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.

Regional 99m technetium diphosphonate uptake in experimental dog heart infarct: relation to duration and severity of ischaemia.

Regional uptake of 99mTechnetium diphosphonate was compared with regional myocardial blood flow 6, 12 and 24 h after the onset of myocardial infarction in dogs, and with regional creatine kinase depletion 24 h after the onset. Uptake of the imaging agent increased from 6 to 24 h, but no consistent relationship could be demonstrated between regional myocardial blood flow and regional uptake of the diphosphonate nor between uptake and regional creatine kinase depletion at the centre or border of the infarct. In addition, inappropriately high levels of 99m Technetium uptake could be demonstrated in the epicardial layer of the normal tissue surrounding the infarct. We conclude that diphosphonate uptake is not quantitatively related to the severity of ischaemia, and that use of this substance for imaging may over-estimate myocardial infarct size.

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.

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.

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.

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.

Predictors of late hospital death in acute myocardial infarction.

Although death from ischemic heart disease occurs in the majority of cases within 24 hr of a new clinical event, study of patients selected by admission to hospital shows a mortality pattern in which most deaths from myocardial infarction happen after the first day. In one hospital, over the last 2 yr, 46% of deaths from infarction have happened from the fourth day onwards. Introduction of a coronary-care unit in this hospital has reduced hospital mortality in patients under 70 yr of age from approximately 21% in 1966-1967 to 13% in 1977-1979, mainly because of improved treatment of arrhythmias. With the decline of cardiac arrhythmias as a mode of dying in hospitals, mechanical complications of shock and cardiac failure now account for up to two-thirds of hospital deaths, with cardiac rupture probably next in importance, accounting for 15%-20% of deaths. Of these 3 mechanisms, death from cardiac failure is most likely to be "late" (from the fourth day onwards). Shock and cardiac failure are directly related to massive destruction of left ventricular myocardium. Therefore, major efforts aimed at reduction of late hospital mortality should be directed towards therapeutic measures, initiated very early after the onset of infarction, which might protect the threatened myocardial tissue and restrict infarct size.

Perioperative myocardial infarction with aortocoronary bypass graft surgery.

In 1975, 160 patients underwent aortocoronary bypass graft surgery at St. Vincent's Hospital, Sydney. The incidence of perioperative myocardial infarction varied between 2-5% and 5-6% depending on the criteria used to diagnose pathological Q waves, and thus compared favourably with other reported series. The low incidence suggested that perioperative infarction should be considered as neither a deterrent to coronary bypass surgery nor a significant cause of postoperative relief of angina.

Arterial counterpulsation in continuing myocardial ischaemia after acute myocardial infarction.

Twenty-six patients underwent arterial counterpulsation for refractory heart failure without shock complicating acute myocardial infarction. Patients were divided into a group of 12 with continuing myocardial ischaemia, evidenced by anginal pain associated with abnormal ST segment elevation, and a group of 14 without continuing ischaemia. Clinical features (apart from pain) and prognostic indices were similar in the two groups when counterpulsation was started but short- and long-term results were different. Hospital survival was 92 per cent (11/12) and 43 per cent (6/14), respectively, in the groups with and without ischaemia and four-year survival was 73 per cent and 7 per cent. Counterpulsation is of greatest value in acute infarction when used to relieve myocardial ischaemia.

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.

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.

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.

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)

Comparison of enzymic with cineangiocardiographic estimations of myocardial infarct size.

Comparisons were made between enzymic indices of myocardial infarct size (total creatine kinase appearance and peak enzyme activity) measured during the acute state of a first myocardial infarct in 32 male patients, and analysis of contraction abnormalities in biplane left ventricular cineangiocardiograms performed one month later. The cineangiocardiograms were analysed independently by two radiologists, each using two different methods for quantification of subjectively classified abnormalities of left ventricular wall motion. A very strong correlation was found between the two enzymic indices of infarct size and somewhat weaker correlations between assessment of contractility abnormalities made by the two radiologists using the same method, or by the same radiologist using the two different methods. Comparisons between enzymic and angiocardiographic indices for all infarcts showed correlation coefficients (r) within the range of 0.53 to 0.72. With all comparisons of enzymic with radiological indices r values were higher for anterior infarcts than for inferior infarcts, and there was a tendency for higher enzyme levels for a given degree of left ventricular damage in inferior than in anterior infarction. This may be the result of variable degrees of right ventricular damage in inferior 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.

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.

Protective effect of propranolol in threatened myocardial infarction.

Propranolol 0.1 mg/kg intravenously followed by 320 mg orally over 27 h was given to 20 randomly selected patients within 4 h of the onset of suspected myocardial infarction unaccompanied by diagnostic electrocardiographic changes. Patients given propranolol had fewer completed infarcts as assessed by serial electrocardiograms, a lower frequency of serum-creatine-kinase levels above the normal range, and lower peak serum-creatine-kinase levels than 23 control subjects. This evidence suggests that threatened myocardial infarction can in some cases be prevented by early beta-adrenoceptor blockade.

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.

Angiocardiography and exercise testing at one month after a first myocardial infarction.

The results of exercise testing (77 patients), left ventriculography and coronary arteriography (78 patients) are presented for men under the age of 60, one month after a first myocardial infarct. Cineangiocardiography revealed that patients with anterior infarction (n = 25) had both poorer left ventricular function and more totally occluded vessels than those with either inferior (n = 33) or subendocardial infarction (n = 20). In contrast, patients with inferior and subendocardial infarction had a greater proportion of myocardium supplied by sub-total lesions likely to be haemodynamically significant (75%-99% cross sectional area loss). Subendocardial infarction was also characterised by the best left ventricular function and the fewest number of total coronary occlusions. Stress testing showed that the combination of ischaemic ST segment changes and angina during exercise was 91% predictive of severe coronary disease (equivalent to triple vessel disease) while no angina in the presence of a negative test was 81% predictive of mild or moderate disease. Stenoses of 75%-99% cross sectional area loss were more common when angina occurred during exercise testing, and both angina and ischaemic ST segment changes occurred within ten minutes in all four patients with haemodynamically significant left main coronary artery lesions. Our data supports the usefulness of exercise testing after a first myocardial infarct and may provide valuable baseline information in the analysis of long term prognosis.