Randomized comparative trial of triflusal and aspirin following acute myocardial infarction.

AIMS: To compare the efficacy and tolerability of the antiplatelet agent triflusal with aspirin in the prevention of cardiovascular events following acute myocardial infarction. METHODS AND RESULTS: In this double-blind, multicentre, sequential design study, patients were randomized within 24 h of acute myocardial infarction symptom onset to receive triflusal 600 mg or aspirin 300 mg once daily for 35 days. The primary end-point was death, non-fatal myocardial reinfarction or a non-fatal cerebrovascular event. The incidences of these individual outcomes and urgent revascularization were secondary end-points. The null hypothesis of no difference between treatments in the primary combined end-point was accepted with 80% power after recruiting 2124 validated patients (odds ratio (OR) for failure [95% confidence interval (CI)]: 0.882 [0.634-1.227]). Non-fatal cerebrovascular events were significantly less frequent with triflusal (OR [95% CI]: 0.364 [0.146-0.908]; P = 0.030). There was no significant difference between treatments for death (OR [95% CI]: 0.816 [0.564-1.179]; P = 0.278), non-fatal reinfarction (OR [95% CI]: 1.577 [0.873-2.848]; P = 0.131) or revascularization (OR [95% CI]: 0.864 [0.644-1.161]; P = 0.334). Overall, both drugs were well tolerated, although there was a trend towards fewer bleeding episodes with triflusal; significantly fewer central nervous system bleeding episodes were observed in triflusal-treated patients (0.27% vs. 0.97%; P = 0.033). CONCLUSION: Triflusal and aspirin have similar efficacy in preventing further cardiovascular events after acute myocardial infarction, but triflusal showed a more favourable safety profile. Triflusal significantly reduced the incidence of non-fatal cerebrovascular events compared with aspirin.

Cholesterol reduction improves myocardial perfusion abnormalities in patients with coronary artery disease and average cholesterol levels.

OBJECTIVES: We sought to evaluate whether pravastatin treatment increases myocardial perfusion, as assessed by thallium-201 single-photon emission computed tomographic (SPECT) dipyridamole testing, in patients with coronary artery disease (CAD) and average cholesterol levels. BACKGROUND: Previous studies in hypercholesterolemic patients have demonstrated that cholesterol reduction restores peripheral and coronary endothelium-dependent vasodilation and increases myocardial perfusion. METHODS: This was a randomized, placebo-controlled study with a cross-over design. Twenty patients with CAD were randomly assigned to receive 20 mg of pravastatin or placebo for 16 weeks and then were crossed over to the opposite medication for a further 16 weeks. Lipid and lipoprotein analysis and dipyridamole thallium-201 SPECT were performed at the end of each period. The SPECT images were visually analyzed in eight myocardial segments using a 4-point scoring system by two independent observers. A summed stress score and a summed rest score were obtained for each patient. Quantitative evaluation was performed by the Cedars-Sinai method. The magnitude of the defect was expressed as a percentage of global myocardial perfusion. RESULTS: Total and low density lipoprotein cholesterol levels during placebo were 214 +/- 29 mg/dl and 148 +/- 25 mg/dl, respectively. These levels with pravastatin were 170 +/- 23 mg/dl and 103 +/- 23 mg/dl, respectively. The summed stress score and summed rest score were lower with pravastatin than with placebo (7.2 +/- 2.3 vs. 5.9 +/- 2.3, p = 0.012 and 3.2 +/- 1.6 vs. 2.4 +/- 2.2, p = 0.043, respectively). Quantitative analysis showed a smaller perfusion defect with pravastatin (29.2%) as compared with placebo (33.8%) (p = 0.021) during dipyridamole stress. No differences were found at rest. CONCLUSIONS: Reducing cholesterol levels with pravastatin in patients with CAD improves myocardial perfusion during dipyridamole stress thallium-201 SPECT.

[Streptokinase-induced jaundice]. / Ictericia inducida por estreptocinasa.

Streptokinase is a thrombolytic agent used very frequently for the early treatment of acute myocardial infarction. A 35-year-old male with inferior acute myocardial infarction was admitted to the Coronary Care Unit and treated with systemic streptokinase. At the time of admission, he was a healthy male and he was not receiving any hepatotoxic agent. Six hours after thrombolysis, he developed high fever, painful hepatomegaly, jaundice and coluric urine. Leucocytosis with left deviation was observed in the hemogram and the liver function tests showed slight enzymatic elevation and hyperbilirubinemia. This condition was progressively improving and the patient was free of symptoms on the eighth day of evolution. Jaundice as secondary effect of streptokinase has been previously communicated in very few medical reports.

[Acute myocardial infarction secondary to Wegener's granulomatosis]. / Infarto agudo de miocardio secundario a granulomatosis de Wegener.

Wegener's granulomatosis (WG) is a necrotizing and granulomatous vasculitis that usually affects the upper and lower respiratory tract and the kidneys. Cardiac involvement is rare although pericarditis, coronary arteritis, myocarditis, valvulitis and arrhythmias have been described. Acute myocardial infarction with clinical expression is an exceptional complication of Wegener's granulomatosis. We report a case of a 30-year-old man with Wegener's granulomatosis who suffered an acute myocardial infarction during the initial phase of the disease, following seven days of treatment with glucocorticoids and cyclophosphamide. Transthoracic echocardiography showed abnormal regional wall motion with septal hypokinesia and apical akinesia. Cardiac catheterization revealed an ectasic segment in the proximal left anterior descending coronary artery and total occlusion in the mid-segment. Medical therapy with prednisone and cyclophosphamide was continued. No complications and initial remission were achieved.

[Endothelial dysfunction and metabolic syndrome]. / Disfunción endotelial y síndrome metabólico.

Endothelial dysfunction and insulin resistance coexist in a significant proportion of subjects. Both are associated with a great number of cardiovascular risk factors which probably explains their relation. Although there are direct mechanisms that physiopathologically may relate both disorders, the practical significance of an independent and direct connection is uncertain.

[Increase of myocardial perfusion during antilipemic treatment in patients with ischemic cardiopathy]. / Incremento de la perfusión miocárdica durante el tratamiento hipolipemiante en pacientes con cardiopatía isquémica.

OBJECTIVES: To evaluate if cholesterol lowering therapy with simvastatin increases myocardial perfusion, assessed by Thallium-201 single photon emission computed tomography (SPECT) after dipyridamole, in patients with coronary artery disease. PATIENTS AND METHODS: Ten hypercholesterolemic subjects with coronary artery disease were selected for a pilot study. Lipid and lipoprotein analysis and Thallium-201 SPECT were performed before and after 16 weeks of treatment with 40 mg of simvastatin QD. SPECT images were qualitatively analyzed in 8 myocardial segments using a 4 point scoring system. Quantitative evaluation was performed in 13 segments. The myocardial region with the maximal mean counts per pixel on the stress study was considered the reference region. TI201 activity in all other myocardial regions was expressed as a percentage of the activity in the reference region. RESULTS: Total cholesterol and LDL cholesterol were reduced by 28.4% and 37.1% with treatment. Global myocardial perfusion was increased in all patients. Qualitative analysis demonstrated that cholesterol lowering improved myocardial perfusion during dipyridamole stress. Quantitative analysis showed an increased global perfusion during stress (41.8% vs 54.6%; p < 0.0001), due to increased perfusion of previous ischemic segments (32.4% vs 49.4%; p < 0.0001) but without changes in previous normally perfused segments (71.5% vs 71.3%). CONCLUSION: Reduction of cholesterol levels in hypercholesterolemic subjects with coronary artery disease increases myocardial perfusion in ischemic segments during dipyridamole stress test as assessed by single photon emission computed tomography (SPECT).

[Urate production in a porcine model of myocardial ischemia-reperfusion]. / Producción de urato en un modelo porcino de isquemia-reperfusion miocárdica.

OBJECTIVE: This study was designed to investigate urate production by swine hearts using an in vivo regionally ischemic-reperfused model. ANIMALS AND METHODS: Ten female pigs underwent 60 minutes of myocardial ischemia by clamping of the left anterior descending artery and afterwards 120 minutes of reperfusion. Epicardial biopsies and blood samples from coronary sinus were taken before ligation, at the end of ischemic period and 5, 30, 60 and 120 minutes upon reperfusion. RESULTS: During ischemia, tissue levels of ATP and ADP greatly declined with a subsequent increase in the concentration of AMP, inosine and hypoxanthine (33 +/- 12 vs 93 +/- 17, 26 +/- 8 vs 768 +/- 86 and 32 +/- 10 vs 219 +/- 26 nmol/g dry weight, p < 0.01 for each). Despite the great increase in the hypoxanthine levels, uric acid concentration remained constant (69 +/- 9 vs 32 +/- 12 nmol/g dry weight, NS). Hypoxanthine, xanthine and uric acid concentrations increased in blood samples obtained from the coronary sinus at the end of ischemic period (17.99 vs 31.03 nmol/ml, p < 0.01, 0.29 vs 1.45 nmol/ml, p < 0.05 and 1.20 vs 2.31 nmol/ml, p < 0.01 respectively) and were enhanced upon reperfusion (35.8 and 3.89 nmol/ml for hypoxanthine and uric acid respectively, p < 0.05) without any significant modifications in their concentrations at the arterial level. CONCLUSION: These results demonstrate that the ischemic-reperfused swine heart produces urate probably outside the myocardium.

Protective effect of triflusal against acute myocardial infarction in patients with unstable angina: results of a Spanish multicenter trial. Grupo de Estudio del Triflusal en la Angina Inestable.

A multicenter, double-blind, placebo-controlled study was carried out to evaluate the effect of a new antiplatelet agent, triflusal (2-acetoxy-4-trifluoromethyl benzoic acid), in the prevention of nonfatal myocardial infarction and cardiac or vascular death (principal end-points) in patients with unstable angina. 281 patients were randomly assigned to triflusal (300 mg t.i.d.; n = 143) or placebo (n = 138). After 6 months of treatment, the incidence of nonfatal acute myocardial infarction was significantly lower in the triflusal than in the placebo group: 6 patients (4.2%) versus 17 (12.3%), p = 0.013. The low number of deaths (2/143 triflusal versus 0/138 placebo recipients) hampered statistical analysis of mortality rates. The need for revascularization was similar in the two groups: 24 patients (16.8%) in the triflusal group and 28 (20.3%) in the placebo group, p = 0.449. In conclusion, the results show that treatment with triflusal can reduce the incidence of myocardial infarction in patients with unstable angina.

Diagnosis of subacute ventricular wall rupture after acute myocardial infarction: sensitivity and specificity of clinical, hemodynamic and echocardiographic criteria.

When ventricular free wall rupture after acute myocardial infarction is not followed by sudden death, it is referred to as subacute ventricular rupture. The sensitivity and specificity of clinical, hemodynamic and echocardiographic diagnostic variables obtained at bedside are unknown and were therefore prospectively studied in 1,247 consecutive patients with acute myocardial infarction including 33 patients with subacute ventricular rupture diagnosed at operation (group A) and 1,214 patients without ventricular rupture (at operation, postmortem study or at discharge) (group B). The incidence of syncope, recurrent chest pain, hypotension, electromechanical dissociation, cardiac tamponade, pericardial effusion, high acoustic intrapericardial echoes, right atrial and right ventricular wall compression identified in two-dimensional echocardiograms and hemopericardium demonstrated during pericardiocentesis was higher in group A than in group B (p less than 0.00001). The presence of cardiac tamponade, pericardial effusion greater than 5 mm, high density intrapericardial echoes or right atrial or right ventricular wall compression had a high diagnostic sensitivity (greater than or equal to 70%) and specificity (greater than 90%). The number of false positive diagnoses was always high for each diagnostic variable alone (greater than 20%), but the combination of clinical (hypotension), hemodynamic (cardiac tamponade) and echocardiographic variables allowed a sensitivity of greater than or equal to 65% with a small number of false positive diagnoses (less than 10%) and provided useful information for therapeutic decisions. The diagnosis of subacute ventricular rupture requires a surgical decision. Twenty-five (76%) of the 33 patients with subacute ventricular rupture survived the surgical procedure and 16 (48.5%) are long-term survivors. Thus, subacute ventricular wall rupture is a relatively frequent complication after acute myocardial infarction that can be accurately diagnosed and successfully treated.

Inversion of the normal interatrial septum convexity in acute myocardial infarction: incidence, clinical relevance and prognostic significance.

Inversion of the normal interatrial septum convexity has been described in patients with right atrial pressure or volume overload, but there is no reference to this abnormality in acute myocardial infarction. A group of 576 consecutive patients with acute infarction and serial echocardiographic studies were prospectively evaluated during a mean follow-up period of 406 days. Inverted interatrial septum convexity was found in 30 patients (5.2%); 29 of the 30 presented with inferior infarction with right ventricular involvement (29 [24.4%] of 119) and the remaining presented with cardiac tamponade secondary to heart rupture. The incidence of inverted interatrial septum convexity rapidly decreased, and after 3 months it was present in only five patients. All patients with inverted interatrial septum convexity had a right atrial pressure greater than or equal to pulmonary capillary pressure, a relation found in only 2 of 43 patients with right ventricular involvement and normal septal convexity. In patients with right ventricular infarction, right atrial pressure was higher in the presence of inverted septal convexity (15.9 +/- 4.1 versus 10.5 +/- 4.1 mm Hg, p less than 0.0001) and the incidence of hypotension (10 [34.4%] of 29 versus 15 [17.4%] of 90, p = 0.04) and third degree atrioventricular block (10 [34.4%] of 29 versus 11 [12.2%] of 90, p = 0.006) as well as the mortality rate after 3 months (9 [31%] of 29 versus 11 [12.2%] of 90, p = 0.04) were higher in the presence of inverted convexity than in patients with normal septal convexity.(ABSTRACT TRUNCATED AT 250 WORDS)

[Usefulness of dobutamine in producing myocardial ischemia. Comparison with ergometry]. / Utilidad de la dobutamina para provocar isquemia miocárdica. Comparación con la ergometría.

Fifty six patients were studied while in the Coronary Care Unit: 17 with unstable angina and 39 with acute myocardial infarction. All patients underwent dobutamine stress testing (doses of 5, 10, 15 and 20 micrograms/kg/min every 5 min) and exercise testing (modified protocol to finish at an energy expenditure of approximately 5 METS): 4-5 days after the last crisis of angina or 6-8 days after the onset of noncomplicated acute myocardial infarction. The heart rate increased from 72 +/- 10 to 104 +/- 12 beat/min with dobutamine (p = 0.00001) and from 84 +/- 11 to 118 +/- 15 beat/min with exercise testing (p = 0.00001). The systolic blood pressure increased from 116 +/- 9 to 138 +/- 11 mmHg with dobutamine (p = 0.00001) and from 117 +/- 8 to 156 +/- 7 mmHg with exercise testing (p = 0.00001). Due to different reasons 33 patients did not finish the exercise protocol, while only 8 patients did not finish the dobutamine testing. The ST segment wast elevated in 22 cases with dobutamine and in 9 cases with exercise, eight of them coinciding in both tests. The ST segment was depressed in 36 cases with dobutamine and in 21 cases with exercise, 20 of them coinciding in both tests. Angina was present in 11 cases with dobutamine and in four exercise, three of them coinciding. If the unfinished tests or those with angina or ST segment depression are considered abnormal, there were 40 abnormal tests with dobutamine and 38 with exercise, 32 of them coinciding.(ABSTRACT TRUNCATED AT 250 WORDS)

[Hemodynamic effect of isosorbide-5-mononitrate in acute cardiac insufficiency secondary to myocardial infarct]. / Efecto hemodinámico del 5-mononitrato de isosorbide en la insuficiencia cardíaca aguda secundaria a infarto de miocardio.

The hemodynamic effects of IS-5-MN were studied in 18 patients with acute myocardial infarction (AMI) complicated with left ventricular failure. Before treatment, 13 patients were in Forrester's hemodynamic class II and 5 in class IV. Hemodynamic monitoring was performed for 3 days, and the following parameters were measured: heart rate (HR), blood pressures (BP), right atrial (RAP), pulmonary artery and pulmonary capillary (PCP) pressures, cardiac index (CI), systemic (SVR) and pulmonary (PVR) vascular resistances, and coronary perfusion pressure (CPP). Patients with clinical symptoms of acute pulmonary edema or systolic BP (BPs) less than 90 mmHg were not included. Twenty mg of 5-IS-MN per os were administered every 8 h. Hemodynamic measurements and IS-5-MN plasma levels were obtained in basal conditions and 1/2, 1, 2, 6 and 8 h after the first and seventh dose of IS-5-MN. A significant decrease of systolic and diastolic BPs, RAP, PCP, SVR and PVR was observed after 1/2 of IS-5-MN administration and was maintained through the study, while CI and CPP increased and HR remained unchanged. The hemodynamic effect was maintained after the seventh dose, with a further decrease of the following parameters: BP, RAC, PCP and PVR. However, 2 patients were withdrawn from the study due to severe symptoms of heart failure. One patient presented headache. IS-5-MN plasma levels were identified after 1/2 h, with a peak level after 1 h, and were similar after the seventh dose. A significant correlation was found between the IS-5-MN levels and the delta RAP and delta PCP after the seventh dose.(ABSTRACT TRUNCATED AT 250 WORDS)