Restenosis after coronary angioplasty: new standards for clinical studies.

With the high initial success rates for coronary angioplasty that are reported regularly, it has become increasingly difficult to demonstrate methods or techniques that are able to provide more beneficial early results than can be achieved by conventional angioplasty. On the other hand, the incidence of late restenosis has remained much the same over the 10 years that angioplasty has been part of clinical practice, and there is still no proved intervention that modifies the restenosis process. Therefore, the problem of restenosis has assumed increasing relevance in determining the clinical value of coronary angioplasty and, accordingly, studies that address the problem of restenosis need to become more exacting. Although numerous articles have addressed the problem of restenosis in the clinical setting, many defining certain factors associated with restenosis and possible interventions to reduce the incidence of restenosis, there is surprisingly little consensus. Most of the discrepancies can be attributed to three factors: 1) the selection of patients, 2) the method of analysis, and 3) the definition of restenosis employed. This review shows how these three factors influence the outcome and conclusions of restenosis studies.

Assessment of "silent" restenosis and long-term follow-up after successful angioplasty in single vessel coronary artery disease: the value of quantitative exercise electrocardiography and quantitative coronary angiography.

Exercise electrocardiographic (ECG) testing during follow-up after coronary angioplasty is widely applied to evaluate the efficacy of angioplasty, even in asymptomatic patients. One hundred forty-one asymptomatic patients without previous myocardial infarction underwent quantitative exercise ECG testing and quantitative coronary angiography 1 to 6 months after successful angioplasty in single vessel coronary artery disease to 1) determine the value of exercise ECG testing to detect "silent" restenosis, and 2) assess the long-term prognostic value of exercise ECG testing and coronary angiography. The prevalence of restenosis (defined as greater than or equal to 50% luminal narrowing at the dilation site) was 12% in this selected study group. Of 26 patients with an abnormal exercise ECG (ST segment depression greater than or equal to 0.1 mV), only 4 (15%) showed recurrence of stenosis. Sensitivity and specificity for detection of restenosis were 24% and 82%, respectively. One hundred thirty-four patients (95%) were followed up 1 to 64 months (mean 35) after exercise ECG testing and coronary angiography. Thirty-two patients (24%) experienced a cardiac event: in 25 patients (78%) the initial event was recurrent angina pectoris (New York Heart Association class III or IV) and in 7 patients (22%) it was myocardial infarction, although cardiac death did not occur. The mean interval between exercise ECG testing and the initial cardiac events was 14 months (range 1 to 55), whereas 47% of the initial events took place less than or equal to 6 months after exercise ECG testing.(ABSTRACT TRUNCATED AT 250 WORDS)

Change in diameter of coronary artery segments adjacent to stenosis after percutaneous transluminal coronary angioplasty: failure of percent diameter stenosis measurement to reflect morphologic changes induced by balloon dilation.

To determine the changes in stenotic and nonstenotic segments of a dilated coronary artery, detailed quantitative angiographic measurements were performed in 342 patients (398 lesions) immediately after angioplasty and at a predetermined follow-up time of 30, 60, 90 or 120 days after the dilation. Measurements of the stenotic segments were expressed as minimal luminal diameter, and the adjacent nonstenotic segments were expressed as interpolated reference diameter (both in millimeters). A follow-up rate of 86% was achieved. In the patients followed up at 30 and 60 days, there was no significant change in either the mean minimal luminal diameter or the mean reference diameter. However, at 90 and 120 days, there was significant deterioration in both the mean minimal luminal diameter (-0.37 and -0.42 mm, respectively) and the mean reference diameter (-0.17 and -0.26 mm, respectively), all of the changes being highly significant (p less than 0.00001). The reference diameter is involved in the dilation process and may be subject to the same restenosis process that takes place in initially stenotic segments. Percent diameter stenosis measurements, which are conventionally used to express the change in the severity of a stenosis after angioplasty, will tend to underestimate the change when there is a simultaneous reduction in the reference diameter.

Restenosis after coronary angioplasty: the paradox of increased lumen diameter and restenosis.

Restenosis after coronary angioplasty is the single complication that most limits this revascularization procedure in clinical practice. The process is largely unpredictable and the lesion-related factors predisposing to restenosis are poorly understood, with little consensus in published reports. In this study using detailed quantitative angiographic measurements to assess 490 lesions, the simple lesion characteristics associated with restenosis were defined and the relation to the restenosis process documented. Restenosis was defined as an absolute deterioration in the minimal lumen diameter by greater than or equal to 0.72 mm, a criterion based on the 95% confidence intervals for repeat angiographic measurements. This was chosen in an attempt to separate spurious changes due to a poor angiographic result and the variability of angiographic measurements from significant changes due to the restenosis process. The principal determinants of restenosis were found to be a large improvement in the minimal lumen diameter at the time of dilation (1.13 mm for the restenosis group compared with 0.86 mm for the no restenosis group [p less than 0.0001]) and an optimal postangioplasty result (minimal lumen diameter 2.28 mm in the restenosis group compared with 2.05 mm [p less than 0.001] in the no restenosis group, corresponding to a 25% and a 30% diameter stenosis, respectively [p less than 0.0001]). These observations reported for the first time suggest that the distinction needs to be made between a "clinical restenosis" of greater than or equal to 50% diameter stenosis and the "restenosis process" as measured by the absolute changes occurring during and after angioplasty.(ABSTRACT TRUNCATED AT 250 WORDS)

The Coronary Artery Revascularisation in Diabetes (CARDia) trial: background, aims, and design.

BACKGROUND: Patients with diabetes have an increased incidence and severity of ischemic heart disease, which leads to an increased requirement for coronary revascularization. Comparative information regarding mode of revascularization--coronary artery bypass graft surgery surgery (CABG) or percutaneous coronary intervention (PCI)--is limited, mainly confined to a subanalysis of the Bypass Angioplasty Revascularization (BARI) trial, suggesting a mortality benefit of CABG over PCI. No prospective trial has specifically compared these modes of revascularization in patients with diabetes. OBJECTIVE: The Coronary Artery Revascularisation in Diabetes (CARDia) trial is designed to address the hypothesis that optimal PCI is not inferior to modern CABG as a revascularization strategy for diabetics with multivessel or complex single-vessel coronary disease. The primary end point is a composite of death, nonfatal myocardial infarction, and cerebrovascular accident at 1 year. METHOD: A total of 600 patients with diabetes are to be randomized to either PCI or CABG, with few protocol restrictions on operative techniques or use of new technology. This gives a power of 80% to detect non-inferiority of PCI assuming that the PCI 1-year event rate is 9%. A cardiac surgeon and a cardiologist must agree that a patient is suitable for revascularization by either technique prior to recruitment into the study. Twenty-one centers in the United Kingdom and Ireland are recruiting patients. Data on cost effectiveness, quality of life, and neurocognitive function are being collected. Long-term (3-5 year) follow-up data will also be collected.

Comparative quantitative angiographic analysis of directional coronary atherectomy and balloon coronary angioplasty.

An attempt to assess the "utility" of directional atherectomy was made using a new quantitative angiographic index. This index can be subdivided into an initial gain component and a restenosis component. The initial gain index is the ratio between the gain in diameter during intervention and the theoretically achievable gain (i.e., reference diameter). The restenosis index is the ratio between the decrease at follow-up and the initial gain during the procedure. The net result at long-term follow-up is characterized by the utility index, which is the ratio between the final gain in diameter at follow-up and what theoretically could have been achieved. For this purpose, 30 coronary artery lesions were selected from a consecutive series of successfully dilated primary angioplasty lesions and were matched with the initial 30 successfully treated primary atherectomy lesions. Matching by location of stenosis and reference diameter resulted in 2 comparable groups with identical preprocedural stenosis characteristics. Atherectomy resulted in an increase in minimal luminal diameter 2 times larger than angioplasty (1.53 vs 0.77 mm; p less than 0.0001). However, at follow-up there was a significant decrease in minimal luminal diameter and a significant increase in percent diameter stenosis in the groups with atherectomy and angioplasty (1.69 +/- 0.58 vs 1.57 +/- 0.58 mm, p = not significant [NS], and 37 +/- 18 vs 47 +/- 18%, p = NS, respectively). The decrease in minimal luminal gain was more pronounced in the group with atherectomy than in that with angioplasty (0.92 +/- 0.69 vs 0.35 +/- 0.51 mm; p = 0.0005).(ABSTRACT TRUNCATED AT 250 WORDS)

Quantitative angiographic assessment of elastic recoil after percutaneous transluminal coronary angioplasty.

Little is known about the elastic behavior of the coronary vessel wall directly after percutaneous transluminal coronary angioplasty (PTCA). Minimal luminal cross-sectional areas of 151 successfully dilated lesions were studied in 136 patients during balloon inflation and directly after withdrawal of the balloon. The circumvent geometric assumptions about the shape of the stenosis after PTCA, a videodensitometric analysis technique was used for the assessment of vascular cross-sectional areas. Elastic recoil was defined as the difference between balloon cross-sectional area of the largest balloon used at the highest pressure and minimal luminal cross-sectional area after PTCA. Mean balloon cross-sectional area was 5.2 +/- 1.6 mm2 with a mean minimal cross-sectional area of 2.8 +/- 1.4 mm2 immediately after inflation. Oversizing of the balloon (balloon artery ratio greater than 1) led to more recoil (0.8 +/- 0.3 vs 0.6 +/- 0.3 mm, p less than 0.001), suggestive of an elastic phenomenon. A difference in recoil of the 3 main coronary branches was observed: left anterior descending artery 2.7 +/- 1.3 mm2, circumflex artery 2.3 +/- 1.2 mm2 and right coronary artery 1.9 +/- 1.5 mm2 (p less than 0.025). The difference was still statistically significant if adjusted for reference area. Thus, nearly 50% of the theoretically achievable cross-sectional area (i.e., balloon cross-sectional area) is lost shortly after balloon deflation.

Coronary blood flow velocity during percutaneous transluminal coronary angioplasty as a guide for assessment of the functional result.

To investigate the clinical usefulness of intracoronary Doppler recordings during percutaneous transluminal coronary angioplasty (PTCA), the changes of intracoronary blood flow velocity during PTCA were assessed in 20 patients with single proximal coronary stenosis, using a Doppler probe end-mounted on the tip of a PTCA catheter. A mean of 4 inflations was performed in each patient. Intracoronary velocities were measured before and after each inflation and during peak reactive hyperemia after each transluminal occlusion. Quantitative analysis of the coronary stenosis was assessed before and after PTCA, and the dilatation resulted in an increase in minimal luminal cross-sectional area from 1.1 +/- 0.8 to 2.7 +/- 1.2 mm2. A gradual and significant improvement in velocities was observed after the first 3 dilatations, but in 15 of the 20 patients the resting and hyperemic velocities were not affected by the fourth dilatation. Coronary flow reserve measured during reactive hyperemia after the last dilatation with the PTCA catheter across the lesion was 1.9. This value of coronary flow reserve is compatible with the residual stenosis measured after PTCA when corrected for the presence of the Doppler balloon catheter (0.68 mm2). This application of the Doppler technique may provide a new method of on-line functional monitoring of the PTCA procedure in individual patients, but does not yet allow an accurate prediction of the change in coronary geometry brought about by PTCA.

Angiographic risk factors of luminal narrowing after coronary balloon angioplasty using balloon measurements to reflect stretch and elastic recoil at the dilation site. The CARPORT Study Group.

Because many ongoing clinical restenosis prevention trials are using quantitative angiography to assess whether a drug is capable of reducing the amount of intimal hyperplasia, quantitative angiographic risk factors for angiographic luminal narrowing after balloon angioplasty were determined, including stretch and elastic recoil at the dilatation site. Quantitative analysis was performed on 666 lesions in 575 patients during angioplasty and at 6-month follow-up. Stretch was defined as balloon diameter minus minimal luminal diameter (MLD) before angioplasty/reference diameter, and recoil as balloon diameter minus MLD after angioplasty/reference diameter. Multivariate analysis was used to yield independent risk factors for luminal narrowing at follow-up. Predictors of absolute change in MLD were (1) relative gain at angioplasty (gain in millimeters normalized for reference diameter) and (2) lesion length. To allow risk stratification, logistic regression analysis was applied using the decrease in MLD as a binary outcome variable. A decrease in MLD at follow-up of greater than or equal to 0.72 mm was considered significant. Variables retained in the model were: relative gain greater than 0.3 mm (rate ratio 2.9), relative gain 0.2 to 0.3 (rate ratio 2.1), stenosis length greater than or equal to 6.8 (rate ratio 1.7), and thrombus after angioplasty (rate ratio 2.6). Although stretch was significantly related to luminal narrowing at univariate analysis, it was not retained in the multivariate models. A large gain in lumen diameter at angioplasty, dilation of long lesions, and angiographically determined thrombus after angioplasty were found to be accompanied by more severe luminal narrowing at follow-up.

Efficacy of coronary angioplasty for the treatment of hibernating myocardium.

OBJECTIVES: To determine the efficacy of coronary angioplasty as the sole method of revascularisation in patients with coronary artery disease and chronically dysfunctional but viable myocardium (hibernating myocardium), and to assess the effect of restenosis on functional outcome. DESIGN AND PATIENTS: 24 consecutive patients with hibernating myocardium were studied. Positron emission tomography was used to assess myocardial viability, blood flow, and flow reserve. One patient refused angioplasty, one had bypass surgery, and one died while waiting for an elective procedure. The procedure failed in three patients. The remaining 18 patients had repeat echocardiography, 15 had repeat coronary angiography, and nine had repeat assessments of blood flow and flow reserve at mean (SD) 17 (2) weeks after angioplasty. In three patients restenosis was documented. RESULTS: The wall motion score index in the revascularised territories improved from 1.71 (0.37) to 1.34 (0.47) (p = 0.008). Thirty of 51 dysfunctional segments improved in territories without restenosis compared with three of 14 in restenosed territories (p = 0.001). Hibernating and normal segments had comparable flows (0.82 (0.26) v 0.89 (0.24) ml/min/g; NS) while flow reserve was lower in hibernating segments (1.55 (0.68) v 2.07 (1.08); p = 0.03). In segments without restenosis flow reserve improved from 2.03 (1.25) to 2.33 (1.4) (p = 0.03). Sensitivity, specificity, and positive and negative predictive accuracy of the viability study were 97%, 77%, 82%, and 96%, respectively. After excluding patients with restenosis, specificity and positive predictive accuracy improved to 90% and 93%. CONCLUSIONS: Angioplasty improves function in hibernating myocardium, and restenosis prevents recovery; hibernating myocardium is characterised by an impairment of flow reserve; restenosis affects the diagnostic accuracy of viability studies.

[Chronology and incidence of restenosis after coronary angioplasty. Comparison of patients with stable and unstable angina]. / Chronologie et incidence de la resténose après angioplastie coronaire. Comparaison des patients présentant un angor stable à ceux présentant un angor instable.

The aim of this prospective study was to compare the incidence of restenosis after percutaneous transluminal coronary angioplasty (PTCA) in patients with stable and unstable angina before the procedure. Between January 1984 and February 1986, 344 patients with stable angina and 228 patients with unstable angina underwent PTCA. The primary success rate was 86.3 per cent in patients with stable angina (297 patients) and 87.7 per cent in patients with unstable angina (200 patients). The patients were recalled for systematic control coronary arteriography at 30, 60, 90, 120 or 150 days, and was obtained in 83.8 per cent of patients with stable angina and in 86 per cent of patients with unstable angina. The degree of stenosis before and the angiographic changes after PTCA and at control coronary arteriography were evaluated by a computer-assisted automatic contour detection system. The three criteria of restenosis were: 1) over 50 per cent loss of the benefit of PTCA, 2) residual post-PTCA stenosis increasing from less than 50 per cent to more than 50 per cent at control arteriography, 3) a decrease in the minimum intraluminal diameter of at least 0.72 mm with respect to the immediate post-PTCA result. A comparison between the two groups of patients showed that the average age was slightly greater in patients with unstable angina (56 +/- 9 years vs 58 +/- 9 years, p = 0.047). Apart from this difference, the two groups were comparable with regards to the average number of lesions dilated per patient, the date of control arteriography, the severity of the coronary artery disease and previous bypass surgery, angioplasty and infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

[Implantation of endoprostheses in aortocoronary bypass. Preliminary experience at the Thoraxcenter of Rotterdam]. / Implantation d'endoprothèses dans les pontages aorto-coronaires. Expérience préliminaire du thoraxcenter de Rotterdam.

An intraluminal stent was implanted in 5 patients after dilatation of an aorto-coronary venous graft. In the first 4 patients the procedure was motivated by restenosis after angioplasty. In the 5th patient the stent was implanted as a first-line measure in a case of dilated venous bypass stenosis. Stent implantation carries a risk of thrombosis and requires effective anticoagulation. Thus, one of our patients had to be reoperated upon for prosthetic thrombosis facilitated by the withdrawal of anticoagulants owing to a gastrointestinal haemorrhage. After a 3-month follow-up, the results seem to be encouraging in spite of a case of restenosis located at the proximal end of the tutor. However, more time will be needed to determine precisely the effectiveness of stents in the prevention of restenosis after venous graft dilatation.

[Effects and chronology of coronary restenosis after percutaneous transluminal coronary angioplasty. Quantitative angiographic analysis at 1, 2, 3, 4 and 5 months]. / Incidence et chronologie de la resténose coronaire après angioplastie coronarienne transluminale percutanée. Analyse angiographique quantitative aux 1er, 2e, 3e, 4e et 5e mois.

Coronary restenosis occurs fairly early after transluminal coronary angioplasty, as suggested by anatomico-clinical, isotopic and angiographic studies. Its incidence, as reported in the literature, varies according to the clinical selection of patients, to the number of patients with follow-up angiography and the timing of this procedure, and to the criteria used to define restenosis. In this prospective study we endeavoured to determine the exact date at which restenosis takes place, as well as its true incidence, by means of 6 different angiographic criteria. The population studied was divided into five groups and each group underwent coronary arteriography at a different date: during the 1st, 2nd, 3rd, 4th and 5th post-angioplasty months respectively. In 424 of the 500 patients thus examined (84.8 p. 100), coronary angiography involved automatic detection of contours and made quantitative analysis possible. Coronary restenosis was found to occur early, with a peak of incidence in the 3rd month. Its incidence varied considerably depending on the criterion used. A critical analysis of the data has prompted us to use a criterion based on absolute values determined by quantitative angiographic analysis.

Can the published cost analysis data for delivery of an efficient primary angioplasty service be applied to the modern National Health Service?

Despite the clinical benefits and safety profile of primary percutaneous coronary intervention (PCI), the health care system in the UK has been slow to adopt this strategy as first line management for ST segment elevation myocardial infarction. The cost implications of a 24 hour a day, seven days per week primary PCI service and the absence of an existing efficient working model within the National Health Service (NHS) framework are two of the major deterrents for provision of such a service. The existent cost effectiveness data for primary PCI is critically reviewed, with particular reference to the NHS.

Acute myocardial infarction: strategies for thrombolytic therapy.

Thrombolytic therapy has revolutionised the treatment of acute myocardial infarction. This has led to a need for rapid and accurate diagnosis of this condition, provision of a triage protocol to achieve initiation of thrombolytic therapy as soon as the diagnosis has been made, and knowledge of the benefit:risk ratio of thrombolytic therapy in different subgroups of patients to allow the most effective use of these agents without compromising patient safety.

Glucose-insulin-potassium therapy for treatment of acute myocardial infarction: an overview of randomized placebo-controlled trials.

BACKGROUND: Glucose-insulin-potassium (GIK) therapy has been advocated for the treatment of acute myocardial infarction. However, the results from the clinical trials have been inconclusive, largely because of the small number of patients recruited and discrepancies between protocols used in these studies. METHOD AND RESULTS: A systematic MEDLINE search for all the randomized placebo-controlled studies of GIK therapy in acute myocardial infarction was made, and a meta-analysis of the mortality data was performed. Fifteen trials were identified, 5 were excluded because of poor randomization, and 1 was excluded because recruitment was limited to diabetic patients. The 9 remaining trials with a total of 1932 patients were included in the analysis. Hospital mortality was reduced from 21% (205 of 972 patients) in the placebo group to 16.1% (154 of 956) in the GIK group (P=.004; odds ratio, 0.72; 95% confidence interval [CI], 0.57 to 0.90). The proportional mortality reduction was 28% (CI, 10% to 43%). The number of lives saved per 1000 patients treated was 49 (95% CI, 14 to 83). CONCLUSIONS: The findings indicate that GIK therapy may have an important role in reducing the in-hospital mortality after acute myocardial infarction. The value of this therapy in the era of thrombolysis and acute revascularization by primary angioplasty can be fully resolved only by conducting a large randomized mortality study.

Restenosis following coronary angioplasty.

The assessment of restenosis following angioplasty has become increasingly important in determining the clinical value of the procedure. Despite this there has been no uniformly accepted methodology for assessing the procedure and consequently the published results have often been misleading with little concensus. In this paper some of the irregularities are documented and practical ways for adapting methodology proposed.

Clinical assessment following coronary revascularization.

There remains a need to establish adequate protocols for investigating the short- and long-term follow-up of revascularization procedures. For coronary angioplasty the most reliable basis for decision-making in managing patients is the symptomatology of the patient. For bypass surgery a protocol should be established to evaluate patients late, at 5 to 10 years following bypass surgery, in particular those with saphenous vein grafting, as graft and patient survival begins to fall after this period. Investigation after this may be too late for many patients who may already have several occluded grafts and poor left ventricular function, two of the most important prognostic factors post bypass surgery. The improvement and refinement of non-invasive investigations has led to a better understanding of the value and limitations of many of these tests, but it is particularly important that the limitations of many investigation are fully appreciated when they are used to influence clinical decisions. In this regard, a study comparing and integrating the predictive value of the persistence or return to symptoms, a positive non-invasive test, and a positive invasive test would surely prove invaluable.