flow would be less likely to be arrhythmogenic. Certainly, when late potentials are used as a marker of the arrhythmogenic substrate, our data and those of Gang et a1. (17) suggest the opposite. However, the mechanisms are not established. The timing of the signal-averaged ECG after myocardial infarction and the development of late potentials plays an important role. Eldar et a1. (42) demonstrated that the incidence of late potentials in the 1st 2 days after myocardial infarction was not significantly different between thrombolytic-treated and control groups (14% versus 11.8%), but

VATTEROTT ET AL. LATE POTENTIALS IN INFARCT-RELATED ARTERIES

335

was different by 7 to 10 days after myocardial infarction (14% versus 22.5%; p < 0.01). This difference is emphasized in our study in which the signal-averaged ECG was obtained a median of 12 days after infarction. Can our results be accounted for by the elimination of ischemia in the group with an open infarct-related artery? It has been shown that the relief of ischemia by revascularization alone may increase electrical stability, as reflected by a decrease in the inducibility of ventricular tachycardia after isolated coronary bypass surgery (43). Data from the Coronary Artery Surgery Study (CASS) (44) documented a marked decrease in the incidence of late sudden cardiac death in patients with chronic angina pectoris who undergo coronary artery bypass surgery. In our study, the incidence of a positive stress test before hospital discharge was 46% and 44% in patients with and without a patent infarct-related vessel, respectively. Although the relative contribution of residual ischemia to the presence of late potentials in our study is unclear, with the high incidence of single vessel disease (particularly among patients undergoing reperfusion therapy) and the 54% incidence of a normal stress test, it is unlikely that relief of ischemia would be the major explanation for the presence of late potentials. Potential beneficial effects of reperfusion on the electrophysiologic substrate. Several clinical studies support the concept that patency of the infarct-related artery may have favorable electrophysiologic consequences. In a study of patients with a large anterior wall infarction, Sager et a1. (15) documented a striking decrease in the incidence of inducible ventricular tachycardia and sudden cardiac death in patients with a patent vessel, despite a similar degree of left ventricular dysfunction. Decreased inducibility of ventricular tachycardia in patients with early reperfusion was also noted by Kersschot et a1. (16), but their data do not distinguish between the impact of reperfusion on left ventricular function and on the electrophysiologic substrate alone. In contrast, McComb et a1. (45) were unable to document any effect of reperfusion on electrical stability, although the mortality rate in their series was very low and several patients were receiving antiarrhythmic drugs. Experimental data (11-14,46-55) imply a potentially beneficial impact of reperfusion on scar healing, infarct expansion and ventricular remodeling with chamber dilation. A link between ventricular remodeling with chamber dilation and electrical "instability" was suggested from a study (56) using the dog model of healed myocardial infarction. Volume loading widened the dispersion in refractoriness among different sites in the heart. Volume loading also increased the inducibility of arrhythmias in that study (56) and was explained on the basis that increased temporal inhomogeneity in refractoriness produced the substrate for reentry. Similar data (57) have been obtained in the isolated rabbit model in which dilation was associated with increased dispersion of refractoriness. An alternative explanation relates to differences in the regional distribution of the parasympathetic and sympa-

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VATTEROTT ET AL. LATE POTENTIALS IN INFARCT-RELATED ARTERIES

thetic jibers in the left ventricle (58). Sympathetic denervation caused by transmural infarction can produce denervation hypersensitivity to catecholamines in viable muscle distal to the site of infarction. Nonuniformity of responses to sympathetic stimulation at different sites in the heart could create the substrate for ventricular arrhythmias by enhancing the temporal inhomogeneity of refractoriness. In a recent study in dogs (59), the absence of reperfusion created homogeneous transmural infarcts and the inducibility of ventricular arrhythmias during sympathetic stimulation was enhanced in comparison with that during nontransmural infarction. Comparison with other signal-averaged ECG studies. Of the signal-averaged ECG variables, QRS duration at the 40 Hz filter setting appeared to be the most powerful correlate with vascular patency. Using multivariate analysis, Gomes et al. (36) found QRS duration at 40 Hz to be the best predictor of arrhythmic events after infarction in comparison with other clinical and signal-averaged ECG variables and other signal-averaged ECG filters. In addition, the 40 Hz filter setting has been shown to be the most reproducible signal-averaged ECG filter. In our study, the correlation between "late potentials" and arterial patency was stronger among patients with inferior infarction than among those with anterior infarction. A similar trend was noted by Gomes et ai. (36) with arrhythmias as an end point. These findings probably can be explained by the late activation of the inferobasilar region of the left ventricle. Late potentials related to septal and anterior wall depolarization may occur in the earlier part of the QRS complex and might not be detected by current techniques. Limitations. The signal-averaged ECG and coronary angiogram were not obtained simultaneously, and neither the timing of reperfusion nor the duration of occlusion was known in most patients. Furthermore, in some patients with an open infarct-related artery at angiography, silent reocclusion at the time the signal-averaged ECG was recorded would not have been detected. Nonetheless, these limitations would have weakened, not strengthened, the correlation between arterial patency and late potentials.

References 1. Braunwald E. Myocardial reperfusion, reduction of infarct size, reduction of left ventricular dysfunction, and improved survival: should the paradigm be expanded? Circulation 1989;79:441-4. 2. Califf RM, Topol E1, Gersh BJ. From myocardial salvage to patient salvage in acute myocardial infarction: the role of reperfusion therapy (editorial). J Am Coli CardioI1989;14:1382-8. 3. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Randomised trial of intravenous streptokinase, oral aspirin. both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. Lancet 1988;2:349-60. 4. Gruppo Italiano per 10 Studio della Streptochinasi nell'lnfarto Miocardico (GISSI). Long-term effects of intravenous thrombolysis in acute myocardial infarction: final report of the GISSI study. Lancet 1987;2:871-4. 5. Van de Werf F, Arnold AER. Intravenous tissue plasminogen activator

6. 7.

8. 9. 10.

II. 12. 13. 14.

15.

16.

17. 18. 19.

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