Pathophysiology of restenosis following percutaneous transluminal coronary angioplasty

Symptomatic restenosis occurs in approximately 30-40% of patients after percutaneous transluminal coronary angioplasty (PTCA). Despite intensive research, the primary pathophysiological mediators have not been defined, and pharmacological therapy has not been effective in preventing restenosis. Restenosis is a multifactorial and sequential process, which is initiated by mechanical injury of the vessel wall, and involves neointima formation caused by the local proliferation of smooth muscle cells and production of an extracellular matrix, followed by vascular remodelling. Numerous mediators are involved in these processes, e.g., protooncogenes, growth factors, cytokines and nitric oxide. This review discusses the pathobiological mechanisms underlying coronary restenosis, and outlines the prospects for future therapy.     

Endovascular beta-irradiation after percutaneous transluminal coronary balloon angioplasty

PURPOSE: Intraluminal beta-irradiation has been shown to markedly decrease fibrointimal proliferation after arterial injury in experimental models. With the aim of reducing the incidence of restenosis after percutaneous transluminal coronary angioplasty (PTCA), we undertook a pilot clinical evaluation to assess both the technical feasibility and the clinical safety of this treatment after balloon coronary angioplasty. METHODS AND MATERIALS: Between June 21 and November 15, 1995, 15 patients (6 women and 9 men, aged 72 +/- 5 years) underwent intracoronary beta-irradiation immediately after a conventional PTCA procedure. Both the PTCA and irradiation procedure were done in a conventional catheterization laboratory, using an endoluminally centered pure metallic 90Y source, a newly developed technique of intracoronary beta-irradiation. This was done after documenting the ability of the system to generate reproducible dose delivery to the arterial wall. RESULTS: Both the PTCA and the irradiation procedure were technically feasible in all attempted cases, and a dose of 18 Gy was delivered with a local exposure time of 391 +/- 206 s (range 153-768). In four patients, the intervention was completed by intraarterial stent implantation because of dissection induced by the initial PTCA. No in-hospital complications occurred, and serial creatine kinase measurements remained within the normal range in all cases. CONCLUSION: Our early experience thus suggests that reliable and reproducible dose delivery can be achieved, and that coronary endoluminally centered beta-brachytherapy is both feasible and safe on a short-term basis in the clinical setting. Whether this novel mode of therapy will favorably influence post-PTCA restenosis in patients, as it does in experimental models, must await long-term angiographic follow-up of the present series as well as further clinical study.     

Management of intracoronary thrombosis complicating percutaneous transluminal coronary angioplasty

With technological advances in equipment and increased experience of operators, the success rates of percutaneous transluminal coronary angioplasty (PTCA) now exceed 90%. However, acute periprocural occlusion continues to complicate approximately 6% of all procedures, and many of these occlusions are due to intracoronary (IC) thrombus. Patients at highest risk for this complication include those with acute ischemic syndromes or with angiographically apparent thrombus. These individuals may be candidates for the use of prolonged heparin infusions prior to dilatation, intracoronary thrombolytic therapy, or monoclonal antibody directed against the platelet glycoprotein IIb/IIIa receptor. All patients undergoing PTCA should receive adequate antiplatelet therapy, including aspirin, and heparin with dosing monitored by activated clotting times (ACT). In addition, some recommend the use of ionic contrast material. When IC thrombus accumulates following intervention, initial therapy should include IC nitroglycerin followed by a combination of redilatation and IC urokinase infusion. Prolonged balloon inflations may be useful, particularly with the use of autoperfusion catheters. Platelet glycoprotein IIb/IIIa receptor antagonists may prove to be beneficial in this situation as well. If the patient's clinical status deteriorates in spite of these measures, emergency coronary artery bypass graft surgery may be required.     

Accuracy of treadmill exercise electrocardiography in detecting restenosis following single-vessel percutaneous transluminal coronary angioplasty

To develop an improved method for diagnosing restenosis using treadmill exercise electrocardiography (ECG) following percutaneous transluminal coronary angioplasty (PTCA), we prospectively evaluated 46 patients who underwent PTCA for the treatment of single-vessel coronary artery disease and who did not have a history of myocardial infarction. Treadmill exercise ECG and coronary angiography were performed 3 months after PTCA to determine their accuracy in diagnosing restenosis based on standard ST-segment depression criteria, the difference between the maximum ST-segment depression before and 3 months after PTCA (< or =0.5 mm: positive; >0.5 mm: negative), and the difference between sigmaST-segment depression before PTCA and 3 months after PTCA (< or = 1.5 mm: positive; > 1.5 mm: negative). The sensitivity, specificity, and diagnostic accuracy of standard ST-segment depression criteria were 65%, 66%, and 65%, respectively. The sensitivity, specificity, and accuracy for the difference in maximum ST-segment depression were 77%, 76%, and 76%, respectively, whereas the values for the difference in sigmaST-segment depression were 77%, 83%, and 80%, respectively. Based on these results, we conclude that using the difference between ST-segment depression before and after PTCA improves the accuracy of treadmill exercise ECG for diagnosing restenosis.     

Quality of life following percutaneous transluminal angioplasty for claudication

Basal cell carcinoma (BCC) is the most common type of skin cancer and the incidence of BCC is expected to rise, with increased demand on dermatology resources. Little is known of the effect on people's lives of having skin cancer. The aim of this study was to quantify the handicap caused gy basal cell carcinomas before and after therapy. Forty-four patients (22 males, mean age = 65 yrs, range = 35-81 yrs) with 48 BCCs were recruited and 37 patients completed the study. Each patient completed the UK Sickness Impact Profile (UKSIP) and the Dermatology Life Quality Index (DLQI) at the initial visit to the dermatology clinic, 1 week after treatment and 3 months after treatment. Lesions had been present for a mean of 25 months (range = 1-240 months), their mean diameter was 9.6mm (range = 3-35mm) and the sites were head and neck (79%), trunk (17%) and limbs (4%). There was no relationship between the quality of life score and size of lesion. Overall the scores at presentation were very low, rising 1 week after treatment and falling to below the initial scores at 3 months (mean UKSIP 0.4%, 0.7%, 0.13%; mean DLQI 5.3% 8.7%, 1.2%). BCCs cause little handicap. This may explain the delay in seeking medical attention and should be considered in planning public health education about BCCs.     

Usefulness of percutaneous transluminal coronary angioplasty in silent myocardial ischemia

The usefulness of percutaneous transluminal coronary angioplasty (PTCA) was assessed in patients with exercise-induced asymptomatic myocardial ischemia (silent ischemia) and compared with exercise-induced symptomatic myocardial ischemia (symptomatic ischemia). Patients with single vessel coronary artery disease (51 with angina pectoris, 40 with old myocardial infarction) and evidence of stress-induced ischemia on thallium-201 single photon emission computed tomography (SPECT) underwent successful PTCA. Thirty-seven percent of angina patients and 60% of infarction patients showed asymptomatic exercise-induced ischemia. There was no significant difference in population characteristics between silent and symptomatic patients. Patients with silent angina had significantly higher percentage thallium uptake and washout rate than symptomatic patients. After PTCA, both percentage diameter stenosis and percentage thallium uptake were improved in all patients with angina irrespective of the presence or absence of symptoms. There were no significant differences in percentage thallium uptake and washout rate between patients with silent and symptomatic infarction. After PTCA, percentage diameter stenosis, percentage thallium uptake, and washout rate improved in all infarction patients irrespective of the symptoms. Zero percent of silent angina patients, 12% of symptomatic angina patients, 12% of silent infarction patients, 19% of symptomatic infarction patients had cardiac events during about 4.5 years after PTCA. The incidence of cardiac events did not significantly differ in any patient group. PTCA improved myocardial perfusion in all patients, and the incidence of cardiac events did not differ between the silent and symptomatic groups. Revascularization with PTCA is suitable for patients with silent as well as symptomatic ischemia.     

Prevention and treatment of restenosis after percutaneous transluminal coronary angioplasty

Restenosis is a clinical problem after coronary angioplasty associated with major ischemic events or repeat interventions in 20-50% of the patients undergoing this procedure. Major efforts have been undertaken in the past decade to successfully prevent or treat restenosis but no pharmacologic approach to the problem has as yet been identified to be effective enough in clinical conditions. New strategies to cope with restenosis are targeted by local application of ionizing radiation which markedly reduces cell proliferation after angioplasty in animal experiments. Preliminary clinical trials indicate that endovascular radiation therapy is a safe and effective means to treat restenosis. Randomized, multicenter studies with long follow-up periods are needed to support these early results.     

Radiofrequency thermal balloon coronary angioplasty: a new device for successful percutaneous transluminal coronary angioplasty

OBJECTIVES: The purpose of this study was to evaluate the effects of thermal balloon percutaneous transluminal coronary angioplasty using radiofrequency energy in the treatment of patients with failed coronary angioplasty and complex lesions. In addition, we evaluated restenosis after radiofrequency thermal balloon applications. BACKGROUND: The efficacy of coronary angioplasty is limited by the relatively low success rate in complex lesions and the high frequency of restenosis. Few reports have studied the combined effects of pressure and laser thermal energy. This study describes a new device for coronary angioplasty using radiofrequency thermal energy. METHODS: Thirty-two patients with failed conventional coronary angioplasty or complex lesions were treated with radiofrequency thermal balloon coronary angioplasty. Radiofrequency energy was delivered up to 11 times in exposures ranging from 30 to 60 s in duration. This combined effect allowed the vascular wall to be heated to temperatures ranging from 60 to 70 degrees C. Follow-up coronary angiography was performed, on average, 6 months after the procedure. RESULTS: Successful radiofrequency coronary angioplasty was achieved in 28 (82%) of 34 lesions. There was one abrupt coronary artery occlusion (3%) and no death, perforation or dissection. Angiographic restenosis occurred in 14 (56%) of 25 lesions. CONCLUSIONS: In patients with failed coronary angioplasty and difficult complex lesions, radiofrequency coronary angioplasty could potentially improve angioplasty success rates and may have important implications for bailout cases with abrupt occlusion. However, restenosis remains a significant problem.     

5 years'' experience in complex percutaneous transluminal coronary angioplasty]

SETTING: A residential program in Barcelona for drug addicts (therapeutic community) admitted between November 1988 and March 1992, and followed until September 1994. OBJECTIVE: To study the incidence of tuberculosis as related to the presence of tuberculosis infection and/or human immunodeficiency virus (HIV) infection, and to evaluate the protective effect of chemoprophylaxis with isoniazid. DESIGN: Prospective cohort study. Incidence rates were compared using the Chi-square test for cohort studies. The effectiveness of chemoprophylaxis was evaluated by the Kaplan-Meier method at the univariate level, and by logistic regression models and proportional risks analysis at the multivariate level. RESULTS: During the study of 361 individuals without previous known tuberculosis or history of anti-tuberculosis chemoprophylaxis, 25 developed tuberculosis, an overall incidence rate of 1.79/100 person-years. For HIV-positive persons, the incidence rate was 3.25/100 person-years, compared with 0.30/100 in those who were HIV-negative (P < 0.05). The highest incidence rates occurred among HIV-positive persons who did not receive chemoprophylaxis and who were either anergic (HIV-positive, purified protein derivative [PPD]-negative, Multitest-negative) or who were infected with Mycobacterium tuberculosis (PPD+), 10.0/100 person-years and 4.64/100 person-years, respectively. Of the 53 persons who received chemoprophylaxis, three developed tuberculosis, an incidence rate of 1.4/100 person-years. In comparison, in the group of 51 patients who were designated to receive chemoprophylaxis but where none was actually taken, 17 developed tuberculosis, an incidence rate of 5.7/100 person-years (P = 0.03). CONCLUSION: HIV-infected intravenous drug users, particularly those who are anergic or who are PPD positive, are at increased risk of developing tuberculosis. Anti-tuberculosis chemoprophylaxis proved effective in this population.     

Rotational atherectomy (Rotablator) for percutaneous transluminal coronary angioplasty

BACKGROUND: The use of Rotablator in percutaneous transluminal coronary angioplasty attempts to reduce the atheromatous plaque abrading it and fragmenting the parietal calcium of the artery. AIM: To report our experience with the use of Rotablator. PATIENTS AND METHODS: Rotational atherectomy was performed in 189 patients aged 60.8 +/- 11 years (154 men). The clinical indication for the procedure was chronic angina in 22%, unstable angina in 44%, myocardial infarction in 21%, silent angina in 7% and re-stenosis in 6%. One hundred seventy seven patients were followed for a mean of 15.9 +/- 6.3 months. RESULTS: Two hundred thirty six stenoses in 215 coronary arteries were treated with a 98.7% angiographic success rate. One patient had a Q infarction and no patient died or required emergency surgery. Fourteen patients had rises in CK MB enzymes (non Q infarction). Three patients had a pseudoaneurism and three had bleedings that required transfusion. Of the followed patients, 33 had a clinically suspected re-stenosis, that was angiographically confirmed in 23. Cardiac mortality was 2.3%. Seventy nine percent of patients had an evolution without angina or coronary events. CONCLUSIONS: Percutaneous transluminal coronary angioplasty with the use of Rotablator had a high immediate success rate and a low incidence of complications. The clinical evolution of patients has been favorable with a low incidence of mortality and ischemic events.     

Outcome of percutaneous transluminal coronary angioplasty in patients with subclinical hypothyroidism

Recent advances in bone research have employed novel cell and molecular biology techniques to determine some of the fundamental mechanisms regulating bone function. Endocrine control of bone cell development and matrix turnover have been defined at a molecular level by studying the interaction of steroid/thyroid hormones with gene promoters. New steroid/thyroid hormone receptors have been cloned, suggesting that our current view of hormonal regulation of bone metabolism is far from complete. The function of one particular steroid hormone receptor, the vitamin D receptor, has come under close scrutiny following the observation that polymorphic variations in this receptor are linked to differences in bone mineral density. Detailed studies of bone cell differentiation have shown that cytokines may be particularly important targets for hormonal control in bone. The role of cell adhesion molecules in regulating bone resorption has also been explored; modulation of their activity may be of benefit in the treatment of diseases such as osteoporosis. Pharmacological intervention via the newly cloned calcium-sensing receptor offers another site for regulation of bone turnover.     

Coronary artery fistula as a complication of percutaneous transluminal coronary angioplasty

The aim of this study was to assess the quality of storage of tetanus vaccine in accident and emergency (A&E) departments and also of the awareness of Department of Health guidelines. A postal questionnaire was sent to 50 randomly selected major A&E departments in the British Isles, enquiring about awareness of Department of Health guidelines (Department of Health, 1990). Forty (80%) A&E departments responded. Only 14 were aware of the Department of Health guidelines and in only 18 was there a member of staff taking responsibility for vaccine storage. The study found that safe storage of vaccine, and therefore guarantee of efficacy, is not occurring in the majority of A&E departments. Unnoticed failure of refrigerators could be exposing patients to the risk of tetanus infection.     

Long-term prognosis of percutaneous transluminal coronary angioplasty in 229 cases]

In order to approach long-term efficacy of percutaneous transluminal coronary angioplasty (PTCA) and the factors affecting its efficacy in Chinese patients, 229 patients who underwent successful PTCA in this institution were followed by direct interview or letters. The rate of follow-up was 95% for the patients who should be followed. The period of follow-up was 0.5-8.4 (mean 2.3 +/- 1.8) years. Angina pectoris recurred in 76 (33.2%) of the patients. In 76% of the patients with recurrence, angina developed within 6 months after PTCA. Cox regression analysis revealed that the relative risk of recurrence of angina pectoris was increased among the patients with triple vessel disease and hypertension. During the period of follow-up, 2 (0.9%) patients died, 6 (2.6%) had non-fatal acute myocardial infarction, 4 (1.7%) had coronary artery bypass graft surgery, and 29 (12.7%) had repeat PTCA. The cardiac event free survival rate calculated by Kaplan-Meier method was 84.8% at 1 year and 70.5% at 8 years. Cox regression analysis revealed that there were positive correlations between stenosis of lesions before PTCA and residual stenosis of LAD after PTCA and the relative risks of cardiac events. In conclusion, the long-term efficacy of PTCA in Chinese patients was good. We suggest that to decrease the residual stenosis of LAD during procedure could probably decrease the relative risk of cardiac events during follow-up.     

Optimizing surgical backup for multiple simultaneous percutaneous transluminal coronary angioplasty procedures

At busy interventional centers, it may be difficult to coordinate surgical backup for multiple simultaneous PTCA procedures. We sought to determine the actual risk of two simultaneous cases requiring surgery, and to identify a group in which multiple simultaneous PTCA procedures could be performed at low risk. We prospectively applied the ACC/AHA A/B/C lesion classification system and an empiric low/medium/high risk classification (based on patients' overall clinical picture) to 1,128 PTCA procedures over a 9 month period; 22 of these patients (1.9%) went directly from the catheterization laboratory to emergency CABG. The incidence of emergency CABG by groups was A-low 1/166, A-medium 1/71, A-high 0/22, B-low 1/116, B-medium 10/481, B-high 2/52, C-low 2/47, C-medium 3/88, and C-high 2/85. The patients were divided into two groups: minimal risk (A + B-low: 3/375 or 0.8%) and increased risk (B-med/high + C: 19/753 or 2.5%). The difference between the groups was significant using chi square with an alpha < 0.05. The risk of two cases requiring surgery at the same time was calculated as a function of the number of simultaneous PTCA procedures performed. Six or fewer minimal risk PTCA, one increased risk plus up to three minimal risk, and a maximum of two increased risk cases were found to have a risk of < 0.001. We conclude that it is possible to identify a group of patients with minimal risk, in whom multiple simultaneous procedures can be performed with a negligible probability of two cases requiring surgery at the same time.(ABSTRACT TRUNCATED AT 250 WORDS)     

Intravascular ultrasound in determining the end point of percutaneous transluminal coronary angioplasty

Intravascular ultrasound (IVUS) imaging was used to measure internal luminal area immediately after percutaneous transluminal coronary angioplasty (PTCA) in 83 patients (59 males, 24 females, mean age 63 +/- 12 years) with angina pectoris to determine the need for additional intervention. The effectiveness of these interventions to prevent restenosis was also studied. Thirty-five patients (42%) with insufficient dilatation revealed an internal luminal area less than 5 mm2 or luminal stenosis greater than 60% as evaluated by IVUS imaging following the procedure. The luminal area increased from 4.5 +/- 1.1 to 7.9 +/- 2.8 mm2 and the percentage luminal stenosis improved from 66 +/- 9% to 54 +/- 9% in patients who underwent further dilatation with a larger size balloon, longer dilatation time, directional coronary atherectomy, or stenting. The insufficient dilatation group exhibited hard plaque and calcification more frequently than in the other group (48 patients, 58%) in whom sufficient dilatation of the target lesion was achieved. The incidence of restenosis in the sufficient dilatation group was 25%, compared to 33% of the patients receiving additional treatment after IVUS imaging and 42% in the 192 patients who underwent PTCA without IVUS imaging. IVUS imaging is a useful method for evaluation of complex luminal morphology to decrease the incidence of restenosis and for determination of the end point and the extent of dilatation required.     

The effect of pravastatin on prevention of restenosis after successful percutaneous transluminal coronary angioplasty

Numerous attempts have been made to prevent late restenosis after successful percutaneous transluminal coronary angioplasty (PTCA), but there is still no effective treatment. This report describes the effect of an oral lipid-lowering agent, pravastatin, on restenosis after successful PTCA. Sixty-six patients who underwent successful elective PTCA were assigned to a pravastatin-treated group (Group 1, n = 29) or an untreated group (Group 2, n = 37) in a prospective and randomized fashion. Pravastatin (5 mg or 10 mg twice a day) was given to Group 1 patients from day 3 after the procedure. Selective coronary angiography was repeated 3 to 5 months later, or sooner if the patient developed angina pectoris. The serum cholesterol level was decreased significantly in Group 1 (from 215.7 +/- 44.3 mg/dl to 181.2 +/- 30.3 mg/dl, p < 0.001), but not in Group 2 (from 191.9 +/- 30.8 mg/dl to 191.8 +/- 33.3 mg/dl, p = ns), at the time of repeat coronary angiography. However, there were no differences between the groups with regard to the recurrence of angina, the need for repeat PTCA, or restenosis, as assessed by quantitative analysis of coronary cineangiograms. These results suggest that oral pravastatin therapy does not effectively prevent late restenosis after successful PTCA by this mode of administration.