A. Betriu

THROMBOLYSIS WITH TISSUE PLASMINOGEN ACTIVATOR IN ACUTE MYOCARDIAL INFARCTION: NO ADDITIONAL BENEFIT FROM IMMEDIATE PERCUTANEOUS CORONARY ANGIOPLASTY

A randomised trial of 367 patients with acute myocardial infarction was performed to determine whether an invasive strategy combining thrombolysis with recombinant tissue-type plasminogen activator (rTPA), heparin, and acetylsalicylic acid, and immediate percutaneous transluminal coronary angioplasty (PTCA) would be superior to a noninvasive strategy with the same medical treatment but without immediate angiography and PTCA. Intravenous infusion of 100 mg rTPA was started within 5 h after onset of symptoms (median 156 min). Angiography was performed 6-165 min later in 180 out of 183 patients allocated to the invasive strategy; 184 patients were allocated to the non-invasive strategy. Immediate PTCA reduced the percentage stenosis of the infarct-related segment, but this was offset by a high rate of transient (16%) and sustained (7%) reocclusion during the procedure and recurrent ischaemia during the first 24 h (17%). The clinical course was more favourable after non-invasive therapy, with a lower incidence of recurrent ischaemia within 24 h (3%), bleeding complications, hypotension, and ventricular fibrillation. Mortality at 14 days was lower in patients allocated to non-invasive treatment (3%) than in the group allocated to invasive treatment (7%). No difference between the treatment groups was observed in infarct size estimated from myocardial release of alpha-hydroxybutyrate dehydrogenase or in left ventricular ejection fraction after 10-22 days. Since immediate PTCA does not provide additional benefit there seems to be no need for immediate angiography and PTCA in patients with acute myocardial infarction treated with rTPA.

Effect of early intravenous heparin on coronary patency, infarct size, and bleeding complications after alteplase thrombolysis: results of a randomised double blind European Cooperative Study Group trial.

OBJECTIVE--To determine whether concomitant treatment with intravenous heparin affects coronary patency and outcome in patients treated with alteplase thrombolysis for acute myocardial infarction. DESIGN--Double blind randomised trial. TREATMENT REGIMENS--Alteplase 100 mg (not weight adjusted) plus aspirin (250 mg intravenously followed by 75-125 mg on alternate days) plus heparin (5000 units intravenously followed by 1000 units hourly without dose adjustment) was compared with alteplase plus aspirin plus placebo for heparin. SETTING--19 cardiac centres in six European countries. SUBJECTS--652 patients aged 21-70 years with clinical and electrocardiographic features of infarcting myocardium in whom thrombolytic therapy could be started within six hours of the onset of major symptoms. MAIN OUTCOME MEASURE--Angiographic coronary patency 48-120 hours after randomisation. RESULTS--Coronary patency (TIMI grades 2 or 3) was 83.4% in the heparin group and 74.7% in the group given placebo for heparin. The relative risk of an occluded vessel in the heparin treated group was 0.66 (95% confidence interval 0.47 to 0.93). Mortality was the same in both groups. There were non-significant trends towards a smaller enzymatic infarct size and a higher incidence of bleeding complications in the group treated with heparin. CONCLUSIONS--Concomitant intravenous heparin improves coronary patency in patients with alteplase. Whether this can be translated into improved clinical benefit needs to be to be tested in a larger trial.

Short-Term Effects of Transdermal Estrogen Replacement Therapy on Coronary Vascular Reactivity in Postmenopausal Women With Angina Pectoris and Normal Results on Coronary Angiograms

OBJECTIVES This study sought to analyze the effect of short-term transdermal estradiol treatment on in vivo coronary endothelial function in postmenopausal women with angina and normal results on coronary arteriograms. BACKGROUND The incidence of coronary heart disease increases in women after menopause. Estrogen replacement therapy has been associated with a global reduction in cardiovascular disease incidence and mortality. In addition, coronary endothelial dysfunction has been demonstrated in a group of postmenopausal women. It has been shown that intravenous or intracoronary estrogens improve endothelial function in postmenopausal women with coronary atherosclerosis. However, the efficacy of this treatment is unknown in patients with angina and normal coronary arteries. METHODS Endothelium-dependent coronary reactivity was analyzed in 15 postmenopausal women with angina and normal coronary arteries at baseline and after 24 h of estradiol transdermal administration (100 microg). RESULTS Estradiol concentration increased from 22 +/- 8 pg/ml (mean +/- SEM) at baseline to 76 +/- 13 pg/ml (p < 0.01) at 24 h. At baseline, acetylcholine induced vasoconstriction, with a mean diameter reduction of -23 +/- 6% (p = 0.002). After estrogen treatment, there was no vasoconstriction with acetylcholine, with a mean diameter change of 0 +/- 4%, significantly different from the pretreatment diameter reduction observed (p = 0.003). Similarly, estimated coronary blood flow significantly increased in response to acetylcholine after estrogen treatment, with a mean change of 50 +/- 30% compared with 5 +/- 24% before estradiol administration (p = 0.04). CONCLUSIONS Early after transdermal estrogen administration, endothelium-dependent coronary vasomotion is improved in postmenopausal women with angina and normal coronary arteries.

Angiographic findings 1 month after myocardial infarction: a prospective study of 259 survivors.

Coronary anatomy as it relates to left ventricular function was assessed prospectively in patients who survived acute myocardial infarction. The study population included 259 consecutive male patients age 60 years or younger who underwent catheterization 30 days after the acute event. Coronary artery obstructive lesions (> 50% reduction in luminal diameter) were found in 241 patients (93%), 118 (45%) of whom had total and 76 (29%) subtotal (> 90%) stenosis) occlusion of at least one coronary artery. Normal coronary vessels were seen in eight patients (3%) and nonobstructive lesions in 10 (4%). One-, two- and threevessel disease were present in 89, 86 and 66 patients, respectively. Patients with normal coronary arteries or nonobstructive lesions had higher ejection fractions than those with obstructive lesions in one, two or three vessels (p < 0.05). Ejection fraction was lower (p < 0.001) and the percentage of akinetic segments higher (p < 0.001) in patients with total or subtotal lesions and no collaterals. Adequate collaterals, seen in 29 patients (11%), significantly improved regional wall motion (p < 0.05) and decreased the percentage of akinetic segments (p < 0.001). Thus, in a substantial number of patients (32% in our series), the infarcted area is spontaneously reperfused by collaterals or through the involved artery. Both mechanisms ameliorate wall motion in corresponding areas.

Coronary artery revascularization in patients with sustained ventricular arrhythmias in the chronic phase of a myocardial infarction : Effects on the electrophysiologic substrate and outcome

OBJECTIVES The objective of this study was to analyze the influence of coronary artery revascularization in patients with ventricular arrhythmias. BACKGROUND Coronary artery revascularization is an effective treatment for myocardial ischemia; however, its effect on ventricular arrhythmias not related to an acute ischemic event has not been carefully studied. METHODS Sixty-four patients (58 men, mean age 65 +/- 8 years old) with prior myocardial infarction, spontaneous ventricular arrhythmias not related to an acute ischemic event (55 ventricular tachycardia, 9 ventricular fibrillation) and coronary lesions requiring revascularization were studied prospectively. Electrophysiological study was performed before and after revascularization, and events during follow-up were analyzed. RESULTS At initial study 61 patients were inducible into sustained ventricular arrhythmias. After revascularization, in 62 survivors, 52 out of 59 patients previously inducible were still inducible (group A), and 10 patients were noninducible (group B). No differences were found in clinical, hemodynamic, therapeutic and electrophysiological characteristics between both groups. During 32 +/- 26 months follow-up, 28/52 patients in group A (54%) and 4/10 patients in group B (40%) had arrhythmic events (p = 0.46). An ejection fraction <30% predicted recurrent arrhythmic events (p = 0.02), but not the presence of demonstrable ischemia before revascularization (p = 0.42), amiodarone (p = 0.69) or beta-adrenergic blocking agent therapy (p = 0.53). Total mortality was 10% in both groups. CONCLUSIONS In patients with ventricular arrhythmias in the chronic phase of myocardial infarction, probability of recurrence is high despite coronary artery revascularization, but mortality is low if combined with appropriate antiarrhythmic therapy. Recurrences are related to the presence of a low ejection fraction but not to demonstrable ischemia before revascularization, amiodarone or beta-blocker therapy nor are they the results of electrophysiological testing after revascularization.

Collaborative angiographic patency trial of recombinant staphylokinase (CAPTORS).

BACKGROUND We undertook an angiographic, dose-finding study of staphylokinase (SAK42D variant) to evaluate its efficacy and safety in patients with acute ST-segment myocardial infarction. METHODS AND RESULTS Patients were studied within 6 hours of symptom onset and received SAK42D as a 30-minute infusion with 20% of the total dose given as a bolus. Eighty-two patients with a median age of 60 years (interquartile range 52 to 69 years), 84% male and 43% with an anterior myocardial infarction, were studied at a median time from symptom onset of 2.7 hours. There was a high degree of Thrombolysis in Myocardial Infarction (TIMI) 3 flow achieved with 15 mg of SAK42D, that is, 62%. Therefore after 21 patients had been studied at this dose the next dose of 30 mg was used and 65% TIMI 3 patency was achieved. At the peak dose of 45 mg, TIMI 3 90-minute patency was 63%. There were no allergic reactions, and no patient had intracranial hemorrhage. Four patients had major and 9 moderate bleeding during the study; 2 of the major and 5 of the moderate bleeding events occurred within 48 hours of commencement of treatment. The majority (62%) of these were related to vascular instrumentation, and there was no relation between the extent of bleeding and dose of SAK42D used. Forty-five minutes after cessation of SAK42D, there were small percent decrements in plasma fibrinogen and plasminogen levels that did not reach statistical significance. However, there were dose-related changes in alpha(2) anti-plasmin that revealed a borderline significant reduction that was dose related (P =.053). CONCLUSION These data revealed similar fibrinolytic efficacy across a 3-fold increment in dose, indicating that this study operated on a flat portion of the dose-response curve. The favorable efficacy/safety profile achieved with staphylokinase is encouraging, and further investigation is warranted.

Feasibility of early discharge after acute Q wave myocardial infarction in patients not receiving thrombolytic treatment

OBJECTIVES The purpose of this study was to analyze the feasibility of early discharge (4 days) after acute myocardial infarction in patients not receiving thrombolytic therapy by first identifying predictors of short-term prognosis and then testing the derived risk profile in an independent cohort of patients. BACKGROUND Previous studies have shown that early discharge after acute myocardial infarction is possible. However, physicians are reluctant to shorten the standard 7- to 10-day hospital stay, presumably because of difficulty in selecting low risk patients. METHODS From January 1985 to November 1986, 358 patients with acute myocardial infarction who did not receive thrombolytic therapy were screened. Those with a Q-wave infarction showing no complications on day 4 were considered candidates for early discharge and were transferred to the ward for a mean of 12 days. During this period, we looked for any event (cardiac or noncardiac) that would have prompted readmission if the patient had been previously discharged. Univariate and multiple regression analysis were performed to identify predictors of these events among 25 baseline variables. The derived risk profile was tested in an independent validation cohort. RESULTS One hundred five (29.3%) of the 358 patients were free of symptoms on day 4, and 29 (27.6%) had at least one cardiac event, including four deaths and one reinfarction. Multivariate analysis selected diabetes, ejection fraction < 40% and age as independent predictors of events. Using the risk profile, 18 (13.2%) of the 136 validation cohort patients were categorized as low risk, and only 1 of them had a major event (progressive angina). Sensitivity for the risk profile was high (91%), but specificity was low (34%). CONCLUSIONS The use of simple clinical variables may allow the safe reduction of hospital stay after infarction in selected patients. However because the proportion of candidates for early discharge is small (12.6%), it seems unlikely that the current policies on length of hospital stay will change in the near future.

Remodelado ventricular izquierdo tras ablación septal percutánea con alcohol en pacientes con miocardiopatía hipertrófica obstructiva: estudio ecocardiográfico

Evaluamos el impacto de la reduccion de la obstruccion en el tracto de salida del ventriculo izquierdo tras la ablacion septal percutanea con alcohol sobre la hipertrofia y el remodelado del ventriculo izquierdo (VI). Pacientes y metodo. Se incluyo a 20 pacientes con miocardiopatia hipertrofica tratados con ablacion septal percutanea. Se realizo ecocardiograma Doppler en situacion basal, inmediatamente despues de la ablacion septal percutanea y a los 3 y 12 meses de seguimiento, en el que se midieron los diametros y grosores del VI y del gradiente de presion en el tracto de salida del ventriculo izquierdo. Resultados. Inmediatamente despues de la ablacion septal percutanea, el gradiente de presion en el tracto de salida del VI disminuyo de 63,0 ± 27,7 a 28,2 ± 24,7 mmHg (p < 0,001), sin que se apreciaran cambios significativos en las dimensiones del VI. Doce meses despues se observo un incremento en los diametros telediastolico (de 47,1 ± 4,9 a 50,8 ± 4,5 mm; p < 0,01) y telesistolico del VI (de 27,1 ± 3,0 a 33,7 ± 4,6 mm; p < 0,01) y una reduccion en los grosores del septo (de 19,5 ± 4,0 a 15,5 ± 2,7 mm; p < 0,01) y de la pared posterior del VI (de 14,0 ± 2,2 a 12,9 ± 1,3 mm; p < 0,01). Los volumenes telediastolico y telesistolico del VI aumentaron (de 106,4 ± 26,9 a 123,1 ± 28,7 ml; p < 0,01, y de 50,2 ± 17,3 a 56,7 ± 18,3 ml; p < 0,01, respectivamente), sin que se observaran cambios en la fraccion de eyeccion del VI. La reduccion del gradiente de presion en el tracto de salida del ventriculo izquierdo observada a los 12 meses de la ablacion septal percutanea se correlaciono de manera significativa con el incremento del diametro telesistolico del VI (r = 0,63; p < 0,01). Conclusiones. La reduccion de la obstruccion en el tracto de salida del ventriculo izquierdo en pacientes con miocardiopatia hipertrofica tratados con ablacion septal percutanea se acompana de un incremento de los diametros y volumenes del VI en el seguimiento. Esto indica el desarrollo de un remodelado cardiaco y de una regresion en la hipertrofia del VI de estos pacientes que podria contribuir a su mejoria sintomatica

MANAGEMENT OF ACUTE MYOCARDIAL INFARCTION IN PATIENTS PRESENTING WITH ST-SEGMENT ELEVATION

The Task Force on the Management of Acute Myocardial Infarction of the European Society of Cardiology.