Influence of tissue affinity of angiotensin-converting enzyme inhibitors on left ventricular remodeling after myocardial infarction.

BACKGROUND: The demonstration of local renin-angiotension systems has raised the question of whether angiotensin-converting enzyme (ACE) inhibitors with different tissue affinities differ with regard to their effects on postinfarction remodeling. HYPOTHESIS: The study was undertaken to investigate the influence of ACE inhibitors with different tissue affinity on morphology and function of the infarcted left ventricle. METHODS: In all, 52 patients (17 women, 35 men, 38-73 years) with large acute myocardial infarction were randomized to receive either 25-75 mg/day captopril or 10-20 mg/day fosinopril beginning on the Day 7 after infarction. Of these, 28 had anterior and 24 had posterior wall infarctions. Infarct size was determined by the creatine kinase integral method. Fifty patients were examined by cinemagnetic resonance imaging (CMRI) 1 and 26 weeks after infarction. The following parameters were determined: left ventricular end-diastolic and end-systolic volume index (LVEDVI, LVESVI), ejection fraction (LVEF), infarct weight, and muscle mass (LVMM). The volume-to-mass ratio (VMR) was calculated and the clinical status according to the guidelines of the New York Heart Association (NYHA) was documented at each examination time. The results were compared with those of a historical sample without ACE-inhibitor therapy examined in an identical manner (n = 31, 10 women, 21 men, 36-75 years). RESULTS: LVEDVI and LVESVI increased in the first 6 months after infarction by 24.9 and 36.6%, respectively, in the historical sample; by 11.0 and 7.8%, respectively, under captopril; and by 13.1 and 10.7%, respectively, under fosinopril. LVEF decreased by 14.9% in the untreated sample, by 3.7% under captopril and by 5.0% under fosinopril. Infarct weight and LVMM increased by 12.7 and 15.3%, respectively, without ACE inhibition, by 5.7 and 10.1%, respectively, in patients treated with captopril, and by 6.1 and 9.3%, respectively, in patients treated with fosinopril. The VMR increased by 7.4% in the historical sample, by 3.5% in the captopril group, and by 1.8% in the fosinopril group. The NYHA clinical status improved by 18.2% without ACE inhibition, by 42.9% in the captopril group, and by 26.3% in the fosinopril group. The differences between the two ACE-inhibitor groups and the reference group were all significant, while the differences between the captopril group and the fosinopril group were significant only for VMR (p < 0.01) and NYHA class (p < 0.05). CONCLUSIONS: Both captopril and fosinopril have a comparable positive influence on postinfarction remodeling and on clinical status. Lipophilicity and tissue affinity do not seem to play a clinically important role in ACE-inhibitor therapy after infarction.

Changes of the left ventricle after myocardial infarction--estimation with cine magnetic resonance imaging during the first six months.

BACKGROUND: In recent years, the interest of cardiologists has focused increasingly on the morphologic and functional changes of the left ventricle after myocardial infarction (MI), due to their great prognostic significance for the patient. HYPOTHESIS: The aim of this study was to evaluate changes in left ventricular morphology and function during the first 6 months following MI. METHODS: In all, 61 patients (17 women, 44 men, age 36-83 years) were examined with cine magnetic resonance imaging (CMRI) 1, 4, and 26 weeks after myocardial infarction. Thirty-two patients had anterior MI and 29 patients had posterior MI. According to enzyme-derived infarct weight, 15 patients had small infarcts (< 20 g), 19 had intermediate-sized infarcts (20-40 g), and 27 patients had large infarcts (> 40 g). CMRI was performed in the true short axis of the left ventricle. In each examination, left ventricular end-diastolic and end-systolic volume indices (LVEDVI, LVESVI), stroke volume index (LVSVI), ejection fraction (LVEF), and regional thickness, mass, and motility of the myocardial wall-diastolic thickness (IDdia), infarct mass (IM) and motility (IMOT) of the infarct area and diastolic and systolic thickness (VDdia, VDsys), muscular mass (VM), and motility (VMOT)-were determined. In addition, patients were divided into subgroups according to New York Heart Association (NYHA) functional status at baseline. RESULTS: In the total group, LVEDVI increased from 73.9 +/- 23.5 ml/m2 to 85.4 +/- 28.1 ml/m2 (p < 0.001) and LVESVI from 40.5 +/- 19.4 ml/m2 to 51.2 +/- 29.0 ml/m2 (p < 0.001). In the subgroups the development depended on infarct size and location. LVSVI and LVEF remained more or less constant except for large anterior infarctions. All changes of the myocardial wall depended on infarct size and location: In all patients IDdia decreased from 10.4 +/- 1.6 mm to 8.9 +/- 1.7 mm (p < 0.001), IMOT from 2.0 +/- 1.6 mm to 0.5 +/- 2.9 mm (p < 0.001). IM increased from 41 +/- 21 g to 45 +/- 25 g (p < 0.001). In the total group, VDdia increased from 11.9 +/- 1.6 mm to 12.4 +/- 1.8 mm (p < 0.05), VDsys from 16.6 +/- 2.5 mm to 17.2 +/- 3.1 mm (p < 0.05). In the subgroups changes varied: VDdia and VDsys decreased markedly in large anterior wall infarctions. VM increased in the total cohort from a mean of 246 +/- 66 g to 276 +/- 80 g (p < 0.001). VMOT decreased from 7.1 +/- 2.4 mm to 6.3 +/- 2.7 mm (p < 0.05). Loss of motility was most pronounced in anterior infarctions. The volume-mass ratio, a measure of the success of compensation of volume increase by myocardial hypertrophy, decreased in small infarcts, remained unchanged in intermediate infarcts, and increased in large infarcts. There was a trend toward improvement of the NYHA functional status during the observation period. CONCLUSIONS: Changes of the left ventricular chamber during the first 6 months following MI are dependent on its size and location, with large anterior infarctions having the worst course. Myocardial wall remodeling is also dependent on infarct size and location, and the volume-mass ratio increases in the presence of large areas of necrosis, indicating the non-compensatory effect of myocardial hypertrophy. However, these changes have no clinical effect during the first half year after MI.

[Effect of infarct size and site, patency of the infarct vessel and perfusion of vital myocardium on remodeling of the left ventricle--studies with cine-magnetic resonance tomography in the first 6 months following myocardial infarct]. / Einfluss von Infarktgrösse und -lokalisation, Offenheit des Infarktgefässes sowie Perfusion des vitalen Myokards auf das Remodeling des linken Ventrikels--Untersuchungen mit der Cine-Magnetresonanztomographie in den ersten 6 Monaten nach Myokardinfarkt.

BACKGROUND: Aim of the study was to evaluate the influence of infarct size and location and patency of the infarction and non-infarction vessels on left ventricular morphology and function in the first 6 months after myocardial infarction. METHODS: 61 patients (17 female, 44 male, 36-83 years) were examined with Cine Magnetic Resonance Imaging (CMRI) 1 and 26 weeks, and with coronary angiography 4 weeks after infarction. 32 patients had anterior, 29 patients posterior myocardial infarction. 15 patients had small infarcts (< 20 gm), 19 intermediate sized (20-40 gm) and 27 patients large infarcts (> 40 gm). CMRI was done in short axis of the left ventricle. Left ventricular enddiastolic and endsystolic volume indices (LVEDVI, LVESVI), ejection fraction (LVEF), muscle mass (VM) and motility (VMOT) of the vital myocardium, mass (IM) and area (IA) of the infarction zone, and volume-mass-ratio (VMR) of the left ventricle were determined on each examination. RESULTS: After 6 months large infarctions had 25% more LVEDVI, 41% more LVESVI, 20% less LVEF, 11% more VM, 13% less VMOT, 13% more IM, 47% more IA, and a 17% increased VMR compared to small infarcts. Anterior infarctions showed 11% more LVEDVI, 19% more LVESVI, 7% less LVEF, 4% more VM, the same VMOT, 5% more IM, 21% more IA, and 6% more VMR than posterior infarctions. If the infarction vessel was not perfused, after 6 months LVEDVI was 12% more, LVESVI 19% more, LVEF 7% smaller, VM 4% less, VMOT the same, IM 5% more, IA 17% more, and VMR 7% more increased than in the group with open infarction artery. When both non-infarction vessels were stenosed, LVEDVI rose 24% more, LVESVI 49% more, LVEF fell 25% more, VM rose 12% more, VMOT fell 26% more, and VMR rose 12% more than in patients with indisturbed perfusion of the vital myocardium. CONCLUSION: Perfusions of the vital myocardium and infarct size seem to be the most important factors for post infarction remodeling of the left ventricle. Infarct location and patency of the infarction vessel are of less influence.

Magnetic resonance angiography as a technique for the visualization of hemodialysis shunts.

In order to test the suitability of magnetic resonance angiography for the visualization of Brescia-Cimino hemodialysis shunts, 20 patients (8 women, 12 men, aged 24-69 years) were examined with this technique. The shunt arm was placed in an extremity coil. The time-of-flight method was applied. Examination time was less than 15 min. Arterial digital subtraction angiography (DSA) of the shunt arm was carried out additionally in 8 patients in whom pathological results had been obtained. Surgery was performed on 2 patients. In all cases, the feeding artery, anastomosis, and shunt were clearly visible. The results corresponded exactly to those of DSA and, in the patients who had undergone surgery, also to the situs. The patients stated that the examination technique was not very disturbing. Magnetic resonance angiography in the time-of-flight technique seems to be recommendable for the examination of Brescia-Cimino dialysis shunts. Compared to DSA, it has major advantages: it is noninvasive, and no ionizing radiation or contrast medium are associated with the procedure.

Granulocyte-macrophage-colony stimulating factor for prevention of neutropenia and infections in children and adolescents with solid tumors. Results of a prospective randomized study.

BACKGROUND: Chemotherapy is an essential modality of curative strategies in pediatric oncology. Dose and dose intensity are, above all, restricted by the myelosuppressive effects of cytotoxic drugs. Neutropenia constitutes an important risk of morbidity and mortality. Granulocyte-macrophage-colony stimulating factor (GM-CSF) is a hematopoietic growth factor that increases the number of circulating neutrophils as demonstrated in adults. METHODS: A prospective randomized study of the effects of GM-CSF was performed with 11 patients who were treated for solid tumors and received GM-CSF for 2 weeks starting 48 hours after completion of chemotherapy. Forty-two intraindividual identical chemotherapy-courses with and 42 without GM-CSF were compared. The monitoring program included the surveillance of the hematological reconstitution and the number and duration of infectious episodes. RESULTS: The average nadir of the absolute neutrophil count (ANC) with GM-CSF was higher than without GM-CSF. The average number of days with an ANC below 500/microliters was significantly reduced by GM-CSF. Fewer infectious episodes were observed among those who received GM-CSF therapy. Erythropoiesis was not significantly influenced by GM-CSF, whereas patients with GM-CSF therapy showed a longer thrombocytopenia without requiring more platelet transfusions. Rashes developed in two patients. CONCLUSIONS: In children and adolescents undergoing intensive chemotherapy for solid tumors, GM-CSF reduces neutropenia and infectious episodes at the cost of mild thrombocytopenia.

[Cine-MRT in the functional and morphological diagnosis of the heart after a myocardial infarct/ A comparison with angiocardiography, 2-dimensional echocardiography, intracardiac scintigraphy and enzymatic infarct size estimation]. / Cine-MRT in der funktionellen und morphologischen Diagnostik des Herzens nach Myokardinfarkt. Vergleich zur Angiokardiographie, zweidimensionalen Echokardiographie, Herzbinnenraumszintigraphie und enzymatischen Infarktgrössenbestimmung.

PURPOSE: The aim of the study was to test the reliability of cine magnetic resonance imaging (cine-MRI) on the infarction heart with its altered geometry. MATERIAL AND METHODS: 61 patients (17 women, 44 men, 36-83 years, 32 with anterior, 29 with posterior wall infarction) received Cine-MRI in the true long and short axis of the heart and two-dimensional echocardiography one and 4 weeks post infarction. Two-level angiocardiography (ACG) and radionuclide ventriculography (RNV) were performed 4 weeks p.i. The size of myocardial infarction was determined enzymatically with the CK integral method. Left ventricular volume indices (EDVI, ESVI, SVI), ejection fraction (EF) and infarction weight (IW) were compared. RESULTS: Excellent correlations existed between cine-MRI in the long and short axis for the volume indices and EF. Between cine-MRI in the short axis and ACG all correlations were excellent as well. They were significantly less satisfactory between cine-MRI and 2DE due to the inhomogeneity of echo quality. Cine-MRI and RNV produced similar EF results (r = 0.884), and a comparison of IW in cine-MRI and CK integral method also showed a good correspondence (r = 0.967). CONCLUSION: Cine-MRI is a reliable method for the morphological and functional examination of post-myocardial infarction.

[Left ventricular dimensions and functions in the acute and chronic phase after myocardial infarct--comparison of cine-magnetic resonance tomography, angiocardiography, 2D-echocardiography and technetium ventricular scintigraphy]. / Linksventrikuläre Dimensionen und Funktion in der akuten und chronischen Phase nach Infarkt--Vergleich von Cine-Magnetresonanztomographie, Angiokardiographie, 2D-Echokardiographie und Technetium-Ventrikelszintigraphie.

To study left ventricular morphological and functional changes in the first six months after acute myocardial infarction, 37 patients (28 male, 9 female, age 42-78 years) underwent cardiac Cine-MRT 1 week, 4 weeks and 6 months after their first myocardial infarction. MR-tomograms were oriented to left ventricular true long and short axis. For comparison, contrast angiocardiographic, radionuclide and echocardiographic left ventricular studies were performed. LV-volume was calculated with the Simpson method for long axis images and by summation of slices for short axis images. Cine MRT results showed the following correlation to angiocardiography: in long axis r = 0.945 for LVEDVI, r = 0.958 for LVESVI, r = 0.869 for LVEF and r = 0.885 for cardiac index; in short axis r = 0.956 for LVEDVI, r = 0.965 for LVESVI, r = 0.917 for LVEF and r = 0.844 for cardiac index. For LVEF correlation to technetium radionuclide ventriculography was r = 0.760 in long and r = 0.861 in short axis. Correlation between Cine-MRT and echocardiography was poor as a consequence of the great variance of echogenity in the study patients. We conclude that Cine-MRT is an excellent method for morphological and functional left ventricular investigation, still limited in clinical praxis by costs and duration. As known from earlier investigations the development of left ventricular dilatation and functional disturbance was influenced by the size and location of the infarction with infarct size being the primary factor in the early and infarct location in the late post-infarction period. Outcome was worst following large anterior infarction.

[Diastolic left ventricular dysfunction--significance for differential diagnosis and therapy of heart failure in the aged]. / Diastolische linksventrikuläre Dysfunktion--Bedeutung für die Differentialdiagnostik und -therapie der Herzinsuffizienz im Alter.

The discrimination of the pathogenesis of the clinical picture "heart failure" as caused by a dominant systolic or diastolic LV-dysfunction is of a special importance in the elderly patient because of the consequences for the choice of pharmacological therapy, resulting from the age-related physiological increase of stiffness of the myocardium. The pathophysiology of diastolic dysfunction is characterized by a prolonged relaxation period as well as by compromised passive filling properties, caused by myocardial and external determinants. Typical clinical signs of diastolic dysfunction are dyspnea or pulmonary edema. Cardiac disorders with a dominance of diastolic dysfunction are coronary and hypertensive heart disease as well as hypertrophic or uremic cardiomyopathies. Diagnosis of diastolic dysfunction easily can be performed noninvasively by means of Doppler-echocardiography. Pharmacological therapy in diastolic dysfunction should prefer beta blocking drugs and calcium-antagonists against vasodilators or digitalis.

[Treatment of chronic stable angina pectoris with angiotensin converting enzyme inhibition--a randomized, placebo-controlled, double-blind cross-over study]. / Behandlung der chronisch stabilen Angina pectoris durch Angiotensin-Converting-Enzym-Hemmung--Eine randomisierte, placebokontrollierte, Doppelblind-cross-over-Studie.

To investigate the potential anti-ischaemic effects of benazepril (10 mg bid) in comparison to placebo, this new ACE-inhibitor was given to 11 patients with chronic stable angina, reproducible exercise-induced ST-segment depression and angiographically verified coronary artery disease. Blood pressure at rest, plasma renin activity, and plasma concentration of atrial natriuretic peptide were measured after treatment periods of two weeks. Bicycle exercise tests at the same time should evaluate ST-segment depression at comparable maximal workload, work capacity, blood pressure, and heart rate at exercise. In comparison to placebo, benazepril reduced arterial blood pressure significantly from 140 +/- 14/90 +/- 11 mm Hg to 125 +/- 16/84 +/- 10 mm Hg (p less than 0.05) and increased plasma renin activity from 2.19 +/- 3.76 ng/ml/h to 9.62 +/- 8.49 ng/ml/h (p less than 0.005). In contrast, ST-segment depression decreased only slightly and not significantly from 2.09 +/- 1.22 mm to 1.91 +/- 1.00 mm. Benazepril had neither an effect on the frequency of episodes of angina pectoris nor did it reduce the amount of GTN-consumption. Also, work capacity and plasma concentration of atrial natriuretic peptide were not changed in comparison to placebo. Although the significant reduction of blood pressure and the highly significant increase of plasma renin activity demonstrate the specific action of benazepril, a significant anti-ischaemic effect could not be established.

[Transdermal nitroglycerin systems with continuous and discontinuous drug release. A comparison of the anti-ischemic and hemodynamic acute and long-term effects]. / Transdermale Nitroglycerinsysteme mit kontinuierlicher und diskontinuierlicher Substanzfreisetzung. Vergleich antiischämischer und hämodynamischer Akut- und Langzeitwirkung.

The anti-ischaemic and haemodynamic effects of two transdermal nitroglycerin systems, each offering 15 mg of nitroglycerine, the first giving continuous release (group 1) and the other discontinuous release (group 2), were compared in 30 men (mean age 56.5 [33-70] years) with coronary heart disease confirmed by angiography. Resting and exercise haemodynamics together with the degree of exercise-induced ST segment depression were measured on the first day, before and two hours after application of the plaster. After one week's therapy these measurements were repeated 24 hours after the application of the plaster on the previous day and two hours after the last application. Two hours after the first application both groups showed significant reduction (P less than 0.01) in exercise-induced ST segment depression (group 1: -60%, group 2: -50%) and in mean pulmonary artery pressure during exercise (group 1: -10%; group 2: -7%). After one week's therapy the reduction in exercise-induced ST segment depression was still significant in group 1 (-60%; P less than 0.01), but in group 2 (-30%) it was no longer significant. After one week had passed there was no longer any significant reduction in mean pulmonary artery pressure in either group (group 1: -6%; group 2: 0%). The acute anti-ischaemic and haemodynamic efficacy of both transdermal nitroglycerin systems was hence comparable; however, the emergence of nitrate tolerance during long-term use was not prevented even by phased release of the drug.

[Doppler echocardiography description of diastolic function disorder in terminal renal failure--new characterization of uremic cardiomyopathy]. / Dopplerechokardiographische Beschreibung einer diastolischen Funktionsstörung bei terminaler Niereninsuffizienz--Neucharakterisierung der urämischen Kardiomyopathie.

In order to characterize left ventricular diastolic filling abnormalities in uremic cardiomyopathy in 50 patients on hemodialysis, the ratio VE/VA of peak early (VE) and late (VA) filling velocity was calculated using CW-Doppler echocardiography. Compared with normal subjects of identical age, VE/VA was found to be significantly lower in patients younger than 40 years, but without, however, significant differences in patients aged 40-60 years and older than 60. Thus, the incidence of diminished VE/VA-ratios fell from 64% in patients younger than 40 years to 5% in patients older than 60. Whereas duration of dialysis, extent of renal anemia and interdialytic volumeload showed no influence, diastolic malfunction was correlated to renal hypertension. Therefore, an actualized characterization of uremic cardiomyopathy can be achieved by CW-Doppler echocardiography, describing diastolic malfunction in most patients with terminal renal failure. In elderly patients, however, a distinction from physiologic alteration of diastolic filling is not possible. Clinical significance of diastolic malfunction is characterized by reduced tolerance of interdialytic volume-expansion, as well as intradialytic volume-depletion.

[Conventional and Doppler echocardiography in the differential diagnosis of right heart failure]. / Konventionelle sowie Doppler-Echokardiographie in der Differential-diagnose der isolierten Rechtsherzinsuffizienz.

In the differential diagnosis of isolated right heart failure 1- and 2-dimensional echocardiography and Doppler echocardiography have proved to be of an increasing significance. In right ventricular dysplasia associated ventricular arrhythmias and regional abnormalities in wall motion of the right ventricle are characteristic. The evaluation of pulmonary heart disease has been extended by the estimation of pulmonary artery pressure using doppler echocardiography. In isolated right heart infarction, echocardiography can detect regional wall motion abnormalities and potential complications like intracavitary mural thrombi. In addition to pericardial calcification on chest x-ray and "dip and plateau" sign on pressure wave form, the abnormal diastolic hemodynamics can be demonstrated studying motion of interventricular septum and posterior left ventricular wall by echocardiography. Separating patients with restrictive cardiomyopathy may be difficult, if demonstration of the characteristic findings--increase of ventricular wall thickness, small ventricular cavities--is impossible. The evaluation of isolated tricuspid valve diseases has become possible non-invasively by Doppler echocardiography. In the diagnosis of the rare right atrial myxomas 2-D-echocardiography is the method of choice.

[Angiography diagnosis in the elderly--current indications in reduced complication rates and expanded therapeutic modalities]. / Angiographische Diagnostik beim alten Menschen--Aktualisierte Indikationsstellung durch reduzierte Komplikationsraten und erweiterte Therapiemodalitäten.

A potential higher rate of complications, recent developments in the technical procedures, and expanding modalities of interventional or operative therapy must be considered in evaluating angiographies in the aged patient. Most frequently, imaging of the pelvic and femoral arteries as well as the cerebral vessels was performed in patients older than 70 years, in 40% as out-patient angiography. The risk of puncture-site, vascular and catheter complications, as well as of neurological deficits was not found increased. A higher rate of cardiovascular problems however requires exact internal investigations and evaluation of the biological age. Angiographic information about vascular morphology as a basis for interventional therapy can be achieved today with an acceptable risk in the aged patient.

[Hemangioma of the left coronary artery with a fistula into the pulmonary artery]. / Hämangiom der linken Koronararterie mit Fistel in die Arteria pulmonalis.

A 32-year-old man had for about four months been suffering from discomfort in the left thorax unrelated to exertion. Coronary angiography revealed a haemangioma, 40 mm in diameter, which arose from the anterior descending branch of the left coronary artery with a connecting fistula to the main pulmonary artery. The tumour could not be demonstrated by either echocardiography or computed tomography, but magnetic resonance imaging showed an inhomogeneous structure in the basal region of the interventricular septum without increased signal intensity after injection of contrast medium. The tumour was not resected because of its small size and the minor symptoms which could not be proven as being tumour related. Repeat examinations (coronary angiography and magnetic resonance imaging) at six-month intervals are planned.