C Layton

Randomised placebo controlled trial of aspirin and dipyridamole in the prevention of coronary vein graft occlusion.

Treatment with the combination of aspirin and dipyridamole is believed to reduce the incidence of coronary vein graft occlusion. A double blind randomised controlled trial was carried out in which aspirin 990 mg and dipyridamole 225 mg daily or placebo were added to the routine postoperative management (warfarin for three months) of 320 patients undergoing coronary bypass grafting. The trial treatment was given for 12 months, after which the results were assessed by coronary and graft angiography. The two randomised groups, each of 160 patients, were comparable in age, sex, symptomatic state, angiographic findings, and operative procedure. Repeat coronary arteriography was carried out on 266 patients, 133 in each group. All grafts and distal anastomoses were patent in 68% (91/133) of the placebo patients and in 75% (100/133) of those receiving active treatment. Overall graft patency was 87% (306/352) and 89% (342/385) respectively. Retrospective subgroup analysis showed patency rates of 72% (26/36) and 78% (39/50) of grafts to vessels requiring preliminary endarterectomy, and 80% (36/45) and 91% (40/44) of distal anastomoses to vessels measured at operation to have a diameter of less than or equal to 1 mm. None of these differences was significant at the 5% level. Thus in this group of patients with high graft patency rates, treatment with aspirin and dipyridamole conferred no appreciable advantage.

Irregular coronary lesion morphology after thrombolysis predicts early clinical instability

After successful thrombolytic treatment for acute myocardial infarction, recurrent ischemia and infarction may occur with little warning. Coronary lesion morphology was analyzed from angiograms performed in 72 consecutive patients at 1 to 8 days after streptokinase treatment for acute myocardial infarction and the data were evaluated in relation to the subsequent clinical course. All patients were clinically stable at the time of angiography and continued to receive heparin infusion for greater than or equal to 4 days after thrombolysis. The infarct-related artery was patent in 55 patients (76%). In the 10 days after angiography, 15 patients developed prolonged episodes of angina at rest; the condition of 4 stabilized with medical treatment, but 11 required urgent medical intervention (coronary angioplasty in 8 and bypass surgery in 3). There were no differences in age, gender, left ventricular function or extent of coronary artery disease between those patients who developed unstable angina and those who had a stable in-hospital course. However, the median plaque ulceration index of the infarct-related lesion was 6.7 (95% confidence limits 6.3, 10) in the 15 patients with an unstable course versus 3.3 (2, 4.4) in those with a stable course (p less than 0.001). There were no differences between the two patient groups in the severity of stenosis, length of diseased segment, symmetry/eccentricity, presence of a shoulder, location at branch point or bend, presence of globular or linear filling defects, contrast staining or collateral supply. These data show that after thrombolysis, the degree of irregularity of the infarct-related artery is a critical determinant of early clinical instability.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary lesion morphology in acute myocardial infarction: Demonstration of early remodeling after streptokinase treatment

Coronary lesion morphology was analyzed in 72 patients 1 to 8 days after streptokinase treatment for acute myocardial infarction and compared with lesion morphology in a control group of 24 patients with stable angina. In the streptokinase group the infarct-related artery was patent in 55 patients (76%). Compared with stenoses in the stable angina group, there were no differences in the stenosis length, severity, calcification or in the proportion located at an acute bend or at a branch point. However, lesions in the streptokinase group were more often irregular (p less than 0.005) and eccentric (p less than 0.01), had a shoulder (p less than 0.0001), globular filling defects (p less than 0.01), linear filling defects (p less than 0.00005) and contrast staining (p less than 0.05). Plaque ulceration index was higher in the streptokinase than in the stable angina group (6.2 +/- 7.9 versus 3.5 +/- 3.4, p less than 0.001). Of the 72 streptokinase-treated patients, 35 were maintained on heparin infusion until angioplasty 2 to 10 days later. At repeat angiography before angioplasty, globular lesion filling defects seen in eight patients had disappeared, whereas linear filling defects persisted in 7 of 14 cases. Fewer lesions were irregular (p less than 0.0001) and the ulceration index decreased from 7.4 +/- 10.4 to 3.0 +/- 1.6 (p less than 0.001). These data show that the lesion in the infarct-related artery after streptokinase treatment is irregular and often associated with filling defects, perhaps corresponding to plaque fissuring and intraluminal thrombosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Correlation of heart rate/ST slope and coronary angiographic findings.

The heart rate/ST slope was evaluated in 49 patients undergoing routine investigation for possible coronary artery disease. The slope correctly predicted the absence of any 75% stenoses in the seven patients to whom this applied; it was, however, correct for only four of 30 with one stenosis, one of 10 with two, and neither of the patients with three. Distinct slope ranges were not found, and the previously published ranges said to be specific for no significant stenosis and one, two, and three vessel disease were not.

What proportion of patients with myocardial infarction are suitable for thrombolysis

Four hundred and three patients were considered for entry into a trial of intravenous streptokinase in suspected myocardial infarction. Three hundred and sixty seven (91%) were excluded. Two hundred and sixty (65%) did not meet the inclusion criteria and 45 of the remaining 143 (35%) patients had contraindications to thrombolysis. This left 98 (24%) patients who were suitable for thrombolysis and 42 of them were over 70 years, the upper age limit. Thus according to this trial protocol 56 (14%) patients were eligible for recruitment; 36 (9%) patients were finally randomised. These data suggest that treatment with intravenous streptokinase may be applicable to only a small proportion of patients with myocardial infarction.

Long term clinical outcome of coronary surgery and assessment of the benefit obtained with postoperative aspirin and dipyridamole.

Three hundred and twenty patients originally entered into a randomised study to assess the effect of aspirin and dipyridamole on the patency of coronary bypass grafts one year after operation were clinically reassessed a mean of 6.6 years (range 4.3-8.6) after operation. Patients were recruited between 1978 and 1982 after the present policy of total revascularisation had been adopted. During the follow up period there were 25 deaths of which 17 were due to cardiac causes (average annual cardiac mortality 0.8%). Of 280 patients available for contact, 250 (89.3%) attended an outpatient interview. Ninety four (37.6%) patients complained of recurrent angina but in only 23 (9.2%) was this severe. Two hundred and eleven (84.4%) of the 250 patients underwent exercise stress testing. There were 73 (34.6%) abnormal tests of which 52 were in the group of 94 patients with recurrent angina. Myocardial infarction occurred in nine of the 250 patients during the follow up period. Twenty six patients (10.4%) had reinvestigation for symptoms. This group had a graft occlusion rate of 52%. Half these patients have required reoperation and 20 of 22 occluded or severely stenosed grafts were replaced. In only two instances were vein grafts inserted into vessels with new disease. Half of the original group were given aspirin (330 mg three times a day) plus dipyridamole (75 mg three times a day). Of the 250 patients interviewed, 122 took aspirin and dipyridamole from the second postoperative day for a mean of 25 months, with warfarin for three months. The other 128 patients took placebo for a mean of 23 months together with warfarin for three months. This long term treatment with aspirin plus dipyridamole conferred no significant benefit for all clinical outcomes measured at a mean of 6.6 years.

Reoperation for recurrent angina.

Forty patients with persistent or recurrent angina after an aortocoronary bypass procedure underwent a second operation. The cause of recurrent angina, defined by angiography, was thought to be isolated graft failure in 13 patients, progression of disease in ungrafted vessels in 4, incomplete revascularisation in 2, and stenoses distal to patent grafts in 1. More than one factor was responsible in 20 patients. There was 1 early postoperative death and 3 perioperative myocardial infarctions. Thirty-four patients have been followed for more than 3 months (4 to 63 months). Of these, 17 had previously bypassed vessels regrafted and 5 are sympton free, 4 have mild angina, and 8 have severe angina. Ten patients had previously ungrafted vessels grafted and 4 are sympton free, 3 have mild angina, 2 have severe angina, and 1 is limited by breathlessness. Seven patients had a combined procedure and 4 are sympton free, 1 has mild angina, and 2 have severe angina. Reoperation can be carried out safely but the results are less satisfactory than for a primary procedure.

Assessment of left ventricular performance during percutaneous transluminal coronary angioplasty: a study by intravenous digital subtraction ventriculography.

Left ventricular performance during percutaneous transluminal coronary angioplasty was assessed in 52 patients by intravenous digital subtraction ventriculography. After injection of contrast into the right atrium ventriculograms were obtained before and during balloon inflation. In 37 patients they were also obtained after the procedure. A 12 lead electrocardiogram was monitored throughout. During balloon inflation the left ventricular ejection fraction fell (from 73% to 57%) in all but one patient; the decreases in patients with single vessel or multivessel disease were similar. The fall in left ventricular ejection fraction during percutaneous transluminal coronary angioplasty of the left anterior descending artery (19%) was significantly greater than that during balloon inflation in the right coronary (10%) or circumflex (8%) coronary arteries. It also reduced anterobasal, anterior, and apical segmental shortening while right coronary percutaneous transluminal coronary angioplasty affected inferior and apical segments. In 33 (63%) patients the ST segment was altered during balloon inflation. The fall in left ventricular ejection fraction correlated significantly with the magnitude of both ST segment elevation (r = 0.637) and ST depression (r = 0.396). Left ventricular ejection fraction and regional wall motion returned to baseline values after the procedure. Balloon inflation during percutaneous transluminal coronary angioplasty produces considerable abnormalities of global and regional left ventricular performance and this indicates the presence of myocardial ischaemia, which may not be apparent on electrocardiographic monitoring. Intravenous digital subtraction ventriculography is useful for monitoring left ventricular performance during controlled episodes of coronary occlusion produced by balloon inflation.

Outcome of early surgery after coronary angioplasty.

Nineteen of 69 patients undergoing coronary angioplasty required immediate coronary surgery after the procedure. Six of these operations were planned as a result of angioplasty that failed without producing any complication. The remaining 13 cases were operated upon because complications occurred during angioplasty. These were coronary artery dissection in four, occlusion in five, continuing severe spasm in two, tamponade in one, and in one other detachment of a guidewire tip. In these 13 cases the vessel in which angioplasty had been attempted was the left anterior descending coronary artery in eight, the right in four, and the circumflex artery in one. This distribution was no different from that in the 56 patients without complications. There was one early postoperative death due to extensive anterior myocardial infarction, and there was electrocardiographic evidence of new infarction in three other patients. A mean of 16 months postoperatively, 16 of the 18 surviving patients had no cardiac symptoms, while angina had improved in the remaining two. Sixteen of the 18 patients had nuclear left ventricular angiography after a mean of 27 months. When the results of this investigation were compared with the left ventricular cineangiograms performed before angioplasty was attempted only two patients showed evidence of a new left ventricular wall motion abnormality. Prompt operation after complications of angioplasty is usually successful with good symptomatic relief and without left ventricular damage. The incidence of complications requiring operation, however, was high in this group of patients, most of whom had single vessel coronary artery disease.

Protective effect of collateral vessels during coronary angioplasty.

To assess the potential protective role of collateral vessels 27 patients undergoing angioplasty of the left anterior descending coronary artery were studied by intravenous digital subtraction left ventriculography. Fifteen patients had no collateral vessels (group 1) and 12 had some degree of collateral supply (group 2). During balloon inflation ST segment elevation in group 1 (4.9 mm) was significantly greater than that in group 2 (0.9 mm). Similarly the reduction in left ventricular ejection fraction was significantly greater in group 1 (24%) than in group 2 (12%). Both the size of ST segment elevation and the fall in ejection fraction correlated inversely with the extent of the collateral supply (r = -0.680 and r = -0.446 respectively). During balloon occlusion of the anterior descending coronary artery the percentage shortening of the anterior and apical segments fell in both groups but apical shortening fell to a lesser extent in group 2. An additional reduction in anterobasal contraction was confined to group 1. Electrocardiographic and ventriculographic manifestations of ischaemia produced by balloon inflation during angioplasty are less pronounced when collateral vessels are present. This suggests that the collateral circulation can protect myocardium at risk of ischaemia after coronary occlusion.