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M L Simoons

Publications and source records attributed to M L Simoons.

At least 127 records · Page 7Linked to original sources
PubMed1997

Comparison of peak serum C-reactive protein and hydroxybutyrate dehydrogenase levels in patients with acute myocardial infarction treated with alteplase and streptokinase.

Peak serum C-reactive protein concentrations were measured in 146 patients randomized to receive streptokinase, alteplase, or a combination of streptokinase and alteplase in the GUSTO-I trial. Those receiving alteplase treatment had lower values than those receiving streptokinase or the combination treatment. Irrespective of treatment, complete reperfusion of the infarct-related artery (TIMI grade 3 flow) was associated with low peak serum C-reactive protein values.

Aged↗
PubMed1997

Difference in countries' use of resources and clinical outcome for patients with cardiogenic shock after myocardial infarction: results from the GUSTO trial.

BACKGROUND: Use of aggressive and invasive interventions is more common in the USA than in other countries. We have compared use of resources for patients with cardiogenic shock after myocardial infarction in the USA and in other countries, and assessed the association between use of resources and clinical outcomes. METHODS: We analysed data for patients with cardiogenic shock after myocardial infarction who were enrolled in the GUSTO-I trial (1891 treated in the USA, 1081 treated in other countries). Patients were randomly assigned combinations of streptokinase, heparin, and accelerated tissue-plasminogen activator (t-PA), then decisions about further interventions were left to the discretion of the attending physician. The interventions included in our analysis were: pulmonary-artery catheterisation, cardiac catheterisation, intravenous inotropic agents, ventilatory support, intra-aortic balloon counterpulsation (IABP), percutaneous transluminal coronary angioplasty (PTCA), and coronary bypass graft surgery (CABG). The primary outcome measure was death from any cause at 30 days of follow-up. FINDINGS: Patients who were treated in the USA were significantly younger than those treated elsewhere (median 68 [IQR 59-75] vs 70 [62-76], p < 0.001), a smaller proportion had anterior infarction (49 vs 53%, p < 0.001), and they had a shorter time to treatment (mean 3.1 vs 3.3 h, p < 0.001). Aggressive diagnostic and therapeutic procedures were used more commonly in the USA than in the other countries: cardiac catheterisation (58 vs 23%); IABP (35 vs 7%); right-heart catheterisation (57 vs 22%); and ventilatory support (54 vs 38%). 483 (26%) of the patients treated in the USA underwent PTCA, compared with 82 (8%) patients in other countries. Patients who underwent revascularisation had better survival in all countries. Adjusted 30-day mortality was significantly lower among patients treated in the USA than among those treated elsewhere (50 vs 66%, p < 0.001). The difference in mortality remained at 1 year-56% of patients treated in the USA died versus 70% of patients treated elsewhere (hazard ratio 0.69 [95% CI 0.63-0.75], p < 0.001). INTERPRETATION: 30-day and 1-year mortality was significantly lower among patients treated in the USA than among those treated in other countries. This difference in mortality may be due to the greater use of invasive diagnostic and therapeutic interventions in the USA.

Aged↗
PubMed1997

Selection of thrombolytic therapy for individual patients: development of a clinical model. GUSTO-I Investigators.

We developed a logistic regression model with data from the GUSTO-I trial to predict mortality rate differences in individual patients who received accelerated tissue plasminogen activator (TPA) versus streptokinase treatment for acute myocardial infarction. A nomogram was developed from a reduced version of this model that approximated the underlying risk of patients treated with streptokinase, and thus the benefit of TPA. The 30-day mortality rate with accelerated TPA was 0.063 versus 0.073 with streptokinase and subcutaneously administered heparin and 0.074 with streptokinase and intravenously administered heparin. No baseline patient characteristics were significantly associated with a different relative effect of TPA. Older patients and those with anterior infarction, higher Killip classification (except Killip class IV), lower blood pressure, and increased heart rate had the greatest absolute benefit with accelerated TPA. Patients with acute myocardial infarction who had more high-risk characteristics derived a greater absolute benefit from treatment with accelerated TPA versus streptokinase.

Age Factors↗
PubMed1997

Thrombolysis-induced coronary reperfusion causes acute and massive interstitial release of cardiac muscle cell proteins.

OBJECTIVE: Reperfusion of the infarct-related artery in patients with acute myocardial infarction limits infarct size, but also causes accelerated release into plasma of cardiac tissue proteins. The latter effect could reflect either enhanced protein washout from the heart or abrupt disruption of myocyte membranes. The present study indicates that the latter mechanism prevails. METHODS: In 26 patients, patency of the infarct-related artery was determined by coronary angiography 90 min and 5-7 days after thrombolytic treatment. Continuous electrocardiography was performed during the first 24 h after admission. Cumulative release of myoglobin (Mb) and creatine kinase (CK) into plasma was calculated from frequently sampled plasma concentrations. RESULTS: In patients with a patent infarct-related artery after 90 min, onset of a rapid (> 50%) decrease in ST-vector magnitude coincided with an equally rapid increase in QRS-vector magnitude, and with a sudden onset of release into plasma of Mb as well as CK. In these patients, a maximal initial release rate was observed and cumulative release conformed closely to a simple model for sudden interstitial liberation of proteins. In contrast, protein release started more gradually and could not be fitted to this model, in patients with persistent occlusion of the infarct-related artery at 90 min and absence of ST-vector normalisation. CONCLUSIONS: Previous studies have demonstrated significant myocardial salvage by timely reperfusion therapy. Nevertheless, this study indicates that the moment of recanalisation of the infarct-related artery coincides with sudden and massive disruption of myocyte membranes. Attenuation of this effect, if possible, could further improve the benefits of reperfusion therapy.

Adult↗
PubMed1997

'Expected infarct size without thrombolysis', a concept that predicts immediate and long-term benefit from thrombolysis for evolving myocardial infarction.

BACKGROUND: Thrombolytic therapy should only be used when expected benefits outweigh the risks. In order to obtain a precise estimation of prognosis, with and without thrombolytic therapy, we postulated that mortality reduction by thrombolytic therapy is a function of the area of myocardium at risk for necrosis. We developed a model to estimate the myocardial area at risk for necrosis from clinical parameters readily available upon hospital admission. This model was validated in relation to long-term prognosis and benefits of thrombolytic therapy. METHODS: Enzymatic infarct size with and without thrombolysis was predicted from the haemodynamic state and the electrocardiogram on hospital admission by multivariate regression analysis in 885 patients in the rt-PA placebo and rt-PA/PTCA trial of the European Cooperative Study Group. This multivariate function was used to validate the 'expected infarct size without thrombolytic treatment' in a test population of 533 patients from the Intracoronary Streptokinase trial of the Interuniversity Cardiology Institute of The Netherlands (ICIN) and 1741 patients from the Intravenous Streptokinase in Acute Myocardial Infarction (ISAM) study, both trials with a non-thrombolysed control group. RESULTS: Expected infarct size correlated well with the actual enzymatic infarct size in the non-thrombolysed patients of the latter two series. Limitation of infarct size by thrombolytic therapy was greatest in patients with a large 'expected infarct size' and absent in patients with a small area at risk. Similarly, one year mortality reduction was greatest in patients with a large 'expected infarct size without thrombolysis'; four deaths were prevented per hundred (95% confidence interval 0 to 9) if the area at risk was large, vs one death (95% confidence interval -2 to 3) in patients with a small area at risk. Benefit was most pronounced in patients with a large area at risk who were treated early within 3 h of symptom onset. A score for the determination of 1 year mortality with and without thrombolytic therapy is presented to help the clinician determine who to treat with thrombolytic therapy. CONCLUSION: 'Expected infarct size without thrombolysis' is a useful tool for clinicians to estimate the amount of myocardium at risk of necrosis in individual patients and to decide whether thrombolytic therapy is warranted. It is the only validated parameter of myocardium at risk for necrosis that is readily available for all patients with myocardial infarction and does not need high-tech equipment.

Electrocardiography↗
PubMed1997

Comparison of usefulness of computer assisted continuous 48-h 3-lead with 12-lead ECG ischaemia monitoring for detection and quantitation of ischaemia in patients with unstable angina.

AIMS: The selection of ECG leads used for ST monitoring may influence detection and quantitation of ischaemia. METHODS: We compared on-line continuous 48-h 12-lead against 3-lead ST monitoring in 130 unstable angina patients (Mortara. ELI-100). Onset and offset of ST episodes were defined by the lead with the first > or = 100 microV ST change relative to baseline and the lead with the latest return to baseline ST level, respectively. ST episodes were calculated for 12 leads and 3 leads (V2, V5, III) separately. RESULTS: ST episodes were detected in 88 patients (77%) by 12-lead and in 71 patients (62%) by 3-lead ST monitoring (P < 0.02). The median number (25.75%) of episodes/patient was 1 (0.3) for 3-lead and 2 (1.6) for 12-lead (P < 0.0001). The total duration of ischaemia detected during 12-lead far exceeded 3-lead monitoring: 12.3 (1, 58.2) and 1.7 (0, 23.3) min respectively (P < 0.0001). The probability of recurrent ischaemia declined most during the first 24 h of monitoring. After a period without ST changes of 1, 12, 24 and 36 h, the probabilities of recurrent ischaemia were 63, 31, 14 and 9%, respectively. CONCLUSIONS: Continuous 12-lead ST monitoring increases detection rate and duration of ST episodes compared to 3-lead ST monitoring. The use of continuous 12-lead ECG monitoring devices on emergency wards and coronary care units is recommended.

Angina, Unstable↗
PubMed1997

Effect of adopting a new histological grading system of acute rejection after heart transplantation.

BACKGROUND: Treatment policy of acute rejection after heart transplantation has been changed after adopting the ISHLT endomyocardial biopsy grading system in 1991. OBJECTIVE: To determine the effect of this policy change on clinical outcome after transplantation. METHODS: The outcome of 147 patients who had a transplant before (early group, median follow up 96 months) and 114 patients who had a transplant after (late group, median follow up 41 months) the introduction of the ISHLT biopsy grading system was studied retrospectively. Initially "moderate rejection" according to Billingham's conventional criteria was treated. From January 1991 grade 3A and higher was considered to require intensification of immunosuppression. RESULTS: There were some differences between the two groups: recipients (50 v 44 years) as well as donors (28 v 24 years) were older in the "late group" and more patients of this group received early anti-T cell prophylaxis (92% v 56%). Despite more extensive use of early prophylaxis more rejection episodes were diagnosed (2.4 v 1.4) and considerably more courses of rejection treatment were instituted in the late compared with the early group (3.2 v 1.5). There were no deaths because of rejection in the late group, however, more infections occurred within the first year (mean 1.8 v 1.4) and more non-skin malignancies within the first 41 months were diagnosed (8 of 57 v 6 of 147, 95% CIs of difference includes 0). The incidence of graft vascular disease in the late group has been comparable to the early group until now. CONCLUSION: The interpretation of the ISHLT grading system resulted in lowering of the threshold for the diagnosis of rejection thereby increasing the number of rejections and subsequently the immunosuppressive load and its complications.

Acute Disease↗
PubMed1996

Early thrombolytic treatment in acute myocardial infarction: reappraisal of the golden hour.

BACKGROUND: There is conclusive evidence from clinical trials that reduction of mortality by fibrinolytic therapy in acute myocardial infarction is related to the time elapsing between onset of symptoms and commencement of treatment. However, the exact pattern of this relation continues to be debated. This paper discusses whether or not appreciable additional gain can be achieved with very early treatment. METHODS: The relation between treatment delay and short-term mortality (up to 35 days) was evaluated using tabulated data from all randomised trials of at least 100 patients (n = 22; 50,246 patients) that compared fibrinolytic therapy with placebo or control, reported between 1983 and 1993. FINDINGS: Benefit of fibrinolytic therapy was 65 (SD 14), 37 (9), 26 (6) and 29 (5) lives saved per 1000 treated patients in the 0-1, 1-2, 2-3, and 3-6 h intervals, respectively. Proportional mortality reduction was significantly higher in patients treated within 2 h compared to those treated later (44% [95% CI 32, 53] vs 20% [15, 25]; p = 0.001). The relation between treatment delay and mortality reduction per 1000 treated patients was expressed significantly better by a non-linear (19.4-0.6x(+)29.3x-1) than a linear (34.7 - 1.6x) regression equation (p = 0.03). INTERPRETATION: The beneficial effect of fibrinolytic therapy is substantially higher in patients presenting within 2 h after symptom onset compared to those presenting later.

Animals↗
PubMed1996

One-year results from the Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries (GUSTO-I) trial. GUSTO-I Investigators.

BACKGROUND: In the randomized Global Utilization of t-PA and Streptokinase for Occluded Coronary Arteries (GUSTO-I) trial, 41021 patients received one of four thrombolytic regimens. Patients treated with accelerated tissue plasminogen activator (TPA) had a lower 30-day mortality rate (6.3%) than those treated with the other regimens (7.3%, combined streptokinase groups). METHODS AND RESULTS: Each patient who was alive at 30 days was sent a return postcard to ascertain vital status at 1 year. If the postcard was not returned, the patient (or an alternate specified at randomization) was contacted by telephone. A locator service was used in the United States for patients who could not be located by these methods. Final follow-up was 96% worldwide. One-year mortality rates remained in favor of accelerated TPA (9.1%) over streptokinase with subcutaneous heparin (10.1%, P = .011) and streptokinase with intravenous heparin (10.1%, P = .009). Combination therapy had an intermediate 1-year mortality (9.9%); this outcome was statistically indistinguishable from that with streptokinase (P = .47) but was marginally different from that with accelerated TPA (P = .05). CONCLUSIONS: The 1-year results demonstrated a saving of 10 lives per 1000 patients treated with accelerated TPA versus streptokinase and subcutaneous or intravenous heparin. Combination thrombolytic therapy had an intermediate benefit but offered no advantage over accelerated TPA treatment alone.

Aged↗
PubMed1996

Time from symptom onset to treatment and outcomes after thrombolytic therapy. GUSTO-1 Investigators.

OBJECTIVES: This study sought to examine the relations among patient characteristics, time to thrombolysis and outcomes in the international GUSTO-I trial. BACKGROUND: Studies have shown better left ventricular function and decreased infarct size as well as increased survival with earlier thrombolysis, but the relative benefits of various thrombolytic agents with earlier administration are uncertain. METHODS: We evaluated the relations of baseline characteristics to three prospectively defined time variables: symptom onset to treatment, symptom onset to hospital arrival (presentation delay) and hospital arrival to treatment (treatment delay). We also examined the relations of delays to clinical outcomes and to the relative 30-day mortality benefit with accelerated tissue-type plasminogen activator (t-PA) versus streptokinase. RESULTS: Female, elderly, diabetic and hypertensive patients had longer delays at all stages. Previous infarction or bypass surgery was an additional risk factor for treatment delay. Early thrombolysis was associated with lower overall mortality rate (< 2 h, 5.5%; > 4 h, 9.0%), but no additional relative benefit resulted from earlier treatment with accelerated t-PA versus streptokinase (p = 0.38). Longer presentation and treatment delays were both associated with increased mortality rate (presentation delay < 1 h, 5.6% and > 4 h, 8.6%; treatment delay < 1 h, 5.4%, and > 90 min, 8.1%). As time to treatment increased, the incidence of recurrent ischemia or reinfarction decreased, but the rates of shock, heart failure and stroke increased. CONCLUSIONS: Earlier treatment resulted in better outcomes, regardless of thrombolytic strategy. Elderly, female and diabetic patients were treated later, adding to their already substantial risk.

Aged↗
PubMed1996

Prognostic significance of precordial ST segment depression during inferior myocardial infarction in the thrombolytic era: results in 16,521 patients.

OBJECTIVES: We examined the prognostic significance of precordial ST segment depression among patients with an acute inferior myocardial infarction. BACKGROUND: Although precordial ST segment depression has been associated with a poor prognosis, this correlation has not been adequately quantified, partly because of small sample sizes and methodologic limitations in previous studies. METHODS: We examined the clinical and angiographic outcomes of 16,521 patients with an acute inferior myocardial infarction who underwent thrombolysis in the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO-I) study. Patients were classified into those without precordial ST segment depression (n = 6,422 [38.9%]), those with ST segment depression in leads V1 to V3 only (n = 5,850 [35.4%]), those with ST segment depression in leads V4 to V6 only (n = 876 [5.3%]) and those with ST segment depression in both leads V1 to V3 and leads V4 to V6 (n = 3,373 [20.4%]) on initial electrocardiography. Outcome measures included postinfarction complications (second- or third-degree heart block, congestive heart failure or shock) and 30-day and 1-year mortality. RESULTS: Patients with precordial ST segment depression had larger infarctions, more postinfarction complications and a higher mortality rate than those without precordial ST segment depression (4.7% vs. 3.2% at 30 days; 5.0% vs. 3.4% at 1 year; both p < 0.001), regardless of whether ST segment depression was noted in leads V1 to V6 or in leads V4 to V6. The magnitude of precordial ST segment depression (sum of leads V1 to V6) added significant independent prognostic information after adjustment for clinical risk factors; the risk of 30-day mortality increased by 36% for every 0.5 mV of precordial ST segment depression. CONCLUSIONS: Assessment of the magnitude of precordial ST segment depression is useful for acute risk stratification in patients with an inferior myocardial infarction.

Electrocardiography↗
PubMed1996

Angiographic findings and outcome in diabetic patients treated with thrombolytic therapy for acute myocardial infarction: the GUSTO-I experience.

OBJECTIVES: This study sought to determine whether diabetes mellitus, in the setting of thrombolysis for acute myocardial infarction, affects 1) early infarct-related artery patency and reocclusion rates; and 2) global and regional ventricular function indexes. We also sought to assess whether angiographic or baseline clinical variables, or both, can account for the known excess mortality after myocardial infarction in the diabetic population. BACKGROUND: Mortality after acute myocardial infarction in patients with diabetes is approximately twice that of nondiabetic patients. It is uncertain whether this difference in mortality is due to a lower rate of successful thrombolysis, increased reocclusion after successful thrombolysis, greater ventricular injury or a more adverse angiographic or clinical profile in diabetic patients. METHODS: Patency rates and global and regional left ventricular function were determined in patients enrolled in the GUSTO-I Angiographic Trial. Thirty-day mortality differences between those with and without diabetes were compared. RESULTS: The diabetic cohort had a significantly higher proportion of female and elderly patients, and they were more often hypertensive, came to the hospital later and had more congestive heart failure and a higher number of previous myocardial infarctions and bypass surgery procedures. Ninety-minute patency (Thrombolysis in Myocardial Infarction [TIMI] flow grade 3) rates in patients with and without diabetes were 40.3% and 37.6%, respectively (p = 0.7). Reocclusion rates were 9.2% vs. 5.3% (p = 0.17). Ejection fraction at 90 min after thrombolysis was similar in diabetic and nondiabetic patients ([mean +/- SEM] 6.10 +/- 1.6% vs. 60.1 +/- 0.7%, p = 0.7), as was regional ventricular function (number of abnormal chords: 19.1 +/- 2.0 vs. 17.5 +/- 0.8, p = 0.3; SD/chord: -2.3 +/- 0.2 vs. -2.4 +/- 0.1, p = 0.6). Diabetic patients had less compensatory hyperkinesia in the noninfarct zone (SD/ chord: 1.3 +/- 0.2 vs. 1.7 +/- 0.1, p < or = 0.01). No significant difference in ventricular function was noted at 5- to 7-day follow-up. The 30-day mortality rate was 11.3% in diabetic versus 5.9% in nondiabetic patients (p < or = 0.0001). After adjustment for clinical and angiographic variables, diabetes remained an independent determinant of 30-day mortality (p = 0.02). CONCLUSIONS: Early (90-min) infarct-related artery patency as well as regional and global ventricular function do not differ between patients with and without diabetes after thrombolytic therapy, except for reduced compensatory hyperkinesia in the noninfarct zone among patients with diabetes. Diabetes remained an independent determinant of 30-day mortality after correction for clinical and angiographic variables.

Aged↗
PubMed1996

Estimated gain in life expectancy. A simple tool to select optimal reperfusion treatment in individual patients with evolving myocardial infarction.

Currently several modes of reperfusion therapy for acute myocardial infarction are available. Streptokinase, accelerated alteplase and direct angioplasty are the most frequently used. These options are increasingly effective, but are also increasingly complex and costly. Since, unfortunately, physicians are often restricted by budget limitations, choices must be made in clinical practice to provide optimal therapy to individual patients. In order to guide such decision making, we developed a model to predict the expected benefit of therapy in terms of gain in life expectancy. Patients' life expectancy will decrease after infarction. Part of this loss can be prevented by early reperfusion therapy. The clinical benefit of therapy ranges from negligible gain in patients with small infarcts treated relatively late to an expected gain of more than 2 years in patients with extensive infarction treated within 3 h of onset of symptoms. The expected benefits are presented in a set of tables and depend on age, previous infarction, estimated infarct size, treatment delay and intracranial bleeding risk. With the help of these table, resources will be allocated in such a manner that patients who will benefit the most will receive the most effective therapy. Patients with similar expected treatment benefit will be offered the same mode of therapy. Future life years were discounted at 5% per year. The arbitrary thresholds currently applied for decision making at the Thoraxcenter are: no reperfusion therapy when the estimated gain in discounted life expectancy was < 1 month, streptokinase for 1-4 months and accelerated alteplase for a gain > or = 5 months. Direct angioplasty is recommended in patients with an estimated gain > or = 12 months, and in patients with an increased risk of intracranial bleeding. In this way, approximately 80% of our patients will be treated with thrombolytics (40% streptokinase and 40% accelerated alteplase), while in 10% direct angioplasty will be initiated. Patients with small infarcts presenting late will not receive reperfusion therapy. These threshold values have been chosen arbitrarily, and different thresholds may be selected in other centres. However, the developed model would guarantee that treatment decisions are made in a consistent manner, to provide optimal therapy for patients with evolving myocardial infarction, in spite of limited resources.

Adolescent↗
PubMed1996

Implementation of a pre-hospital decision rule in general practice. Triage of patients with suspected myocardial infarction.

OBJECTIVE: To improve pre-hospital triage of patients with suspected acute cardiac disease. DESIGN: Prospective study. SUBJECTS. Patients with symptoms suggestive of acute cardiac pathology, who were seen by a general practitioner, for whom acute admission into hospital was requested, and in whom a pre-hospital electrocardiogram was recorded by the ambulance service. METHODS: The study consisted of two phases. In the first phase, a decision rule was developed based on clinical characteristics and electrocardiographic findings in 1005 patients with suspected acute cardiac pathology. In the second phase, the decision rule was prospectively validated. Symptoms were recorded by a standardized questionnaire by the general practitioner and a computerized electrocardiogram was made by the ambulance nurses at the patient's home. Three electrocardiographic outcomes were available: 'normal electrocardiogram', 'possible myocardial infarction' or 'extensive myocardial infarction'. By use of the predictive model, the general practitioner could decide if hospitalization was necessary or not. MAIN OUTCOME MEASUREMENTS: Identification of patients at low (stable angina, atypical chest pain, other pathology) and high (myocardial infarction, unstable angina) probability of acute cardiac pathology. RESULTS: Among 977 patients with a complete pre-hospital evaluation in the validation phase of the study, the decision rule recommended 'no hospitalization' in 227 patients (23%). The general practitioner followed this advice in 44% of these patients. Although seven of them developed a non-Q wave myocardial infarction, no complications occurred in patients not admitted. In addition, the general practitioner did not hospitalize 19 (2%) of 750 patients for whom the decision rule recommended admission. Pre-hospital triage by the general practitioner resulted in a 12% (118 of 977 patients) reduction of the number of patients admitted to the Coronary Care Units. CONCLUSIONS: Pre-hospital triage by the general practitioner was facilitated using a standardized questionnaire and pre-hospital electrocardiography, and resulted in a reduction in the number of patients admitted to the Coronary Care Unit, and proved to be safe.

Aged↗