Prognostic implications of loss of late potentials following acute myocardial infarction.

The prognosis of patients following myocardial infarction is adversely affected by the finding of late potentials at the time of hospital discharge. Loss of late potentials has been previously reported during serial testing during the first year after infarction, but it is not known whether such patients remain at risk of arrhythmic events. This study prospectively followed 243 patients after myocardial infarction. Late potentials were observed in 92 patients (group I) at the time of hospital discharge. Of these patients, 23 no longer had late potentials at 6-week follow-up and 8 had had an arrhythmic event (sudden death or ventricular tachycardia). In patients with loss of late potentials, overall QRS duration had decreased from 109 +/- 11 msec at discharge to 104 +/- 11 msec (P < 0.01), terminal QRS voltage rose from 15 +/- 4 microV to 31 +/- 9 microV (P = 0.001), and late potential duration fell from 42 +/- 6 msec to 28 +/- 6 msec (P = 0.001) at the 6-week study. Predictors of loss of late potentials were: initial duration of the QRS duration (P < 0.001) and terminal voltage (P < 0.005); non-Q wave infarction (P < 0.001); and being a male (P < 0.05). After the 6-week assessment, 11 additional arrhythmic events occurred during median follow-up of 31 months. The risk of arrhythmic events was similar in patients with loss of late potentials and those who retained late potentials in group I (9% vs 11%, P = NS) but significantly greater than patients with no late potentials at discharge (group II, 2%).(ABSTRACT TRUNCATED AT 250 WORDS)

Noninvasive predictors of cardiac events after myocardial infarction. Complementary value of exercise testing and signal-averaged electrocardiography.

Signal-averaged electrocardiography, resting radionuclide ventriculography and Holter monitoring were performed prior to hospital discharge, to assess their value in predicting recurrent cardiac events in 210 survivors of acute myocardial infarction. In addition, 153 of these patients also underwent exercise radionuclide ventriculographic assessment. During median follow-up of 14 months (6-24 months), there were 16 cardiac deaths, 15 patients had recurrent infarction and 7 patients represented with symptomatic ventricular tachycardia. Cox regression analysis identified independent predictors of 'ischemic events' (death or re-infarction) as a previous history of infarction (p = 0.01), Killip class III-IV (p = 0.03) and an abnormal exercise radionuclide study (p = 0.04); and predictors of 'arrhythmic events' (sustained ventricular tachycardia or sudden death) as an abnormal signal-averaged electrocardiograph (p = 0.01) and left ventricular ejection fraction less than 40% (p = 0.03). Patients with an abnormal signal-averaged electrocardiograph and reduced left ventricular ejection fraction had a 34% incidence of arrhythmic events during the first 6 months compared with a 4% incidence among patients without late potentials. In those patients who underwent exercise testing and signal averaging, 85% of total cardiac events and all cardiac deaths were predicted by an abnormality of either noninvasive test. In addition, exercise testing and signal-averaged ECG were independent predictors of outcome. Hence, using a combination of noninvasive tests, patients can be stratified according to the risk of recurrent life-threatening cardiac events after myocardial infarction; such patients may be suitable for intensive investigation and considered for trials involving active intervention.

Natural history of late potentials in the first ten days after acute myocardial infarction and relation to early ventricular arrhythmias.

Serial signal-averaged electrocardiograms (ECGs) were performed every 48 hours in 50 patients admitted to the coronary care unit with acute myocardial infarction. The prevalence of late potentials was 32% at presentation (mean time to recording 12.4 +/- 6.6 hours after onset of chest pain) and increased progressively throughout the hospital stay. New late potentials were recorded in patients with no prior acute myocardial infarction as early as 3 hours after the onset of chest pain and as late as 8 days. Late potentials appeared transiently in only 3 patients. The detection of late potentials in the initial signal-averaged ECG identified patients with clinically significant early ventricular arrhythmias with a sensitivity of 80% and specificity of 72%. The predictive accuracy was 38% for a positive test and 94% for a negative test. Patients with early ventricular arrhythmias had significantly lower voltage in the terminal 40 ms of the filtered QRS complex (16 +/- 8 vs 32 +/- 19 microV, p less than 0.01) than those without arrhythmias. The signal-averaged ECG may be useful in identifying patients at high risk of developing clinically significant early ventricular arrhythmias after acute myocardial infarction.

Enhanced prediction of major cardiac events after myocardial infarction using exercise radionuclide ventriculography.

Exercise radionuclide ventriculography (RVG) was performed 7-12 days after acute myocardial infarction (MI) in 153 patients to assess its value in identifying those at risk of serious recurrent cardiac events. In addition to electrocardiogram (ECG) features of the exercise test, clinical and hemodynamic features were also considered: the exercise test was abnormal if there was a fall in blood pressure of 10 mmHg or more, development of angina, or inability to complete three minutes of exercise. RVG was used to measure left ventricular ejection fraction and to assess wall motion at rest and at peak exercise. After a median follow-up of 14 months, there were 18 cardiac events: six deaths and 12 patients with recurrent MI. In addition, 18 patients underwent coronary artery bypass surgery; the decision to perform surgery was predicted by ST segment depression or a fall in blood pressure during exercise (p less than 0.005). The sensitivity of the exercise test for identifying patients with a cardiac event increased progressively as additional parameters were considered in a cumulative fashion; hence, ST depression identified 28% of patients with events, whereas addition of clinical and hemodynamic parameters increased this to 61%. The addition of RVG increased the sensitivity further to 88%, but with a specificity of 50%. Although exercise-induced ST depression of up to 1 mm did not predict outcome significantly, a positive exercise RVG did predict cardiac events: 17% of patients with a positive test had an event, compared with 6% of those with a normal study (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Prediction of serious arrhythmic events after myocardial infarction: signal-averaged electrocardiogram, Holter monitoring and radionuclide ventriculography.

Noninvasive assessment was undertaken before hospital discharge in 210 patients who had recovered from acute myocardial infarction. This comprised signal-averaged electrocardiography, Holter monitoring and radionuclide left ventriculography. An abnormal signal-averaged electrocardiogram was defined as the presence of a low voltage signal less than 20 microV in the terminal 40 ms of the filtered QRS complex or a long filtered QRS complex greater than 120 ms. During a follow-up period of 6 months to 2 years (median 14 months), 15 patients had arrhythmic events: eight died suddenly and seven presented with sustained, symptomatic ventricular tachycardia. Using univariate analysis, abnormalities in each of the three noninvasive tests were able to predict arrhythmic events. Stepwise logistic regression demonstrated that each test was independently significant in predicting outcome, with a left ventricular ejection fraction less than 40% being the most powerful variable (beta = 2.8, p less than 0.005). This process generated an algorithm that allowed assessment of combinations of variables: the finding of an abnormal signal-averaged electrocardiogram in the presence of an ejection fraction less than 40% identified patients with a 34% probability of arrhythmic events. By contrast, in patients with left ventricular dysfunction but a normal signal-averaged tracing, the risk of arrhythmic events was 4% (p less than 0.001). This combination of variables was associated with a sensitivity of 80% and a specificity of 89%. Hence, using a combination of noninvasive tests after myocardial infarction, patients can be stratified according to risk of serious arrhythmic events.

Late potentials detected after myocardial infarction: natural history and prognostic significance.

The risk of developing spontaneous ventricular tachycardia (VT) and/or sudden death ("arrhythmic events") was prospectively assessed in 165 patients who survived acute myocardial infarction. Signal-averaged electrocardiograms (ECGs) were performed before hospital discharge and then serially at regular intervals over the following year. In addition, 24 hr Holter monitoring was performed and left ventricular ejection fraction was determined. Sixty-five patients (group 1) had abnormal signal-averaged ECGs (voltage in the last 40 msec of the filtered QRS less than 20 microV or filtered QRS duration greater than 120 msec), 92 had normal signal-averaged ECGs (group 2), and eight had bundle branch block (excluded from analysis). In group 1, spontaneous normalization of the voltage in the last 40 msec of the QRS complex occurred in 30% of patients after 12 months, although total filtered QRS duration did not change overall. During follow-up of up to 20 months (median 11), seven patients died suddenly and six presented again with spontaneous, symptomatic VT. Eleven of 65 (17%) group 1 patients had an arrhythmic event compared with one of 92 patients (1%) in group 2 (p less than .001). The sensitivity of the signal-averaged ECG as a predictor of arrhythmic events was 92% with a specificity of 62%. Patients with subsequent arrhythmic events had considerably lower voltage in the last 40 msec of the QRS (11.0 +/- 8.3 vs 32.0 +/- 21.9 microV; p less than .001) than those without such events, and longer filtered QRS complexes (121 +/- 14 vs 105 +/- 12 msec; p less than .001). Multivariate logistic regression determined that the signal-averaged ECG provided independent prognostic information from the presence of complex ventricular ectopy and the degree of left ventricular dysfunction assessed at the time of hospital discharge. Signal-averaged ECGs provide important prognostic information in identifying patients at risk of arrhythmic events after myocardial infarction. Dynamic changes in the terminal QRS voltage are observed during the first year after myocardial infarction.

Signal-averaged electrocardiogram for evaluation of recurrent syncope.

Signal-averaged electrocardiography (ECG) was performed in 150 consecutive patients presenting with syncope, to determine its diagnostic role in identifying patients with ventricular tachycardia (VT) and in determining their long-term prognosis. Patients also underwent a standardized investigational protocol to independently determine a cause of syncope. Twenty-nine patients had a late potential, 107 had a normal signal-averaged electrocardiogram and 14 had bundle branch block on 12-lead ECG. Signal-averaged ECG identified a late potential in 16 of 22 patients with VT and was normal in 101 of 114 patients in whom syncope was attributed to causes other than VT or remained unexplained (sensitivity 73%, specificity 89%, predictive accuracy 55%). In patients with coronary artery disease, the predictive accuracy increased to 82%. Absence of a late potential identified a group of patients with a very low incidence of VT. During follow-up of 1 to 20 months (median 11), 15 patients (10%) died, 6 suddenly. There was no significant difference in survival or recurrence of syncope between patients with and without a late potential. Signal-averaged ECG can noninvasively identify patients with serious ventricular arrhythmias among an unselected group presenting with syncope.

The role of signal averaged electrocardiography in the investigation of unselected patients with syncope.

The cause of syncope is often not determined, despite extensive investigations, yet it is important to identify the high risk group who may be in danger of sudden death due to ventricular arrhythmias. Recent studies have shown that the signal averaged electrocardiogram (SA ECG) can identify low amplitude signals in the terminal portion of the QRS and ST segment (late potentials) recorded from the body surface, which represent areas of delayed conduction in small areas of diseased myocardium in patients with ventricular tachycardia (VT). Sixty-five consecutive patients presenting to hospital with syncope were prospectively evaluated to determine a cause of syncope; this included quantitative analysis of the terminal QRS complex using SA ECG. A cardiac cause of syncope was assigned to 49% of patients, a non-cardiac cause to 20%, and no cause was found in the remaining 31%. Initial history and physical examination established a diagnosis in 14% of patients. A prior history of heart disease was an important indicator to a cardiac cause for syncope. Continuous electrocardiographic monitoring was diagnostic in 23% and the yield for electrophysiological testing (in a selected subgroup) was 40%. Ancillary cardiac and neurological investigations were of little diagnostic value, although they were useful in defining the severity and extent of clinically suspected conditions. SA ECG identified a late potential in 11 of 13 patients with VT, but was normal in all except three of the remaining patients who were not considered to have VT (sensitivity 85%, specificity 94%). We conclude that high frequency analysis of the signal averaged ECG is a reliable non-invasive indicator of syncope due to VT.

Severity of canine myocardial infarcts in relation to indices of oxygen demand: preservation of myocardial creatine kinase activity by vagal stimulation and propranolol.

The left anterior descending coronary artery was ligated in 58 open-chest anaesthetised dogs; 23 were controls, 15 were given intravenous propranolol 1 mg . kg-1 before and at 6 h intervals after coronary ligation, nine had bilateral cervical vagal nerve stimulation (VS) before and for 4 to 6 h after coronary ligation, and 11 had both VS and propranolol. None of the 20 dogs undergoing VS developed ventricular fibrillation within the first hour after coronary ligation compared to nine of the remaining 38 (P less than 0.05). Compared to controls, myocardial creatine kinase (CK) depletion in the epicardial layer of the infarct centre measured 24 h after coronary ligation was significantly less in the groups treated separately with vagal nerve stimulation and propranolol. Myocardial blood flow (MBF) measured at 15 min after coronary ligation was reduced to the normal myocardium by the interventions, but was unchanged at the infarct centre. Severely ischaemic myocardium (MBF less than or equal to 20% of normal) was better protected by the interventions than was moderately ischaemic myocardium. At 15 min after coronary ligation, the heart rate--blood pressure product (RPP) was reduced compared with controls by propranolol (18% reduction, P less than 0.05), reduced more by vagal stimulation (by 37%, P less than 0.001) and still more by vagal stimulation with propranolol (by 43%, P less than 0.001). Preservation of CK in myocardium with MBF less than or equal to 20% of normal was improved by VS and propranolol given separately roughly in proportion to reduction in RPP, but further reduction in RPP by VS and propranolol together did not improve CK levels further. We conclude that there may be an optimum level of indices of oxygen demand for preservation of very ischaemic myocardium in experimental infarction.

Emergency coronary artery recanalisation in acute myocardial infarction.

A 48-year-old man presented to hospital with prolonged ischaemic chest pain. No electrocardiographic or enzymic changes of acute myocardial infarction were found. Angiography performed five days later showed 75% luminal narrowing of the proximal left anterior descending (LAD) coronary artery, but no other significant abnormality. On the following day, he developed an acute anterior myocardial infarct. On repeat angiography, undertaken within 2 1/2 hours of the onset of symptoms, the LAD was found to be totally occluded. A guidewire was immediately passed through the occlusion, and streptokinase was infused through the left coronary artery for approximately 30 minutes. The vessel became patent immediately after the insertion of the guidewire, and remained so during the infusion of streptokinase. Coronary artery bypass graft surgery was successfully undertaken after the completion of the procedure.

Serum myoglobin, creatine kinase and creatine kinase-MB as mutually supportive indices of myocardial infarction and infarct size.

A comparison was made between the appearance of serum myoglobin and creatine kinase in 22 patients with acute myocardial infarction who were admitted to a coronary-care unit within four hours of onset of chest pain. The MB isoenzyme of creatine kinase was measured in 12 patients. The more rapid appearance and disappearance of myoglobin relative to creatine kinase and creatine kinase-MB was confirmed, as was the correspondence between their respective peak values. A significant correlation was also obtained between the area under the myoglobin time-course and the respective peak levels. Whereas creatine kinase activity declined exponentially from a single peak, myoglobin appeared in multiple episodes inadequately represented by a single peak value and having no clear clinical correlation. The role of myoglobin as a diagnostic aid in myocardial infarction is probably limited to its ability to support creatine kinase and creatine kinase-MB as indices of infarct size.

New South Wales intensive care ambulance system: outcome of patients with ventricular fibrillation.

Four hundred and thirty-four (2%) of the 22210 patients transported by the Intensive Care Ambulance system in Sydney, Newcastle and Wollongong during 1979, were patients with ventricular fibrillation (VF). Two hundred and eighty-two (65%) of these were pronounced dead on arrival in hospital, 152 (35%) were admitted to hospital, and 91 (21%) survivors were discharged from hospital. For 240 patients with witnessed cardiac arrest, the mean delay before the arrival of the paramedics was 15.9 +/- 3.1 SE minutes. Only one of 41 patients attended by paramedics later than 10 minutes after cardiac arrest survived to be discharged from hospital, compared with 39 of 169 patients attended by paramedics within 10 minutes of cardiac arrest. With the assistance of the Intensive Care Ambulance, 91 patients survived pre-hospital VF in New South Wales in 1979; consideration should be given to methods of minimising delays in attending these patients.

Depletion of myocardial creatine kinase, lactate dehydrogenase, myoglobin and K+ after coronary artery ligation in dogs.

In order to compare the time-course of disappearance of macromolecules and electrolytes from ischaemic myocardium, measurements of creatine kinase and lactate dehydrogenase activity and myoglobin, K+ and Na+ concentration were made on myocardial extracts from dogs which had left anterior descending coronary artery ligation for 3, 6, 12 and 24 h (4 groups of 6 dogs each). Intensity of ischaemia was assessed by myocardial blood flow measured with 15+/- 5 micrometers microspheres at 15 min after ligation. Creatine kinase and lactate dehydrogenase activities and K+/Na+ concentration ratios were at all times correlated with the magnitude of collateral blood flow in the ischaemic myocardium, while myoglobin concentration was correlated with blood flow only at 12 and 24h. Comparisons of the intensity of depletion at the various times after ligation showed that K+, K+/Na+ and creatine kinase had all reached a steady state at 12 h after ligation while lactate dehydrogenase and myoglobin had still to reach a steady state at 24 h. We conclude that these indices are mutually supportive markers of the intensity of ischaemia of 24 h duration, but K+ or K+/Na+ may be the most reliable indices for shorter periods of ischaemia of 3 to 6 h duration.

Nifedipine in medically refractory angina pectoris.

Nifedipine was administered to 21 patients with angina pectoris which was refractory to conventional medication. In no case had coronary artery spasm been demonstrated. The condition of 13 patients (62%) improved with nifedipine, and eight patients (38%) had a long-term response. Nitrate-type side effects were reported by seven patients (33%), all of whom were being treated concurrently with isosorbide dinitrate. We conclude that nifedipine is a promising drug in the management of angina pectoris, even in the absence of documented coronary spasm.

Randomized controlled trial of intraaortic balloon counterpulsation in early myocardial infarction with acute heart failure.

The value of intraaortic balloon counterpulsation in limiting infarct size and improving survival was studied in patients with early transmural myocardial infarction complicated by acute heart failure. Thirty such patients, previously well, were randomly assigned to counterpulsation (14 patients) or standard therapy (16 patients). Counterpulsation was begun 4.8 to 13.7 hours (mean 7.1) after the onset of pain and continued for less than 1 to 11 days (mean 4.5). Peak creatine kinase was 1,794 +/- 846 IU/liter (mean +/- standard deviation) in patients receiving counterpulsation compared with 1,688 +/- 908 for those receiving standard therapy; cumulative creatine kinase was 3,590 +/- 1,936 IU/liter for patients receiving counterpulsation and 2,945 +/- 1,803 for those receiving standard therapy. Hospital mortality was similar (counterpulsation, 7 of 14; standard therapy, 7 of 16 [p = 0.05 for 25 percent mortality reduction]) as was mortality at follow-up (counterpulsation, 8 of 14; standard therapy, 10 of 16 [p = 0.09 for 25 percent mortality reduction]). Functional class at follow-up examination 1 to 36 months (mean 15) after infarction was also similar in the two groups. Counterpulsation did not appear to modify infarct size or to alter morbidity or mortality when initiated as primary therapy 4.8 to 13.7 hours after the onset of symptoms of myocardial infarction.