The impact of fibrinolytic therapy for ST-segment-elevation acute myocardial infarction.

As privileged witnesses of the initiation and widespread use of reperfusion therapy the authors review the history of fibrinolytic therapy and of tissue-plasminogen activator (t-PA) more particularly and the current indications for its use in the era of mechanical reperfusion.

Variations in the use of emergency PCI for the treatment of re-infarction following intravenous fibrinolytic therapy: impact on outcomes in HERO-2.

BACKGROUND: Patients who suffer re-infarction during initial hospitalization for ST-elevation myocardial infarction (STEMI) have decreased survival compared to patients without re-infarction, so treatment of re-infarction may influence survival. METHODS AND RESULTS: To determine whether the utilization of reperfusion therapies varied within 12 h of re-infarction and was associated with 30-day mortality, we studied 552 patients with re-infarction of 17,073 patients with STEMI enrolled in HERO-2 in five regions (Russia, Eastern Europe, Western Countries, Asia, and Latin America). Patients presenting within 6 h of symptom-onset were randomized to receive either bivalirudin or unfractionated heparin intravenously just prior to streptokinase. Re-infarction occurred in 2.8 and 3.6% of bivalirudin and heparin treated patients, respectively (P = 0.004), but treatment assignment did not influence mortality after re-infarction. Patients with re-infarction had a higher 30-day mortality than those without re-infarction (24 vs. 10%; P < 0.001 by Cox model). Within 12 h of re-infarction, fibrinolytic therapy was administered to 12.0 and 8.2% underwent percutaneous coronary intervention (PCI); these two treatments were more frequently utilized in patients from Western countries (n = 112), compared to patients from other countries (n = 440) (34.8 and 16.1% compared to 6.1 and 6.1%, respectively, P < 0.001). Mortality was 15% in patients receiving reperfusion therapy for re-infarction and 27% for those with conservative management, hazard ratio (HR) 0.53 (95% CI 0.32-0.88), P = 0.01. In multiple Cox regression analysis which included adjustment for clinical variables and randomized treatment assignment, 30-day mortality after re-infarction varied by region (highest Latin America 29%, lowest Western countries 15%; P = 0.01). Other independent prognostic factors included age, time from randomization to re-infarction, and Killip class at randomization. The HR for PCI treatment of re-infarction was 0.18 [(95% CI 0.04-0.76), P = 0.02] in analyses which excluded deaths within 12 h. CONCLUSION: Treatment of re-infarction with reperfusion therapies was markedly under-utilized, especially in non-western countries. PCI for re-infarction, in particular, was associated with a lower 30-day mortality, which may reflect both patient selection and effects of treatment.

Will oral antithrombin agents replace warfarin?

The new oral direct thrombin inhibitor ximelagatran is at least equivalent to warfarin for stroke prevention in patients with non-valvar atrial fibrillation, and seems to be a promising adjunct to aspirin after acute coronary syndrome

Relation between different methods for analysing ST segment deviation and infarct size as assessed by positron emission tomography.

OBJECTIVE: To study the relation between resolution of ST segment deviation and infarct size using positron emission tomography. METHODS: 45 patients with ST segment elevation acute myocardial infarction treated with thrombolysis or percutaneous coronary intervention were studied prospectively. An ECG was taken before and at (mean (SD)) 100 (45) min after reperfusion therapy. ECGs were analysed by three methods. Residual ST segment deviation, obtained from the ECG immediately after completion of reperfusion therapy, was defined by summation for each of the three methods. Relative resolution of ST segment deviation was defined as the absolute resolution divided by the ST segment deviation score at baseline x 100 (%). After 29 (14) hours, myocardial blood flow was measured with 13NH3. For each patient, the regions with a myocardial blood flow < 80% of normally perfused myocardium ( = hypoperfusion) and < 50% ( = no reflow) were automatically delineated. RESULTS: Substantial differences were found between different ECG analysis methods. There were moderate correlations between the area with myocardial hypoperfusion and ST segment deviation scores at baseline and after reperfusion therapy. After reperfusion therapy, residual ST segment deviation in the single lead with maximum ST segment deviation was as good at discriminating between tertiles of myocardial damage as summed ST segment elevation. Relative ST segment resolution did not discriminate between different degrees of myocardial damage. CONCLUSIONS: In the individual patient, residual ST segment deviation after reperfusion in the single lead with maximum ST segment deviation is at least as good as summed ST elevation in predicting final myocardial damage.

Is there a change in myocardial nonlinearity during the cardiac cycle?

The distortion of a sound wave during propagation results in progressive transfer of the energy from fundamental to higher harmonics, and is dependent on the nonlinearity of the medium. We studied if relative changes in acoustical nonlinearity occur in healthy myocardium during the cardiac cycle. Radiofrequency data were acquired from transthoracic echocardiography (2.5 and 3.5 MHz), parasternal long axis view, from five dogs and nine healthy volunteers. Integrated backscatter was calculated after filtering for fundamental (FIB) and second harmonic frequencies (SHIB), from a region in the posterior myocardial wall. The results suggest that there is little difference between the SHIB and FIB, although there were large variations between individuals. The maximal changes in nonlinearity, as estimated by SHIB/FIB ratio, mostly occurred during systole. SHIB presented similar cyclic variation with FIB (p = NS). Further studies are necessary to separate the role of myocardial nonlinearity, attenuation, propagating distance, or acoustical properties of the blood. The results are important in further tissue characterization studies employing second harmonic data.

Noninvasive measurements of infarct size after thrombolysis with a necrosis-avid MRI contrast agent.

BACKGROUND: Gadophrin-2 is a new MRI contrast agent with high affinity for necrotic myocardium. The aim of the study was to evaluate whether noninvasive measurements of infarct size after thrombolysis are possible with gadophrin-2-enhanced MRI. METHODS AND RESULTS: Coronary artery thrombosis was induced in 3 groups of dogs by the copper-coil technique. Thrombolytic therapy together with aspirin and heparin was initiated after 90 minutes of occlusion. One day (group A), 2 days (group B), or 6 days (group C) after infarction, gadophrin-2 was injected intravenously (50 micromol. kg-1). In vivo T1-weighted segmented turbo-FLASH, in vivo T2-weighted segmented half-Fourier turbo spin echo (HASTE), and T1- and T2-weighted spin-echo MRI of the excised heart were performed 24 hours after gadophrin-2 injection. Regions of strong enhancement were observed on T1-weighted images. Planimetry of short-axis MR images and of corresponding triphenyltetrazolium chloride (TTC)-stained left ventricular (LV) slices showed a close correlation between the enhanced areas and TTC-negative areas for both in vivo (r2=0.98, P<0.0001; mean difference, 0.9+/-2.0% [SD] of the LV volume [LVV]) and postmortem (r2=0.99, P<0.0001; mean difference, 0.9+/-1.4% of LVV) measurements. T2-weighted images overestimated the infarct size by 8.1+/-5.4% of LVV. The mean infarct size was 10.8+/-11.6% of LVV (group A), 22.4+/-11.7% (group B), and 5.1+/-9.3% (group C). CONCLUSIONS: In this animal model, in vivo gadophrin-2-enhanced MRI could precisely determine infarct size after thrombolytic therapy. This technique may be very useful for the noninvasive evaluation of infarct size after reperfusion for AMI.

Thrombolysis for acute myocardial infarction.

Thrombolytic therapy has been a major advance in the management of acute myocardial infarction. Unfortunately, it continues to be underused or is administered later than is optimal. Thrombolytic therapy works by lysing infarct artery thrombi and achieving reperfusion, thereby reducing infarct size, preserving left ventricular function, and improving survival. The most effective thrombolytic regimens achieve angiographic epicardial infarct-artery patency in only approximately 50% of patients within 90 minutes. Bleeding requiring transfusion occurs in approximately 5% of patients and stroke in approximately 1.8% with these regimens, which include adjunctive aspirin and intravenous heparin. There are several ways in which reperfusion rates and thus patient outcomes might be improved, such as different dosing regimens of established agents; combinations of different agents; improved adjunctive therapy such as direct antithrombin agents, low-molecular-weight heparin, or glycoprotein IIb/IIIa receptor antagonists; or the development of novel thrombolytic agents with enhanced fibrin specificity, resistance to native inhibitors, or prolonged half-lives allowing bolus administration. All of these strategies are being tested in clinical trials. The best approach currently is to administer thrombolytic therapy as soon as possible to all patients without contraindications who present within 12 hours of symptom onset and have ST-segment elevation on the ECG or new-onset left bundle-branch block, unless an alternative reperfusion strategy is planned.

Tomographic and planar quantitation of perfusion defects on technetium 99m-labeled sestamibi scans: evaluation in patients treated with thrombolytic therapy for acute myocardial infarction.

BACKGROUND: Our segmentation algorithm for single-photon emission computed tomographic perfusion studies was tested in 244 patients treated by thrombolysis within 5 hours after onset of symptoms. This algorithm uses radial slices to approximate true three-dimensional gradients, determines the apex and basal plane, and creates a perfusion and volume polar map. METHODS AND RESULTS: Perfusion defect size was compared with enzymatic infarct size and global and regional function. All patients underwent rest planar and tomographic 99mTc-labeled sestamibi scanning, contrast coronary angiography, and ventriculography 10 to 14 days after the start of treatment. Manual correction had to be performed in only 10% of the cases and presented no problems. The correlation coefficients (r) between planar and relative tomographic perfusion defects versus enzymatic infarct size were 0.71 and 0.73. A negative correlation was found with left ventricular ejection fraction: r = -0.65 and r = -0.60. A comparable correlation was also found between regional wall motion and perfusion defect size. Most correlations were higher in the case of anterior infarction. An excellent correlation was found between planar and tomographic defect size (r = 0.83). CONCLUSIONS: In most cases, our segmentation algorithm delineates myocardial edges and basal plane automatically. A good correlation was found between perfusion defect size, enzymatic infarct size, and global and regional ventricular function.

Constrictive pericarditis due to ingestion of a toothpick.

A case of a 53-year-old man with constrictive pericarditis due to the ingestion of a toothpick is presented. Computed tomography was unable to show the toothpick, and the diagnosis was made during the operation. Ingested toothpicks have often been reported as a cause of gastrointestinal injuries but in this rare case a toothpick actually migrated into the pericardium.