Reduced frequency of ventricular fibrillation after early thrombolysis in myocardial infarction.
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Biomedical subjects
Publications and source records attributed to J Lubsen.
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The relative value of predischarge clinical variables, bicycle ergometry, radionuclide ventriculography and 24 hour ambulatory electrocardiographic monitoring for predicting survival during the first year in 351 hospital survivors of acute myocardial infarction was assessed. Discriminant function analysis showed that in patients eligible for stress testing the extent of blood pressure increase during exercise slightly improved the predictive accuracy beyond that of simple clinical variables (history of previous myocardial infarction, persistent heart failure after the acute phase of infarction and use of digitalis at discharge), whereas radionuclide ventriculography and 24 hour electrocardiographic monitoring did not. The predictive value for mortality was 12% with clinical variables alone and 15% with the stress test added. Radionuclide ventriculography and 24 hour electrocardiographic monitoring were slightly additive to clinical information in the whole group of patients independent of the eligibility for stress testing (predictive value for mortality 24% with clinical variables alone and 26% with radionuclide ejection fraction and 24 hour electrocardiographic monitoring added). It is concluded that the appropriate use of simple clinical variables and stress testing is sufficient for risk stratification in postinfarction patients, whereas radionuclide ventriculography and 24 hour electrocardiographic monitoring should be limited to patients not eligible for stress testing.
The effect of thrombolysis in acute myocardial infarction on enzymatic infarct size, left ventricular function, and early mortality was studied in subsets of patients in a randomized trial at The Netherlands Interuniversity Cardiological Institute during a 5-year period. Early thrombolytic therapy with intracoronary streptokinase (152 patients) or with intracoronary streptokinase preceded by intravenous streptokinase (117 patients) was compared to conventional treatment (264 patients). All 533 patients were admitted to the coronary care unit within 4 hours after onset of symptoms indicative of acute myocardial infarction. There were 488 patients eligible for this detailed analysis, of whom 245 were allocated for thrombolytic therapy. Early angiography was performed in 212 of the 245 patients. Patency of the infarct-related artery was achieved in 181 patients (85%). Enzymatic infarct size measured from cumulative alpha HBDH release was smaller in patients allocated to thrombolytic therapy (median 760 U/l vs. 1179 U/l in controls, p = 0.0001). LVEF measured by radionuclide angiography before discharge was higher after thrombolytic therapy (median 50% vs. 43% in controls, p = 0.0001). The 12-month mortality was lower in patients allocated to thrombolytic therapy (8% vs. 16% in the control group, p < 0.01). In multivariate regression analysis, infarct size limitation, improvement of LVEF, and a 3-month mortality were predicted by ST, time from onset of symptoms to admission, and Killip class at admission. Thrombolysis was most useful in patients admitted within 2 hours after onset of symptoms and in patients with ST of 1.2 mV or more. On the other hand, no beneficial effects of streptokinase on enzymatic infarct size, left ventricular function, or mortality were observed in the subset of patients with ST less than 1.2 mV admitted 2 to 4 hours after onset of symptoms. In the long term, improved survival and enhanced quality of life are most evident after thrombolytic therapy in patients with larger anterior wall infarction, and less pronounced in patients with smaller inferior wall infarction.
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In a double-blind randomised trial 129 patients with first myocardial infarction of less than 6 h duration were allocated to treatment with human recombinant tissue-type plasminogen activator (rt-PA) given intravenously over 90 min, or to placebo infusion. Coronary angiography at the end of this infusion showed that the infarct-related vessel was patent in 61% of 62 assessable coronary angiograms in the rt-PA-treated group compared with 21% in the control group. Treatment with rt-PA was not accompanied by any major complications. In the rt-PA group the circulating fibrinogen level at the end of the catheterisation was 52 +/- 29% (mean +/- SD) of the starting value.
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In a single-blind randomised trial in patients with acute myocardial infarction of less than 6 h duration, the frequency of coronary patency was found to be higher after intravenous administration of recombinant human tissue-type plasminogen activator (rt-PA) than after intravenous streptokinase. 64 patients were allocated to 0.75 mg rt-PA/kg over 90 min, and the infarct-related coronary artery was patent in 70% of 61 assessable coronary angiograms taken 75-90 min after the start of infusion; 65 patients were allocated to 1 500 000 IU streptokinase over 60 min, and the infarct-related vessel was patent in 55% of 62 assessable angiograms. The 95% confidence interval of the differences ranges from +/- 30 to -2% (p = 0.054). Bleeding episodes and other complications were less common in the rt-PA patients than in the streptokinase group. Hospital mortality was identical in the 2 treatment groups. At the end of the rt-PA infusion the circulating fibrinogen level was 61 +/- 35% of the starting value, as measured by a coagulation-rate assay, and 69 +/- 25% as measured by sodium sulphite precipitation. After streptokinase infusion, corresponding fibrinogen levels were 12 +/- 18% and 20 +/- 11%. In the rt-PA group only 4.5% of the fibrinogen was measured as incoagulable fibrinogen degradation products, compared with 30% in the streptokinase group. Activation of the systemic fibrinolytic system was far less pronounced with rt-PA than with streptokinase.
For the prediction of cardiac death significant prognostic information can be derived from ambulatory 24-hr ECGs when they are recorded on indication in the cardiological outpatient-clinic. In both CHD and non-CHD patients, ventricular arrhythmias, supraventricular arrhythmias and conduction disturbances are all of importance in the assessment of prognosis. These conclusions are based on a review of all 123 cardiac deaths and 433 randomly selected survivors from a cohort of 5095 patients who underwent 24-hr ECG-recording on clinical indication and whose survival status was ascertained 18 months after the recording date.
In a clinical trial we studied left ventricular performance at rest in 50 patients with unstable angina by radionuclide techniques. Thallium-201 scintigraphy was performed on admission in 38 patients and repeated after 48 hr in 32 patients. Also dynamic blood pool scintigraphy was performed in 37 patients on admission and in 45 patients after 48 hr. Of the 50 patients, 27 (54%) had no recurrent episodes of myocardial ischemia, but 23 (46%) patients showed recurrent ischemic episodes of whom 11 (22%) patients developed a myocardial infarction. The thallium-201 images showed perfusion defects in 27 (71%) of the 38 patients studied on admission and in 20 (63%) of the 32 patients studied at 48 hr. No relation between clinical outcome and presence or absence of defects was observed. Left ventricular ejection fraction was abnormal (less than 50%) in 19 (51%) of the 37 patients on admission and in 29 (64%) of the 45 patients studied at 48 hr. As with thallium-201, no relation could be established between clinical outcome and left ventricular ejection fraction. It is concluded that radionuclide techniques are useful to provide insight into the pathophysiological mechanism of unstable angina, but they are not helpful for the short-time assessment of clinical outcome.
In order to evaluate the independent prognostic information provided by exercise testing in populations with a high prevalence of coronary artery disease, survival rates were calculated with the life table method in 372 men, mean age 48 years, referred for coronary arteriography. The prevalence of angiographic coronary artery disease was 82%. During a mean follow-up of 29 months (1 to 8 years), 32 patients died and 27 patients had a nonfatal event (acute infarction or hospitalization for disabling angina). Both the history (presence or absence of typical angina pectoris or of a previous myocardial infarction) and the exercise test results (abnormal if angina and/or ST segment changes greater or equal to 0.1 mV occurred) had a significant prognostic value for the 5 year survival rate (P less than 0.001). In patients with a positive history, the 5 year cumulative survival rate was 76% if the exercise test was abnormal versus 94% if it was normal (P less than 0.001). The following 8 noninvasive and 2 invasive variables were submitted to a Cox regression analysis: age, typical angina pectoris, previous myocardial infarction, maximal heart rate and workload, maximal ST segment depression and elevation, angina pectoris during exercise testing, number of diseased vessels, and wall motion score on contrast ventriculography. By univariate analysis, the age and the maximal workload reached during exercise were the only noninvasive predictive variables for survival or cardiac events (P less than 0.05). By multivariate analysis, and combining all noninvasive and invasive variables, survival was predicted by the wall motion score, the presence or absence of 3 vessel disease, and age.(ABSTRACT TRUNCATED AT 250 WORDS)
Ninety four patients with mild hypertension (average supine diastolic blood pressure (phase V) 95-110 mm Hg) were allocated at random to receive restriction of dietary sodium (maximum allowed 70 mmol(mEq)/24 h) or a normal diet. In addition, they received in random order 25 mg chlorthalidone, 200 mg metoprolol (slow release), and a fixed combination of these two drugs. Each drug treatment was given for four weeks and alternated with four weeks of placebo. Forty four patients were allocated to sodium restriction (group 1) and 50 to normal diet (group 2). The mean 24 hour urinary sodium excretion in group 1 was 74 (SD 31) mmol(mEq)/24 h, and in group 2 132 (51) mmol/24 h. Compared with the screening blood pressure the average decrement of the supine blood pressure in group 1 was 16.0/8.6 mm Hg with placebo, 21.7/11.5 mm Hg with the diuretic, 28.5/17.8 mm Hg with the beta blocker, and 28.9/18.4 mm Hg with the combined agent; in group 2 these values were 13.3/6.1, 20.3/9.7, 21.3/12.9, and 29.4/16.8 mm Hg, respectively. There was a sharp decrease of the average potassium concentration during chlorthalidone and combination treatment periods (average value 3.3 mmol(mEq)/1). These results suggest that moderate salt restriction used as sole treatment has a limited though demonstrable blood pressure lowering effect but that when it is used as an adjuvant to beta blocker treatment its value is greatly enhanced.
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The first 1041 patients who underwent an isolated aorto-coronary bypass operation in the same institution since it opened in 1971, were followed for up to 10 years to determine their prognosis. The mean follow-up time was 3.5 years. The probability of survival at five years was 94 +/- 2% (95% confidence limits). This was similar to the survival of the general Dutch population matched for age and sex. Multivariate survival analysis with the proportional hazards model did reveal a relationship of the rate of death with sex and age at operation; however this was not significant. There was a trend to a higher death rate with more vascular involvement (rate ratio of 3 vessel-versus 1 vessel disease of 1.9, N.S.) and a significant association with a low ejection fraction (EF) (ratio EF less than or equal to 0.30 v. EF greater than or equal to 0.55 of 2.7. P less than 0.05). Though surgery seems to eradicate the poor longterm outlook for patients with more serious vascular disease, the adverse influence of decreased left ventricular function on survival is not changed.
Ten instances of sudden cardiac death documented with longterm ambulatory electrocardiography are described. All had coronary artery disease. The lethal arrhythmia was ventricular fibrillation in seven, bradyarrhythmia ending in asystole in two, and electromechanical dissociation in one. There was no specific arrhythmia pattern in the preceding hour of the terminal event and no predictable electrical trigger for the lethal arrhythmia. The literature on the subject has been reviewed. It appears from the information available that larger series of documented sudden death cases are needed if one wishes to define subgroups with a preventable case of sudden cardiac death.