Biomedical subjects
Publications and source records attributed to J H Reiber.
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Ambulatory 24-h Holter monitoring was carried out in 198 patients who had been admitted because of suspected acute myocardial infarction (AMI) due to chest pain, but in whom AMI was not confirmed. During a follow-up period of 12-24 months (median 14 months) 16 cardiac events (i.e., nonfatal AMI or cardiac death) occurred. Ventricular premature beats (VPBs) were found in 65.2% of the patients, complex VPBs in 28.8%. Pairs of VPBs which were seen in 10.0% of the patients were the only important type of VPBs significantly related to an impaired prognosis. Thallium-201 scintigraphy was performed in 144 of the patients. VPBs were significantly related to scar formation (i.e., to permanent defects, but not to ischemia, specifically, to transient defects). It is concluded that ventricular arrhythmias in this patient category indicate presence of chronic ischemic heart disease, and that pairs of VPBs seem to identify patients at risk for cardiac events.
Relations between lipoprotein fractions, lipoprotein lipase activities, thyroid hormones and coronary lesion growth were studied among 35 male patients with severe coronary atherosclerosis, who had participated in the lipid lowering, dietary Leiden Intervention Trial. Coronary arteriographies were performed at the beginning of the study and 2 years later at termination. The coronary anatomy was quantitated with a computer-based analysis system to assess the progression rate of coronary atherosclerosis on the basis of the absolute arterial dimensions in a patient's coronary tree; for these purposes an absolute coronary score was computed. On the basis of the absolute coronary scores, the entire group of patients could be divided into a no lesion growth group (14 patients) and a progression group (21 patients). Lipoprotein fractions, lipoprotein lipases and thyroid hormones were determined at the end of the trial. No significant difference was found between the no lesion growth and progression groups of patients for total cholesterol (TC) and LDL-cholesterol (LDL-C). The VLDL-cholesterol (VLDL-C) and triglycerides (TG) were significantly higher (P less than 0.05) and HDL-C was almost significantly lower (P less than 0.10) in the progression group. Hepatic lipase (HL) values were significantly higher in the no lesion growth group, as compared to the progression group, whereas lipoprotein lipase (LPL) values were not significantly different. Triiodothyronine (T3) was significantly lower (P less than 0.01) in the progression group. Multivariate regression analysis showed HL to be the most important determinant of changes in coronary atherosclerotic lesions. T3 and HDL were also independently inversely related to coronary atherosclerotic lesion growth.(ABSTRACT TRUNCATED AT 250 WORDS)
Quantitative angiography was performed in 68 out of 123 patients treated with intravenous rt-PA for acute myocardial infarction. At 90 min angiography, the median minimal cross-sectional area was 1.11 mm2 and the median percentage area stenosis was 80%. A percentage area stenosis greater than 70% was seen in 78% of the patients. Patients with a patient infarct related artery at the first angiogram were randomized to receive subsequent infusions either of rt-PA + heparin or placebo + heparin. There was a persistent trend of improvement in minimal lumen diameter and percentage diameter stenosis of the residual stenosis in the infarct related artery in both treatment groups when re-examined 6-24 hours later and at the time of hospital discharge. A reduction in 'plaque area', the area between the detected and the reference contours of the infarct related segment, was more frequently seen in patients receiving a second infusion of rt-PA than in patients with no prolonged thrombolytic therapy (83% versus 57%, P less than 0.025, chi square).
The vasodilatory action of molsidomine was studied by intracoronary injection of its active metabolite, Sin 1. In 10 patients repeat coronary angiography in multiple projections was performed before and 2 minutes after administration of 1 mg of Sin 1, and before and after a second injection 60 minutes later. Contours of obstructed and non-obstructed segments of the left coronary artery were quantitatively analysed with a computer-based angiography analysis system. Immediately after its administration, Sin 1 increased the mean diameters of 44 normal coronary segments by 12% (P less than 0.001). Significant vasodilation (8%) was still observed after 60 minutes. At that time, repeated administration of Sin 1 increased the vasodilation by an additional 14% with respect to the control situation. An increase in obstruction diameter was observed in 6 out of 8 obstructed segments. Mean increase in the minimal obstruction diameter was still 10% after 60 minutes.
To study the relationship between the quantitatively assessed coronary artery dimensions and the regional coronary flow reserve as measured by digital subtraction cineangiography, we investigated 17 coronary arteries with a single discrete proximal stenosis and 12 normal coronary arteries before and after intracoronary administration of papaverine. Coronary flow reserve was found to be curvilinearly related to minimal luminal cross-sectional area (r = .92, SEE = 0.73) and to percentage area stenosis (r = .92, SEE = 0.74). Normal coronary arteries had a coronary flow reserve of 5.0 (+/- 0.8 [SD]), which differed significantly from the coronary flow reserve of the coronary arteries with obstructive disease, in which values ranging from 0.5 to 3.9 were found. Coronary arteries with a percentage area stenosis between 50% and 70% and a minimal luminal cross-sectional area between 2 and 4.5 mm2 differed significantly (p = .001), with respect to the coronary flow reserve, from coronary arteries with a percentage area stenosis in excess of 70% and a minimal luminal cross-sectional area less than 2 mm2. With the use of hemodynamic equations that describe the pressure loss over a stenosis, a theoretical pressure-flow relationship can be inferred that characterizes the severity of the stenosis. Based on this theoretical pressure-flow relationship, coronary arteries that have a limited coronary flow reserve and critical stenosis (distal coronary perfusion pressure below 40 mm Hg at coronary flow of 3 ml/sec) can be identified with high sensitivity (83%) and specificity (82%). Thus, in coronary artery disease the consequent reduction in coronary flow reserve can be predicted with reasonable accuracy by quantitative assessment of coronary artery dimensions.
Relationships between lipoprotein fractions, lipoprotein lipase activities, thyroid hormones, and coronary lesion growth were studied among 35 male patients with severe coronary atherosclerosis, who had participated in the Leiden Intervention Trial, a lipid-lowering dietary intervention program. Coronary arteriography was performed at the beginning of the study and again 2 years later at its termination. The lesions were quantified using a computer-based analysis system to assess the progression rate of coronary lesions based on absolute arterial dimensions in a patient's coronary tree. For this reason an absolute coronary score was computed. Based on absolute coronary scores, patients could be divided into a no-lesion growth group (14 patients) and a progression group (21 patients). Lipoprotein fractions, lipoprotein lipases, and thyroid hormones were determined at the end of the trial. No significant differences were found between the no-lesion growth and progression groups for total cholesterol and low-density lipoprotein (LDL) cholesterol. In the progression group very-low-density lipoprotein (VLDL) cholesterol and triglycerides were significantly higher (p less than 0.05) and high-density lipoprotein (HDL) cholesterol was almost significantly lower (p = 0.058). Hepatic lipase (HL) values were significantly higher in the no-lesion growth group, when compared with the progression group, whereas lipoprotein lipase (LPL) values were not significantly different. Triiodothyronine (T3) was significantly lower (p less than 0.01) in the progression group. Multivariate regression analysis showed HL to be the most important determinant of changes in coronary atherosclerotic lesions. T3 and HDL cholesterol were also independently inversely related to coronary lesion growth.(ABSTRACT TRUNCATED AT 250 WORDS)
In 1981, a large, double-blind, randomized, multicenter trial was started in The Netherlands to evaluate the therapeutic effects of nifedipine or metoprolol in patients with unstable angina. This study, called the Holland Interuniversity Nifedipine Trial (HINT), included several hundred patients to establish potential therapeutic effects. From December 1982 until January 1984 the effects of nifedipine on left ventricular (LV) performance in a subgroup of 37 HINT patients were studied using radionuclide techniques. All patients (18 treated with nifedipine, 19 with placebo) underwent radionuclide angiography and 33 underwent thallium-201 scintigraphy just before and 48 hours after the start of treatment with the experimental medication. Radionuclide angiographic studies were also performed 1 hour (29 patients) and 4 hours (31 patients) after the start of treatment. The thallium-201 images showed defects in 24 (73%) of the baseline images and in 21 (64%) of the 48-hour images. No significant differences were seen between patients receiving nifedipine or placebo in the incidence of new defects or in the disappearance of defects at 48 hours. Changes in thallium-201 images were not related to recurrence of myocardial ischemia or the development of acute myocardial infarction. Nineteen of the 37 patients (51%) with baseline blood pool images had a reduced LV ejection fraction (EF) (38 +/- 10%) and 18 patients (49%) had a normal LVEF of 56 +/- 5%. LVEF improved after 48 hours in 8 patients receiving nifedipine and in only 1 patient receiving placebo (p less than 0.02). This effect was not present at 1 and 4 hours after treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
In 1981, a large, double-blind, randomized trial was started in The Netherlands to evaluate the therapeutic effects of nifedipine and/or metoprolol in patients with unstable angina. This study has been called the Holland Interuniversity Nifedipine/metoprolol Trial (HINT) and required several hundred patients to establish potential therapeutic effects. From December 1982 to January 1984 the effects of nifedipine on left ventricular (LV) performance in a subgroup of 52 HINT patients were studied using radionuclide techniques. All patients (23 on nifedipine, 29 controls) underwent thallium-201 scintigraphy or radionuclide angiography just before and 48 h after the start of experimental medication. The radionuclide angiographic studies were also performed at 1 and 4 h after treatment. Nifedipine did not influence the incidence or disappearance of perfusion defects on the 48-h thallium images. No significant differences in overall LV ejection fraction (EF) were seen at any time between nifedipine-treated patients and controls. However, paired observations in 37 patients showed improvement of LVEF after 48 h in 8 patients on nifedipine and in only 1 control patient. Scintigraphic measurements on admission were not related to clinical outcome after 48 h. Concomitant administration of metoprolol did not influence LVEF in either group. It is concluded that nifedipine improves LVEF after 48 h in a subset of patients with unstable angina without affecting myocardial perfusion. This finding indicates that nifedipine has a predominant effect on afterload reduction in patients with unstable angina. However, early scintigraphic measurements had no significant predictive value for subsequent cardiac events.
In this study the hypothesis is tested that the motion pattern of small anatomic landmarks, recognizable at the left ventricular endocardial border in the contrast angiocardiogram, reflects the motion of the endocardial wall. To verify this, minute metal markers were inserted in the endocardium of eight pigs with a novel retrograde transvascular approach. Marker motion was subsequently recorded with roentgen cinematography and compared with the motion of the landmarks on the endocardial contours detected from the contrast ventriculogram with an automated contour detection system. Linear regression analysis of the directions of the systolic metal marker and endocardial landmark pathways yielded a correlation coefficient of 0.86 and a standard error of the estimate of 10.3 degrees. Landmark pathways were also measured in 23 normal human left ventriculograms. Normal left ventricular endocardial wall motion during systole, as observed in the 30 degrees right anterior oblique view, is characterized by a dominant inward transverse motion of the opposite anterior and inferoposterior walls and a descent of the base toward the apex. The apex itself is almost stationary. On the basis of these observations, a widely applicable model for the assessment of left ventricular wall motion is described in mathematical terms.
Three hundred and two patients with acute myocardial infarction were enrolled in a randomized multicenter trial to compare conventional treatment with attempted recanalization by intracoronary streptokinase. In a subgroup of patients, the effects of thrombolysis on left ventricular function were evaluated within 48 hr, at 2 wk, and at 3 mo after admission. Global left ventricular ejection fraction (LVEF) was obtained by radionuclide angiography and analyzed with an automatic detection program. Paired data were determined in 160 patients (control 78, thrombolysis 82) within 48 hr and at 2 wk, and in 143 patients (control 71, thrombolysis 72) at 48 hr, 2 wk, and 3 mo. It was shown that LVEF significantly improved in the thrombolysis group as compared with controls both at 2 wk (delta LVEF thrombolysis 3.9 +/- 7.9%, p less than 0.001 compared with delta LVEF control 0.6 +/- 9.7%, p = N.S.) and at 3 mo (delta LVEF thrombolysis 3.1 +/- 12.4%, p less than 0.05 compared with delta LVEF control 2.1 +/- 12.2%, p = N.S.). When patients were divided according to infarct site, however, significant improvement at 3 mo was only observed in the patients with anterior infarction (delta LVEF thrombolysis 5.5 +/- 13.1%, p less than 0.05 compared with delta LVEF control 3.3 +/- 10.4%, p = N.S.). It was shown that acute intervention with intracoronary streptokinase has a potentially favorable and lasting effect on left ventricular function in patients with anterior myocardial infarction. This improvement might be related to the rather rapid administration of thrombolytic therapy with a median time of approximately 4 hr after onset of symptoms.
We studied the relation between diet, serum lipoproteins, and the progression of coronary lesions in 39 patients with stable angina pectoris in whom coronary arteriography had shown at least one vessel with 50 per cent obstruction before intervention. Intervention consisted of a two-year vegetarian diet that had a ratio of polyunsaturated to saturated fatty acids of at least 2 and that contained less than 100 mg of cholesterol per day. Dietary changes were associated with a significant increase in linoleic acid content of cholesteryl esters and a significant lowering of body weight, systolic blood pressure, serum total cholesterol, and the ratio of total to high-density lipoprotein (total/HDL) cholesterol. Angiographic examination was performed after 24 months; angiograms were assessed visually (with blinding) and by computer-assisted image analysis. Both types of assessment indicated progression of disease in 21 of 39 patients but no lesion growth in 18. Coronary lesion growth correlated with total/HDL cholesterol (r = 0.50, P = 0.001) but not with blood pressure, smoking status, alcohol intake, weight, or drug treatment. Disease progression was significant in patients who had values for total/HDL cholesterol that were higher than the median (greater than 6.9) throughout the trial period. No coronary-lesion growth was observed in patients who had lower values for total/HDL cholesterol (less than 6.9) throughout the trial or who initially had higher values (greater than 6.9) that were significantly lowered by dietary intervention.
The value of exercise testing and thallium scintigraphy in predicting recurrence of angina pectoris and restenosis after a primary successful transluminal coronary angioplasty (PTCA) was prospectively evaluated. In 89 patients, a symptom-limited exercise electrocardiogram (ECG) and thallium scintigraphy were performed 4 weeks after they had undergone successful PTCA. Thereafter, the patients were followed for 6.4 +/- 2.5 months (mean +/- standard deviation) or until recurrence of angina. They all underwent a repeat coronary angiography at 6 months or earlier if symptoms recurred. PTCA was considered successful if the patients had no symptoms and if the stenosis was reduced to less than 50% of the luminal diameter. Restenosis was defined as an increase of the stenosis to more than 50% luminal diameter. The ability of the thallium scintigram (presence of a reversible defect) to predict recurrence of angina was 66%, vs 38% for the exercise ECG (ST-segment depression or angina at peak workload). Restenosis was predicted in 74% of patients by thallium scintigraphy, but only in 50% of patients by the exercise ECG. Thus, thallium scintigraphy was highly predictive but the exercise ECG was not (p less than 0.005). These results suggest that restenosis had occurred to some extent already at 4 weeks after the PTCA in most patients in whom it was going to occur.
In the quantitative assessment of coronary arterial dimensions from coronary cineangiograms, the contrast catheter is usually used as a scaling device, requiring the definition of the catheter contours by semi- or fully automated contour detection procedures. The image quality of the x-ray radiated catheter is dependent on the catheter material, concentration of the contrast agent in the catheter, and kilovoltage of the x-ray source. The effects of these variables on the image quality and accuracy of the size-measurement of the filmed catheters were studied for four different catheter materials: woven dacron (wd), polyvinylchloride (pv), polyurethane (pu), and nylon. The following parameters were studied: measured size, image contrast, and average brightness gradient along the edges of the displayed catheters. The average differences of the angiographically measured size with the true size for the wd, pv, pu, and nylon catheters were +0.2, -3.2, -3.5, and +9.8%, respectively. The image contrast at various fillings of the catheters was roughly identical for the wd, pv, and pu catheters, and significantly lower for the nylon catheter. Image gradient was highest for the wd catheter, followed by the pv and pu catheters, and lowest for the nylon catheter. From these data it may be concluded that the woven dacron catheter is most suitable for quantitative coronary angiographic studies. The polyvinylchloride and polyurethane catheters perform about equally well but slightly less than the woven dacron catheter. The nylon catheter should not be used for such quantitative studies.
An overview is presented on different techniques for data acquisition and analysis of technetium-99m gated blood pool scintigrams. The basic principles for semi- and fully automated boundary detection of the left ventricular activity structure in one or more frames and for the selection of the background region of interest are described. Methods for the computation of global and regional ejection fraction are discussed and comparative data from scintigraphic and contrast left ventricular angiography presented. Finally, an overview of commercially available state of the art computer programs for the computation of global and regional ejection fraction is presented.
In a clinical trial we studied left ventricular performance at rest in 50 patients with unstable angina by radionuclide techniques. Thallium-201 scintigraphy was performed on admission in 38 patients and repeated after 48 hr in 32 patients. Also dynamic blood pool scintigraphy was performed in 37 patients on admission and in 45 patients after 48 hr. Of the 50 patients, 27 (54%) had no recurrent episodes of myocardial ischemia, but 23 (46%) patients showed recurrent ischemic episodes of whom 11 (22%) patients developed a myocardial infarction. The thallium-201 images showed perfusion defects in 27 (71%) of the 38 patients studied on admission and in 20 (63%) of the 32 patients studied at 48 hr. No relation between clinical outcome and presence or absence of defects was observed. Left ventricular ejection fraction was abnormal (less than 50%) in 19 (51%) of the 37 patients on admission and in 29 (64%) of the 45 patients studied at 48 hr. As with thallium-201, no relation could be established between clinical outcome and left ventricular ejection fraction. It is concluded that radionuclide techniques are useful to provide insight into the pathophysiological mechanism of unstable angina, but they are not helpful for the short-time assessment of clinical outcome.
Restenosis of the dilated vessel after percutaneous transluminal coronary angioplasty can be detected by non-invasive procedures but their ability to predict later restenosis soon after a successful angioplasty as well as recurrence of angina has not been assessed. A maximal exercise test and myocardial thallium perfusion scintigraphy were, therefore, performed in 91 asymptomatic patients a median of 5 weeks after they had undergone a technically successful angioplasty. Primary success of the procedure was confirmed by the decrease in percentage diameter stenosis from 64(12)% to 30(13)% as measured from the coronary angiograms and in the trans-stenotic pressure gradient (normalised for mean aortic pressure) from 0.61(0.16) to 0.17(0.09). A clinical follow up examination (8.6(4.9) months later) was carried out in all patients and a late coronary angiogram obtained in 77. The thallium perfusion scintigram showing the presence or absence of a reversible defect was highly predictive for restenosis whereas the exercise test was not. The positive predictive value of an abnormal scintigram was 82% compared with 60% for the exercise test (ST segment depression/or angina or both at peak workload). Angina or a new myocardial infarction occurred in 60% of patients with abnormal and in 21% of patients with normal scintigrams.
The value of a QRS scoring system derived from 12 lead electrocardiograms to estimate left ventricular ejection fraction was assessed in a prospective study of 285 hospital survivors of myocardial infarction. In these patients both the QRS score and ejection fraction were measured by radionuclide ventriculography at discharge. The correlation between ejection fraction and QRS score was weak. In 22 patients who died during six to 12 months follow up the ability of the ejection fraction and QRS score to predict mortality was assessed in terms of sensitivity, specificity, predictive value of a positive and negative test, and efficiency. For ejection fraction less than 40% and a QRS score greater than or equal to 6 sensitivity was respectively 73% and 64%, specificity 73% and 56%, predictive value of a positive test 18% and 11%, predictive value of a negative test 97% and 95%, and efficiency 73% and 56%. Both ejection fraction and QRS score may be used to identify patients at low and high risk during one year follow up, but, contrary to initial expectations, the QRS score appears to be of little value in estimating ejection fraction and is less accurate than ejection fraction in predicting late survival in hospital survivors of myocardial infarction.