Effect of thrombolytic treatment delay on myocardial infarct size.
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Drug Administration Schedule↗
Biomedical subjects
M L Simoons
Publications and source records attributed to M L Simoons.
Well shaped ST segment and risk of cardiovascular mortality.
OBJECTIVE: To investigate the prognostic value of frequently occurring slight variations in the ST segment for cardiovascular mortality in healthy subjects. DESIGN: Follow up study of mortality in relation to variations in ST segment level in a cohort over the 28 years from 1953 to 1981. A case-cohort sampling design was applied to limit the number of electrocardiograms that had to be coded by hand. SETTING: General health examination carried out in 1953 of civil servants in Amsterdam and assessment of subsequent mortality. SUBJECTS: Apparently healthy civil servants aged 40 to 65 years: 1583 men and 1508 women. MAIN OUTCOME MEASURES: Relative risk of variations in ST segment level for mortality from all causes, cardiovascular disease, and coronary heart disease. RESULTS: In men the multivariate relative risks of 15 year mortality from cardiovascular disease and coronary heart disease of slight ST elevation at 80 ms past the J point (compared with isoelectric ST segment) were 0.5 (95% confidence interval 0.3 to 0.9) and 0.4 (0.2 to 0.8), respectively. As expected, ST segment depression (greater than 0.25 mm) was associated with increased risk: 1.9 (1.1 to 3.0) and 2.2 (1.2 to 3.9), respectively. In women associations were weaker. The full 28 year period showed a similar pattern of somewhat weaker associations for men; among women, however, no predictive value was apparent. CONCLUSION: These results are empirical evidence for the intuitive opinion among doctors that a curved, upward sloping ST segment, resulting in slight ST elevation at 80 ms, indicates low risk compared with the isoelectric flat, stretched ST segment.
Adult↗
5-Hydroxytryptamine-induced contractions of the human isolated saphenous vein: involvement of 5-HT2 and 5-HT1D-like receptors, and a comparison with grafted veins.
The receptors mediating the contractile effect of 5-hydroxytryptamine (5-HT) on the human isolated saphenous vein, obtained from 42 patients undergoing coronary bypass surgery, have been further characterized using a number of 5-HT-related drugs. The rank order of agonist potency was 5-carboxamidotryptamine (5-CT) approximately 5-HT greater than methysergide approximately sumatriptan approximately alpha-methyl-5-HT approximately 5-methoxy-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indolesuccinate (RU 24969) approximately 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI) greater than 2-methyl-5-HT greater than 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT). Flesinoxan was inactive as an agonist. Ketanserin (1 mumol/l) hardly affected sumatriptan-induced contractions but it caused a rightward shift of the upper part of the concentration-response curve of 5-HT and 5-CT. The same concentration of ketanserin caused a parallel rightward shift of the concentration-response curves of alpha-methyl-5-HT and DOI with pKB values of 7.1 and 7.1, respectively. The responses to sumatriptan were antagonized by methiothepin (0.1 mumol/l), metergoline (0.1 and 1 mumol/l), rauwolscine (1 mumol/l) and cyanopindolol (1 mumol/l); the calculated pKB values were 7.3, 6.9, 7.3, 6.7 and 6.5, respectively. Contractions to 5-HT were antagonized by methysergide (1 mumol/l), methiothepin (0.1 mumol/l; pKB = 7.1), ICS 205-930 (1 mumol/l; pKB = 5.9) and flesinoxan (30 mumol/l; pKB = 5.3). Remarkably, the contractions elicited by 2-methyl-5-HT were not attenuated by ICS 205-930, but were antagonized by methiothepin (0.1 mumol/l) and, more markedly, by ketanserin (1 mumol/l).(ABSTRACT TRUNCATED AT 250 WORDS)
Coronary Artery Bypass↗
Intracranial hemorrhage in association with thrombolytic therapy: incidence and clinical predictive factors.
In a period of 18 months, 2,469 patients with acute myocardial infarction treated with a thrombolytic agent were prospectively registered in 61 hospitals. Most patients (73%) were treated with streptokinase. Intracranial hemorrhage was observed in 24 patients, corresponding to an incidence rate of 1% (95% confidence interval 0.6% to 1.3%). The median time interval between the start of thrombolytic therapy and the first clinical signs of intracranial bleeding was 16 h (range 3 to 36). In total, 16 (66%) of the 24 patients died as a result of cerebral hematoma. To determine clinical predictive factors, a case-control study was conducted. For every patient with intracranial hemorrhage, two control patients who received thrombolytic therapy because of acute infarction in the same hospital and in the same period were selected. Detailed clinical characteristics of 22 of the 24 patients as well as of 7 other patients with documented intracerebral bleeding from the European Cooperative Study Group and of 2 patients who sustained intracranial hemorrhage outside the registry period were compared with 62 control patients. The results of multivariate logistic regression analysis indicate that patients taking an oral anticoagulant before admission, patients with a body weight less than 70 kg and those greater than 65 years old are at higher risk for intracranial hemorrhage during thrombolytic therapy.
Aged↗
Too early for cardiac transplantation--the right decision?
In 109 out of 479 patients who were referred for cardiac transplantation it was considered to be too early to put them on the waiting list for a donor heart. The clinical course of these 109 patients was analysed in order to verify whether this decision had been right. The mean age of the patients was 43 years, half of them suffered from ischaemic heart disease. The systolic left ventricular function of the patients was severely depressed (mean left ventricular ejection fraction 21%) and the left ventricular cavity was markedly dilated (mean echocardiographic end diastolic dimension 73 mm). Functional capacity, measured by bicycle ergometry, was low: mean maximal workload 62% of the expected load for gender, height and age. The median follow-up duration was 31 months. The survival rate of the patients was better than that of 175 patients who were accepted for transplantation after referral, 92%, 87%, 81%, 71% and 73%, 73%, 71%, 68% after 1, 2, 3 and 4 years respectively. Re-assessment was necessary in 29% of the patients within 1 year and in 52% within 3 years. Twenty patients died: 12 patients died before re-assessment had been initiated (eight sudden deaths), six patients because of progressive heart failure before heart transplantation could be performed and two patients died after heart transplantation. Left ventricular ejection fraction, pulmonary capillary wedge pressure and transpulmonary gradient were not reliable predictors of the course of the patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Prehospital thrombolysis with alteplase (rt-PA) in acute myocardial infarction.
The improvement in survival in patients undergoing thrombolytic therapy in myocardial infarction is determined by the delay between coronary occlusion and reperfusion. The REPerfusion in Acute Infarction Rotterdam (REPAIR) study was designed to examine the feasibility and safety of prehospital thrombolysis with alteplase (rt-PA, 'Actilyse'). A small portable ECG computer system is used to confirm the presence of a large myocardial infarction (at least 1.0 mV ST-deviation) 'on the spot'. Between 22 June 1988 and 1 January 1991, 226 patients were treated by the ambulance service after the evaluation of 9052 patients complaining of chest pain. Therapy could be initiated within an average of 100 +/- 56 min (SD) after the onset of symptoms, and within 22 +/- 9 min after ambulance arrival. Three patients were defibrillated during transportation. Six patients (3%) died after arrival in the hospital. The time gained by prehospital treatment was 47 min (95% confidence limits 44-51 min) in comparison with 220 patients who did not meet the criteria for prehospital thrombolysis, but received thrombolytic therapy as soon as possible after hospital admission. The developed procedure allows rapid and safe initiation of thrombolytic therapy in selected patients, even in the absence of a physician. The observed low mortality supports the concept that prehospital thrombolytic therapy is indeed beneficial to the patient.
Adult↗
Effect of early intravenous heparin on coronary patency, infarct size, and bleeding complications after alteplase thrombolysis: results of a randomised double blind European Cooperative Study Group trial.
OBJECTIVE: To determine whether concomitant treatment with intravenous heparin affects coronary patency and outcome in patients treated with alteplase thrombolysis for acute myocardial infarction. DESIGN: Double blind randomised trial. TREATMENT REGIMENS: Alteplase 100 mg (not weight adjusted) plus aspirin (250 mg intravenously followed by 75-125 mg on alternate days) plus heparin (5000 units intravenously followed by 1000 units hourly without dose adjustment) was compared with alteplase plus aspirin plus placebo for heparin. SETTING: 19 cardiac centres in six European countries. SUBJECTS: 652 patients aged 21-70 years with clinical and electrocardiographic features of infarcting myocardium in whom thrombolytic therapy could be started within six hours of the onset of major symptoms. MAIN OUTCOME MEASURE: Angiographic coronary patency 48-120 hours after randomisation. RESULTS: Coronary patency (TIMI grades 2 or 3) was 83.4% in the heparin group and 74.7% in the group given placebo for heparin. The relative risk of an occluded vessel in the heparin treated group was 0.66 (95% confidence interval 0.47 to 0.93). Mortality was the same in both groups. There were non-significant trends towards a smaller enzymatic infarct size and a higher incidence of bleeding complications in the group treated with heparin. CONCLUSIONS: Concomitant intravenous heparin improves coronary patency in patients with alteplase. Whether this can be translated into improved clinical benefit needs to be to be tested in a larger trial.
Adult↗
Changes in left ventricular function and wall thickness in heart transplant recipients and their relation to acute rejection: an assessment by digitised M mode echocardiography.
OBJECTIVE: Assessment of changes in left ventricular diastolic function and wall thickness after heart transplantation to verify whether these changes predicted acute rejection assessed by endomyocardial biopsy. DESIGN: Follow up according to a predefined protocol of consecutive patients from the first week after transplantation. SETTING: Heart transplantation unit of the Thoraxcentre, University Hospital Rotterdam Dijkzigt, The Netherlands. PATIENTS: All 32 patients undergoing orthotopic heart transplantation from 1 January 1989 to 31 March 1990 were examined. Two were excluded from the analysis. Patients were treated with cyclosporin and low dose steroids. MAIN OUTCOME MEASURES: Data obtained by digitised M mode echocardiography were compared with the results of endomyocardial biopsy (Billingham classification). Mean values for left ventricular wall thickness, internal dimension, and their standardised rates of change and fractional shortening were determined from 4-6 consecutive expiratory beats. Mean values and individual trends during follow up were also investigated for each ultrasound variable. The results of these average values were compared with values in a group of 10 healthy volunteers. RESULTS: Median follow-up was 177 days (range 10-399). Two hundred and sixty three consecutive M mode studies were examined in relation to concurrent biopsy results. No significant differences were observed between the ultrasound variables at the time of moderate acute rejection (Billingham class 2, n = 37) and other biopsy classes (n = 226). Nor did changes in individual patients predict (moderate) acute rejection episodes. Twenty six of the 30 patients had an abnormal (slow) left ventricular relaxation pattern throughout follow up. CONCLUSIONS: Digitised left ventricular M mode echocardiography did not predict the presence of acute rejection. In most patients there was a persistent slow left ventricular relaxation pattern.
Acute Disease↗
Recombinant tissue-type plasminogen activator and immediate angioplasty in acute myocardial infarction. One-year follow-up. The European Cooperative Study Group.
BACKGROUND: The European Cooperative Study Group conducted two randomized trials in patients with suspected myocardial infarction to assess the effect of 100 mg single-chain recombinant tissue-type plasminogen activator (rt-PA, alteplase) on enzymatic infarct size, left ventricular function, morbidity and mortality relative to placebo (alteplase/placebo trial) and to assess the effect of immediate percutaneous transluminal coronary angioplasty (PTCA) in addition to alteplase (alteplase/PTCA trial). One-year follow-up results are reported. METHODS AND RESULTS: In the alteplase/placebo trial, 721 patients with chest pain of less than 5 hours and extensive ST-segment elevation were allocated at random to 100 mg alteplase or placebo (double-blind) over 3 hours. In the alteplase/PTCA trial, 367 similar patients received alteplase and subsequently were allocated at random to immediate coronary angiography and angioplasty of the infarct-related vessel or control. All patients received aspirin and intravenous heparin. In the alteplase/placebo trial, mortality during the first year was reduced by 36% with alteplase (from 9.3% to 5.6%; difference, -3.7%; 95% confidence interval, -7.5% to 0.2%). Revascularization was performed more frequently after alteplase, and more patients in the alteplase group were in New York Heart Association functional class I or II. Reinfarction tended to occur more frequently after alteplase than after placebo. In the alteplase/PTCA trial, reinfarction was less common after immediate PTCA, and revascularization procedures were less frequent. However, this benefit was offset by a high rate of immediate reocclusion and early recurrent ischemia and by higher mortality at 1 year (9.3% versus 5.4%; difference, 3.9%; 95% confidence interval, -1.5% to 9.2%) in the invasive group. In a multivariate analysis of 1,043 hospital survivors, mortality after discharge was related to coronary anatomy, left ventricular function, age, and previous infarction but not to initial treatment allocation. Reinfarction after hospital discharge tended to be more common after alteplase and related to coronary anatomy. CONCLUSIONS: Benefit from treatment with alteplase, heparin, and aspirin is not diminished at 1 year. Routine immediate PTCA does not confer additional benefit. Prognosis after hospital discharge mainly is determined by coronary anatomy and residual left ventricular function and is unrelated to initial treatment assignment.
Angioplasty, Balloon, Coronary↗
Thrombocythemia and coronary artery disease.
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Adult↗
Tissue plasminogen activator in refractory unstable angina. A randomized double-blind placebo-controlled trial in patients with refractory unstable angina and subsequent angioplasty.
To evaluate the effect of recombinant tissue plasminogen activator (alteplase) on the clinical course, angiographic changes and the outcome of subsequent coronary angioplasty, 36 patients with angina at rest, despite bedrest and medical treatment including heparin, and with concomitant ECG changes, were studied. After diagnostic angiography, patients were randomized to receive either alteplase 100 mg in 3 h (19 patients), or placebo (17 patients). The mean interval between qualifying anginal episode and initial angiography was 10 and 9 h for the alteplase and placebo group, respectively. Angiography was repeated and angioplasty was performed within 24 hours. Between the first and the second angiogram, five patients in the alteplase and seven in the placebo group had recurrent ischaemic episodes, while four alteplase and three placebo patients showed signs of myocardial necrosis (creatine kinase (CK) rise greater than or equal to twice the upper limit for normal). Intracoronary clots were recognized in three alteplase patients and one placebo patient at the first angiogram, while two alteplase patients and one placebo patient showed total occlusion of the ischaemic-related vessel. After infusion, thrombi were present in four alteplase patients and one placebo patient, and total occlusion in three alteplase patients and one placebo patient. Quantitative coronary angiography showed no change in the percentage diameter stenosis of the ischaemia-related segment after drug infusion, (alteplase 67 +/- 16 to 69 +/- 16%; placebo 65 +/- 11 to 63 +/- 12%). Angioplasty was successful in 14 of 19 alteplase and 14 of 16 placebo patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Strategies for pre-hospital thrombolysis: an overview.
Improvement in survival as a result of thrombolytic therapy in patients with myocardial infarction is determined by the delay between coronary occlusion and reperfusion. Treatment at home can reduce this delay, provided that appropriate patients can be identified. Different strategies for pre-hospital thrombolysis have been developed. Most studies require ECG confirmation of evolving myocardial infarction. In many, the ECG is interpreted by a physician in the ambulance. Others transmit the ECG to a remote physician or use computer analysis of an ECG made 'on the spot', A few studies use no ECG criteria at all. The pooled data show that with physician interpretation, 723 patients in 14 studies could be treated within 103 min after onset of symptoms (range 60-138 min) with a time gain of 51 min (range 30-74 min), compared with thrombolytic treatment after hospital admission. The therapeutic delay was 93 +/- 45 min (SD) with time gains of 62 and 86 min in two studies with ECG transmission (61 patients). In another study using computer analysis, ambulance nurses were able to treat 300 patients within 102 +/- 63 min after onset of symptoms, resulting in a time gain of 48 +/- 2 min. Without ECG confirmation, cardiologists accompanying the ambulance could administer thrombolysis within 83 +/- 4 min after onset of symptoms with a time gain of 45 min in one study. The diagnostic accuracy of this last approach was 42%. With each of the four approaches, patients can be treated within approximately 100 min after onset of symptoms, resulting in a time gain of 45 min or more.(ABSTRACT TRUNCATED AT 250 WORDS)
Ambulatory Care↗
[Risks and precautions in stress testing].
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Adult↗
QRS changes in coronary artery disease.
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Coronary Disease↗
Quantitative analysis of exercise electrocardiograms.
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Computers↗
Computer-assisted exercise testing.
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Coronary Disease↗
Model studies on activation of the heart.
Multiple dipole models of activation of the heart, in combination with a model of the thorax as an electrical conductor relate the action of individual cells to features of the electrocardiogram. The models can be used to develop diagnostic electrocardiographic criteria for ventricular hypertrophy, myocardial infarction or conduction disorders. Criteria derived with the use of Holt, Barnard and Lynn's model proved to be superior to well-established empirical rules. Their approach restricts position, direction and polarity of the current dipole vectors in the model. In the Selvester model, and later in the Ritsema van Eck model, in addition to these restrictions time-constraints are imposed on the dipole activity. In a validation study of the Ritsema van Eck model activation of a beating dog heart is compared in detail with simulated activation in a computer replica of the same heart. Myocardial spread of activation is found to be stimulated correctly. Simulated spread of activation along the Purkinje fiber network however, differs considerably from reality. In apical regions excitation spreads in reality much faster than in the model, in basal regions much slower. The model can be improved by slowing endocardial excitation from apex to base with the time-course of activation. Further improvement is obtained by the use of a more detailed pattern of endocardial excitation, based on studies of endocardial excitation in opened ventricles. The model can predict the time-course of activation with an accuracy of 5% of total ventricular activation time.
Action Potentials↗