R. Uebis

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.

RANDOMISED TRIAL OF INTRAVENOUS RECOMBINANT TISSUE-TYPE PLASMINOGEN ACTIVATOR VERSUS INTRAVENOUS STREPTOKINASE IN ACUTE MYOCARDIAL INFARCTION: Report from the European Cooperative Study Group for Recombinant Tissue-type Plasminogen Activator

In a single-blind randomised trial in patients with acute myocardial infarction of less than 6 h duration, the frequency of coronary patency was found to be higher after intravenous administration of recombinant human tissue-type plasminogen activator (rt-PA) than after intravenous streptokinase. 64 patients were allocated to 0.75 mg rt-PA/kg over 90 min, and the infarct-related coronary artery was patent in 70% of 61 assessable coronary angiograms taken 75-90 min after the start of infusion; 65 patients were allocated to 1 500 000 IU streptokinase over 60 min, and the infarct-related vessel was patent in 55% of 62 assessable angiograms. The 95% confidence interval of the differences ranges from +/- 30 to -2% (p = 0.054). Bleeding episodes and other complications were less common in the rt-PA patients than in the streptokinase group. Hospital mortality was identical in the 2 treatment groups. At the end of the rt-PA infusion the circulating fibrinogen level was 61 +/- 35% of the starting value, as measured by a coagulation-rate assay, and 69 +/- 25% as measured by sodium sulphite precipitation. After streptokinase infusion, corresponding fibrinogen levels were 12 +/- 18% and 20 +/- 11%. In the rt-PA group only 4.5% of the fibrinogen was measured as incoagulable fibrinogen degradation products, compared with 30% in the streptokinase group. Activation of the systemic fibrinolytic system was far less pronounced with rt-PA than with streptokinase.

Early recovery of left ventricular function after thrombolytic therapy for acute myocardial infarction: an important determinant of survival

Thrombolytic therapy for acute myocardial infarction reduces early mortality, but full recovery of left ventricular function after reperfusion is delayed. Therefore, the relations among reperfusion, survival and the time course of left ventricular functional recovery were examined in 226 patients treated with intracoronary streptokinase; 77% (134 patients) had sustained reperfusion and 31 patients had no reperfusion or had reocclusion by day 3. Wall motion was measured from contrast ventriculograms performed in the acute period and 3 days later in the central and peripheral infarct regions and the noninfarct region by the centerline method in 165 patients. Patients with reperfusion had better survival (p less than 0.05, mean follow-up 4.5 years) and a higher ejection fraction at 3 days (52 +/- 12 versus 46 +/- 10%, p less than 0.02) attributable to a significantly different change in peripheral infarct region function between the acute and 3 day studies (0.1 +/- 1.0 versus -0.3 +/- 0.9 SD, p less than 0.05). These early functional changes were significant in patients with anterior myocardial infarction and showed similar trends in those with inferior myocardial infarction. On Cox regression analysis, function measured at 3 days was more predictive of survival than was function measured acutely (chi square for acute ejection fraction = 11.48 versus 24.59 at 3 days). Although, as previously reported, greater than 45% of total recovery of left ventricular function occurs later, the ejection fraction achieved by day 3 is already predictive of survival. Thus, the mechanism by which successful thrombolytic therapy enhances survival is improvement of regional and global left ventricular function early after acute myocardial infarction.

Myocyte degeneration and cell death in hibernating human myocardium

OBJECTIVES The aim of this study was to analyze the morphologic characteristics of myocyte degeneration leading to replacement fibrosis in hibernating myocardium by use of electron microscopy and immunohistochemical techniques. BACKGROUND Data on the ultrastructure and the cytoskeleton of cardiomyocytes in myocardial hibernation are scarce. Incomplete or delayed functional recovery might be due to variable degree of cardiomyocyte degeneration in hibernating myocardium. METHODS In 24 patients, regional wall motion abnormalities were analyzed by use of the centerline method before and 6 +/- 1 months after coronary artery bypass surgery. Preoperative technetium-99m sestamibi uptake was measured by single-photon emission computed tomography for assessing regional perfusion. Fluorine-18 fluorodeoxyglucose uptake was measured by positron emission tomography to assess glucose metabolism. Transmural biopsy specimens were taken during coronary artery bypass surgery from the center of the hypocontractile area of the anterior wall. RESULTS The myocytes showed varying signs of mild-to-severe degenerative changes and an increased degree of fibrosis. Immunohistochemical analysis demonstrated disruption of the cytoskeletal proteins titin and alpha-actinin. Electron microscopy of the cell organelles and immunohistochemical analysis of the cytoskeleton showed a similarity in the degree of degenerative alterations. Group 1 (n = 11) represented patients with only minor structural alterations, whereas group 2 (n = 13) showed severe morphologic degenerative changes. Wall motion abnormalities showed postoperative improvements, and nuclear imaging revealed a perfusion-metabolism mismatch without significant differences between the groups. CONCLUSIONS Long-term hypoperfusion causes different degrees of morphologic alterations leading to degeneration. Preoperative analysis of regional contractility and perfusion-metabolism imaging does not distinguish the severity of morphologic alterations nor the functional outcome after revascularization. The insufficient act of self-preservation in hibernating myocardium may lead to a progressive structural degeneration with an incomplete and delayed recovery of function after restoration of blood flow.

Recovery of regional left ventricular dysfunction after coronary revascularization. Impact of myocardial viability assessed by nuclear imaging and vessel patency at follow-up angiography

OBJECTIVES This study sought to evaluate an imaging approach using technetium-99m sestamibi scintigraphy and positron emission tomography with fluorine-18 fluorodeoxyglucose for assessment of myocardial viability proved by serial quantitative left ventricular angiography. Furthermore, the influence of successful long-term revascularization on functional recovery was studied. BACKGROUND Previous studies using positron emission tomography of myocardial perfusion and metabolism have demonstrated accurate identification of myocardial viability. However, most of these studies used a qualitative or semiquantitative wall motion analysis approach. METHODS Nuclear imaging with semiquantitative analysis of tracer uptake was performed in 193 patients with regional wall motion abnormalities. Regions were categorized as normal, viable with perfusion/metabolism mismatch, viable without mismatch (intermediate) and scar. Seventy-two of 103 patients with subsequent revascularization underwent follow-up angiography. In 52 of 72 patients, changes in regional wall motion were measured by the centerline method from serial angiography. RESULTS Wall motion improved in mismatch regions from -2.2 +/- 1.0 to -1.1 +/- 1.4 SD (p < 0.001). In contrast, regions with an intermediate pattern and those with scar did not improve. Restenosis or graft occlusion influenced functional outcome because regions with preoperative mismatch and successful long-term revascularization improved at follow-up (from -2.3 +/- 1.0 to -0.8 +/- 1.4 SD, p < 0.001), whereas wall motion did not change with recurrent hypoperfusion. Metabolic imaging added diagnostic information, particularly in regions with mild and moderate perfusion defects. CONCLUSIONS This imaging approach allows detection of viability in regions with myocardial dysfunction. Wall motion benefits most in myocardium with perfusion/metabolism mismatch and successful long-term revascularization.

Myocardial infarction and thrombolysis. Electrocardiographic short term and long term results using precordial mapping.

In a consecutive series of 56 patients with acute myocardial infarction, ST segment depression and elevation in the electrocardiographic limb leads I, II, and III were summated for each patient before and immediately after intracoronary streptokinase infusion and the results compared with the angiographic findings. Forty three patients had angiographically confirmed reperfusion of an initially occluded vessel and showed a significant decrease in summated ST shift. The ST segment changes in the limb leads virtually returned to normal in all 43 patients, and in most, inverted T waves developed. Thrombolysis was unsuccessful in 10 patients, and the infarct related coronary artery was already patent in three. When these two groups are combined, all 13 patients without reperfusion showed no significant change in summated ST segment shift. During percutaneous transluminal angioplasty inflation of the balloon in the vessel that was previously occluded simulated reocclusion and was followed by new ST elevation if the artery supplied viable myocardium. In a further consecutive study of 54 patients with anterior myocardial infarction, the precordial R waves and Q waves were studied over the four to six months following infarction using a standardised 48 electrode mapping system. All patients underwent a repeat angiogram after four to six months. In 36 patients the infarct related vessel was patent. They showed a significant mean increase in summated precordial R wave amplitude and a reduction in the mean number of precordial leads without R waves. In 18 patients with unsuccessful thrombolysis or reocclusion there was a further reduction in mean summated R wave amplitude and an increased number of precordial leads not showing R waves. Precordial R wave mapping seems to be a valuable non-invasive method of assessing the salvage of myocardium after reperfusion and the damage caused by reocclusion. Loss of R waves in the acute phase of myocardial infarction does not necessarily mean an irreversibly damaged myocardium.

99Tcm-methoxyisobutylisonitrile stress/rest SPECT in patients with constant complete left bundle branch block.

Numerous studies have revealed frequent false positive septal findings of 201Tl stress imaging in patients with left bundle branch block (LBBB) even with angiographically excluded significant coronary artery disease (CAD). To scrutinize this phenomenon for stress/rest 99Tcm-methoxyisobutylisonitrile (MIBI) single photon emission computed tomography (SPECT) was used to review 22 patients with constant LBBB. The findings were reversible septal defect in one patient, partially reversible septal defect in one patient and irreversible septal defects in eight patients. In four patients 99Tcm-MIBI scans were entirely normal. Thus, 12/22 (55%) patients revealed normal septal 99Tcm-MIBI uptake. Both patients with a stress-induced septal defect revealed a significant left anterior descending artery stenosis on coronary angiography. These preliminary results suggest, that 99Tcm-MIBI might be more specific and accurate than 201Tl in the evaluation of CAD in patients with LBBB because of apparently rare or absent false positive septal findings.

Myocardial ischaemia in a case of a solitary coronary ostium in the right aortic sinus with retroaortic course of the left coronary artery: documentation of the underlying pathophysiological mechanisms of ischaemia by intracoronary Doppler and pressure measurements

Only a few cases of a single coronary ostium and retroaortic course of the coronary artery have been described. Almost all cases reported so far had additional coronary artery or valvar disease. However, myocardial ischaemia may be caused by the coronary malformation alone. A 40 year old woman with severe myocardial ischaemia in the absence of clinically relevant coronary atherosclerosis is described. To clarify the origin and mechanisms of ischaemia, intracoronary Doppler, pressure and ultrasound studies were performed using microtransducers. In its outer portion along the course behind the ascending aorta, coronary blood flow velocities were increased, there was an external elliptical compression, and distal coronary flow reserve was reduced. Furthermore, an overshoot in diastolic pressure above aortic pressure was detectable within this portion. Dobutamine stimulation exaggerated the observed intracoronary haemodynamics and induced myocardial ischaemia. The intracoronary diagnostic procedures performed were helpful in clarifying the pathophysiological mechanisms of functional coronary obstruction and ischaemia in this malformation. Bypass surgery was successfully performed with symptomatic improvement.

Influence of Balloon Size on Recurrence Rate of Coronary Artery Stenosis. Results of a Prospective Investigation

Restenosis of a successfully dilated coronary artery is one of the problems of coronary angioplasty. There are three definitions of restenosis: (a) loss of initial gain of the diameter of more than 20%, (b) loss of more than 50% of initial gain, and (c) restenosis of more than 30% of initial gain. As the definition for a successful angioplasty is an increase of the diameter of the dilated vessel of more than 20%, the first defintion of a restenosis seems to be the most reasonable one. However, different groups use different definitions when reporting restenosis rates. Therefore, it is difficult to compare long-term results with regard to the recurrence rates of different centers; they range from 12% to 36% [1–5, 11]. Restenosis may be influenced by selection of patients, technique used for dilatation, medical treatment before, during, and after PTCA, and treatment and elimination of risk factors (see Table 1).

MRI Measurements of Left Ventricular Systolic Wall Thickening Compared to Regional Myocardial Perfusion as Determined by 201Tl SPECT in Patients with Coronary Artery Disease

Magnetic resonance imaging (MRI) of the left ventricle (LV) is an excellent method of measuring systolic wall thickening (SWT). The aim of the present study was (a) to describe a new approach for measurement of SWT and (b) to define the relationship between SWT and regional myocardial perfusion as determined by 201Tl SPECT. 79 patients -51 with and 28 without history of earlier myocardial infarction - underwent SPECT and, within the next two weeks. MRI. End-diastolic and end-systolic spin echo images were obtained by a reduced permutation technique. For MRI measurements, only long-axis sections through the LV in the equatorial plane were used. Slice orientation was selected according to the findings of SPECT, imaging the infarcted wall segment by single or double angulation. At 7 equidistant points around the LV wall SWT was measured and compared with the corresponding regional myocardial uptake values from SPECT in percent of maximal perfusion. Wall thickness of the anterior wall was normal. Because the majority of myocardial infarctions were posterior-inferior (55%), thickness of the posterior wall was markedly decreased. A close relationship of perfusion to SWT was found. Higher perfusion areas (greater than 50% of maximal TI uptake) corresponded with normal SWT (greater than 3.0 mm), a marked decrease of SWT (less than 1 mm) was found in areas with perfusion deficits (less than 40%). Thus, a 201TI uptake value at rest of 41-50% of the respective myocardial maximum acts as a threshold by discriminating normal from severely reduced SWT.