Aspirin, clopidogrel, and warfarin: is the combination appropriate and effective or inappropriate and too dangerous?

OBJECTIVE: To review the rationale, clinical practice guideline recommendations, and clinical trial data describing bleeding and clinical outcomes associated with the use of the combination of aspirin, a thienopyridine, and warfarin. DATA SOURCES: An English-language literature search was conducted using MEDLINE (1966-March 2008) and the search terms aspirin, clopidogrel, ticlopidine, thienopyridine, warfarin, antiplatelet, anticoagulant, myocardial infarction, atrial fibrillation, and percutaneous coronary intervention (PCI). Additional references were identified by reviewing reference citations of articles retrieved. STUDY SELECTION AND DATA EXTRACTION: Applicable data were extracted from published reports and studies that included either clinical outcomes or adverse events. DATA SYNTHESIS: Clinical guidelines recommend the combination of antiplatelets and anticoagulants based largely on writing committee consensus. To date, only one randomized clinical trial has evaluated the safety and efficacy of adding warfarin to dual antiplatelet therapy (ie, triple antithrombotic therapy). Other published data are from case series, observational studies, and case-controlled studies primarily of patients undergoing PCI with intracoronary stent placement. Four of 12 studies reported no increased risk of major bleeding events. In the other 8 studies, a 3- to 6-fold increase in bleeding events was reported with triple antithrombotic therapy. Ischemic events were reported in only 6 of the studies. Only 2 studies observed an additional benefit in the reduction of ischemic events, and 1 study reported worsened ischemic outcomes with the triple antithrombotic regimen compared with dual antithrombotic therapy. CONCLUSIONS: Available guidelines pertaining to the concomitant administration of aspirin, a thienopyridine, and warfarin are based on limited trial data and consensus judgment. Overall, selection of triple antithrombotic therapy for patients with vascular disease is considered a matter of clinical judgment for an individual patient based on the prescriber's perceived balance between the patient's risk for recurrent ischemic events, expected duration of treatment, and patient's risk for bleeding.

Rationale and design of ACTIVE: the atrial fibrillation clopidogrel trial with irbesartan for prevention of vascular events.

BACKGROUND: Atrial fibrillation (AF) is the most frequently occurring cardiac arrhythmia with often serious clinical consequences. Many patients have contraindications to anticoagulation, and it is often underused in clinical practice. The addition of clopidogrel to aspirin (ASA) has been shown to reduce vascular events in a number of high-risk populations. Irbesartan is an angiotensin receptor-blocking agent that reduces blood pressure and has other vascular protective effects. METHODS AND RESULTS: ACTIVE W is a noninferiority trial of clopidogrel plus ASA versus oral anticoagulation in patients with AF and at least 1 risk factor for stroke. ACTIVE A is a double-blind, placebo-controlled trial of clopidogrel in patients with AF and with at least 1 risk factor for stroke who receive ASA because they have a contraindication for oral anticoagulation or because they are unwilling to take an oral anticoagulant. ACTIVE I is a partial factorial, double-blind, placebo-controlled trial of irbesartan in patients participating in ACTIVE A or ACTIVE W. The primary outcomes of these studies are composites of vascular events. A total of 14000 patients will be enrolled in these trials. CONCLUSIONS: ACTIVE is the largest trial yet conducted in AF. Its results will lead to a new understanding of the role of combined antiplatelet therapy and the role of blood pressure lowering with an angiotensin II receptor blocker in patients with AF.

Comparative study of cerebral blood flow between postural tachycardia and neurocardiogenic syncope, during head-up tilt test.

We assessed the cerebral blood flow velocity response to head-up tilt test in patients with typical neurocardiogenic syncope compared with patients showing postural tachycardia. Fifty patients (21 men) with history of orthostatic intolerance, younger than 50 years (mean 27 +/- 10), participated in the study. Transcranial Doppler sonography of the middle cerebral artery, heart rate and brachial blood pressure were recorded during a head-up tilt test. According to the outcome of the test, patients were categorized in two groups: neurocardiogenic syncope (29 patients) and postural tachycardia (21 patients). The clinical history of the two groups was similar. During baseline in the supine position, no differences in haemodynamic parameters were observed. From the first min of tilt, the heart rate was higher in patients with postural tachycardia than in patients with neurocardiogenic syncope. Although, during tilt, the absolute values of the cerebral blood flow parameters were similar in the two groups, throughout tilt, continuous observation of the Doppler recording in patients with postural tachycardia showed intermittent fluctuation of the blood flow velocity, with an oscillatory pattern, which were not observed in the recordings in patients with neurocardiogenic syncope. Comparison of patients with neurocardiogenic syncope, and those with postural tachycardia also showed larger variations of the pulsatility index (P < 0.05) in the postural tachycardia group. These findings support the possibility that abnormalities within the central nervous system play a pivotal role in the pathogenesis of postural tachycardia.

Orthostatic hypotension, 2001.

Upright posture requires rapid and effective circulatory and neurologic compensations to maintain blood pressure and consciousness. Although it has been recognized over the past 100 years or more that the act of standing may cause hypotension in patients with autonomic dysfunction, only recently several of the pathophysiologic mechanisms resulting in orthostatic intolerance have been discovered. In patients with orthostatic hypotension, failure of reflex vasoconstriction causes pooling of blood in the legs during standing. Not everyone with a postural blood pressure drop requires treatment, nor does everyone with posturally induced symptoms have orthostatic hypotension. This review will discuss current knowledge of a broad, heterogeneous group of disturbances in the autonomic nervous system, each of which is manifested by hypotension, orthostatic intolerance, and often syncope.

Repeatability of heart rate variability during simple cardiovascular reflex tests on healthy subjects.

BACKGROUND: Our purpose was to determine the repeatability, after 2 weeks, of frequency domain measures of heart rate variability (HRV) during simple cardiovascular reflex tests. METHODS: Twenty healthy volunteers aged 29.3 +/- 2.5 years were assessed twice (at weeks 0 and 2). Continuous electrocardiogram and minute-to-minute blood pressure were recorded during spontaneous and metronome-paced breathing (0.2 Hz). Under paced breathing, two tests were performed: 1) active change of posture: 5 min supine position, 5 min seated upright, and 5 min standing up, and 2) cold pressor test: the right hand was immersed in cold water (5 degrees C) for 2 min. RESULTS: Paced breathing elicited a significant increase of the high-frequency (HF) component of HRV. This effect was repeatable on 95% of the subjects. Active change of posture induced a significant increase of the heart rate with an increase of the low-frequency/high-frequency ratio of HRV. Although repeatability was better for the response to being seated upright than for the response to being standing up, it was always higher than 90%. The cold pressor test induced a significant increase of the heart rate and blood pressure, but with variable changes on the HRV measurements (either a decrease or an increase). Repeatability of responses was evident for 95-100% of the subjects. Although repeatability of HRV measurements in the same subject during the tests was higher than 95%, coefficients of repeatability reflected large differences among the subjects. CONCLUSIONS: The results suggest that it is not advisable to use isolated HRV changes to interpret the response to simple cardiovascular reflex tests in groups of healthy subjects.

Evidence of a linkage between neurocardiogenic dysfunction and reactive hypoglycemia.

OBJECTIVE: Reactive hypoglycemia is a common medical problem whose pathophysiology is not completely understood. The objective of this study was to investigate the prevalence of autonomic nervous system abnormalities in patients with reactive hypoglycemia compared with controls. METHODS: Six women, mean age 31 +/- 5 years, with reactive hypoglycemia, and 5 healthy controls women aged 24 +/- 4 years were studied. We investigated the heart rate variability and blood pressure changes after an upright tilt with and without an isoproterenol infusion. A positive result was defined as syncope or presyncope associated with bradycardia, hypotension or both. RESULTS: In response to the orthostatic stress alone or in conjunction with a 4 micrograms isoproterenol infusion, 5 of 6 patients had a positive test as did one of the five control subjects. Patients had a baseline hyperadrenergic tone, with a sympathetic to parasympathetic ratio of 2.3 +/- 0.8 under basal conditions and 10.1 +/- 4.1 during the isoproterenol infusion, compared to 0.7 +/- 0.3 (p = 0.06) and 0.5 +/- 0.1 (p < 0.01) respectively, in the control group. CONCLUSION: Patients with reactive hypoglycemia may be at the extreme end of a spectrum of normal biologic variability, they may have an hyperadrenergic tone and, after a provocative stimulus, sympathetic nerve firing and or synaptic release of NE may not be sufficient to maintain an adequate vascular tone. Alternatively, the vascular response to NE may be impaired. An excessive and paradoxic vasovagal or parasympathetic response was not observed.

Tilt testing in neurocardiogenic syncope: isosorbide versus isoproterenol.

OBJECTIVE: To compare the diagnostic value of pharmacological stimulation with sublingual isosorbide dinitrate and intravenous isoproterenol during tilt testing in patients with neurocardiogenic syncope and with a negative tilt test without pharmacological provocation. METHODS AND RESULTS: One hundred and twenty patients with a history of neurocardiogenic syncope (aged 15 to 77 years) and 50 healthy volunteers (aged 25 to 70 years) were prospectively submitted to head-up tilt (HUT). Those who did not develop syncope or presyncope during passive HUT for 30 minutes underwent repeated HUT with isoproterenol infusion at 4 microg/min (ISOP HUT), for 10 minutes, and, subsequently, were tilted after sublingual administration of 5 mg of isosorbide dinitrate (ISDN HUT) for another 12 minutes. ISDN HUT was always performed after ISOP HUT. Sensitivity and specificity of passive HUT were 41% (95% C.I. 32.9% to 51.0%) and 100%, respectively. Sensitivity of ISOP HUT was 51.4% (95% C.I. 39.2% to 63.6%) and specificity 70% (95% C.I. 55.4% to 82.1%) and for ISDN HUT were 70% (95% C.I. 57.9% to 80.4%) and 88% (95% C.I. 75.7% to 95.5%), respectively. The accuracy of ISDN HUT was significantly higher than the accuracy of ISOP HUT 77.5% (95% C.I. 68.9% to 84.6%). There were fewer side effects during ISDN HUT. CONCLUSION: Sublingual isosorbide dinitrate is at least as sensitive as isoproterenol to assess patients with suspected neurocardiogenic syncope and with a negative tilt test without provocation. The low rate of side effects and the higher accuracy of ISDN HUT, along with the simplicity of this challenge compared to ISOP HUT, suggest that sublingual isosorbide dinitrate should be preferred as a provocative agent to evaluate neurocardiogenic syncope after a negative passive tilt test.

Differences in heart rate variability between cardioinhibitory and vasodepressor responses to head-up tilt table testing.

BACKGROUND: Patients with syncope show different responses to head-up tilt (HUT) test, which may be due to different pathophysiological mechanisms. METHODS: HUT (70 degrees) was performed in 24 patients who experienced recurrent syncope. Nine patients had a cardioinhibitory (CI) response, 7 patients had a vasodepressor (VD) response, and 8 patients had a mixed (MX) response. Heart rate variability was analyzed at 60-sec periods during HUT. RESULTS: Total spectrum (TS) was greater at rest and 1 min after syncope in the CI and MX groups as compared to the VD group. Low frequency spectrum (LF) was significantly greater during rest and the first minute after syncope in the CI groups as compared with the VD group. After the rest period, the CI and MX groups showed more elevated high frequency spectrum (HF) values than the VD group (p < 0.01). One minute after syncope, the HF increased in the CI and MX groups but not in the VD group (p < 0.01). The VD group showed higher LF/HF ratio from the beginning of rest (3.9 +/- 4.1) as compared to the CI and MX groups (p < 0.01). This difference was most significant 2 min before syncope occurred. The CI and MX groups showed greater pNN50 and rMSSD as compared to the VD group. CONCLUSIONS: Our results suggest that vagal tone is higher in subjects showing cardioinhibitory and mixed responses to HUT. In contrast, patients with a vasodepressor response showed predominantly sympathetic activity. These findings suggest that there are different pathophysiological mechanisms underlying syncope.

Successful radiofrequency ablation of an accessory pathway during pregnancy.

The preexcitation syndrome is a rare entity during pregnancy. We present a 20-week pregnant patient with Wolff-Parkinson-White syndrome and recurrent episodes of tachycardia with hemodynamic compromise refractory to medical treatment that required electrical cardioversion several times. Due to the poor evolution we performed a successful radiofrequency ablation of a right posteroseptal accessory pathway using 70 seconds of total fluoroscopy time without complications. We consider this is an alternative and safer treatment in those cases in which the tachyarrhythmias compromise the hemodynamic state during pregnancy.

Positive head-up tilt table test in patients with the long QT syndrome.

AIMS: Syncope in patients with the long QT syndrome is commonly attributed to a ventricular arrhythmia (torsades de pointes). The susceptibility of patients with the long QT syndrome (LQTS) to neurally mediated syncope is currently unknown. METHODS AND RESULTS: Head-up tilt table testing (70 degrees) was performed in six patients with the long QT syndrome and a history of syncope. All patients had syncope with a mixed response. The RR interval was significantly decreased 2 min before the onset of syncope (980 +/- 125 ms vs 630 +/- 91 ms, P=0.003), and significantly increased during syncope (983.17 +/- 224.71; P=0.006). Non-significant changes in QT intervals were observed. Baseline QT was 513 +/- 86 ms and decreased to 450 +/- 59 ms 2 min before the onset of syncope (P=0.11). Although not statistically significant, QT intervals during syncope were longer than at 2 min before syncope (485 +/- 85 ms vs 450 +/- 59 ms; P=0.29). CONCLUSION: Our results suggest that patients with the LQTS are susceptible to neurally mediated syncope. Whether this susceptibility differs from control populations remains unresolved. From a clinical standpoint, neurocardiogenic syncope should be considered a diagnostic alternative in patients with LQTS.

The dysautonomia of fibromyalgia may simulate lupus.

Some overlap between features of fibromyalgia and systemic lupus erythematous (SLE) is well-recognized. Our objective is to describe eight patients with an original diagnosis of SLE, in whom, after re-evaluation, the multi-system symptoms could be explained on the basis of the dysautonomia that occurs in fibromyalgia.Seven of the eight patients were females. Their mean age was 31 years. All of them fulfilled the American College of Rheumatology criteria for fibromyalgia. Their lupus-like features that could later be explained by dysautonomia were the following: diffuse arthralgias with subjective feeling of swelling, malar erythema, syncopal episodes, profound fatigue, and distal vasospastic changes. Six patients had low titer ANA. None of the patients had signs of organic damage. Autonomic dysfunction was demonstrated by means of circadian studies of heart rate variability (6 patients) and/or tilt table testing (3 patients). We conclude that autonomic dysfunction may be an explanation for the lupus-like symptoms present in some patients with FM.

Circadian studies of autonomic nervous balance in patients with fibromyalgia: a heart rate variability analysis.

OBJECTIVE: To determine the accumulated 24-hour cardiovascular autonomic modulation and its circadian variations in patients with fibromyalgia, by means of heart rate variability analysis. METHODS: Thirty patients with fibromyalgia and 30 age- and sex-matched controls were studied prospectively. Assessments included a 24-hour ambulatory recording of heart rate variability, time-domain analysis of the accumulated 24-hour R-R interval variations, and power spectral analysis to determine the sympatho/ vagal balance at different hours (calculated as the power spectral density of the low-frequency [0.04-0.15-Hz] sympathetic band divided by the power of the high-frequency [0.15-0.50-Hz] parasympathetic band). RESULTS: Fibromyalgia patients had diminished accumulated 24-hour heart rate variability, manifested by a decreased standard deviation of all R-R intervals (mean +/- SD 126 +/- 35 ms, versus 150 +/- 33 ms in controls; P = 0.008) and a decreased ratio of pairs of adjacent R-R intervals differing by >50 ms (mean +/- SD 12.0 +/- 9.0% versus 20.1 +/- 18.0%; P = 0.031). Patients lost the circadian variations of sympatho/vagal balance, with nocturnal values significantly higher than those of controls at time 0 (mean +/- SD 3.5 +/- 3.2 versus 1.2 +/- 1.0; P = 0.027) and at 3 hours (3.3 +/- 3.0 versus 1.6 +/- 1.4; P = 0.01). CONCLUSION: Individuals with fibromyalgia have diminished 24-hour heart rate variability due to an increased nocturnal predominance of the low-frequency band oscillations consistent with an exaggerated sympathetic modulation of the sinus node. This abnormal chronobiology could explain the sleep disturbances and fatigue that occur in this syndrome. Spectral analysis of heart rate variability may be a useful test to identify fibromyalgia patients who have dysautonomia.

[Radiofrequency ablation in the treatment of supraventricular arrhythmias in pediatrics. Experience with 203 consecutive patients]. / Ablación con radiofrecuencia en tel tratamiento de las arritmias supraventriculares en pediatría. Experiencia en 203 Pacientes consecutivos.

We report the results of radiofrequency catheter ablation in 203 patients under 18 years of age with supraventricular tachyarrhythmias between April 1992 and June 1997. The presence of an accessory pathway caused the tachyarrhythmia in 181 patients (89.1%) with a total of 187 accessory pathways; atrioventricular nodal reentry caused the arrhythmia in 18 patients (8.8%) and atrial flutter in only 4 patients (1.9%). We eliminated the accessory pathway in 171 patients (91.4%), 23 patients showed recurrence of the tachycardia and we had complications in 4 patients (2.1%). The procedure was successful in the treatment of the atrioventricular nodal reentry in the 18 cases, with ablation of the slow pathway in 17 cases and in only one patient of the fast pathway, one patient showed total A-V block, and recurrence of the arrhythmia in 3 cases (16.6%). Finally the procedure was successful in the 4 cases of atrial flutter with one recurrence (25%). In the total of the series, the radiofrequency catheter ablation was successful in 193 patients (95%), with recurrence of the arrhythmia in 27 cases (13.3%) and with complications in only 5 patients (2.6%). Radiofrequency catheter ablation is a safe and effective procedure for the definitive treatment of supraventricular tachyarrhythmias in children.

Relationship between the site of a myocardial infarction and signal-averaged electrocardiogram indices.

We evaluated the relationship between the site of a myocardial infarction (MI) and signal-averaged electrocardiogram (SAECG) indices in both time-domain (TDA) and spectral turbulence (STA) analyses, and their implications in the prediction of infarct-related artery (IRA) patency, in 114 survivors of a first MI. They were divided into two groups based on MI location (57 anterior and 57 inferior). Patients with bundle branch block were not included. Fifty patients had been treated with thrombolytic therapy (TT). The STA was done in both XYZ-leads and in vector magnitude. Forty patients had an abnormal SAECG in TDA and 37 in STA, but only 22 (19%) in both (71% of agreement, kappa=0.35). Fifty-four patients (47%) had an occluded IRA. The best predictors from multivariate analysis of having an occluded IRA in the inferior MI group were: an abnormal Y-lead in STA (odds ratio 4.9; P=0.005); an abnormal RMS40 in TDA (odds ratio, 4.8; P=0.02); absence of TT (odds ratio, 9.15; P=0.001). Conversely, in the anterior MI group they were: an abnormal SAECG in TDA (odds ratio 6.83; P=0.005); absence of TT (odds ratio, 4.3; P=0.02). The multivariate receiver operator characteristic curves clearly showed the effect of MI location on the SAECG indices. This study suggests that the myocardial infarction site is an important factor for the variability and poor concordance between TDA and STA. Such differences may alter the predictive accuracy of SAECG. TDA and STA should be complementary methods, and the exploration in each orthogonal lead appears to be better than in vector magnitude.

Orthostatic sympathetic derangement in subjects with fibromyalgia.

OBJECTIVE: To assess the sympathetic-parasympathetic balance in individuals with fibromyalgia (FM), and its response to orthostatic stress, by power spectral analysis of heart rate variability. METHODS: We studied 19 women with FM and 19 age matched controls. A high resolution electrocardiogram was obtained in supine and standing postures after achieving a stable heart rate. Spectral analysis of R-R intervals was done by the fast Fourier transform algorithm. RESULTS: Analyses of the different frequency components revealed significant difference between the 2 groups in the low frequency (0.050-0.150 Hz) band, which reflects modulation of the sympathetic nervous system. Controls displayed an increased power spectral density upon standing (+0.081 +/- 0.217 Hz); individuals with FM had a discordant response (-0.057 +/- 0.097 Hz) (p = 0.018). CONCLUSION: In FM, there is a deranged sympathetic response to orthostatic stress. This abnormality may have implications regarding the pathogenesis of FM.

[Usefulness of exercise test in programming dual chamber pacemakers]. / Utilidad de la prueba de esfuerzo en la programación de los marcapasos bicamerales.

Prospectively, we studied 42 patient to evaluate the usefulness of treadmill exercise to programme pacemaker DDD in relation to the functioning upper frequency (relation between block frequency of pacemaker and the upper rate frequency). We excluded patient who had no treadmill exercise test after implant pacemaker. During stress 7 (17%) patient presented AV conduction 1:1 (group I); 16 (38%) second degree AV block type Wenckebach (group II); 14 (33%) second degree AV block 2:1 (group III); and 5 (12%) showed inhibition of the pacemaker by intrinsic activity (group IV). Block frequency of the pacemaker in group I and II was superior in regard of the upper rate frequency, 156.85 +/- 22.16 vs 141.43 +/- 20.82 and 135.25 +/- 11.54 vs 121.25 +/- 5.9, respectively. In group III and IV, it was lower, 120.36 +/- 15.31 vs 138.57 +/- 13.29 and 121.0 +/- 7.38 vs 142.0 +/- 14.39. The comparative analysis of the block frequency of the pacemaker in relation with the upper rate frequency showed statistically significant differences (p < 0.05) between groups I and II, and between the group I and III. The appearance of second degree AV block 2:1 is nonphysiologic, is rather due to an abrupt falling in the cardiac output. This phenomenon is able to be predicted and corrected by programming with the use the telemetry with parameters as the AV delay, as well as upper rate frequency and post-ventricular refractory atrial period.

Risk stratification for malignant arrhythmic events in patients with an acute myocardial infarction: role of an open infarct-related artery and the signal-averaged ECG.

BACKGROUND: There is increasing evidence that an open infarct-related artery results in increased electrical stability of the heart and that this effect is at least in part responsible for the favorable outcome of these patients. In the thrombolytic era the optimal strategy for risk stratification remains controversial. This study examined the predictors of serious arrhythmic events during the first year after myocardial infarction. METHODS: A total of 222 patients with acute myocardial infarction, 41.4% of whom were treated with thrombolysis, were studied. At hospital discharge, signal-averaged electrocardiography was performed on 196 subjects and Holter monitoring on 200. One hundred and ninety-seven patients underwent coronary angiography. Left ventricular ejection fraction was determined in 201 subjects. RESULTS: An open infarct-related artery was documented in 106 patients. The incidence of late potentials was 34% (66 patients). Twenty-four patients (10.8%) had an arrhythmic event during follow-up (sudden death in seven, sustained ventricular tachyarrhythmias in 15, unexplained syncope in two). Signal-averaged electrocardiography had a sensitivity of 94% and a specificity of 72% for prediction of arrhythmic events. An occluded infarct-related artery was 78% sensitive and 58% specific, a left ventricular ejection fraction below 40% had a sensitivity of 71% and specificity of 80%, and Holter monitoring was only 38% sensitive and 92% specific. A combination of late potentials plus an occluded infarct-related artery was 68% sensitive and 84% specific. Positive predictive value was low for all variables examined, but could be improved by the combination of several risk factors. The highest positive predictive value was provided by the combination of an abnormal signal-averaged ECG and complex ventricular arrhythmias on ambulatory ECG. On multivariate analysis, in rank order, presence of late potentials, ejection fraction below 40%, high-grade ventricular ectopic activity and an occluded infarct-related artery were predictive of arrhythmic events. CONCLUSION: Among patients surviving an acute myocardial infarction, the occurrence of malignant arrhythmic events can be reliably predicted by the combination of an abnormal signal-averaged ECG, left ventricular dysfunction, complex ventricular arrhythmias on Holter monitoring and an occluded infarct-related artery at the time of hospital discharge.

Effects of delayed recanalization of an occluded acute myocardial infarction-related artery using coronary angioplasty on late potentials.

BACKGROUND: Recent evidence suggests that late reperfusion of an occluded infarct-related artery after an acute myocardial infarction may reduce the frequency of subsequent arrhythmic events. Late mechanical reperfusion by percutaneous transluminal coronary angioplasty (PTCA) under these circumstances has a high success rate. The present study was performed to test the hypothesis that the late mechanical restoration of anterograde flow in an occluded infarct artery after an acute myocardial infarction causes a resolution of late potentials. METHODS: Twenty subjects (10 men, one woman; aged 32-77 years) suffering a first acute myocardial infarction, with signal-averaged electrocardiographic (ECG) recordings and a severely occluded infarct-related artery, were prospectively identified. RESULTS: Eighteen patients underwent successful PTCA of the occluded artery 6-32 days after a first acute myocardial infarction. Late potentials were observed in 14 patients 5-22 days after the infarction. A follow-up signal-averaged ECG was performed 1-8 days later. In the subgroup of 12 patients with successful reperfusion and an abnormal signal-averaged ECG before PTCA, seven (58.3%) showed resolution of the late potentials at follow-up; in these patients the filtered QRS duration showed a significant reduction (112.1 +/- 14.2 to 96.7 +/- 12.7 ms, P = 0.02), the root-mean-square voltage increased (9.8 +/- 6.5 to 33.1 +/- 15.5 microV, P = 0.017), and the duration of low-amplitude signals < 40 microV decreased after angioplasty (46.3 +/- 11.0 to 28.5 +/- 6.5 ms, P < 0.022). In contrast, two patients with late potentials before PTCA and unsuccessful reperfusion had no significant changes in signal-averaged ECG. CONCLUSIONS: In some patients with an acute myocardial infarction, late mechanical reperfusion of the culprit vessel may reduce the incidence of abnormalities on the signal-averaged ECG. Whether this will improve long-term survival has yet to be confirmed in a large trial.