PubMed Health⌕ Search

Biomedical subjects

A E Arnold

Publications and source records attributed to A E Arnold.

At least 19 recordsLinked to original sources
PubMed2001

Impaired glucose metabolism predicts mortality after a myocardial infarction.

Diabetes is a risk factor for increased mortality after a myocardial infarction. Whether this applies for patients with hyperglycemia during the acute phase of a acute myocardial infarction is unclear. Therefore we determined the relation between admission plasma glucose level and mortality in a prospectively collected series of 336 consecutive AMI patients. Patients were divided in four groups based on WHO criteria for glucose levels: I: <5.6 mmol/l, II: 5.6--8.3 mmol/l, III: 8.4--11.0 mmol/l, IV: 11.1 mmol/l. The average age was 68+/-11 years with a peak CK of 1378+/-160 U/l, 34% were anterior wall AMIs and 52% were treated with thrombolysis. All patients had a long-term follow-up control at an average of 14.2 months. One year mortality rate was 19.3% and rose to 44% in patients with glucose levels >11.1 mmol/l. The mortality was higher in diabetic patients than in non-diabetic patients (40 vs. 16%; P<0.05). Multivariate analysis revealed an independent effect of glucose level on mortality. In conclusions, our study in an unselected patient population demonstrates that admission plasma glucose level independently predicts 1 year mortality even in absence of diagnosed diabetes mellitus. Further studies evaluating the effect of acute insulin intervention in reducing mortality are warranted.

Aged↗
PubMed2001

Variability in treatment advice for elderly patients with aortic stenosis: a nationwide survey in The Netherlands.

OBJECTIVE: To determine how the decisions of Dutch cardiologists on surgical treatment for aortic stenosis were influenced by the patient's age, cardiac signs and symptoms, and comorbidity; and to identify groups of cardiologists whose responses to these clinical characteristics were similar. DESIGN: A questionnaire was produced asking cardiologists to indicate on a six point scale whether they would advise cardiac surgery for each of 32 case vignettes describing 10 clinical characteristics. SETTING: Nationwide postal survey among all 530 cardiologists in the Netherlands. RESULTS: 52% of the cardiologists responded. There was wide variability in the cardiologists' advice for the individual case vignettes. Six groups of cardiologists explained 60% of the variance. The age of the patient was most important for 41% of the cardiologists; among these, 50% had a high and 50% a low inclination to advise surgery. A further 24% were influenced equally by the patient's age and by the severity of the aortic stenosis and its effect on left ventricular function; among these, 62% had a high and 38% a low inclination to advise surgery. Finally, 23% of the cardiologists were mainly influenced by the left ventricular function and 12% by the aortic valve area. The presence of comorbidity always played a minor role. CONCLUSIONS: There were systematic differences among groups of cardiologists in their inclination to advise aortic valve replacement for elderly patients, as well as in the way their advice was influenced by the patients' characteristics. These results indicate the need for prospective studies to identify the best treatment for elderly patients according to their clinical profile.

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↗
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

Modulation of plasma fibrinogen levels by ticlopidine in healthy volunteers and patients with stable angina pectoris.

Elevated plasma fibrinogen levels are associated with an increased risk for cardiac events. Ticlopidine is a drug that inhibits the ADP-induced aggregation of blood platelets and it also has been described that ticlopidine can decrease the plasma fibrinogen level in patients with vascular diseases. The mechanism of this decrease has not yet been elucidated and therefore mechanisms that are known to affect fibrinogen levels were studied, viz, the acute phase reaction, total fibrin plus fibrinogen degradation (TDP) levels and the polymorphisms of the fibrinogen beta-gene. The fibrinogen lowering effect of ticlopidine was studied in 26 healthy volunteers, selected on genotype of the Bcl] polymorphism of the fibrinogen beta-gene, and in 26 patients with stable angina pectoris in a double blind, randomized cross-over study. Functional plasma fibrinogen levels were measured with the Clauss assay. Fibrinogen antigen, C-reactive protein (CRP) and TDP levels were measured using an enzyme immuno assay (EIA). In the healthy volunteers the functional fibrinogen levels had decreased by 0.20 g/l (9%, p = 0.005 using the paired Student l-test) after 4 weeks of 250 mg bid ticlopidine administration, whereas fibrinogen antigen, CRP and TDP levels were not significantly changed. In the stable angina pectoris patients the pre-treatment fibrinogen, CRP and TDP levels were significantly higher than in the volunteer group. After four weeks 250 mg bid ticlopidine administration the functional fibrinogen levels had decreased by 0.38 g/l (11%, p < 0.005), whereas the fibrinogen antigen, CRP and TDP levels were not significantly changed. The levels of functional and antigen fibrinogen, CRP and TDP did not change significantly during the placebo period in the volunteers or the patients. Neither in the volunteers nor in the patients was the effect of ticlopidine on the fibrinogen levels associated with the fibrinogen beta-gene polymorphisms. Therefore, the fibrinogen lowering effect of ticlopidine is likely to be a modulation of the functionality of the molecule and unlikely to be modulated by the acute phase reaction, TDP-levels or the fibrinogen beta-gene polymorphisms.

Adult↗
PubMed1995

Benefit of thrombolytic therapy is sustained throughout five years and is related to TIMI perfusion grade 3 but not grade 2 flow at discharge. The European Cooperative Study Group.

BACKGROUND: Long-term follow-up in patients treated with thrombolysis for acute myocardial infarction thus far has been reported in a few studies only, and no long-term follow-up is available for patients who underwent additional percutaneous transluminal coronary angioplasty (PTCA). This report describes 5-year survival as collected in patients who received placebo, recombinant tissue plasminogen activator (rTPA), or rTPA with additional immediate PTCA in two European Cooperative Study Group trials. Determinants for long-term survival were assessed in 1043 patients discharged alive. METHODS AND RESULTS: Five-year follow-up information on mortality was collected. Hospital mortality was lower after rTPA than placebo (2.5% versus 5.7%, P = .04) and higher after rTPA with immediate PTCA compared with rTPA without additional intervention (6.0% versus 2.2%, P = .07). Of the 1043 hospital survivors, data were available for 923 patients, of whom 109 died. In the placebo group, mortality after hospital discharge was 10.7% versus 11.0% in the comparative rTPA group. The patients treated with rTPA and immediate PTCA had a mortality rate of 10.5% versus 8.9% in the rTPA group without PTCA (all P = NS). Significant determinants of mortality in multivariate proportional hazards analysis were enzymatic infarct size, indicators of residual left ventricular function, number of diseased vessels and TIMI perfusion grade at discharge. Patients with TIMI grade 2 flow had mortality rates similar to those with TIMI flow grades 0 and 1, while prognosis was better in patients with TIMI flow grade 3. CONCLUSIONS: The initial in-hospital benefit of thrombolysis with intravenous rTPA is maintained throughout 5 years, with no early or late beneficial effect of systematic immediate PTCA. Enzymatic infarct size, left ventricular function, and extent of coronary artery disease are predictors for long-term survival. TIMI perfusion grade 2 at discharge should be considered as an inadequate result of therapy.

Angioplasty, Balloon, Coronary↗
PubMed1995

Thrombolytic therapy for evolving myocardial infarction needs an approach that integrates benefit and risk.

Thrombolytic therapy is a major step forward in the treatment of acute myocardial infarction and results in substantial reduction of mortality. However, in individual patients the benefits and bleeding risk are difficult to estimate, especially when benefit seems small or outweighed by the risk of intracranial bleeding. For this and other reasons less than half the patients with evolving myocardial infarction are treated with thrombolytic therapy. We propose to approach the decision 'to treat or not to treat' in a systematic way, integrating estimated benefit and intracranial bleeding risk in individual patients. According to a decision-model developed with currently available medical knowledge, thrombolytic therapy appears beneficial in the majority of patients with evolving myocardial infarction provided that ST segment elevation is present and treatment can be started within 12 h of onset of symptoms. Thrombolytic therapy is warranted in the absence of risk factors for intracranial haemorrhage, even if the risk of cardiac death in the first year without thrombolytic therapy is as low as 2.3% (patients with small inferior wall infarctions). For patients with increased intracranial bleeding risk, the cardiac baseline risk without thrombolytic therapy and treatment delay become important variables to take into account when selecting thrombolytic therapy. Precise thresholds for these variables are presented.

Cerebral Hemorrhage↗
PubMed1993

Prediction of mortality following hospital discharge after thrombolysis for acute myocardial infarction: is there a need for coronary angiography? European Cooperative Study Group.

The role of coronary angiography before hospital discharge after myocardial infarction was assessed in 1043 hospital survivors of the alteplase/placebo and the alteplase/PTCA trial of the European Cooperative Study Group. Forty-two of 1043 patients (4.0%) died after 1 to 489 days after predischarge coronary angiography. In survivors, follow-up ranged from 34 to 1106 days. In a stepwise multivariate regression model (Cox), use of diuretics and/or digitalis, a history of previous infarction and age exceeding 60 years were retained in the model with clinical data only. In addition, inability to perform exercise testing and less than 30 mmHg exercise-induced systolic blood pressure increase were selected by multivariate analysis. Large enzymatic infarct size, radionuclide left ventricular ejection fraction below 40%, and multivessel disease were also determinants of mortality after hospital discharge. The risk function, including coronary angiography, performed no better in late mortality prediction than functions based on clinical data and non-invasive testing. Patients without a history of previous infarction, not treated with diuretics and/or digitalis and with a systolic blood pressure increase of 30 mmHg or more during exercise had an excellent survival (98.6%) in the first year after hospital discharge, irrespective of whether symptoms of recurrent ischaemia occurred. This low risk group formed 47% of the total patient population and does not benefit from coronary angiography.

Analysis of Variance↗
PubMed1993

Tailored thrombolytic therapy. A perspective.

BACKGROUND: In contrast with current standard regimens, it seems more appropriate to tailor thrombolytic therapy to individual patient characteristics. A proposed model for such tailored therapy is based on individual assessment of benefits and risks of thrombolytic therapy, taking into account the response of individual patients to the therapy given. METHODS AND RESULTS: Potential benefits of thrombolysis in individual patients can be predicted by use of demographic patient characteristics (age, sex, history of previous infarction) together with indicators of the ischemic area at risk (total ST segment deviation) and treatment delay. Using these parameters, the number of "lives saved" by thrombolytic therapy for specific patient characteristics can be estimated. Similarly, the risk of intracranial hemorrhage during thrombolytic therapy can be estimated from the patient's age, blood pressure at admission, and body weight. Depending on benefit/risk estimates, a choice can be made between regimens with high, medium, or modest thrombolytic efficacy. Continuous multilead ECG ischemia monitoring and rapid assays of myocardial proteins in serum can be used to assess the occurrence or absence of reperfusion and to detect signs of reocclusion. Such data help to decide whether thrombolytic therapy should be continued or intensified or might be discontinued in individual patients before the total standard dose has been administered. Such tailored reduction of the total thrombolytic dose will reduce the risk for bleeding complications in some of the patients. CONCLUSIONS: The concept of tailoring thrombolytic therapy and the models presented for benefit/risk assessment should be tested in clinical studies and may subsequently help the physician to select the optimal approach in individual patients.

Adult↗
PubMed1992

Pseudo infarction ECG pattern occurring during intravenous treatment with flecainide acetate.

A 79-year-old woman presented with atrial flutter and anginal complaints, which remitted on nitroglycerin but the flutter did not respond to digoxin and verapamil. Flecainide acetate was given intravenously; administration was stopped because of development of a significant increase in the QRS duration, existence of prominent deep Q waves and marked ST elevation in leads V1 to V4. These abnormalities mimicked the ECG changes seen in myocardial infarction. However, the presence of an acute myocardial infarction could be ruled out. On a second admission intravenous flecainide acetate resulted in comparable marked ECG changes.

Aged↗
PubMed1992

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↗
PubMed1992

Plasma fibrinopeptide A levels in patients with acute myocardial infarction treated with alteplase. Correlation with concomitant heparin, coronary artery patency, and recurrent ischemia. The European Cooperative Study Group.

BACKGROUND: Fibrin generation during and after therapy with alteplase may depend on the level of concomitant anticoagulation. The hypothesis that fibrinopeptide A (FPA) levels, as markers of ongoing in vivo fibrin formation, correlate with the angiographic and clinical outcome of thrombolysis is tested. METHODS AND RESULTS: Serial plasma FPA levels were determined in 334 patients of the randomized European Cooperative Study Group trial comparing heparin versus placebo plus alteplase and aspirin in patients with acute myocardial infarction. Median FPA levels (with the 10th to 90th percentiles) were 21 ng/ml (2-390 ng/ml) before treatment in placebo-allocated patients (n = 166) and increased to 49 (15-580), 34 (4-320), 27 (2-240), 29 (2-430), and 30 (3-390) ng/ml after 0.75, 3, 12, 24, and 36 hours, respectively. In heparin-allocated patients (n = 168), median baseline FPA values were 18 ng/ml (2-210 ng/ml) and decreased to 6 (1-110), 5 (1-75), 5 (1-60), 7 (1-100), and 10 (1-170) ng/ml at corresponding time points (p less than 0.0001 for the difference at each time point). Adequate anticoagulation, defined as no activated partial thromboplastin time value below twice the pretreatment value at 3, 12, 24, and 36 hours after initiation of treatment, was obtained in 48 patients assigned to heparin. It was associated with normal median FPA levels (less than or equal to 4 ng/ml) at all time points compared with 12 (2-80), 16 (2-240), and 15 (2-240) ng/ml at 12, 24, and 36 hours, respectively, in heparin-assigned but inadequately anticoagulated patients (n = 102, p less than 0.001 for each time point). In the heparin-treated group, median FPA values tended to be lower at all time points in patients with patent vessels than in patients with occluded arteries, but the difference was significant only at 24 hours (p = 0.04). FPA levels did not correlate with clinically apparent recurrent ischemia or with left ventricular thrombosis on two-dimensional echocardiography. CONCLUSIONS: During and after thrombolytic therapy with alteplase, the enhanced fibrin generation is suppressed by sustained concomitant anticoagulation with intravenous heparin. Adequate anticoagulation warrants individual titration of the heparin dose. High plasma FPA levels 24 hours after alteplase therapy are specific but insensitive markers of vessel occlusion in anticoagulated patients. They do not correlate with clinical outcome.

Coronary Vessels↗
PubMed1992

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↗