M. van den Brand

Incidence of restenosis after successful coronary angioplasty: a time-related phenomenon. A quantitative angiographic study in 342 consecutive patients at 1, 2, 3, and 4 months.

Data from experimental, clinical, and pathologic studies have suggested that the process of restenosis begins very early after coronary angioplasty. The present study was performed to determine prospectively the incidence of restenosis with use of the four National Heart, Lung, and Blood Institute and the 50% or greater diameter stenosis criteria, as well as a criterion based on a decrease of 0.72 mm or more in minimal luminal diameter. Patients were recatheterized at 30, 60, 90, or 120 days after successful percutaneous transluminal coronary angioplasty (PTCA). After PTCA all patients received 10 mg nifedipine three to six times a day and aspirin once a day until repeat angiography. Of 400 consecutive patients in whom PTCA was successful (less than 50% diameter stenosis), 342 underwent quantitative angiographic follow-up (86%) by use of an automated edge-detection technique. A wide variation in the incidence of restenosis was found dependent on the criterion applied. The incidence of restenosis proved to be progressive to at least the third month for all except NHLBI criterion II. At 4 months a further increase in the incidence of restenosis was observed when defined as a decrease of 0.72 mm or more in minimal luminal diameter, whereas the criteria based on percentage diameter stenosis showed a variable response. The lack of overlap between the different restenosis criteria applied affirms the arbitrary nature of angiographic definitions currently in use. Restenosis should be assessed by repeat angiography, and preferably ascertained according to the change in absolute quantitative measurements of the luminal diameter.

Left ventricular performance, regional blood flow, wall motion, and lactate metabolism during transluminal angioplasty.

The response of left ventricular function, coronary blood flow, and myocardial lactate metabolism during percutaneous transluminal coronary angioplasty (PTCA) was studied in a series of patients undergoing the procedure. From four to six balloon inflation procedures per patient were performed with an average duration per occlusion of 51 +/- 12 sec (mean +/- SD) and a total occlusion time of 252 +/- 140 sec. Analysis of left ventricular hemodynamics in 19 patients showed that the relaxation parameters, peak negative rate of change in pressure, and early time constants of relaxation, responded earliest to short-term coronary occlusion (peak effect at 17 +/- 7 sec) while other parameters, such as peak pressure, left ventricular end-diastolic pressure, and peak positive rate of change in pressure, responded more gradually, suggesting a progressive depression of myocardial mechanics throughout the procedure. Left ventricular angiograms, available for 14 patients, indicated an early onset of asynchronous relaxation concurrent with the early response in peak negative dP/dt and the time constant of early relaxation. All hemodynamic functions fully recovered within minutes after the end of PTCA. Mean blood flow in the great cardiac vein and proximal coronary sinus and the hyperemic response were measured in 20 patients. Before PTCA mean flow in the great cardiac vein was 69 +/- 17 ml/min and in the coronary sinus it was 129 +/- 34 ml/min. Reactive hyperemia (great cardiac vein) was 55% after the first PTCA and 91% after the third. A more pronounced reaction was observed when the residual functional coronary stenosis was reduced in subsequent dilatations. Arteriovenous lactate difference appeared constant during the first two occlusions (control +0.11 mmol/liter, first PTCA -0.87 mmol/liter, and second PTCA -0.82 mmol/liter) and did not increase during subsequent occlusions. Within minutes after the procedure lactate balance was again positive, demonstrating the reversibility of the metabolic disturbances after repeated ischemia. The results of this study indicate that there is no permanent dysfunction of global or regional myocardial mechanics, myocardial blood flow, or lactate metabolism after PTCA with four to six coronary occlusions of 40 to 60 sec.

Transluminal coronary angioplasty and early restenosis. Fibrocellular occlusion after wall laceration.

Transluminal coronary angioplasty was performed in a 51 year old man with a localised narrowing of the proximal segment of the left anterior descending coronary artery. Initial inflations with a small size balloon catheter were unsuccessful. A second attempt, during the same procedure, using a larger calibre catheter relieved the obstruction but produced a dissection. Angina pectoris reappeared approximately three months later. Another attempt to relieve the obstruction by angioplasty, five months after the initial procedure, induced ST segment elevation before angioplasty, followed by ventricular fibrillation and death. The necropsy showed a split in the pre-existent sclerotic plaque and a dissecting aneurysm of the media. A proliferation of fibrocellular tissue filled the false channel and almost totally occluded the pre-existent arterial lumen. The observation suggests that wall laceration with exposure of smooth muscle cells to blood may have initiated the excessive fibrocellular tissue response. This event may be the underlying pathogenetic mechanism for the occurrence of early restenosis after transluminal coronary angioplasty.

Randomized trial of a GPIIb/IIIa platelet receptor blocker in refractory unstable angina. European Cooperative Study Group.

BackgroundPatients with unstable angina despite intensive medical therapy, ie, refractory angina, are at high risk for developing thrombotic complications: myocardial infarction or coronary occlusion during percutaneous transluminal coronary angioplasty (PTCA). Chimeric 7E3 (c7E3) Fab is an antibody fragment that blocks the platelet glycoprotein (GP) Ib/IIIa receptor and potently inhibits platelet aggregation. Methods and ResultsTo evaluate whether potent platelet inhibition could reduce these complications, 60 patients with dynamic ST-T changes and recurrent pain despite intensive medical therapy were randomized to c7E3 Fab or placebo. After initial angiography had demonstrated a culprit lesion suitable for PTCA, placebo or c7E3 Fab was administered as 0.25 mg/kg bolus injection followed by 10 μg/min for 18 to 24 hours until 1 hour after completion of second angiography and PTCA. During study drug infusion, ischemia occurred in 9 c7E3 Fab and 16 placebo patients (P = .06). During hospital stay, 12 major events occurred in 7 placebo patients (23%), including 1 death, 4 infarcts, and 7 urgent interventions. In the c7E3 Fab group, only 1 event (an infarct) occurred (3%, P = .03). Angiography showed improved TIMI flow in 4 placebo and 6 c7E3 Fab patients and worsening of flow in 3 placebo patients but in none of the c7E3 Fab patients. Quantitative analysis showed significant improvement of the lesion in the patients treated with c7E3 Fab, which was not observed in the placebo group, although the difference between the two treatment groups was not significant. Measurement of platelet function and bleeding time demonstrated >90% blockade of GPIIb/IIIa receptors, >90% reduction of ex vivo platelet aggregation to ADP, and a significantly prolonged bleeding time during c7E3 Fab infusion, without excess bleeding. ConclusionsCombined therapy with c7E3 Fab, heparin, and aspirin appears safe. These pilot study results support the concept that effective blockade of the platelet GPIIb/IIIa receptors can reduce myocardial infarction and facilitate PTCA in patients with refractory unstable angina.

Is transluminal coronary angioplasty mandatory after successful thrombolysis? Quantitative coronary angiographic study.

Percutaneous transluminal coronary angioplasty has been advocated as a mandatory procedure to prevent reocclusion after successful thrombolysis in acute myocardial infarction. This study describes our experience with both procedures over a 12 month period. Out of 105 patients catheterised in the acute phase of myocardial infarction, 64 were recanalised with 250 000 units of streptokinase, while in 25 patients recanalisation could not be achieved. In the remaining 16, the infarct related vessel was patent at the time of the procedure. Eighteen of the 78 patients who had a patent infarct related vessel at the end of the recanalisation procedure underwent transluminal angioplasty immediately afterwards. Post lysis angiograms were analysed quantitatively with a computerised measurement system. The contours of the relevant arterial segments were detected automatically. Reference diameter, minimal obstruction diameter, length of the lesions, and percentage diameter stenosis were averaged from multiple views. In 31% of our patients a diameter stenosis of less than 5O0/o was found whereas one of 70% or more was seen in only 19%. Eleven stenotic lesions, recanalised at the acute stage, reoccluded in the short term, and in the long term eight other patients sustained a reinfarction in the same myocardial territory. Seventeen of these 19 recanalised lesions had a diameter stenosis of 580/o or more. In view of these results, we felt justified in combining recanalisation and angioplasty in 18 patients selected from the most recent admissions. In these patients, the mean diameter stenosis decreased from 590/o to 30% and mean pressure gradient from 41 to 8 mmHg. Late follow up showed reocclusion in one

Coronary artery atherosclerosis: severity of the disease, severity of angina pectoris and compromised left ventricular function

To determine if the severity of angina pectoris and the degree of altered left ventricular function correlated with the severity and extent of the underlying coronary artery disease, a coronary scoring system was derived. The system was based on the severity of luminal diameter narrowing and weighted according to the usual flow to the left ventricle in each coronary vessel. Thus, the most weight was given to the left main coronary artery, followed by the left anterior descending, circumflex, and right coronary arteries. The resultant number was an indicator of the overall severity of the obstructive coronary artery disease. A coronary arterial system with no obstructive disease was scored as zero and the greater the degree of obstructive disease present, the higher the coronary score. From 202 subjects, four groups were evaluated: group 1—coronary score = 0.5–4.5 (n = 10); group 2—coronary score = 10.5–12.5 (n = 11); group 3—coronary score = 17.5–20.5 (n = 11); and group 4—coronary score = 25.0–36.0 (n = 11). All subjects had coronary artery bypass surgery and had preoperative and l-year postoperative cardiac catheterization, including atrial pacing to maximal heart rate. The groups could not be separated on the basis of angina frequency, resting heart rate, cardiac index, left ventricular end-diastolic pressure, peak paced left ventricular end-diastolic pressure, dP/dt, V max, left ventricular end-diastolic volume index, left ventricular end-systolic volume index, stroke volume index, ejection fraction or mean circumferential fiber shortening velocity. Thus, based on this study, the severity of coronary artery disease does not statistically correlate with the frequency of angina pectoris or produce a predictable degree of altered left ventricular function. The frequency of angina pectoris cannot be used to predict prognosis orthe adequacy of myocardial revascularization.

Limitation of infarct size and preservation of left ventricular function after primary coronary angioplasty compared with intravenous streptokinase in acute myocardial infarction.

BackgroundEarly and effective flow through the infarct-related vessel is probably of paramount importance for limitation of infarct size and preservation of left ventricular function in patients with acute myocardial infarction. Primary coronary angioplasty may offer advantages in these respects compared with thrombolytic therapy. The purpose of the present study was to assess the effects on estimated enzymatic infarct size and left ventricular function in patients with acute myocardial infarction randomly assigned to undergo primary angioplasty or to receive intravenous streptokinase. Methods and ResultsWe evaluated 301 patients with signs of acute myocardial infarction and without contraindications for thrombolysis who presented within 6 hours after onset of symptoms or between 6 and 24 hours if there was evidence of ongoing ischemia. One hundred fifty-two patients were randomly assigned to undergo primary angioplasty, and 149 patients were assigned to receive treatment with streptokinase (1.5 million U IV). Infarct size was estimated from enzyme release. Global left ventricular ejection fraction and regional wall motion, if possible in combination with exercise testing, were evaluated by radionuclide ventriculography before discharge. Thrombolysis in Myocardial Infarction (TIMI) flow grade 3 through the infarct-related vessel within 120 minutes after admission was achieved in 92% of all patients assigned to receive primary angioplasty therapy. Myocardial infarct size was 23% smaller in the angioplasty group compared with patients assigned to receive streptokinase (1003±784 versus 1310±1198 U/L, P=.012). Global left ventricular ejection fraction (50±9% versus 45±11%, P<.001) and regional wall motion in the infarct-related zones (42±14% versus 34±13%, P<.001) were better in the angioplasty group, which could mainly be contributed to myocardial salvage in the infarct-related areas. The observed differences were more pronounced in patients with an anterior wall myocardial infarction, although patients with a nonanterior infarct location also showed a beneficial effect of primary coronary angioplasty on left ventricular function compared with streptokinase therapy. Furthermore, the observed differences appeared to be more pronounced in patients presenting relatively early (within 2 hours) after onset of symptoms. ConclusionsIn patients with acute myocardial infarction, primary angioplasty results in a smaller infarct size and a better preserved myocardial function compared with patients randomized to receive treatment with intravenous streptoki-nase. This is probably due to early and optimal blood flow through the infarct-related vessel, as can be accomplished in a very high percentage of patients undergoing primary coronary angioplasty.

Quantitative angiography of the left anterior descending coronary artery: correlations with pressure gradient and results of exercise thallium scintigraphy

To evaluate, during cardiac catheterization, what constitutes a physiologically significant obstruction to blood flow in the human coronary system, computer-based quantitative analysis of coronary angiograms was performed on the angiograms of 31 patients with isolated disease of the proximal left anterior descending coronary artery. The angiographic severity of stenosis was compared with the transstenotic pressure gradient measured with the dilation catheter during angioplasty and with the results of exercise thallium scintigraphy. A curvilinear relationship was found between the pressure gradient across the stenosis (normalized for the mean aortic pressure) and the residual minimal area of obstruction (after subtracting the area of the angioplasty catheter). This relationship was best fitted by the equation: normalized mean pressure gradient = a + b . log [obstruction area], r = .74. The measurements of the percent area of stenosis (cutoff 80%) and of the transstenotic pressure gradient (cutoff 0.30) obtained at rest correctly predicted the occurrence of thallium perfusion defects induced by exercise in 83% of the patients.

Predictive value of reactive hyperemic response on reperfusion on recovery of regional myocardial function after coronary angioplasty in acute myocardial infarction.

BACKGROUND The objective of the study was to determine the coronary vasodilatory reserve in reperfused myocardium in patients with acute myocardial infarction and its relation to regional myocardial function. METHODS AND RESULTS The study population consisted of 22 patients with acute myocardial infarction who underwent successful coronary angioplasty. The vasodilatory reserve in the reperfused myocardium was assessed quantitatively using computer-assisted digital subtraction cine-angiography immediately after angioplasty and at follow-up angiography before hospital discharge. Myocardial contrast medium appearance time and density were determined before and after pharmacological hyperemia induced by an intracoronary injection of 12.5 mg papaverine. Global and regional left ventricular functions were determined from contrast angiography. After papaverine, the mean contrast medium appearance time decreased significantly from 3.5 +/- 0.7 to 2.7 +/- 0.7 cardiac cycles (P < .000005) immediately after successful coronary angioplasty and from 3.8 +/- 0.7 to 2.7 +/- 0.9 cardiac cycles (P < .000005) at angiography before hospital discharge. The mean contrast medium density increased significantly from 48.7 +/- 13.8 to 61.0 +/- 19.0 pixels (P < .003) and from 49.6 +/- 19.7 to 80.3 +/- 29.6 pixels (P < .000005), respectively. As a consequence, the calculated coronary flow reserve increased significantly from 1.8 +/- 0.7 to 2.6 +/- 1.0 (P < .0008). The global ejection fraction increased significantly from 52 +/- 12% to 58 +/- 14% (P < .03), primarily because of a significant improvement in the regional myocardial function of the infarct zone from 20.8 +/- 9.0% to 26.0 +/- 10.5% (P < .001). Coronary flow reserve correlated well with regional myocardial function both during the acute phase (R = .79, P < .002) and at follow-up angiography (R = .82, P < .000004). Interestingly, coronary flow reserve measurement on reperfusion, immediately after angioplasty, correlated significantly with regional myocardial function at follow-up angiography (R = .81, P < .00003). CONCLUSIONS The results indicate that there is a pharmacologically inducible vasodilatory reserve in reperfused ischemic myocardium after successful coronary angioplasty in patients with acute myocardial infarction and that this is increased at 10-day follow-up angiography. More important, the degree of reactive hyperemic response on reperfusion has a predictive value regarding the ultimate degree of recovery of regional myocardial function. Quantitative assessment of reperfusion may be useful in investigating the role of coronary reperfusion and salvage of myocardial function.

One year cost effectiveness of sirolimus eluting stents compared with bare metal stents in the treatment of single native de novo coronary lesions: an analysis from the RAVEL trial

Objective: To assess the balance between costs and effects of the sirolimus eluting stent in the treatment of single native de novo coronary lesions in the RAVEL (randomised study with the sirolimus eluting Bx Velocity balloon expandable stent in the treatment of patients with de novo native coronary artery lesions) study. Design: Multicentre, double blind, randomised trial Setting: Percutaneous coronary intervention for single de novo coronary lesions Patients: 238 patients with stable or unstable angina. Interventions: Randomisation to sirolimus eluting stent or bare stent implantation. Main outcome measures: Patients were followed up to one year and the treatment effects were expressed as one year survival free of major adverse cardiac events (MACE). Costs were estimated as the product of resource utilisation and Dutch unit costs. Results: At one year, the absolute difference in MACE-free survival was 23% in favour of the sirolimus eluting stent group. At the index procedure, sirolimus eluting stent implantation had an estimated additional procedural cost of €1286. At one year, however, the estimated additional cost difference had decreased to €54 because of the reduction in the need for repeat revascularisations in the sirolimus group (0.8% v 23.6%; p < 0.01). After adjustment of actual results for the consequences of angiographic follow up (correction based on data from the BENESTENT (Belgium Netherlands stent) II study), the difference in MACE-free survival was estimated at 11.1% and the additional one year costs at €166. Conclusions: The one year data from RAVEL suggest an attractive balance between costs and effects for sirolimus eluting stents in the treatment of single native de novo coronary lesions. The cost effectiveness of drug eluting stents in more complex lesion subsets remains to be determined.