Arnold, A.E.R.

Validity of conjoint analysis to study cardiologists' decisions for elderly patients with aortic stenosis (Article)

2004-08-01T00:00:00Z

Objective Written case simulations are increasingly being used to investigate clinical decision making. Our study was designed to determine the validity of written case simulations within a conjoint analysis approach. Study design and setting We developed a series of 32 written case simulations that differed with respect to nine clinical characteristics. These case simulations represented elderly patients with aortic stenosis. The clinical characteristics varied according to a fractional factorial design. We analyzed retrospectively all consecutive patients of 70 years of age or older with an aortic stenosis in three university hospitals. Results 34 cardiologists from three Dutch hospitals gave their treatment advice to each of these case simulations on a six-point scale (ranging from ‘certainly no’ to ‘certainly yes’ to surgical treatment). We compared the influence that the clinical characteristics had on the responses to these case simulations with their influence on the actual treatment decision for 147 actual patients in the same three hospitals. We found a strong agreement. This agreement was only slightly affected by the cut-off value used to dichotomize the treatment advice into a recommendation in favor of or against surgical treatment. Conclusion Written case simulations reflect well how clinicians are influenced by specific clinical characteristics of their patients.

Variability in treatment advice for elderly patients with aortic stenosis: a nationwide survey in the Netherlands (Article)

2001-01-01T00:00:00Z

OBJECTIVETo 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. DESIGNA 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. SETTINGNationwide postal survey among all 530 cardiologists in the Netherlands. RESULTS52% 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. CONCLUSIONSThere 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.

Estimated gain in life expectancy (Article)

1996-01-01T00:00:00Z

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.

Benefit of Thrombolytic Therapy is Sustained Throughout Five Years and Is Related to TIMI Perfusion Grade 3 But Not Grade 2 Flow at Discharge (Article)

1995-01-01T00:00:00Z

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.

Thrombolytic therapy for evolving myocardial infarction needs an approach that integrates benefit and risk (Article)

1995-01-01T00:00:00Z

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.

Tailored thrombolytic therapy. A perspective (Article)

1993-01-01T00:00:00Z

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.

Recombinant tissue-type plasminogen activator and immediate angioplasty in acute myocardial infarction. (Article)

1992-01-01T00:00:00Z

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.

Reasons for the lack of benefit of immediate angioplasty during recombinant tissue plasminogen activator therapy for acute myocardial infarction: a regional wall motion analysis (Article)

1991-01-01T00:00:00Z

Regional ventricular wall motion analysis utilizing three different methods was performed on predischarge left ventriculograms from 291 of 367 patients enrolled in a randomized trial of single chain recombinant tissue-type plasminogen activator (rt-PA), aspirin and heparin with and without immediate angioplasty in patients with acute myocardial infarction. With univariate analysis, no difference in regional wall motion variables between the two treatment groups was observed. However, with individual baseline risk assessment by multivariate linear regression analysis using baseline characteristics known to be related to left ventricular function after thrombolytic therapy or outcome of coronary angioplasty, or both, an excess of high risk patients in the invasive treatment group was detected. To adjust for this unequal distribution of baseline risk, multivariate linear regression analysis was performed. No benefit of immediate coronary angioplasty was observed after adjustment. Reocclusion or reinfarction, or both, occurred more frequently in the invasive than in the noninvasive treatment group (18% versus 13%, respectively). Among patients with a patent infarct-related vessel on angiography between days 10 and 22 and without reinfarction before angiography, there was a trend toward benefit from the invasive strategy, indicating that reocclusion and reinfarction might be responsible for the lack of benefit of the invasive strategy. This implies that immediate coronary angioplasty may be beneficial in selected patients, provided that these complications can be prevented.

Increased serum levels of fibrinogen degradation products due to treatment with recombinant tissue-type plasminogen activator for acute myocardial infarction are related to bleeding complications, but not to coronary patency (Article)

1989-01-01T00:00:00Z

The association of increasing serum levels of fibrinogen degradation products after recombinant tissue-type plasminogen activator (rt-PA) therapy with bleeding and early coronary patency was assessed in 242 patients with acute myocardial infarction. After administration of 5,000 IU heparin, a median of 40 mg (range 35 to 60) of double chain rt-PA was given intravenously in 90 min. Bleeding occurred in 62 patients; in 73% of patients it was observed within the 1st 24 h and 84% of events consisted of hematoma or prolonged bleeding, or both, at puncture sites. Bleeding events occurred 2.12 times as often in patients with serum levels of fibrinogen degradation products greater than 85 mg/liter as in patients with serum levels less than 22 mg/liter (95% confidence interval 1.01 to 4.43). The infarct-related coronary vessel was patent in 65% of patients at 90 min after the start of rt-PA infusion. In patients with high serum levels of fibrin(ogen) degradation products, coronary patency at 90 min after the start of rt-PA infusion was not better (13% less, 95% confidence interval - 33%, 13%) than in patients with low serum levels. This uncoupling of thrombolytic effect in terms of coronary patency and systemic fibrinogenolysis confirms the experimentally demonstrated fibrin specificity of double chain rt-PA in human subjects. Because fibrin specificity of single chain rt-PA is at least similar to that of double chain rt-PA, the observations in this analysis most likely hold also for single chain rt-PA.(ABSTRACT TRUNCATED AT 250 WORDS)

Trombolytische therapie van het acute hartinfarct (Article)

1989-01-01T00:00:00Z

Trombolytische behandeling van het hartinfarct is één van de belangrijkste aanwinsten van de laatste jaren voor het therapeutisch arsenaal van de medicus practicus. Elders in dit tijdschrift worden de belangrijkste onderzoeksresultaten samengevat.1 De eerste onderzoekingen naar de baten van trombolyse bij het hartinfarct dateren van meer dan 20 jaar geleden. Doordat geen metingen van infarctgrootte of functie van de linker hartkamer werden verricht en de onderzoekingen steeds te klein waren om sterftereductie door trombolyse aan te kunnen tonen, konden er geen conclusies uit worden getrokken. Dit is wél mogelijk bij de onderzoekingen die gedurende de laatste jaren zijn uitgevoerd.

Capita Selecta. Trombolytische therapie van het acute hartinfarct anno 1988 (Article)

1989-01-01T00:00:00Z

Thrombolysis with tissue plasminogen activator in acute myocardial infarction: no additional benefit from immediate percutaneous coronary angioplasty (Article)

1988-01-30T00:00:00Z

A randomised trial of 367 patients with acute myocardial infarction was performed to determine whether an invasive strategy combining thrombolysis with recombinant tissue-type plasminogen activator (rTPA), heparin, and acetylsalicylic acid, and immediate percutaneous transluminal coronary angioplasty (PTCA) would be superior to a noninvasive strategy with the same medical treatment but without immediate angiography and PTCA. Intravenous infusion of 100 mg rTPA was started within 5 h after onset of symptoms (median 156 min). Angiography was performed 6-165 min later in 180 out of 183 patients allocated to the invasive strategy; 184 patients were allocated to the non-invasive strategy. Immediate PTCA reduced the percentage stenosis of the infarct-related segment, but this was offset by a high rate of transient (16%) and sustained (7%) reocclusion during the procedure and recurrent ischaemia during the first 24 h (17%). The clinical course was more favourable after non-invasive therapy, with a lower incidence of recurrent ischaemia within 24 h (3%), bleeding complications, hypotension, and ventricular fibrillation. Mortality at 14 days was lower in patients allocated to non-invasive treatment (3%) than in the group allocated to invasive treatment (7%). No difference between the treatment groups was observed in infarct size estimated from myocardial release of alpha-hydroxybutyrate dehydrogenase or in left ventricular ejection fraction after 10-22 days. Since immediate PTCA does not provide additional benefit there seems to be no need for immediate angiography and PTCA in patients with acute myocardial infarction treated with rTPA.

Thrombolysis with rt-PA in acute myocardial infarction: no additional benefit of immediate PTCA (Miscellaneous)

1988-01-30T00:00:00Z

Acute coronary thrombolysis with recombinant human tissue-type plasminogen activator: initial patency and influence of maintained infusion on reocclusion rate (Article)

1987-01-01T00:00:00Z

An intravenous infusion of 40 mg of recombinant tissue-type plasminogen activator (rt-PA) was given intravenously over 90 minutes to 123 patients with acute myocardial infarction (AMI) of less than 4 hours' duration. A coronary angiogram was recorded at the end of the infusion in 119 patients. Central assessment of the angiograms revealed a patent infarct-related artery in 78 patients (patency rate 66%, 95% confidence limits 57 to 74%). Patients with a patent infarct-related artery at the first angiogram were randomized in a double-blind manner to receive a subsequent 6-hour infusion of either 30 mg of rt-PA or placebo. All patients had received an initial bolus of 5,000 IU of heparin and then 1,000 IU/hour until a second angiogram was recorded 6 to 24 hours after the start of the second perfusion. At central assessment of the second coronary angiogram the reocclusion rate was 2 of 36 patients who received rt-PA at the second infusion and 3 of 37 patients not receiving this drug (or the 2 groups combined 7%, 95% confidence limits 2 to 15%). Three of 60 patients (5%, 95% confidence limits 1 to 14%) with patent arteries on both previous angiograms had a later occlusion as judged on the angiogram recorded at hospital discharge. No difference in late reocclusion rates between the 2 treatment groups was observed.

Effect of continued rt-PA administration on the residual stenosis after initially successful recanalization in acute myocardial infarction - a quantitative coronary angiography study of a randomized trial (Article)

1987-01-01T00:00:00Z

Assessment of the bradycardic and inotropic properties of ST 567 using a new scheme of administration (Article)

1987-01-01T00:00:00Z

In 10 patients undergoing diagnostic cardiac catheterisation a bolus of 15 mg ST 567 was administered intravenously in 1.5 min followed by a 30 min infusion of 7.5 mg. The maximal plasma level was 343 +/- 131 ng ml-1 (mean +/- s.d.) 1 min after bolus injection and stabilised around 179 ng ml-1 thereafter. Heart rate decreased from 71 +/- 10 beats min-1 at baseline to 66 +/- 10 beats min-1 at the end of the bolus injection (-7%). This decrease in heart rate persisted during the whole observation period. Also there was an 8% reduction in peak positive first derivative of LV pressure. Cardiac output measured by thermodilution during atrial pacing decreased from 5.9 +/- 1.1 l min-1 to 5.3 +/- 0.7 l min-1 (P less than 0.02). In 3 patients with the largest decrease in cardiac output, the end diastolic LV pressure at the end of the observation period decreased, which may reflect a decrease in pre-load. Only in 1 patient the decrease in end diastolic LV pressure exceeded twice the standard deviation of the random error component of duplicate measurements. Thus, although normal therapeutic plasma levels were achieved, ST 567 demonstrated negative inotropic properties independent of changes in heart rate with this scheme of administration.

Coronary angioplasty of the unstable angina related vessel in patients with multivessel disease (Article)

1986-01-01T00:00:00Z

This study is a retrospective analysis of the efficacy of percutaneous transluminal coronary angioplasty of the ischaemia-related vessel in patients with unstable angina. Forty-three patients had multivessel disease with dilatation of the ischaemia-related vessel only (group I; partial revascularization) while 111 patients had single vessel disease only (group II; total revascularization). The initial success rate in both groups was identical (88 versus 88%). The need for emergency coronary artery bypass surgery was similar in the two groups (group I 12% versus group II 9%; NS). The total post PTCA myocardial infarction rate (despite urgent CABG) was also similar in the two groups (group I 9% versus group II 10%; NS). The results of electrocardiographic exercise testing and Thallium-201 scintigraphy provide objective evidence for incomplete revascularization in group I. The maximum workload achieved was lower, and the frequency of exercise induced angina, ST-segment depression and reversible perfusion defect was higher than in group II. Moreover, at 6 months follow-up the recurrence rate of angina pectoris rate was higher in group I than in group II (29% versus 16% P less than 0.05). It is concluded that dilatation of the ischaemia related vessel only in patients with unstable angina and multivessel disease is as effective in the management of the acute phase of unstable angina as is dilatation of the ischaemia related vessel in patients with single vessel disease. However, due to only partial revascularization the recurrence rate of angina pectoris is higher.

Emergency coronary angioplasty in refractory unstable angina (Article)

1985-01-01T00:00:00Z

We performed percutaneous transluminal coronary angioplasty as an emergency procedure in 60 patients with unstable angina pectoris that was refractory to treatment with maximally tolerated doses of beta-blockers, calcium antagonists, and intravenous nitroglycerin. The initial success rate for angioplasty was 93 per cent (56 patients). There were no deaths related to the procedure, although total occlusion occurred in four patients. Despite emergency bypass grafting, all four sustained a myocardial infarction. All the patients were followed for at least six months. Late cardiac death occurred in one patient, whereas eight had recurrent angina pectoris. There was no progression to myocardial infarction. The restenosis rate was 28 per cent (13 of 46) in the patients with initially successful coronary angioplasty who had repeat angiography. Improved cardiac functional status after sustained successful coronary angioplasty was demonstrated by an almost normal capacity on bicycle exercise testing and the absence of ischemia during thallium isotope studies in 80 per cent. We conclude that emergency percutaneous transluminal coronary angioplasty may be useful for the treatment of selected patients with unstable angina pectoris who are unresponsive to intensive pharmacologic treatment.