Randomized, double-blind study comparing saruplase with streptokinase therapy in acute myocardial infarction: the COMPASS Equivalence Trial. Comparison Trial of Saruplase and Streptokinase (COMASS) Investigators.

OBJECTIVES: This study sought to demonstrate the equivalence of saruplase and streptokinase in terms of 30-day mortality. BACKGROUND: The use of thrombolytic agents in the treatment of acute myocardial infarction is well established and has been shown to substantially reduce post-myocardial infarction mortality. METHODS: Three thousand eighty-nine patients with symptoms compatible with those of acute myocardial infarction for < 6 h entered the study at a total of 104 centers and were randomized to receive streptokinase (1.5-MU infusion over 60 min) or saruplase (20-mg bolus and 60-mg infusion over 60 min). In the saruplase group, a bolus of heparin (5,000 IU) was administered before saruplase, and a corresponding blinded double-dummy placebo bolus was administered before streptokinase. All patients received intravenous heparin infusions for > or = 24 h starting 30 min after the end of the thrombolytic infusions; the infusions were titrated to maintain an activated partial thromboplastin time at 1.5 to 2.5 times that of normal. RESULTS: Death of any cause up to 30 days after randomization occurred in 88 (5.7%) of 1,542 patients randomized to receive saruplase and 104 (6.7%) of 1,547 patients randomized to receive streptokinase (odds ratio 0.84, p < 0.01 for equivalence). Hemorrhagic strokes occurred more often in patients receiving saruplase (0.9% vs. 0.3%), whereas thromboembolic strokes were more prevalent in the streptokinase-treated patients (0.5% vs. 1.0%). The rate of bleeding was similar in the two treatment groups (10.4% vs. 10.9%). Hypotension and cardiogenic shock occurred less frequently in the saruplase group. Reinfarction rates were similar. CONCLUSIONS: Saruplase is a clinically safe and effective thrombolytic medication. This profile ranks saruplase favorably among the currently available thrombolytic agents.

Pulmonary veno-occlusive disease in a patient with unilateral absence of right pulmonary artery.

A 25-year-old patient had unilateral absence of the right pulmonary artery (UARPA) and severe left pulmonary artery hypertension. After death from congestive right heart failure, autopsy revealed histologic signs of pulmonary veno-occlusive disease (PVOD) and pulmonary hypertension (PH). An accessory arterial vessel that was thrombotically occluded was found connecting the ascending aorta and the right pulmonary hilum. There was also histologic evidence of arterial thrombi within the right lung arterial vascular bed. The PH in UARPA usually occurs very early during the course of disease. From histologic findings and medical history, it is likely that in this case, late-onset elevation of pulmonary pressures was triggered by the occurrence of PVOD. This is the first case of UARPA and PVOD--a congenital unilateral arterial malformation in the presence of bilateral involvement in a possibly acquired venous obliterative disease.

Leaflet fracture in Edwards-Duromedics bileaflet valves.

Two cases of leaflet fracture in the Edwards-Duromedics valve at 36 and 38 months after implantation are reported. Both patients were immediately reoperated on and recovered well. In one valve an older housing fracture with partial tissue ingrowth was noted beside a recent transverse leaflet fracture. In the other valve the leaflet was fractured near the pivot mechanism. All larger embolized parts were detected in the iliac artery region by computed tomographic scan and were subsequently removed. Problems in diagnosis and the importance of immediate reoperation, even without exact diagnosis, are discussed. Technical evaluation of the valve revealed crack growth and arrest, giving evidence of fatigue fracture. Scanning electron microscopic examination revealed several areas of pitting and erosion. Although the exact cause of mechanical disruption remains speculative, pyrolytic carbon seems to have the characteristic of fatigue fracture as well as erosion damage. A connection between the two might exist.

The effect of anticoagulant therapy in primary and anorectic drug-induced pulmonary hypertension.

In a retrospective study, we tested the hypothesis that anticoagulant therapy with warfarin sodium (Coumadin) has a beneficial influence on the long-term prognosis in patients with primary pulmonary hypertension (PPH) and aminorex-induced plexogenic pulmonary hypertension. The study included a total of 173 patients from two European cities. One hundred four of these patients took the anorectic drug aminorex (Menocil), which was available in some European countries almost 30 years ago; 69 patients had pulmonary hypertension of unexplained etiology, ie, PPH. Fifty-six of the 104 aminorex-treated patients and 24 patients in the PPH group received warfarin after diagnosis was established. For analysis, patients were divided into four groups according to their history of aminorex intake and anticoagulant therapy. Survival time, changes in hemodynamics (pulmonary arterial pressure), and improvement in quality of life (scored by the New York Heart Association [NYHA] classification) were compared and analyzed. We found that aminorex-treated patients had a better long-term prognosis than those with PPH (7.5 vs 3.9 years; p < or = 0.001). The best mean survival time of 8.3 years was found in anticoagulated aminorex-treated patients, compared to 6.1 years in nonanticoagulated aminorex-treated patients. Moreover, aminorex-treated patients who received anticoagulant therapy soon after the onset of symptoms showed significantly better prognosis (10.9 years) than those who commenced treatment 2 years thereafter (5.9 years) (p < or = 0.05). In patients with PPH, systolic pulmonary pressure was shown to influence survival time significantly (p < or = 0.0005); however, this correlation was not found in aminorex-treated patients. An improvement of symptoms like dyspnea on exertion was seen in 44.8% of the anticoagulated aminorex-treated patients, while deterioration was evident in 72.2% of the nonanticoagulated aminorex-treated patients. In conclusion, our study has shown that anticoagulant therapy had a positive influence on long-term survival and a significant improvement in quality of life in patients with PPH, in particular in patients with a history of anorectic drug intake.

Platelet-mediated pulmonary hypertension and hypoxia during pulmonary microembolism: reduction by platelet inhibition.

The literature indicates that vasoactive substances released from platelets contribute to the pulmonary pressor response and hypoxemia during pulmonary microembolism. Hence, removal of the platelets or inhibition of their function should reduce these effects. The purpose of this study was, therefore, to investigate the pulmonary effects of experimental embolism with glass beads in dogs rendered thrombocytopenic with platelet antiserum and to compare these effects to the effects in dogs pretreated with sulfinpyrazone (Anturane) or heparin, both substances that affect the function of platelets, probably by inhibiting the release of platelets. In all three groups the pulmonary hypertension was reduced by more than half, and hypoxemia was lessened or abolished. The results of this study indicate the platelets contribute to the effects of pulmonary microembolism and that administration of sulfinpyrazone or heparin reduces the embolism-induced pulmonary hypertension to the same extent as the depletion of platelets. Platelet-inhibiting drugs might therefore be useful prophylactically in human pulmonary microembolism.

Implantation of the Duromedics bileaflet cardiac valve prosthesis in 400 patients.

From September, 1983, to April, 1986, 451 Duromedics bileaflet cardiac valve prostheses were implanted in 400 patients at our institution in Vienna. Aortic valve replacement was done in 190 patients, 157 underwent mitral valve replacement (1 patient also underwent tricuspid valve replacement), 52 underwent double valve replacement, and 1 patient underwent isolated reoperation for tricuspid valve replacement. Concomitant procedures were performed in 86 patients (21.5%). Sixty-one patients (15.2%) had undergone previous cardiac surgery; 32 (8%) had undergone earlier valve replacement. The early mortality rate (within 30 days) was 6.25% (25 patients). Follow-up was done on 337 surviving Austrian citizens; this represents 429 patient-years. The late mortality rate was 2.1% per patient-year (9 patients). We observed paravalvular leak in 3 patients (0.7% per patient-year), thromboembolism in 4 (0.9%), prosthetic valve endocarditis in 5 (1.2%), and anticoagulant-related hemorrhage in 10 (2.3%). Valve failure occurred in 8 patients (1.8%). We conclude, therefore, that good clinical results and a low complication rate can be achieved with this new type of valve.

Course of thrombin activation markers in patients implanted with Palmaz-Schatz stents: first experiences with a post-interventional anticoagulation regimen.

Following implantation of coronary Palmaz-Schatz stents, 29 patients were anticoagulated with a combination of heparin, phenprocoumon and aspirin following a standard protocol. After removing the arterial and venous lines, post-interventional intravenous (i.v.) heparin treatment started with 1500 IU/h for patients > 80 kg and 1250 IU/h for patients < 80 kg. Heparin was monitored by the activated partial thromboplastin time (aPTT) and adjusted by increasing or reducing i.v. heparin by 250 IU/h to maintain the aPTT within the therapeutic range. Phenprocoumon therapy began the day after stent implantation (day 2) and lasted for 3 months. aPTT, Heptest, prothrombin fragment F1 and 2 (F1.2) and thrombin-antithrombin III complexes (TAT) were monitored at standard intervals for 10 days (mean monitoring time: 9.7 +/- 2.3 days). Anticoagulation was efficient with aPTT levels remaining within the therapeutic range on day 9 and the simultaneous, moderate-onset oral anticoagulation within the therapeutic range of the International Normalized Ratio (INR; 2.15-4.80) on day 8 on average, the mean INR being 2.43 +/- 0.76. On day 4, F1.2 levels were significantly higher than on the day of stenting (1.16 +/- 0.30 nmol/l vs 1.04 +/- 0.53 nmol/l; P < 0.005). F1.2 levels fell after day 5, the difference becoming significant from day 8 on (P < 0.05). F1.2 was negatively correlated with the Heptest (P < 0.05) and fell significantly as a function of the INR during phenprocoumon administration (P < 0.001). After phenprocoumon therapy was discontinued over 3 weeks, 25 patients were followed up by angiography. Despite adequate anticoagulation, mean F1.2 levels in patients showing restenosis at follow-up angiography were significantly higher (P < 0.005) than in those without restenosis. In one patient who developed subacute stent thrombosis, clotting factors were determined 20 min before stent occlusion. The levels of F1.2 and TAT were less than all other patients on this day (F1.2: 0.98 nmol/l vs 1.11 +/- 0.40 nmol/l; TAT: 2.7 micrograms/l vs 3.21 +/- 3.38 micrograms/l). Thus, neither F1.2 nor TAT predicted the occurrence of thrombotic stent failure in individuals. Efficient anticoagulation by a combination of anticoagulants is imperative for stent implantation. Using only current routine methods, this way of monitoring anticoagulation is effective for managing combined anticoagulation therapy.

[Magnetic resonance tomography in pulmonary hypertension]. / Magnetresonanztomographie bei pulmonaler Hypertension.

We examined 23 patients with pulmonary hypertension of varying aetiology by MRI and compared the results with those of right heart catheterisation. The best correlation was obtained between right ventricular mural thickness and mean pulmonary pressure (R = 0.91, p = 0.001). There was significant correlation (R = 0.85, p = 0.001) for the diameter of the inferior vena cava, which was dilated in all patients with pulmonary hypertension. There was no significant correlation between mean pulmonary pressure and the diameters of the superior vena cava or the main pulmonary artery branches (R = 0.55 and 0.75 respectively, p less than 0.05). Amongst functional measurements there was a correlation between right ventricular ejection fraction and mean pulmonary artery pressure (R = 0.71, p = 0.001). There was no correlation between right ventricular end-systolic and end-diastolic volume. In all patients with pulmonary hypertension, dynamic flow sensitive gradient echo sequences showed the presence of tricuspid insufficiency. A further semiquantitative criterion for the presence of pulmonary hypertension in 4 patients (17%) was an abnormal signal from the main pulmonary artery in early to mid-systole shown on T1-weighted transverse sections.

[Thallium scintigraphy of the myocardium. Uniform research protocols of the Austrian Society for Nuclear Medicine]. / Die Thalliumszintigraphie des Myokards. Einheitliches Untersuchungsprotokoll der Osterreichischen Gesellschaft für Nuklearmedizin.

A uniform protocol for thallium scintigraphy of the myocardium has been issued in Austria to avoid difficulties in interpreting results and to avoid repeated examinations to save expenses and radiation burden. From the beginning of 1995 this protocol will be used in the Austrian departments of Nuclear Medicine, differences from this protocol have to be mentioned separately. In this protocol the procedure of examination, bicycle and pharmacological stress testing and vasodilatation, acquisition techniques for planar and SPECT imaging, data processing and quality control of devices are defined.

[Pathophysiology of non-cardiogenic pulmonary hypertension]. / Pathophysiologie der nicht kardialen pulmonalen Hypertension.

The pathophysiology of non cardiogenic pulmonary hypertension consists mainly of pulmonary vascular changes and alveolar hypoxia. Pulmonary vascular changes might have different etiologies. First the vessel itself with local thrombosis, embolic obstruction, vasoconstriction and endothelial cell dysfunction with intimal proliferation. Secondly parenchymal changes with secondary vascular affection could contribute to pulmonary hypertension. The mechanism of hypoxic pulmonary vasoconstriction is unknown, a direct interaction of oxygen with the smooth muscle cell is possible. The interaction of activated circulating cells - i.e. platelets or leukocytes - and - possibly predamaged - endothelial cells could be the initiating mechanism for several forms of pulmonary hypertension. This could be especially true for the so called primary forms or for dietary pulmonary hypertension e.g. after ingestion of toxic oil.

[Cardiac resuscitation - a seven-year report (author's transl)]. / Reanimation bei akutem Herz-Kreislauf-Stillstand

Over the 7-year period 1966 to 1973, cardiac resuscitation was performed in 315 cases. The reasons were circulatory arrest (ventricular fibrillation or asytole) in 228 and other life-threatening disturbances in 87 cases. During daytime, especially from 8 a.m. to 12 noon and from 4 to 8 p.m., a higher percentage of cases was successfully resuscitated and during these periods emergency personnel seemed to be more readily available. The underlying disease is one of the determinants for the prognosis, whereas age is without relevance. Over the last few years, together with a decrease in the frequency of emergency calls, the percentage of cases of successful resuscitation increased. 14.3% of all patients in whom resuscitation was undertaken were discharged from hospital.

[Diastolic murmurs in atrial septal defect (author's transl)]. / Zur Frage diastolischer Intervallgeräusche beim Vorhofseptumdefekt

No correlation was found between the presence of a diastolic murmur in about 50% of patients with artrial septal defect and the calculated shunt volume. A significant correlation was found in respect to the age of the patient, the majority of the murmurs being found in young patients and especially in young patients with tachycardia. Similar murmurs were found in healthy persons and, hence, a functional stenosis of the AV-valve ring could be the reason for this diastolic murmur, which may occur more frequently in patients with atrial septal defect on account of an alteration in the blood stream patterns.

[Return to work following myocardial infarct]. / Arbeitswiederaufnahme nach Herzinfarkt.

The aim of this retrospective study involving 471 patients was to investigate the percentage of patients who returned to work after acute myocardial infarction. In the group of 350 patients who did not undergo subsequent aortocoronary bypass operation 70% returned to work, whereby half of these patients started work again within 6 months after infarction. A significantly higher number of patients who were enrolled in a cardiac rehabilitation programme returned to work as compared with patients not participating in such a programme (72% vs. 59%, respectively; p less than 0.04). There was, however, no difference between these 2 groups with respect to either the time point of resumption of work after myocardial infarction or the duration of employment between infarction and eventual retirement. Of the 121 patients who underwent an aortocoronary bypass operation, only 38% returned to work (p less than 0.001 vs. patients without bypass surgery).

[Maximum exercise testing during hypobaria and normoxia (author's transl)]. / Maximale Belastung bei subatmosphärischem Umagebungsdruck und normoxischer Atmung.

The effects of high altitude (3000 m, low-pressure chamber) on maximum exercise and maximum oxygen uptake were studied in four normal subjects. In order to separate the effects of hypobaria and of hypoxia, exercise testing was performed under normoxic, hypobaric conditions and compared with the results under normoxic, normobaric conditions. There was no significant difference in performance, nor in the effects of exercise on the measured cardiovascular parameters.

[Antiarrhythmic effect and side effects of amiodarone]. / Antiarrhythmischer Effekt und Nebenwirkungen von "Amiodarone".

UNLABELLED: Amiodarone (AM) is one of the most potent antiarrhythmic drugs, the value of which is limited by reversible and irreversible side-effects (SE). 59 patients, 50 male, 9 female (age 33 to 81 years) entered the study with ventricular tachycardia (VT, 68%), WPW-tachycardia (12%), non-sustained VT (12%) or untreatable paroxysmal atrial fibrillation or supraventricular tachycardia (8%). Prior to AM the patients had received 1 to 8 different antiarrhythmic drugs (m 3.5) and maximal 9 different combinations of antiarrhythmics. The drug regimen started with a loading dose of 1200 mg/d for 1 to 2 weeks and was continued with a maintenance dose of 200 to 600 mg/d. The patients were followed up 1 to 41 months (m 14 m). The drug effect was evaluated using clinical criteria (recurrence of arrhythmias, death), computer-assisted analysis of several 24 hr long-term ECGs and programmed electrophysiological stimulation. Three- to six-monthly the patients were seen in our outpatient department for check up and blood-sample analysis (liver, thyroid gland etc.). Also in the majority of the patients frequent ophthalmological and dermatological investigations, as well as lung functions tests were carried out. RESULTS: under AM therapy the initial arrhythmias were no longer detectable in 41% of the patients. In 37% a significant amelioration of the formerly life-threatening arrhythmias was found. 7 patients (12%), predominantly with reduced left ventricular function, died during follow up. No pulmonary, hepatotoxic or neurological SE were found. All patients developed reversible AM keratopathy. In 27% ETR and T4 were elevated, but only one patient developed hyperthyroidism with an increase in TT3. Another patient showed signs of hypothyroidism with an elevated TSH prior to TRH stimulation. Increased phototoxicity was found in 31%, whereas in two patients typical AM hyperpigmentation occurred, especially on the face. In conclusion, AM is a highly effective antiarrhythmic agent, despite a negatively selected collective, but it should only be used in patients with refractory arrhythmia in view of the SE.

[Secondary prevention following coronary intervention. Survey of 13 intervention centers in Austria]. / Sekundärprävention nach Koronarintervention. Vorgangsweise an 13 Interventionellen Zentren in Osterreich.

Risk factor control has been shown to reduce the incidence of coronary events in patients with or without preceding infarction. Secondary prevention should therefore be borne in mind by every cardiologist. In order to test this concept and/or to promote secondary prevention in our country, the following survey was conducted by our working group for epidemiology and prevention. All interventional centres of the country (7 million inhabitants) were asked to report relevant data of 50 consecutive patients with PTCA in a structured questionnaire. Thirteen centres responded and we report the data of 650 patients. The mean proportion of women was 28%, the mean age 61.1 years and the mean stent rate 49.8%. The indications for PTCA varied widely: stable angina 10-74%, unstable angina 10-86%, primary PTCA 0-22%. The risk factor history was distributed as follows: diabetes 12-46% (mean 22.3%), hypertension 32-68% (mean 54.2%), current smoking 6-56% (mean 21.9%), and total cholesterol (TChol) > 200 mg/dl: 30-78% (mean 60.3%). Current lipid values were available for T chol. in 44-100% (mean 84.5%) and for LDL in 4-100% (mean 67.1%). Dietary counselling by a dietician was done in 4-100% of patients (mean 35.6%) Information concerning the hazards of smoking was given to 25-100% (mean 83.6%) of current smokers. Drug treatment at hospital discharge was as follows: 84-100% (mean 93.1%) received ASA, 24-74% (mean 49.8%) ticlopidine, 6-84% (mean 53.3%) nitrates, 34-82% (mean 60.2%) beta blockers, 10-70% (mean 39.5%) ACE inhibitors, 4-74% (mean 4 7.2%) lipid lowering drugs, 7-48% (mean 17.8%) calcium antagonists, 0-12% (mean 6.1%) digitalis and 0-28% (mean 13.6%) diuretics. Follow-up data were collected in 4 centres at 6 months post discharge and were available for 174 patients. Here we found an increase in the prescription of calcium antagonists, digitalis and statins. The following conclusions were drawn at a conference in which all centres participated: lipid values should be available for each patient at PTCA, dietary counselling should be initiated for every patient during hospitalisation (and continued by the family physician) and the national cardiac society should promote guidelines for the use of drugs in which the variation in use is too wide at present. It should be ensured that these guidelines are implemented not only in patients after AMI but also in those after PTCA.

[Brain natriuretic peptide for postoperative monitoring of the fluid balance in a cardiac surgery patient]. / Brain-natriuretisches Peptid für die postoperative Uberwachung der Flüssigkeitsbelastung bei einem herzchirurgischen Patienten.

Brain natriuretic peptide is a neurohormone used for estimation of left ventricular wall tension and volume overload. We describe the use of this parameter in a postoperative cardiac surgery patient for detection and monitoring of left ventricular failure in a postoperative intensive care unit at a tertiary care center. Left ventricular failure was detected by brain natriuretic peptide levels, while x-ray and values obtained by the pulmonary artery catheter were inconclusive.

[Disorders of thrombocyte function and/or endothelial cell damage as a cause of primary pulmonary hypertension?]. / Thrombozytenfunktionsstörung und/oder Endothelzellschädigung als Ursache der "primären" pulmonalen Hypertension?

The pathophysiology of pulmonary hypertension is, in many cases, unclear and this is true especially for patients with dietary pulmonary hypertension. This paper discusses the hypothesis that platelets, directly or through their interaction with the pulmonary endothelial cell, are involved in the development of pulmonary hypertension. Platelets release vasoactive substances during aggregation or activation and these substances lead to pulmonary vasoconstriction and pulmonary hypertension. The primary target of the activated platelets could be the endothelial cell which has also been demonstrated in animal experiments with crotalaria-induced pulmonary hypertension. Changes in thromboxane--platelets and prostacyclin--endothelial cell interactions could be the basic mechanism responsible for endothelial proliferation and pulmonary vasoconstriction. It has not been ascertained, however, whether the activation of platelets or endothelial dysfunction is the primary lesion. In various animal experiments, changes in platelet function and endothelial damage, as well, have been shown to be initiated by exogenous influences. The investigation of platelets or endothelial cell function in patients with pulmonary hypertension showed evidence of platelet activation but not platelet hyperreactivity. An impaired fibrinolytic activity, which was found in the majority of these patients, was regarded as indicative of endothelial dysfunction. An interference in the physiological interaction of circulating platelets and endothelial cells in the lung with resulting endothelial proliferation and vessel occlusion could well be the initial factor. This process would be self-perpetuating in the development of pulmonary hypertension. An additional example of dietary-induced pulmonary hypertension was observed in patients in Spain after the ingestion of toxic oil.(ABSTRACT TRUNCATED AT 250 WORDS)