Biomedical subjects
Publications and source records attributed to R von Essen.
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The aim of this study was to evaluate the influence of vessel dilation on restenosis after successful percutaneous transluminal coronary angioplasty (PTCA) on the basis of quantitative angiographic analysis. To have the best comparison possible, we restrospectively studied a homogenous series of patients from the early 1980s treated according to a standardized PTCA procedure. The study group consisted of 86 patients with stable angina pectoris and single-vessel disease, all of whom underwent successful PTCA for a short concentric lesion in proximal vessel parts. The overall restenosis rate was 27%. Angiographically measured balloon size remained below specifications. The size of the inflated balloon at the site of minimal lumen diameter averaged 2.6 +/- 0.5 mm, and nominal balloon size was 3.3 +/- 0.4 mm (p < 0.001). In 22 patients with an oversized balloon (mean balloon/artery ratio 1.1 +/- 0.16) the restenosis rate was 5% compared with 34% in the corresponding group (p = 0.02). Minimal lumen diameters that were similar after the procedure (2.4 +/- 0.3 vs 2.3 +/- 0.4, NS) were 2.3 +/- 0.4 mm and 1.8 +/- 0.7 mm, respectively, at follow-up (p = 0.002). Multivariate analysis revealed balloon/vessel size ratio (p < 0.001), postprocedure diameter stenosis (p = 0.02), and percentage diameter increase produced by PTCA (p = 0.04) as independent correlates of the late outcome. Postangioplasty minimal lumen diameter was not related to restenosis. The strongest and most significant predictor of late PTCA outcome both by univariate and multivariate analysis was balloon/vessel size ratio, especially when balloon expansion at the site of minimal lumen diameter was regarded. In patients with continued success at follow-up, the ratio was 0.81 +/- 0.15 compared with 0.60 +/- 0.11 in patients with restenosis (p < 0.001). Our results suggest that the late angiographic outcome of PTCA is strongly influenced by procedural factors. It appears that in a selected group of patients, an increased balloon/artery ratio, supposedly associated with increased vessel wall stretch, favorably affects the restenosis process.
This retrospective analysis reviewed 183 patients with acute myocardial infarction who were given front-loaded recombinant tissue-type plasminogen activator (rt-PA) and r-hirudin (HBW 023) in 1 of 4 dose groups (bolus dose of 0.07, 0.1, 0.2, or 0.4 mg/kg, followed by an infusion of 0.05, 0.06, 0.1, or 0.15 mg/kg/hour over 48 hours). Activated partial thromboplastin time (aPTT) levels were determined at baseline and at 4, 8, 12, 16, 20, 24, 32, 40, and 48 hours. Of the 178 patients with r-hirudin treatment for > or = 12 hours, anticoagulation was optimal in 55.1% (all aPTTs > 2 x baseline), suboptimal in 33.7% (lowest aPTT > 1.5 but < 2 x baseline), and inadequate in 11.2% (> or = 1 aPTT but < 1.5 x baseline). Optimal anticoagulation was observed more frequently in the higher dose groups (dose 1, 15%; dose 2, 44.4%; dose 3, 63.4%; dose 4, 73.4%; p for trend < 0.0001). Patency (according to Thrombolysis in Myocardial Infarction trial grade 2 or 3) of the infarct artery after 36 to 48 hours was higher in the group with optimal anticoagulation compared with those with suboptimal or inadequate anticoagulation: 97.9%, 88.4%, and 85%, respectively (p = 0.03 optimal vs suboptimal or inadequate anticoagulation). In conclusion, r-hirudin in a dose of 0.1 or 0.15 mg/kg/hour achieves an optimal anticoagulation in about 63% or 74% of patients, which is associated with an enhanced patency 24 to 48 hours after rt-PA. A subsequent study revealed that this effective anticoagulation may be accompanied by an increased risk of severe bleeding complications after thrombolysis.
As a Result of echocardiographic diagnostic criteria that took too little account of underlying pathology, mitral valve prolapse has, in the past, been diagnosed far too frequently, and has been associated with commonly occurring unspecific symptoms (mitral valve prolapse syndrome). The results of epidemiological studies have led to a new definition of diagnostic criteria. The diagnosis mitral valve prolapse is established in the first instance by auscultation. Echocardiography supports the diagnosis, provides information about the prognosis, and, with a high level of reliability, detects complications. Major complications of this condition are endocarditis and mitral valve insufficiency, as also--less well documented--cerebral embolism and sudden heart death. Particularly at risk of developing complications are those patients with a systolic murmur reflecting an already present mitral valve insufficiency. This patient group must be monitored for progressive mitral insufficiency and, in the presence of relevant exposure, requires endocarditis prophylaxis.
We present a case of left ventricular rupture and formation of a pseudoaneurysm after silent myocardial infarction in a patient with Schmidt syndrome (polyglandular deficiency syndrome including Addison's disease, lymphocytic thyroiditis and diabetes mellitus). This case illustrates the possibility of myocardial rupture without hemodynamic collapse and a possible role of chronic steroid substitution.
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Recombinant hirudin, a specific thrombin inhibitor, has been shown to accelerate thrombolysis and reduce reocclusions in experimental models. In a pilot trial recombinant hirudin (HBW 023) was used as an adjunctive therapy to thrombolysis with front-loaded tissue plasminogen activator (t-PA) (100 mg.90 min-1) in 40 patients with acute myocardial infarction whose duration of symptoms was less than 6 h. Patients received a bolus of r-hirudin of 0.07 mg.kg-1 b.w. followed by an infusion of 0.05 mg.kg-1.h-1 over 48 h. Complete patency (TIMI grade 3) of the infarct-related artery at 30, 60 and 90 min after the start of thrombolytic therapy was seen in 38.5%, 64.1% and 71.0% of patients, respectively. After 24-48 h, 80% of patients had a complete patent infarct vessel. A very early, complete and sustained patency (TIMI grade 3 at 60 and 90 min and at 24-48 h) was observed in 55% of patients. Reocclusions during the hirudin therapy appeared in six (16.1%) patients, two of whom had a PTCA at 90 min. The only reinfarction was seen after 6 h; this was successfully treated with additional thrombolysis. Major bleedings, mostly related to the invasive procedure, were observed in three patients. Spontaneous organ bleedings and intracerebral haemorrhages did not occur. There was one in-hospital death due to a late retroperitoneal bleeding. In was concluded that, with regard to safety and efficacy, the general feasibility of r-hirudin as adjunctive therapy to thrombolysis with front-loaded t-PA, has been demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)
Enhanced lipid peroxidation, reported to take place in rheumatoid joints and suggested to play a significant role in joint inflammation, led us to study the occurrence of antibodies against oxidised low-density lipoprotein (Ox-LDL Ab) in patients with juvenile chronic arthritis. Enzyme-linked immunosorbent assay was used to detect Ox-LDL Ab and antiphospholipid antibodies (aPL Ab) in sera from 84 patients and 91 controls. Elevated levels of Ox-LDL Ab were found in 14 patients (17%) as opposed to 4 controls (4%; p < 0.01). Similarly, 14 patients had an elevated aPL Ab level and a fairly good correlation between Ox-LDL Ab and aPL Ab (r = 0.52) existed in the patients. The increased frequency of elevated levels of Ox-LDL Ab may reflect lipid peroxidation occurring in rheumatoid joints but crossreactivity with aPL Ab for the induction of Ox-LDL Ab cannot be excluded.
Patients from 4 German multicenter studies on thrombolysis in acute myocardial infarction (AMI) were retrospectively evaluated to assess the incidence of optimal reperfusion, defined as a completely perfused infarct vessel after 90 minutes, without subsequent death or reinfarction, and without reocclusion or deterioration of flow in control angiograms. Of 907 patients with a 90-minute angiogram, 75% had an open infarct vessel by conventional definition (perfusion grade 2 or 3 according to the criteria of the Thrombolysis in Myocardial Infarction [TIMI] study). However, only 62% had TIMI grade 3 complete perfusion. Of the 561 patients with such primary treatment success, 106 (19%) had secondary treatment failure by death, reinfarction, or subtotal or total reocclusion of the infarct vessel. In a subset of 668 patients with a first angiogram after 60 minutes, conventional patency was 70%, complete perfusion 51%, and an optimal perfusion result was achieved in only 42%. The efficacy of thrombolysis in AMI is substantially overestimated by conventional 90-minute patency rates.
The mortality associated with myocardial infarction can be considerably reduced by the use of thrombolysis, the success rate being determined largely by the time elapsing between attack and treatment. Despite various campaigns to inform the public, the time elapsing between symptom onset and alerting the doctor continues to be measured in hours. In view of the possible complications that may occur already during patient transport to the hospital, the emergency physician should be involved immediately. Basic treatment comprises the administration of oxygen, sedatives, analgesics and nitrates. Initiation of thrombolysis by the emergency physician is associated with a number of difficulties (uncertainty of diagnosis, equipment, experience). Since prehospital thrombolysis has not yet been shown to be of general advantage, it may be recommended only when transport is long and when the personnel and equipment requirements are met. The greatest benefit is to be expected from a shortening of the time lapse before alerting the doctor.
Atrial fibrillation is the second most common arrhythmia after ventricular premature beats. For years, prophylactic anticoagulation has been recommended in patients with atrial fibrillation in underlying rheumatic heart disease. With the aim of establishing the risk of embolism in non-rheumatic atrial fibrillation, and the justification for prophylactic anticoagulation therapy, five prospective studies were carried out. The results obtained indicate that all patients with chronic atrial fibrillation should receive anticoagulation therapy wherever possible (INR 2.0 to 3.0). The sole exception are patients aged under 55 years with no other organic heart disease. For this group, the risk of a stroke is appreciably reduced, so that treatment with ASA suffices.
OBJECTIVES: The aim of this study was to determine the appropriate dose of a novel recombinant tissue-type plasminogen activator (BM 06.022) for thrombolysis in patients with acute myocardial infarction. BACKGROUND: BM 06.022 is a mutant of tissue-type plasminogen activator expressed in Escherichia coli that can be given as a single bolus because of a prolonged half-life, which might obviate the need for complicated regimens. METHODS: BM 06.022 given as a single bolus was investigated in 142 patients in a multicenter sequential dose-finding study. Efficacy of the drug was assessed from infarct-related artery patency by coronary angiography. RESULTS: With the first dose of 10 MU of BM 06.022, the predefined minimal 90-min patency of 70% was not achieved, as indicated by the sequential probability ratio test after treatment of 42 patients (group A). The second dose of 15 MU of BM 06.022 was given subsequently in the preset maximum of 100 patients (group B). Angiography 30, 60 and 90 min after the bolus injection of BM 06.022 revealed a patent infarct-related artery (Thrombolysis in Myocardial Infarction trial [TIMI] grade 2 or 3) in 65% and 66%, 73% and 74% and 66% and 75% of patients in groups A and B, respectively. Very early reocclusion up to the 90-min angiogram occurred in 17% and 13%, late reocclusion until predischarge angiography occurred in 7% and 5%, and rescue percutaneous transluminal coronary angioplasty after the 90-min angiogram was performed in 6 and 14 patients in groups A and B, respectively. Plasma fibrinogen decreased from 2.79 g/liter (range 0.94 to 4.75) to 1.69 g/liter (range 0.0 to 3.95) in group A and from 2.54 g/liter (range 0.0 to 5.02) to 0.92 g/liter (range 0.0 to 2.68) in group B. Two bleeding complications requiring transfusion or surgical intervention and one nonfatal intracranial hemorrhage were encountered. Eight patients had a reinfarction, and five patients died, all of cardiac causes. CONCLUSIONS: With BM 06.022 given as a single bolus, a high early patency rate of the infarct-related coronary artery can be achieved. The speed of thrombolysis seems to be superior to standard thrombolytic drugs. The compound warrants further evaluation with respect to safety and efficacy by clinical end points.
BACKGROUND: Adjunctive therapy for thrombolysis in acute myocardial infarction consists of platelet inhibition with aspirin and thrombin inhibition with heparin. Thrombin inhibition may be improved by the use of hirudin as indicated by experimental and phase II clinical studies. The randomized, double-blind phase III r-Hirudin for Improvement of Thrombolysis study (HIT III) compared a recombinant hirudin (HBW 023) with heparin. The primary end point was the incidence of death or reinfarction. METHODS AND RESULTS: Seven thousand patients with acute myocardial infarction and a duration of symptoms of less than 6 hours were to be randomized to receive intravenous heparin (70 IU/kg body wt bolus and 15 IU.kg-1.h-1) or hirudin (0.4 mg/kg body wt bolus and 0.15 mg.kg-1.h-1) infused over 48 to 72 hours and adjusted to an activated partial thromboplastin time of 2 to 3.5 times baseline values. In a pilot phase, 1000 patients receiving front-loaded alteplase for thrombolysis were to be recruited by 93 German centers. After enrollment of 302 patients, the trial was stopped after an increased rate of intracranial bleeding was observed in the hirudin group (5 of 148, 3.4%) compared with the heparin group (0 of 154). The overall stroke rate was 3.4% in the hirudin group and 1.3% in the heparin group. Other major bleeding occurred in five versus three patients and ventricular rupture occurred in three versus one patient in the hirudin and heparin groups, respectively. There were 19 in-hospital deaths, with 13 of them from the hirudin group. CONCLUSIONS: Although the number of patients was too small for a definite benefit-risk assessment, at the dosage tested, hirudin in combination with front-loaded alteplase and aspirin may be associated with an increased rate of intracranial hemorrhage. Our findings are consistent with the observations of the GUSTO-II and TIMI-9 trials, where higher doses of another recombinant hirudin were used. Therefore, the therapeutic range of hirudin as an adjunct to thrombolysis may be smaller than previously thought, and reappraisal of dose finding should be considered.
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325 coronary lesions in 300 consecutive patients (257 male, 43 female, 52 +/- 8 years) undergoing either single-vessel (n = 275) or double-vessel PTCA in two independent procedures (n = 25) were prospectively randomized to either one (group A, n = 167) or three (group B, n = 168) balloon inflations. By clinical and angiographic criteria, PTCA was successful in 295/325 lesions (90.8%) with no significant difference for group A (88.6%) and B (93.0%). Clinical follow-up was achieved in 92% of patients and angiographic follow-up was obtained in 261/295 (88.5%) successfully dilated lesions (A: 87.8%; B: 89.1%). Angiographic appearance of the dilated lesion (in % diameter stenosis) prior to PTCA, directly following PTCA and at follow-up was comparable for both groups: gr. A: 71 +/- 11%, 32 +/- 10%, and 40 +/- 21%; gr. B: 70 +/- 11%, 30 +/- 10%, and 40 +/- 20% resp. Restenosis rate was similar with 26.9% in group A and 29.8% in group B. The randomization had to be abandoned in 144/325 cases (44.3%) due to medical reasons. Results of only those lesions where it was possible to follow the initial randomization demonstrated a different pattern. Success rate was slightly higher in those with 3 inflations (gr. B1, n = 111) with 93.0% as compared to lesions with only one inflation (gr. A1, n = 70) with 88.6% success (p = ns). Subsequently, the initial angiographic result was slightly better for B1 with a reduction in diameter stenosis from 69 +/- 11% to 29 +/- 10% compared to A1 (71 +/- 11% and 32 +/- 10% resp.).(ABSTRACT TRUNCATED AT 250 WORDS)
The novel recombinant plasminogen activator (r-PA) (BM 06.022) is a mutant of tissue-type plasminogen activator expressed in escherichia coli which can be given as a bolus because of a prolonged half-life. The primary objective of this trial was to determine the efficacy of an intravenous r-PA double bolus (first bolus of 10 MU followed by 5 MU after 30 minutes) in patients with acute myocardial infarction. All patients received heparin intravenously and acetylsalicylic acid orally. Efficacy was assessed from infarct artery patency by coronary angiography (Thrombolysis in Myocardial Infarction trial perfusion grades 2 or 3) in 50 patients. Ninety minutes after administration of the first r-PA bolus, the infarct-related coronary artery was patent in 39 of 50 patients (78%; 95% confidence interval 64 to 88%). An angiographically confirmed reocclusion occurred in 1 patient between 90 minutes and 24 to 48 hours. The reocclusion rate was influenced by 8 interventions and 1 angiogram missing at 24 to 48 hours. Measurements of hemostatic parameters showed a decrease in fibrinogen to 37% of baseline value. There were 3 clinical reinfarctions before discharge and 2 major puncture site hemorrhages. No further serious bleeding and no serious adverse event with lethal outcome occurred. The 10 + 5 MU r-PA double bolus regimen appears to be effective with regard to patency and the success of thrombolysis. The incidence of reocclusion is very low. From the limited number of patients treated in this study, one need not be concerned about the safety profile of r-PA.
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OBJECTIVE: This study evaluated the impact of early patency of the infarct-related vessel on short-term mortality after thrombolysis for acute myocardial infarction. BACKGROUND: Different thrombolytic regimens for acute myocardial infarction proved to be equally effective in large scale mortality trials despite significant differences in their efficacy with respect to early infarct-related vessel patency as shown in smaller angiographic trials. METHODS: Patients from four German multicenter studies of thrombolysis in acute myocardial infarction were retrospectively evaluated. Of 939 patients with acute myocardial infarction (duration of symptoms < 6 h) treated with thrombolysis, 907 (96.6%) had an angiogram of the infarct-related artery 90 min after the initiation of thrombolytic therapy. The perfusion status was graded according to the Thrombolysis in Myocardial Infarction (TIMI) study criteria. RESULTS: Complete reperfusion (TIMI grade 3) was found in 561 of 907 patients and partial reperfusion (TIMI grade 2) in 122 of 907. Overall, the in-hospital mortality rate was 4.6% (43 patients). In patients with complete reperfusion of the infarct-related vessel, the mortality rate was only 2.7% versus 7.1% in patients with an occluded vessel at the 90-min angiogram. This difference was highly significant in univariate as well as in multivariate analysis. In patients with partial perfusion of the infarct vessel, the mortality rate was 6.6%. CONCLUSIONS: The early perfusion status of the infarct-related artery is an independent predictor of short-term survival. However, only complete early reperfusion is associated with a reduced in-hospital mortality rate whereas patients with partial perfusion (TIMI grade 2) have a short-term prognosis similar to that of patients with persistently occluded infarct vessels. Therefore, when used as a surrogate end point for mortality, only TIMI grade 3 perfusion of the infarct vessel should be interpreted as a treatment success of thrombolysis in acute myocardial infarction.