influence of thrombolysis on signal-averaged electrocardiogram and late arrhythmic events after...

Influence of Thrombolysis on Signal-Averaged Electrocardiogram and Late Arrhythmic Events

After Acute Myocardial Infarction Roberto Pedretti, MD, Antonio Laporta, MD, Mario D. Etro, MD, Adelia Gementi, MD,

Roberto Bonelli, MD, Claudio Anza, MD, Enrica Colombo, MD, Franc0 Maslowsky, MD, Francesco Santoro, MD, and Bruno Car& MD

The influence of intravenous thrombolysis on both prevalence of ventricular late potentials and incidence of late arrhythmic events was evaluated in 174 consecutive patients surviving a first acute myocardial infarction; 106 patients (61%) received thrombolysis (group A) and 66 (34%) had conventional therapy (group B). In group A, 18 patients (17%) had late potentials compared with 23 (34%) in group B (p <O.OS); mean left ventricular ejection fraction was not different (0.50 f 0.09 vs 0.50 f 0.10; p = not significant [NS]). Of 63 patients who underwent coronary arteriography because of postinfarction ischemia, 28 (44%) had a closed infarct-related artery; of these, 11 (39%) had late potentials compared with 3 of 35 (9%) with a patent artery (p <O.Ol). Mean left ventricular ejection fraction was not significantly different between the 2 groups (0.49 f 0.09 vs 0.53 f 0.09; p = NS). At a mean follow-up of 14 f 8 months, 8 of 161 patients (5%) had a late arrhythmic event; 6 of 8 (75%) with and 28 of 153 (18%) without events had late potentials (p <O.OOl). In group A, 4 of 99 patients (4%) had events compared with 4 of 62 (6%) in group B (p = NS, relative risk 1.6). Of 24 patients with anterior wall AMI and left ventricular dyskinesia, 6 events occurred. In this group of patients, a higher rate of events was observed (25%); 3 of 16 (19%) treated with thrombolysis had an event compared with 3 of 8 (37%) treated conventionally (p = NS, relative risk 2.6). Thrombolysis and patency of the infarct- related artery significantly reduce the rate of late potentials independently of global left ventricular function. Although no significant difference was found in the follow-up results, the reduced rate of late potentials suggests an improved ventricular electrical stability both in patients treated with thrombolysis and in those with a patent vessel.

(Am J Cardiol 1992;69:866-672)

From the Fondazione Clinica de1 Lavoro, Istituto di Ricovero e Cura a Carattere Scientifico, Divisione di Cardiologia, Centro Medico di Tra- date, Italy. Manuscript received August 15, 1991; revised manuscript received and accepted December 3,199 1.

Address for reprints: Roberto Pedretti, MD, Fondazione Clinica del Lavoro, Istituto di Ricovero e Cura a Carattere Scientifico, Divi- sione di Cardiologia, Centro Medico di Tradate, Via Roncaccio 16/ 18, 21049, Tradate (VA), Italy.

T he early fibrinolytic treatment of acute myocardial infarction (AMI) improves survival by reduc- ing infarct size and left ventricular dysfunction.’

However, thrombolytic therapy decreases mortality also in the absence of demonstrable myocardial salvage, and patency of the infarct-related coronary artery appears to be an important independent predictor of survival.’ Therefore, the reduction of left ventricular impairment is not the only mechanism responsible for improved survival in patients treated with thrombolysis; both limitation of remodeling of the left ventricle and increased electrical heart stability could have an important role.’ The signal-averaged electrocardiogram (SAECG) al- lows the noninvasive detection of late potentials at the end of or after the QRS complex.2 Late potentials represent low-amplitude fractionated electrical activity, are markers for an “arrhythmogenic substrate” that may become the site for re-entry,3 and provide important prognostic information in identifying patients at risk of arrhythmic events after AMI.4-8 Controversial data are available concerning the influence of fibrinolytic treatment on the prevalence of ventricular late potentials,g-15 and the effect of both thrombolysis and coronary reperfusion on late arrhythmic events after AM1 is unknown. Furthermore, no data are available concerning a possible influence of thrombolysis on the predictive ability of the SAECG for post-AM1 arrhythmic events.16 We performed a prospective study of unselected patients surviving a first AM1 to assess: (1) the influence of intravenous thrombolysis on both the rate of late potentials and ventricular ectopic activity, (2) the influence of patency of the infarct-related coronary artery on the SAECG, (3) the possible influence of intravenous thrombolysis on late potentials as markers of future malignant ventricular tachyarrhythmias, (4) and the possible influence of fibrinolysis on the occurrence of late arrhythmic events after AMI.

METHODS Patient population: From May 1989 to December

1990, 174 consecutive patients surviving a first AMI, and admitted to our institute for functional evaluation and cardiac rehabilitation were enrolled in the present study. Of patients included in the study, 106 (61%) received intravenous thrombolytic therapy within 6 hours of the onset of symptoms, and 68 (39%) were treated conventionally because of late hospitalization or contra- indications to fibrinolytic treatment. In the group treated with thrombolysis, 58 patients (55%) received streptokinase (1.5 million U over 30 to 60 minutes), 17

666 THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 69 APRIL 1, 1992

(16%) received urokinase (1.5 to 2 million U over 60 minutes), and 31 (29%) received recombinant tissue- type plasminogen activator (100 mg over 180 minutes). All patients aged >70 years with bundle branch block, flutter or atria1 fibrillation (or both), ventricular paced rhythm, heart failure, unstable angina, balloon angioplasty or coronary artery grafting before being admitted to our institute, or on amiodarone treatment, and with poor quality echocardiograms were excluded from the study. Patients (159 men and 15 women) had a mean age of 54 f 8 years. AM1 was anterior in 76 patients (44%), inferior in 98 (56%), and non-Q-wave in 43 (25%). Ventricular fibrillation during the first 5 days after AM1 occurred in 21 patients (12%).

Study desigm A maximal exercise test, Holter monitoring and an SAECG were performed with pharmacologic wash-out in all except 5 patients. In 3 and 2 cases exercise testing and Holter monitoring, respectively, were performed with pharmacologic treatment, owing to technical problems. These 5 tests were excluded from the analysis of the results. The period of washout from digitalis, p blockers, calcium antagonists and antiarrhythmic drugs was 25 times the half-life of the drug. In all patients, 2-dimensional echocardiography was performed on admission to our institute. Antiarrhyth- mic agents were administered to 6 patients after the occurrence of a late sustained ventricular arrhythmia. Antiarrhythmic drugs were administered to 12 subjects who were asymptomatic for late sustained ventricular arrhythmias. These patients (considered at high risk of late arrhythmic events after the noninvasive evaluation owing to the presence of 12 of the following criteria: left ventricular ejection fraction <0.40, ventricular late potentials, and Lown 4A-B class ventricular ectopic beats) received antiarrhythmic therapy, because sustained monomorphic ventricular tachycardia was induc- ible by programmed electrical stimulation. They were excluded from the analysis of the follow-up results, because drug therapy may modify the spontaneous occurrence of late arrhythmic events. The use of fl-adrenergic blocking agents was not standardized and was left to the discretion of the attending physician.

Follow-up data of 162 patients were analyzed; 82 (51%) were recalled for assessment of clinical status, and 80 (49%) had follow-up contact by phone. A “late arrhythmic event” was defined as sudden death or the occurrence of symptomatic or sustained ventricular arrhythmia 5 days after AMI. Sudden death was defined as a witnessed, unexpected death occurring within 1 hour of the onset of symptoms. Sustained ventricular arrhythmia was defined as spontaneous ventricular li- brillation or tachycardia lasting >30 seconds or necessi- tating cardioversion because of hemodynamic collapse.

Signal-averaged electrocardiogram: An SAECG was obtained in all patients 26 f 10 days (range 8 to 49) after AM1 using a commercial Fidelity Medical LP 3000 system. With standard bipolar orthogonal X, Y and Z leads, signals from 175 f 55 beats were ampli- fied, digitized, averaged and then filtered (band-pass filter range 40 to 250 Hz) with a Butterworth bidirec- tional filter. The signals from each of the 3 leads were combined into a vector magnitude composite electro-

gram obtained by taking the square root of the sum of the squares of the readings from the individual leads. A computerized algorithm determined the onset and offset of the QRS complex and calculated the filtered QRS duration, the duration of the terminal low-amplitude QRS signals (<40 pV), and the root-mean-square voltage of the last 40 ms of the filtered QRS complex. Mea- surement of the duration of the QRS complex was confirmed visually in each case by 2 investigators. Record- ings with a noise level >0.5 PV were rejected. The mean noise level in the late ST segment was 0.36 f 0.16 pV. Recently, for a band-pass filter range of 40 to 250 Hz, the normal values of an SAECG were defined as follows: filtered QRS duration I1 14 ms, root-mean- square voltage 220 pV, and terminal low-amplitude signal duration 138 rn18.l’ We confirmed similar normal values using the Fidelity Medical LP 3000 system. We recorded the SAECG with a band-pass filter range of 40 to 250 Hz in a group of 24 normal subjects (mean age 26 f 5 years; group I); mean filtered QRS duration was 96 f 11 ms, root-mean-square voltage was 57 f 40 pV, and terminal low-amplitude signal duration was 30 f 5 ms. Measurements from group I were used to cal- culate the 95% confidence limits of normal subjects, considering SAECG determinants to be in a Gaussian distribution. Normal values of duration of both filtered QRS (I 114 ms) and terminal low-amplitude signals (138 pV) were defined as mean f 1.645 standard deviation. The root-mean-square voltage was between 17 and 20 WV in 4 normal subjects (17%). Of 21 patients (mean age 53 f 9 years; group II) randomly selected from a group of 180 consecutive patients with previous AM1 and absence of late sustained or nonsustained ventricular tachycardia, root-mean-square voltage was <20 PV in 5 (24%) and <17 PV in 4 (19%). Of 13 consecutive patients (mean age 57 f 9 years; group III) who developed late sustained ventricular tachycardia or fibrillation, or both, root-mean-square voltage was <20 PV in 9 (69%) and <17 PV in 7 (54%). Even if >5% of normal subjects had root-mean-square voltage <20 pV, a value of <20 PV was considered abnormal for both the sake of uniformity and comparative purposes, because most laboratories use this value for defining an abnormal value when assessing this variable at 40 Hz. Furthermore, 2 of 13 patients (15%) with a late sustained ventricular arrhythmia had root-mean-square voltage between 17 and 20 WV. At least 2 SAECG determinants were abnormal in 9 of 13 patients (69%) in group III, in 4 of 2 1 (19%) in group II, and in no sub- ject in group I. Therefore, late potentials were considered present if 12 SAECG determinants were abnormal. In 110 of 174 patients (63%) also, an SAECG with a band-pass filter range of 25 to 250 Hz was available. According to the criteria of Simson using 25 Hz high- pass filtering, the normal values of the SAECG were defined as follows: filtered QRS duration I120 ms, and root-mean-square voltage 125 pV. The abnormality of 11 of these criteria defined the test as pathologic.

Holter monitoring: Holter monitoring (recorded 23 f 9 days after AM1 with pharmacologic washout) was available in 172 patients: 112 (65%) underwent 48-hour Holter monitoring, and 60 (35%) had 24-hour monitor-

THROMBOLYSIS AND LATE POTENTIALS 867

ii ng. A 3-channel electrocardiogram (ECG) was analyzed with a Marquette Electronics Holter 8000 T analysis system; 4 investigators verified the detection and interpretation of ventricular arrhythmias. Lown class and the number of premature ventricular complexes were assessed.

TABLE I Characteristics of Patients With and Without Thrombolysis for Acute Myocardial Infarction

Thrombolysis No Thrombolysis (n = 106) In = 68) p Value

Clinical data Age (yr) 53 f 9 55 r 8 NS Men/women 100/6 5919 NS VF O-5 days after AMI 14/106 (13) 7/68 (10) NS Anterior AMI (%) 44/106 (41) 32168 (47) NS Inferior AMI (%) 62/106 (59) 36/68 (531 NS Non-Q-wave AMI (%) 20/106 (19) 23/68 134) <0.05

2-dimensional echocar- diographic data

LVEF 0.50 +- 0.09 0.50 ZF 0.10 NS Dyskinesia (%) 21/106 (20) 14/68 (21) NS

Signal-averaged ECG data LP(%) 18/106 (17) 23/68 (34) <0.05 QRSD (ms) 99 k 10 103 k 11 <0.05 RMS40 (IL’.‘) 48 f 35 37 k 32 <0.05 LAS40 (ms) 31 z 14 34+ 11 NS

Holter monitoring data VPCs/hours (n) 7 f 25 10 t 24 NS Lown l-3 VPCs (%) 52/105 (50) 36167 (54) NS Lown 4A VPCs (%I 18/105 (17) 14/67 (21) NS Lown 4B VPCs (%) 32/ 105 (30) 16/67 (24) NS

Exercise test data No VPCs (%) 68/106 (64) 39/65 (60) NS Lown l-3 VPCs (%) 32/106 (30) 19/65 (29) NS Lown z 4 VPCs (%) 6/106 (6) 7/65 (11) NS

Continuous variables are expressed as mean t 1 SD. AMI = acute myocard!al infarction; ECG = electrocardiographic; LAS40 = duration

of low-amplitude si nals ~40 bV; LP = late potentials: LVEF = left ventricular ejection fraction; N I- ” - not slgnlficant; QRSD = duration of filtered QRS complex; RMS40 = root-mean-square voltage of !ast 40 ms of filtered QRS complex; VF = ventricular fibrillation; VPCs = ventricular premature complexes.

Other diagnostic proeedm In all patients, a 2-dimensional echocardiogram using a Ving Med CFM 750 unit was obtained 21 f 10 days after AMI. Evaluation of left ventricular ejection fraction by Simpson’s formu- la, and detection of left ventricular dyskinesia were performed. With pharmacologic washout, a maximal exercise test according to Bruce’s protocol was performed by 17 1 patients on a Marquette Electronics Case 12 tread- mill 27 f 10 days after AMI, and the Lown class of ventricular ectopic beats was evaluated. Owing to post- AM1 myocardial ischemia, coronary arteriography was performed in 63 patients (36%) 43 f 22 days after AMI. Cardiac catheterization was performed by angi- ographers who were not investigators in this study. The artery involved in the AM1 was identified on the basis of the location of the AM1 as determined by electrocardiography. The infarct-related artery was considered open in the case of partial or complete anterograde perfusion. The complete absence of anterograde perfusion defined the artery as occluded.

%atistical analysis: Continuous variables were compared using Student’s unpaired t test, and proportional

TABLE II Characteristics of Patients With and Without Late Potentials

Late Potentials No Late Potentials (n = 41) (n = 133) p Value

Clinical data Age (yr) 56 k 8 53 f 8 co.05 Men/women 3615 123/10 NS VF O-5 days after AMI 8/41 (19) 13/133 (10) NS Anterior AMI (%) 16/41 (39) 60/133 (45) NS Inferior AMI (%) 25/41 (61) 73/133 (55) NS Non-Q-wave AMI (%) 9/41 (22) 34/ 133 (26) NS


LVEF 0.45 2 0.11 0.51 f 0.08 <O.OOl Dyskinesia (%) 12/41 (29) 23/133 (17) NS

Holter monitoring data VPCs/hours (n) 8 k 22 8 -c 26 NS Lown l-3 VPCs (%I 23/39 (59) 64/133 (48) NS Lown 4A VPCs (%) 8/39 (21) 24/133 (18) NS Lown 48 VPCs (%) 8/39 (21) 40/133 (30) NS

Exercise test data No VPCs (%) 24/38 (63) 83/ 133 (62) NS Lown l-3 VPCs (%) 12/38 (32) 39/133 (29) NS Lown r4 VPCs (%) 2138 (5) 11/133 (8) NS

Abbreviabons as in Table I.

differences were compared by chi-square analysis with Yates’ correction for continuity. Continuous variables were expressed as mean f 1 standard deviation. Logis- tic regression analysis was performed with late potentials as the dependent variable, and age, AM1 location, development of pathologic Q waves, left ventricular ejection fraction, and dyskinesia, thrombolytic therapy and status (patent or closed) of infarct-related artery as independent variables. A p value <0.05 was considered statistically significant. The standard definitions for sensitivity, specificity, and positive and negative predictive values were used.

RksULTS Comparison of pafits with and without thrambo-

lytic therapy: Prevalence of both non-Q-wave AM1 and ventricular late potentials was significantly different between the 2 groups of patients. Prevalence of non-Q- wave AM1 was significantly (p <0.05) lower in the group treated with thrombolysis, as well as rate of late potentials (p <0.05), using a band-pass filter range of 40 to 250 Hz (Table I). In the group treated with thrombolysis, filtered QRS duration was significantly (p <0.05) lower, and terminal root-mean-square voltage was significantly (p <0.05) higher than in the control group; no significant difference was observed regarding duration of terminal low-amplitude signals (Table I). Of 58 patients treated with streptokinase, 10 (17%) had late potentials compared with 4 of 3 1 (13%) treated with recombinant-tissue plasminogen activator, and 4 of 17 (23%) treated with urokinase (p = not significant [NW.

In 110 patients, an SAECG with both band-pass filter ranges of 40 to 250 and 25 to 250 Hz was available. We compared 75 patients (68%) treated with throm-


TABLE III Characteristics of Patients With and Without a Patent Infarct-Related Artery

Patency of Occlusion of the Infarct- the Infarct-

Related Artery Related Artery (n = 35) (n = 28) p Value

Clinical data Age (yr) 49 k 8 52 + 8 NS Men/women 3213 2711 NS VF O-5 days after AMI 5135 (14) 3/28 (11) NS Anterior AMI (%I 18/35 (51) 13/28 (46) NS Inferior AMI (%) 17135 (49) 15/28 (54) NS Non-Q-wave AMI (%) 14135 (40) 7128 (25) NS Thrombolysis (%) 23/35 (66) IO/28 (36) < 0.05 No thrombolysis (%) 12/35 (34) 18/28 (64) <0.05


LVEF 0.53 + 0.09 0.49 k 0.09 NS Dyskinesia (%) 6135 (17) 7128 (25) NS

Signal-averaged ECG data LP (%) 3135 (9) 1 l/28 (39) < 0.01 QRSD (ms) 97 ‘- 7 105 2 11 <O.Ol RMS40 (IL!‘) 52 + 29 31 -c 35 <0.05 LAS40 (ms) 27 t 6 36 r 12 <O.OOl

Holter monitoring data VPCs/hours (n) 4 + 14 7 + 19 NS Lown l-3 VPCs (%) 15/35 (43) 15/28 (54) NS Lown 4A VPCs (%) 9/35 (26) 2/28 17) NS Lown 46 VPCs (%I 11/35 (31) 1 l/28 (39) NS

Exercrse test data No VPCs (%) 27135 (77) 16127 (59) NS Lown l-3 VPCS f%) 6/35 (17) lo/27 (37) NS Lown 24 VPCs (%) 2135 (6) l/27 (4) NS

Abbrevlatfons as in Table I,

bolysis with 35 (32%) treated conventionally. With a band-pass filter range of 40 to 250 Hz, we observed significant differences in filtered QRS duration (98 f 10 vs 105 f 11 ms; p <O.Ol), terminal root-mean- square voltage (53 f 36 vs 32 f 25 pV; p <O.Ol) and duration of terminal low-amplitude QRS signals (29 f 9 vs 36 f 12 ms; p <O.Ol). The rate of late potentials was significantly lower in the group treated with thrombolysis (10 of 75 [13%] vs 15 of 35 [43%]; p <O.Ol). With a band-pass filter range of 25 to 250 Hz, no significant difference was observed regarding filtered QRS duration (105 f 10 vs 104 f 14 ms; p = NS), terminal root-mean-square voltage (64 f 47 vs 71 f 48 pV; p = NS), duration of terminal low-amplitude QRS signals (28 f 12 vs 26 f 9 ms; p = NS) and prevalence of SAECG abnormalities (17 of 75 [23%] vs 9 of 35 [26%]; p = NS).

Comparison of patients with and without vemtricu- lar late potentials: Among the variables considered, only age and left ventricular ejection fraction were significantly different between the 2 groups of patients: mean age was significantly (p <0.05) higher and mean ejection fraction significantly (p <O.OOl) lower in the group with late potentials (Table II).

Comparison of pathts with and without patency of the infarct-related coronary artery: Of patients with a closed infarct-related artery, the prevalence of late potentials was significantly (p <O.Ol) higher than in the

TABLE IV Characteristics of Patients With and Without Late Arrhythmic Events

Arrhythmic No Arrhythmic Events Events

(n = 8) (n = 153) p Value

Clmical data Age (yr) 53 ‘- 9 54 k 8 NS Men/women 8/O 139/14 NS VF O-5 days after AMI 118 (12) 18/153 (12) NS Anterior AMI t%) 718 (88) 621153 (40) <0.05 lnfenor AMI (%) l/8 (12) 91/153 (60) <0.05 Non-Q-wave AMI (%) l/8 (12) 40/153 (26) NS Thrombolysis (%I 4/8 (50) 95/153 (62) NS No thrombolysis (%) 4/8 (50) 58/153 (38) NS

2-dimensional echocar- diographrc data

LVEF 0.35 2 0.06 0.51 k 0.08 <O.OOl Dyskinesia (%) 618 (75) 25/153 (16) <O.OOl

Signal-averaged ECG data LP(%) 618 (75) 28/153 (18) <O.OOl QRSD (ms) llli 10 99 2 10 co.01 RMS40 t&V) 18 lr 16 46 + 35 <0.05 LAS40 (ms) 42 f 13 31 A 13 <0.05

Halter monitoring data VPCsihours (n) 16 2 32 8 AZ 25 NS Lown l-3 VPCs !%) l/6 (17) 871153 (57) NS Lown 4A VPCs (%) O/6 (0) 311153 (20) NS Lown 4B VPCs (%) 516 (83) 35/153 (23) <O.Ol

Exercrse test data No VPCs (%I 316 (50) 95/152 162) NS Lown l-3 VPCs (%) 3/6 (50) 45/152 (30) NS Lown t 4 VPCs (%) O/6 (0) 121152 (8) NS

Ahhmmtlonz IF ,n Table I

group with a patent vessel (Table III); also, filtered QRS duration (p <O.Ol), duration of terminal low-amplitude signals (p <O.OOl), and terminal root-mean- square voltage (p <0.05) were significantly different (Table III). Late potentials had sensitivity and specificity for a closed infarct-related coronary artery of 39 and 91%, respectively. The positive and negative predictive values were 79 and 65%, respectively. No other compar- isons were statistically significant, except for the thrombolytic therapy rate in the group with a patent artery; a significantly (p <0.05) higher number of patients than that in the group with a closed vessel received thrombolysis (Table III).

Of 63 patients who underwent coronary arteriography, 30 (48%) did not receive thrombolysis; 12 (40%) of these had patency of the infarct-related artery, whereas 18 (60%) had a closed vessel. In the group with a patent artery, 1 of 12 patients (8%) had late potentials compared with 7 of 18 (39%) with a closed artery (p = NS). We compared mean values of filtered QRS duration (101 f 8 vs 103 f 10 ms; p = NS) and terminal root-mean-square voltage (48 f 24 vs 35 f 41 pV; p = NS); no significant difference was found between the 2 groups. Conversely, duration of terminal low-amplitude QRS signals (26 f 8 vs 35 f 10 ms; p <0.05) was significantly lower in the group with a patent vessel. Mean left ventricular ejection fraction was not significantly different (0.5 1 f 0.10 vs 0.54 f 0.09; p = NS).


Fdlow-up data: At a mean follow-up of 14 f 8 months after AMI, 8 of 161 patients (5%) developed a late arrhythmic event; 6 of 8 events (75%) occurred in the first 2 months after AM1 (mean 21 f 18 days, range 6 to 55). Conversely, only 2 events (25%) were observed 11 and 16 months after AMI. Sudden death occurred in 2 patients, 4 had sustained ventricular tachycardia, and 2 had aborted sudden death with evi- dence of ventricular fibrillation at the time of cardioversion. Syncope and cardiac arrest with recovery of spontaneous cardiac activity after a short cardiopulmonary reanimation were observed in 1 patient. In this patient, heart rhythm during the cardiac arrest was not docu- mented, and the electrophysiologic study was not performed, because the patient did not consent. Therefore, this event was not included in the statistical analysis. None of 6 patients with late sustained ventricular tachyarrhythmias developed new Q waves on ECG..

Anterior site of AM1 (p <0.05), left ventricular dyskinesia (p <O.OOl) and ejection fraction (p <O.OOl), late potentials (p <O.OOl), filtered QRS duration (p <O.Ol), terminal root-mean-square voltage (p <0.05), duration of terminal low-amplitude signals (p <0.05), and Lown 4B-class ventricular ectopic beats on Holter monitoring (p <O.Ol) had a significant relation to late arrhythmic events (Table IV).

In the general population of the study, sensitivity, specificity, and positive and negative predictive values of late potentials for late arrhythmic events were 75, 82, 18 and 98%, respectively. Of 99 patients treated with thrombolysis, the significant relation between late potentials and arrhythmic events was preserved. Ar- rhythmic events occurred in 4 of 99 patients (4%) treated with thrombolysis; 3 (75%) of these had late potentials compared with 13 of 95 (14%) without events (p <0.05). In the group treated with thrombolysis, sensitivity, specificity, and positive and negative predictive values of late potentials for late arrhythmic events were 75, 86, 19 and 99%, respectively.

Regarding the prevalence of thrombolytic therapy, no significant difference was found between the 2 groups of patients with and without events (Table IV). Patients with conventional therapy had a relative risk of developing late arrhythmic events of 1.6 compared with those treated with thrombolysis. Of patients with late arrhythmic events, 6 of 8 (75%) had both anterior wall AM1 and left ventricular dyskinesia; thus, in this group the event rate was 25% (6 of 24). Regarding fibrinolytic treatment, 16 of 24 patients (67%) received thrombolysis, and 8 (33%) were treated conventionally. In the group treated with thrombolysis, 3 of 16 patients (19%) developed late arrhythmic events compared with 3 of 8 (37%) in the control group (p = NS). Mean left ventricular ejection fraction was not significantly different (0.38 f 0.09 vs 0.38 f 0.06; p = NS). Of patients with anterior wall AM1 and left ventricular dyskinesia, the relative risk of developing late arrhythmic events was 2.6 without thrombolytic therapy.

Multivariate analysis: We performed a stepwise lo- gistic regression analysis to assess the relation between late potentials and independent variables such as age,

AM1 location, development of pathologic Q waves, left ventricular ejection fraction and dyskinesia, and thrombolytic therapy. Left ventricular ejection fraction (p <O.OOl), AM1 location (p <O.Ol) and thrombolytic therapy (p <O.Ol) were found to be independent predictors of late potentials. We performed a similar analysis in the group of 63 patients who underwent coronary arteriography, including the status of the infarct-related coronary artery among independent variables. The status of the infarct-related artery was found to be the only independent predictor of late potentials (p <O.Ol); left ventricular ejection fraction and thrombolytic therapy did not reach levels of significance.

DISCUSSION This study, in agreement with other re-

prts,9,10,12,13,15 f ound a significantly lower prevalence of late potentials in the group treated with thrombolysis. Regarding the rate of late potentials and the SAECG quantitative analysis, a significant difference between the 2 groups of patients with and without thrombolysis was observed only using a band-pass filter range of 40 to 250 Hz; no difference was present using 25 Hz high- pass filtering. This result is in agreement with the data of Chew et a1.i3 Therefore, a band-pass filter range of 25 to 250 Hz could undervalue the presence of late potentials, as found by Gomes et ali* and Denes et al.lg Therefore, in the study of Turitto et al” the absence of a significant difference in the prevalence of late potentials between patients treated with thrombolysis and control subjects could be related to the use of 25 Hz high-pass filtering.

According to other investigators,8,20q21 the presence of late potentials seemed to characterize patients with greater left ventricular dysfunction. Greater infarct size and left ventricular dysfunction are associated with late potentials. Therefore, early reperfusion and reduction of the left ventricular impairment could prevent SAECG abnormalities. In our study, as in others,gJ3-15*22 a significant correlation between patency of the infarct-related coronary artery and reduced prevalence of late potentials was found, and the multivariate analysis showed the status (patency or occlusion) of the infarct-related artery to be the only independent predictor of late potentials. Therefore, occlusion of the infarct-related coronary artery appears to be the most important cause of late potentials, independent of global left ventricular function. Late potentials were specific markers of ccclu- sion of the infarct-related coronary artery; this finding could have great clinical relevance, because patency of the infarct-related artery represents an independent predictor of surviva1.l However, in the present study, cardiac catheterization was performed because of post-AM1 ischemia, and this fact may represent a possible selec- tion bias; even the small number of patients who underwent coronary arteriography represents a limitation of our study.

No data are available concerning the influence of late reperfusion on the prevalence of late potentials. Vatterott et ali4 found that a patent vessel was not associated with a statistically significant reduction in the


rate of late potentials without reperfusion therapy in the acute stage of AMI. Nevertheless, of patients not un- dergoing early therapy directed toward achieving reperfusion, a significantly lower filtered QRS duration was observed when the infarct-related artery was patent. In our study, coronary arteriography was available in 30 patients not treated with thrombolysis. In this group, spontaneous reperfusion may have been a late phenome- non beyond the conventionally accepted period during which reperfusion can modify infarct size. Quantitative analysis of the SAECG showed that the duration of terminal low-amplitude signals was significantly lower in the group with a patent vessel. The number of patients studied (48 in the study of Vatterott et a1,14 and 30 in our study) is too small to advance conclusions, but a beneficial effect of late reperfusion on the development of late potentials can be hypothesized, because statistical analysis showed a favourable effect of patency of the infarct-related coronary artery on 2 determinants of the SAECG (filtered QRS duration in Vatterott’s study,14 and duration of terminal low-amplitude signals in our study). The results of a recent study by Lacroix et a12’ were in compliance with this possibility; in fact, in a group of patients with coronary artery disease, they doc- umented a reduction of 65% in the prevalence of late potentials after coronary bypass surgery.

The detection of frequent or complex, or both, ventricular ectopic beats on a predischarge Holter recording represents an independent prognostic factor for late arrhythmic events after AMI.23-26 Some studiesi1J2J5,27 evaluated the influence of reperfusion and thrombolytic therapy on late ventricular ectopic activity; the results were controversial. We used maximal exercise testing and Holter monitoring to evaluate the ventricular ectopic activity in our patients. The majority of patients underwent 48-hour recording for better detection of complex ventricular arrhythmias (couplets and ventricular tachycardia). We did not find any significant difference in both frequency and complexity of ventricular ectopic beats between patients treated with thrombolysis and control subjects. Furthermore, late ventricular ectopic activity was not significantly different between patients with and without patency of the infarct-related coronary artery.

In the follow-up studies we found that late potentials were significantly related to late arrhythmic events. Several investigators4-8 evaluated the prognostic significance of late potentials; in these studies it was not men- tioned how many patients received thrombolysis. Fur- thermore, most of these studies were performed before the extensive use of fibrinolytic therapy. We analyzed the possible influence of thrombolysis on the predictive ability of late potentials for a post-AM1 arrhythmic event, as suggested in a recent editoriall$ also, in the group of 99 patients treated with thrombolysis, late potentials were significantly related to late arrhythmic events. Therefore, detection of late potentials is a useful marker of future malignant ventricular tachyarrhythmias after thrombolytic therapy.

We evaluated a possible difference in arrhythmic event rate between patients treated with and without

thrombolysis in both the general population of the study and the group with anterior wall AM1 and left ventricular dyskinesia (higher event rate). We did not observe any significant difference; in any case there was a significantly higher relative risk of developing arrhythmic events in the conventionally-treated group. The small number of arrhythmic events and the short follow-up prevent us from advancing conclusions.

An extremely low mortality rate was observed in patients with reperfusion compared with in those without.’ This finding contrasts strikingly with the relatively modest changes in left ventricular function observed between the 2 groups of patients. Conversely, a significant difference in the rate of late potentials is appreciable in both reperfused patients and those treated with thrombolysis.9JoJ2-15 Our data are in agreement with these findings. Moreover, in agreement with other studies,4-8 late potentials were significantly related to late arrhythmic events, and several investigators5,‘,* have found late potentials to be independent predictors of malignant ventricular tachyarrhythmias after AMI. The mechanism responsible for reduced mortality after tibrinolysis has not yet been examined.28 The results of this and other studies strongly suggest increased electrical heart stability as a potential mechanism for the improvement in prognosis after thrombolysis. The prevention of the development of an arrhythmogenic substrate in reperfused patients could have an important role in increas- ing survival after AMI.

Acknowledgment: We wish to acknowledge the as- sistance of Luigi Ballardini (electronics engineer), and Emanuela Radice (information specialist) for data analysis.

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