Prospective randomised comparison between thrombolysis, rescue PTCA, and primary PTCA in patients with extensive myocardial infarction admitted to a hospital without PTCA facilities: a safety and feasibility study.

OBJECTIVE: To assess the safety and feasibility of acute transport followed by rescue percutaneous transluminal coronary angioplasty (PTCA) or primary PTCA in patients with acute myocardial infarction initially admitted to a hospital without PTCA facilities. DESIGN: In a multicentre randomised open trial, three regimens of treatment of acute large myocardial infarction were compared for patients admitted to hospitals without angioplasty facilities: thrombolytic treatment with alteplase (75 patients), alteplase followed by transfer to the PTCA centre and (if indicated) rescue PTCA (74 patients), or transfer for primary PTCA (75 patients). RESULTS: Between 1995 and 1997 224 patients were included. Baseline characteristics were distributed evenly. Transport to the PTCA centre was without severe complications in all patients. Mean (SD) delay from onset of symptoms to randomisation was 130 (75) minutes and from randomisation to angiography 90 (25) minutes. Death or recurrent infarction within 42 days occurred in 12 patients in the thrombolysis group, in 10 patients in the rescue PTCA group, and in six patients in the primary PTCA group. These differences were not significant. CONCLUSIONS: Acute transfer for rescue PTCA or primary PTCA in patients with extensive myocardial infarction is feasible and safe. Efficacy of rescue PTCA or primary PTCA in this setting will have to be tested in larger series before this approach can be implemented as "routine treatment" for patients with extensive myocardial infarction.

Left ventricular function at 3 months after successful thrombolysis. Impact of reocclusion without reinfarction on ejection fraction, regional function, and remodeling.

BACKGROUND: After successful thrombolysis for acute myocardial infarction, reocclusion is observed in about 30% of patients after 3 months and usually occurs without reinfarction. We studied the impact of reocclusion without reinfarction on global and regional left ventricular function and on remodeling during that period. METHODS AND RESULTS: The patients for this analysis constituted a subset of those enrolled in the APRICOT-trial, which was designed to study the efficacy of antithrombotics on the prevention of reocclusion. Patients were selected who had a left anterior descending- or right coronary artery-related myocardial infarction, had an angiographically patent infarct-related vessel when studied < 48 hours after intravenous thrombolysis, and underwent repeat cardiac catheterization at 3 months. Paired contrast ventriculograms of quality sufficient to analyze regional wall motion, global ejection fraction, and ventricular volumes were analyzed in 129 patients. Enzymatic infarct size and baseline left ventricular function as well as other baseline characteristics were similar in patients with (n = 34) and without (n = 95) reocclusion. Ejection fraction improved in anterior infarction without reocclusion from 47 +/- 10% to 54 +/- 13% (P = .0001) but not with reocclusion (baseline, 48 +/- 13%; 3 months, 48 +/- 16%). No improvement was seen in inferior infarction with or without reocclusion. Persistent patency allowed preservation of end-systolic volume index (ESVI) at 3 months (37 +/- 14 mL/m2) to baseline level (38 +/- 13 mL/m2), with a better chance for improvement of > 10 mL/m2 without reocclusion in those with baseline values > 40 mL/m2. After reocclusion, in contrast, ESVI increased from 37 +/- 14 to 43 +/- 20 mL/m2 (P = .08). Comparable mean changes of ESVI in response to persistent patency or reocclusion were seen in anterior versus inferior infarction. Recovery of infarct zone contractility was impaired by reocclusion, both in terms of abnormality of segment shortening and expressed in the number of segments showing abnormal wall motion. In anterior but not in inferior infarction, infarct zone contractility was better with good collaterals to the reoccluded artery compared with poor collaterals. CONCLUSIONS: After successful thrombolysis for acute myocardial infarction, reocclusion without reinfarction withholds salvaged myocardium from regaining contractility. This has deleterious consequences for regional and global left ventricular function and for remodeling. To further optimize prognosis in patients after thrombolysis, future research should focus on the prevention of reocclusion and should evaluate revascularization therapy in patients with reocclusion.

The renal handling of pepsinogen A isozymogens in man.

Pepsinogen A (PGA) isozymogens are low molecular weight proteins that are present in serum and urine. The differences in the molecular structure of PGA-isozymogens involve only 2-4 amino acid substitutions. In a previous study, performed in 13 subjects only, a remarkable difference between the fractional renal clearances of the main PGA-isozymogens (PGA-3, PGA-4 and PGA-5) has been demonstrated. The aim of the present study was to further investigate these differences in fractional clearance between PGA-isozymogens and to determine whether these differences are caused by differences in glomerular sieving. For this purpose the fractional clearances of PGA-isozymogens were measured in 57 subjects. In accordance with the previous study, the median fractional clearance of PGA-5 (13%) was lower than the median fractional clearance of PGA-4 (17%; p < 0.02) and the median fractional clearance of PGA-4 was lower than the median fractional clearance of PGA-3 (26%; p < 0.001). The glomerular sieving coefficients of PGA-isozymogens were measured in 11 subjects during an elective heart catheterization by means of the fractional renal extraction method. No significant difference between the glomerular sieving coefficients of PGA-isozymogens could be demonstrated, being 0.81 for PGA-3, 0.96 for PGA-4 and 0.84 for PGA-5. It is concluded that the differences in renal handling between PGA-isozymogens must be explained by differences in tubular reabsorption. These differences in tubular reabsorption between PGA-isozymogens support the hypothesis that positively charged amino acid residues of proteins are involved in the tubular protein reabsorption.

Culprit lesion morphology and stenosis severity in the prediction of reocclusion after coronary thrombolysis: angiographic results of the APRICOT study. Antithrombotics in the Prevention of Reocclusion in Coronary Thrombolysis.

OBJECTIVES: In the APRICOT study (Antithrombotics in the Prevention of Reocclusion In Coronary Thrombolysis), we sought to determine whether angiographic characteristics of the culprit lesion could predict reocclusion after successful thrombolysis and to analyze the influence of three antithrombotic treatment regimens. BACKGROUND: After successful thrombolysis, reocclusion is a major problem. Prediction of reocclusion by angiographic data and choice of antithrombotic treatment would be important for clinical management. METHODS: After thrombolysis, patients were treated with intravenous heparin until initial angiography was performed within 48 h. Patients with a patent infarct-related artery were eligible. Three hundred patients were randomly selected for treatment with coumadin, aspirin (300 mg once daily) or placebo. Patency on a second angiographic study after 3 months was the primary end point of the study. RESULTS: Reocclusion rate was 25% with aspirin, 30% with coumadin and 32% with placebo (p = NS). Lesions with > 90% stenosis reoccluded more frequently (42%) than did those with < 90% stenosis (23%) (p < 0.01). Reocclusion rate of smooth lesions was higher (34%) than that of complex lesions (23%) (p < 0.05). In lesions with < 90% stenosis, the reocclusion rate was lower with aspirin (17%) than with coumadin (25%) or placebo (30%) (p < 0.01). In complex lesions, the reocclusion rate was lower with aspirin (14%) than with coumadin (32%) or placebo (25%) (p < 0.02). Multivariate analysis showed only stenosis severity > 90% to be an independent predictor of reocclusion (odds ratio 2.31, 95% confidence interval 1.28 to 4.18, p = 0.006). CONCLUSIONS: Angiographic features of the culprit lesion after successful coronary thrombolysis significantly predict the risk of reocclusion: high grade (> 90%) stenoses reoccluded more frequently. Aspirin was effective only in complex and less severe lesions (< 90% stenosis). These findings should prompt investigation of the effects of an aggressive approach to patients with severe residual stenosis.

Aspirin versus coumadin in the prevention of reocclusion and recurrent ischemia after successful thrombolysis: a prospective placebo-controlled angiographic study. Results of the APRICOT Study.

BACKGROUND: Successful coronary thrombolysis involves a risk for reocclusion that cannot be prevented by invasive strategies. Therefore, we studied the effects of three antithrombotic regimens on the angiographic and clinical courses after successful thrombolysis. METHODS AND RESULTS: Patients treated with intravenous thrombolytic therapy followed by intravenous heparin were eligible when a patent infarct-related artery was demonstrated at angiography < 48 hours. Three hundred patients were randomized to either 325 mg aspirin daily or placebo with discontinuation of heparin or to Coumadin with continuation of heparin until oral anticoagulation was established (international normalized ratio, 2.8-4.0). After 3 months, in which conservative treatment was intended, vessel patency and ventricular function were reassessed in 248 patients. Reocclusion rates were not significantly different: 25% (23 of 93) with aspirin, 30% (24 of 81) with Coumadin, and 32% (24 of 74) with placebo. Reinfarction was seen in 3% of patients on aspirin, in 8% on Coumadin, and in 11% on placebo (aspirin versus placebo, p < 0.025; other comparison, p = NS). Revascularization rate was 6% with aspirin, 13% with Coumadin, and 16% with placebo (aspirin versus placebo, p < 0.05; other comparisons, p = NS). Mortality was 2% and did not differ between groups. An event-free clinical course was seen in 93% with aspirin, in 82% with Coumadin, and in 76% with placebo (aspirin versus placebo, p < 0.001; aspirin versus Coumadin, p < 0.05). An event-free course without reocclusion was observed in 73% with aspirin, in 63% with Coumadin, and in 59% with placebo (p = NS). An increase of left ventricular ejection fraction was only found in the aspirin group (4.6%, p < 0.001). CONCLUSIONS: At 3 months after successful thrombolysis, reocclusion occurred in about 30% of patients, regardless of the use of antithrombotics. Compared with placebo, aspirin significantly reduces reinfarction rate and revascularization rate, improves event-free survival, and better preserves left ventricular function. The efficacy of Coumadin on these end points appears less than that of aspirin. The still-high reocclusion rate emphasizes the need for better antithrombotic therapy in these patients.

Renal handling of insulin and C-peptide in patients with non-insulin-dependent diabetes mellitus.

The kidney is responsible for a considerable part of the clearance of insulin and C-peptide. Two routes are thought to be involved in the renal extraction of insulin and C-peptide from the circulation: (1) glomerular filtration, and (2) uptake by tubular cells from peritubular capillaries. The aim of the present study was to investigate these processes in non-insulin-dependent diabetes mellitus (NIDDM). For this purpose we measured the renal extraction of inulin, insulin, and C-peptide in 12 NIDDM patients and 16 control subjects during elective heart catheterization. In addition, a 24-h urine sample was obtained from all subjects to assess the fractional clearance of the peptides. The total renal extraction of both insulin and C-peptide exceeded the amount that was extracted by filtration, confirming the supposition that both peptides are cleared by an additional mechanism, most probably peritubular uptake. The peritubular uptake of insulin in the NIDDM group was not significantly different from that in the control subjects, whereas the insulin extraction over the legs was significantly lower in NIDDM than in the controls. The peritubular uptake of C-peptide was significantly lower in NIDDM, while the fractional clearance of C-peptide was significantly higher. The latter indicates that the reabsorption of C-peptide from the luminal side of the tubular cell is impaired in diabetes mellitus. It is therefore concluded that urinary C-peptide excretion is not a reliable index for insulin production in NIDDM.(ABSTRACT TRUNCATED AT 250 WORDS)

Transesophageal color flow Doppler mapping in the assessment of native mitral valvular regurgitation: comparison with left ventricular angiography.

Transesophageal echocardiography (TEE) was performed within 24 hours after cardiac catheterization in 45 patients for assessment of native mitral valvular regurgitation. Color flow mapping was used in evaluating systolic regurgitant jet sizes. A jet demonstrated by TEE was 96% sensitive and 44% specific for angiographic mitral regurgitation. The presence of angiographic mitral regurgitation was best predicted by (single measurement) (1) a holosystolic jet, (2) a jet length greater than 2.5 cm, and (3) a jet area greater than 2 cm2. Severe angiographic mitral regurgitation (grades 3 and 4) was best predicted by (single measurement) (1) a jet area greater than 5 cm2, and (2) a jet length greater than 4 cm. It is concluded that the assessment of angiographic mitral regurgitation by TEE is improved by the measurement of these jet parameters, which have a high sensitivity and higher specificity than the presence of a jet alone. Furthermore, with TEE one is able to differentiate severe (grades 3 and 4) from absent or mild mitral regurgitation (grades 0, 1, and 2).

"Spontaneous" catheter fracture and embolization of a totally implanted venous access port.

A case of "spontaneous" fracture of the catheter of a totally implanted venous access device is reported. The distal part of the catheter migrated into a pulmonary artery branch and could not be retrieved. The cause and consequences of this rare complication are discussed. It is emphasized that the integrity of a totally implanted venous access device should be ascertained before cytostatic agents are administered.