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Conference scene of the satellite meeting of the 14th International Congress on Atherosclerosis, on "Physical activity, exercise and cardiovascular health"

Background Elevations of the MB isoform of creatine kinase (CK) and cardiac troponin T seem to confer an adverse prognosis in unstable angina. We examined whether this prognostic influence is also present for cardiac troponin I (cTnI), a new and even more specific marker of myocardial injury. Methods and Results We studied 106 patients with the clinical diagnosis of unstable angina showing chest discomfort at rest within 48 hours of admission, ECG evidence of myocardial ischemia, and normal values of total CK over the initial 16 hours of observation. The primary end point was death or nonfatal myocardial infarction (MI) at 30 days; the secondary end point was the incidence of cardiac events at 1 year. Blood was drawn every 8 hours for 3 days. Thirteen patients were excluded because of increased CK-MB mass concentrations within 16 hours of admission (non–Q-wave MI) and 2 because of inadequate blood sampling. Of the remaining 91 patients, 22 had cTnI elevations on admission (n=7) or after 8 hours (n=15). At 30 days, no deaths (0%) and 4 MIs (5.8%) occurred in the 69 patients with normal cTnI compared with 2 deaths (9.1%) and 4 MIs (18.2%) in the 22 patients with elevated cTnI. The combined incidence of death and nonfatal MI was 5.8% and 27.3%, respectively ( P =.02). At 1 year, only 68% of patients with elevated cTnI were free of cardiac events, compared with 90% of those without elevations ( P =.01). Conclusions These data indicate that cTnI is an important prognostic variable in patients with unstable angina. Elevations of cTnI predict an adverse short- and long-term prognosis.

The aim of this study was to compare the prognostic efficacy of cardiac troponin T (cTnT) and I (cTnI) in patients with clinical unstable angina.We studied 74 patients with chest pain at rest, electrocardiographic evidence of myocardial ischemia, and normal (6.7 ng/mL) values of creatine kinase-MB. cTnT was measured with a commercial assay (cutoff level 0.1 ng/mL) and cTnI with a preliminary research application (cutoff level 3.1 ng/mL). All patients had blood drawn at baseline and 8 hours thereafter. The prospectively defined end point was the proportion of patients identified by each assay as having myocardial damage.cTnT and cTnI were elevated in the same percentage of patients (18 of 74; 24%). Overall, 23 patients had elevations of 1 or both markers. In 13 there were elevations of both. Ten patients had elevations of only one (5 for each marker). In 51 patients, no elevations were present. Death or nonfatal myocardial infarction was more frequent in patients with elevated cTnI (27.7% vs 5.3%; P =.02) than those with normal values. The prognostic influence of cTnT was less (17% vs 8.5%; P =.2). However, the difference between the 2 markers when compared directly was not statistically significant (27.7% vs 17%; P = NS).These data indicate that both markers identify myocardial damage in equal numbers of patients with clinical unstable angina. Patients with elevations had a worse short-term outcome. The significance of the minor differences in prognostic value will require additional studies.

We monitored ST segment continuously for at least 3 h after the beginning of lytic treatment in 103 patients undergoing early coronary thrombolysis for acute myocardial infarction in order to ascertain whether this technique, which has been shown to be useful to assess recanalization of the infarct-related artery, is also able to identify the improvement in left ventricular function associated with successful reperfusion. Global left ventricular function (assessed in the 30 degrees right anterior oblique projection with the area/length method) and infarct zone wall motion (studied with the centerline method) were evaluated at least 4 weeks after the event. Reperfusion was thought to be achieved when ST segment elevation dropped50% relative to the most abnormal peak documented at any time in the study. Eighty patients (78%) met the criterium for successful reperfusion (group 1), and 23 (22%) did not (group 2). Both groups had similar clinical and angiographic characteristics. All indexes of global left ventricular function were significantly better in group 1 than in group 2 patients (end-diastolic volume: 176 +/- 51 vs. 209 +/- 76 ml, end-systolic volume: 66 +/- 40 vs. 97 +/- 55 ml, ejection fraction: 65 +/- 13 vs. 57 +/- 11%, respectively, all P0.02). Also the severity (-1.6 +/- 1.3 vs. -2.6 +/- 1.01 S.D./chord, respectively, P0.001) and the extension of hypokinesia in the infarct zone (number of chords with2 S.D.: 13 +/- 16 vs. 28 +/- 17, respectively, P0.0001) were less in group 1 than in group 2 patients. Furthermore, in reperfused patients, both global left ventricular function and regional wall motion were better in those admitted60 min from onset of pain. In conclusion, patients with rapid (50%) decrease of ST segment elevation have smaller infarct size and better global left ventricular function than patients without electrocardiographic signs of reperfusion as assessed by continuous ST segment monitoring. This suggests that this non-invasive technique is a powerful tool able to identify patients most benefiting from thrombolytic therapy.

Background In the experimental setting, it has been demonstrated that preconditioning myocardium before prolonged occlusion with brief ischemic episodes affords substantial protection to the cells by delaying lethal injury, thereby limiting infarct size. Whether the same occurs in humans remains unknown. Methods and Results This study was undertaken to determine whether new-onset prodromal angina, defined as chest pain episodes limited to the 24 hours before myocardial infarction, is the clinical correlate of the ischemic preconditioning phenomenon. Twenty-five patients with their first anterior myocardial infarction treated with thrombolysis (recombinant tissue plasminogen activator [r-TPA], 100 mg/3 hours) were retrospectively included in the study because they met the following criteria: (1) 50%), (3) a patent infarct-related coronary artery with TIMI 3 flow and complete absence of collateral circulation to the infarct related artery (assessed at 24±5 days), and (4) the presence of new-onset prodromal angina, ie, typical chest pain episodes occurring at rest within 24 hours or, alternatively, a complete absence of symptoms before onset of infarction. Therefore, on the basis of their clinical status before infarction, the patients were divided into two groups: group 1, 13 patients without prodromal angina, and group 2, 12 patients with prodromal angina. Despite no difference in time to treatment (81±19 versus 75±21 minutes in group 1 and group 2, respectively; P =NS) and time to reperfusion (58±34 versus 46±24 minutes; P =NS), the peak of CKMB release was markedly lower in group 2 (86.3±66 versus 192.3±108.3 IU/L; P P =NS), the final infarct size (11±7.5 versus 5.6±4 hypokinetic segments, P P P =.01) in the group of patients with prodromal angina. Also, the third index, that is, the ECG, showed a favorable trend toward a lesser number of Q waves and a higher Σ R waves, although the values did not reach statistical significance. Conclusions Despite a similar area at risk, patients with new-onset prodromal angina showed a significantly smaller infarct size compared with patients without prodromal symptoms. Since the two groups had similar times to reperfusion and no evidence of collateral circulation to the infarct related artery, the protection afforded by angina in group 2 patients might be explained by the occurrence of ischemic preconditioning.

Nitroglycerin given with tissue-type plasminogen activator (t-PA) has been shown to decrease the thrombolytic effect of t-PA in animal models of coronary artery thrombosis. The present study was conducted to determine whether such an interaction between nitroglycerin and t-PA occurs in patients with acute myocardial infarction undergoing thrombolytic treatment. Patients with acute myocardial infarction were treated with t-PA plus saline solution (group 1; n = 11) or t-PA plus nitroglycerin (group 2; n = 36). Stable coronary artery reperfusion assessed by continuous ST-segment monitoring in 2 electrocardiographic leads, and release of creatine kinase occurred in 91% of group 1 patients and in 44% of group 2 patients (95% confidence interval, 14% to 82%; p0.02). Plasma levels of t-PA antigen were consistently (p0.005) higher in group 1 than in group 2 patients up to 6 hours after t-PA infusion. Conversely, plasminogen activator inhibitor-1 (PAI-1) levels were slightly higher in group 2 than in group 1 patients. These observations indicate that nitroglycerin given with t-PA significantly decreases the plasma t-PA antigen concentrations and impairs the thrombolytic effect of t-PA in patients with acute myocardial infarction.

One hundred seventy-two patients with 1-vessel disease documented at predischarge angiography who had been followed for 43 ± 30 months after an initial Q-wave acute myocardial infarction were retrospectively evaluated to investigate the prognostic value of infarct-related artery patency and left ventricular (LV) function. Multiple logistic regression analysis revealed that only infarct artery patency (Thrombolysis in Myocardial Infarction [TIMI] grades 2–3 vs 0–1) (Z = 2.24; p < 0.05) and end-systolic volume index (Z = −2.67; p < 0.01) were independently related to survival. Sixteen cardiac deaths were observed; all 16 patients had LV dysfunction (defined as end-systolic volume index 40 ml/m2), and 15 had an occluded infarct-related artery. In the subgroup with LV dysfunction, the 10-year percent survival rate was 20% among patients with TIMI grade 0 to 1 versus 96% with grade 2–3 (p < 0.001). Patency of the infarct-related artery was also the only independent predictor of recurrent ischemia (Z = 2.59; p < 0.01). In conclusion, both infarct-related artery patency and LV function are independent predictors of survival after Q-wave acute myocardial infarction. Patients with normal LV function have an excellent long-term prognosis, which is only partially counterbalanced by the tendency toward clinical instability observed in those with an open infarct-related vessel. However, when an occluded infarct-related artery is observed in the setting of LV dysfunction, the long-term outcome appears to be relatively poor.

Objectives. This study was designed to define the extent of inhibition of thrombin activity achieved with conjunctive fixed dose intravenous sodium heparin compared with fixed dose subcutaneous calcium heparin in patients receiving intravenous streptokinase for acute myocardial infarction. Background. The role of heparin therapy during coronary thrombolysis with streptokinase is controversial, in part because the efficacy of different conjunctive heparin regimens in inhibiting early increases of thrombin activity is not known. Methods. Twenty-eight patients treated with 1.5 million U of streptokinase and 165 mg of aspirin for acute myocardial infarction were randomly assigned to receive fixed dose subcutaneous heparin therapy (12,500 U every 12 h delayed until 4 h after the end of streptokinase therapy [n = 14]) or fixed dose intravenous heparin (5,000-U bolus followed by 1,000-U/h infusion [n = 14]). Anticoagulation was assessed with serial measurements of activated partial thromboplastin time, and thrombin activity by measuring fibrinopeptide A and thrombin-antithrombin III complex levels. Plasma concentrations of creatine kinase (CK) MM isoforms were measured for 3 h to determine recanalization (increase la activity > 0.18%/min). Results. Recanalization occurred in 27%, 64% and 79% of patients given subcutaneous heparin versus 43%, 76% and 86% of those given intravenous heparin at 1, 2 and 3 h, respectively (p = 0.6). Concentrations of fibrinopeptide A (mean ± SEM) at 1 h were higher in patients without (n = 5) than in those with (n = 23) CK-MM isofona criteria for recanalization (76.4 ± 25.7 vs. 25.2 ± 52 nmol/liter, p = 0.02), and at 1, 2 and 3 h were significantly lower with fixed dose intravenous heparin (18.4 ± 4.8 vs. 46.7 ± 102 nmol/liter at 1 h, p = 0.004) than without heparin. After fixed dose subcutaneous heparin at 4 h, fibrinopeptide A levels were similar in both groups despite lower activated partial thromboplastin times in patients who received fixed dose subcutaneous heparin. However, fibrinopeptide A was not consistently suppressed in either group (fixed dose subcutaneous heparin 8.7 ± 1.8 nmol/liter vs. fixed dose intravenous heparin 11.8 ± 5.2 nmol/liter) at 48 h (p = 0.4). No significant changes in the concentration of thrombin-antithrombin III complexes were found between the two groups. Conclusions. Fixed dose intravenous heparin attenuates increases in fibrinopeptide A early after streptokinase. Subsequent fixed dose intravenous and subcutaneous heparin have similar effects but are relatively ineffective in suppressing thrombin activity, suggesting a role for more potent antithrombin agents during coronary thrombolysis with streptokinase.

SummaryIncreases in thrombin activity occur in patients treated with streptokinase, but conjunctive therapy with intravenous heparin does not appear to improve either the rate of early infarct artery patency or survival in patients with acute myocardial infarction. In a recent study we found that concentrations of fibrinopeptide A, a marker of thrombin-mediated fibrin formation, were lower in the first 3 h in patients treated with intravenous heparin (5000 U bolus followed by a fixed-dose 1000 U/h infusion, n = 14) compared with subcutaneous (12,500 U every 12 h, started 4 h after streptokinase, n = 14) administration, but were increased in both groups of patients, consistent with persistent thrombin activity. To determine whether the differential effects of the intensity of heparinization on thrombin formation were reflected in differences in fibrin degradation, we measured cross-linked fibrin degradation products (XL-FDP) before and 1,2,3,8,12, and 24 h after streptokinase in the same cohort of patients, with a new ELISA with a D-dimer-specific capture antibody (MAb 3B6) and a fibrin-specific tag antibody (MAb 1D2, Agen, Brisbane, Australia). The incidence of early coronary recanalization assessed by creatine-kinase MM isoforms (increase in activity ≥0.18%/min), was similar in both groups (79 vs 86%). Concentrations of XL-FDP were similar in patients with and without recanalization, but were lower in patients treated with intravenous compared with subcutaneous heparin at 8 h, but the results did not reach statistical significance (627 ±151 ng/ml versus 1007 ± 157 ng/ ml, p = 0.06), and were significantly lower at 12 h (327 ± 72 versus 781 ± 162 ng/ml, p = 0.03 at 12 h) (mean ± SEM). Concentrations of cross-linked fibrin degradation products were also lower in patients in whom the activated partial thromboplastin time was greater than two times the control, compared with those with inadequate anticoagulation (498 ± 105 versus 1084 ± 179 ng/ml; p = 0.02) (mean ± SEM). Thus, more effective inhibition of thrombin with conjunctive intravenous heparin therapy results in less cross-linked fibrin turnover in the first 12 h after thrombolysis with streptokinase. This probably reflects decreased fibrin formation with therapeutic anticoagulation.