Pierre de Guise

Probucol and Multivitamins in the Prevention of Restenosis after Coronary Angioplasty

BACKGROUND Oxidizing metabolites generated at the site of coronary angioplasty can induce chain reactions that may lead to restenosis. Antioxidants may counter oxidative stress and modify neointimal formation and vascular remodeling. Experimental data and small clinical studies have suggested that antioxidants may prevent restenosis after angioplasty. In a double-blind, randomized trial, we studied whether drugs with antioxidant properties decrease the incidence and severity of restenosis after angioplasty. METHODS One month before angioplasty, 317 patients were randomly assigned to receive one of four treatments: placebo, probucol (500 mg), multivitamins (30,000 IU of beta carotene, 500 mg of vitamin C, and 700 IU of vitamin E), or both probucol and multivitamins-all given twice daily. Patients were treated for four weeks before and six months after angioplasty. Patients received an extra 1000 mg of probucol, 2000 IU of vitamin E, both probucol and vitamin E, or placebo 12 hours before angioplasty, according to their treatment assignments. Base-line and follow-up angiograms were interpreted by blinded investigators using a quantitative approach. RESULTS The mean (+/-SD) reduction in luminal diameter six months after angioplasty was 0.12 +/- 0.41 mm in the probucol group, 0.22 +/- 0.46 mm in the combined-treatment group, 0.33 +/- 0.51 in the multivitamin group, and 0.38 +/- 0.50 mm in the placebo group (P = 0.006 for those receiving vs. those not receiving probucol, and P = 0.70 for those receiving vs. those not receiving vitamins. Restenosis rates per segment were 20.7 percent in the probucol group, 28.9 percent in the combined-treatment group, 40.3 percent in the multivitamin group, and 38.9 percent in the placebo group (P = 0.003 for probucol vs. no probucol). The rates of repeat angioplasty were 11.2 percent. 16.2 percent, 24.4 percent, and 26.6 percent, respectively (P = 0.009 for probucol vs. no probucol). CONCLUSIONS The antioxidant probucol is effective in reducing the rate of restenosis after balloon coronary angioplasty.

Improvement in Exercise Capacity in Asymptomatic and Mildly Symptomatic Adults After Atrial Septal Defect Percutaneous Closure

Background—Controversy exists as to whether secundum atrial septal defects (ASDs) in asymptomatic or mildly symptomatic New York Heart Association (NYHA) class I or II adult patients should be closed. Methods and Results—Thirty-seven patients (24 females; mean age 49.4 years, range 19 to 76) with a mean pulmonary to systemic flow ratio (Qp:Qs) of 2.1 (1.2 to 3.4) had a maximal oxygen uptake (Vo2max) determination and echocardiographic measurement of right ventricular dimensions before and 6 months after elective percutaneous closure of ASD. At baseline, mean Vo2max was 23.5±6.4 mL/kg per minute and was higher in the 15 NYHA I patients than in the 22 NYHA II patients (27±6.9 versus 20.8±4.6 mL/kg per minute;P =0.0015). Vo2max increased significantly at 6 months (23.5±6.4 to 26.9±6.9 mL/kg per minute;P <0.0001). Improvement was as marked in NYHA I (+22%;P <0.0001) as in NYHA II patients (+12%;P <0.0001), in patients with Qp:Qs 1.2 to 2.0 (+16%;P <0.0001) as in those with Qp:Qs >2 (+12%;P <0.0001), and in patients ≥40 years of age (+14%;P <0.0001) as in those <40 years of age (+16%;P <0.0001). Compared with 15 of 37 patients before closure, 35 of 37 patients were in NYHA I at 6 months. Right ventricular dimensions decreased significantly (P <0.0001). Conclusions—Adult ASD patients significantly increase their functional capacity after percutaneous defect closure. This is observed even in patients classified as asymptomatic, in those with lesser shunts, and in older patients. These findings suggest that ASD closure in an adult population should be considered even in the absence of symptoms.

Multiple coronary angioplasty: A model to discriminate systemic and procedural factors related to restenosis

To assess the interrelation of clinical and procedural factors responsible for restenosis, 119 patients undergoing coronary arteriography were studied a mean of 5.8 +/- 3 months after successful multiple percutaneous transluminal coronary angioplasty. In all clinical, angiographic and procedural variables, the 119 patients undergoing repeat catheterization were similar to the 87 patients that did not. Overall, restenosis occurred in 74 (34%) of 215 lesions. Sixty-three patients had no restenosis, 44 had at least one restenosis and 12 had restenosis at all angioplasty sites. The statistical distribution of restenoses did not follow a binomial model, suggesting that restenosis is more than a lesion-specific phenomenon. Of all the clinical and procedural variables assessed by multivariate logistic regression analysis, only percent stenosis before angioplasty (p less than 0.01), diabetes mellitus (p less than 0.01) and percent stenosis after angioplasty (p less than 0.05) were predictive of restenosis in the entire group. Patients with no restenosis and patients with restenosis at all sites were not different with respect to procedural variables; however, patients with restenosis at all sites more often (p less than 0.05) had diabetes and recent onset angina. In contrast, patients with no restenosis differed from patients with isolated restenosis with respect to procedural variables: severity of stenosis before and after angioplasty, balloon/artery lumen ratio and maximal inflation pressure. Thus, procedural factors may be more related to isolated restenosis, but patient-related factors such as diabetes and recent onset angina may play a more important role in patients with multiple restenoses.

Symptom-limited versus low level exercise testing before hospital discharge after myocardial infarction.

OBJECTIVE This study was undertaken to compare a low level and a symptom-limited test performed before hospital discharge after an uncomplicated myocardial infarction. BACKGROUND Exercise testing after myocardial infarction provides useful prognostic information. Usually either a low level test is performed before hospital discharge or a symptom-limited test is performed at 3 weeks. METHODS The study group comprised 202 patients with an uncomplicated myocardial infarction; 58 patients had a non-Q wave infarction and 115 patients had received thrombolytic therapy. Both a low level and a symptom-limited exercise test were performed in 200 of the 202 study patients in randomized order on consecutive days, a mean of 7.4 +/- 2.3 days after infarction. RESULTS The symptom-limited test required a considerably greater effort than the low level test: exercise duration was 554 +/- 209 versus 389 +/- 125 s (p less than 0.0001), and peak work load was 5.7 +/- 1.8 versus 4.2 +/- 1.1 METs (p less than 0.0001). The peak heart rate was higher during the symptom-limited test (121 +/- 20 vs. 108 +/- 14 beats/min, p less than 0.0001), as was the rate-pressure product. The number of patients who developed ST segment depression greater than or equal to 1 mm increased from 56 during the low level test to 89 during the symptom-limited test (p less than 0.0001). ST segment depression greater than or equal to 2 mm occurred in 22 patients during the low level test and in 41 patients during the symptom-limited test, an 86% increase (p less than 0.0001). The number of patients with either angina or ST depression greater than or equal to 1 mm increased from 66 to 105 (p less than 0.0001) with the symptom-limited test. Exercise test results were similar for patients with a Q wave or a non-Q wave infarction. Exercise duration was longer and exercise-induced ST depression less frequent in patients who had received thrombolytic therapy. CONCLUSIONS A symptom-limited exercise test performed before hospital discharge after uncomplicated myocardial infarction provides a significantly greater cardiovascular stress than does a low level test and is associated with an ischemic response nearly twice as frequently. The prognostic significance of a positive response at higher work loads has not been defined.

Angiographic features of vein grafts versus ungrafted coronary arteries in patients with unstable angina and previous bypass surgery.

OBJECTIVES The aim of the study was to compare the angiographic features of culprit coronary lesions located in grafts with those in native coronary arteries in patients with unstable angina and previous coronary artery bypass graft surgery (CABG). BACKGROUND Deterioration of angina in patients with previous CABG is usually due to progression of atherosclerosis in coronary arteries or in vein grafts, but the relative importance of graft versus native coronary artery disease as well as the morphologic features of the culprit lesions in unstable angina have not been systematically assessed. METHODS Disease progression and angiographic features of vein grafts and ungrafted and grafted coronary arteries were assessed in 95 consecutive patients admitted with unstable angina or non-Q wave myocardial infarction with CABG > 6 months previously. All patients were receiving aspirin and heparin, and 46 had received streptokinase during the acute phase in a doubleblind, placebo-controlled study. Coronary and vein angiography was performed within 8 days after admission (mean [+/- SD] 5 +/- 2 days). The most recent angiogram served to assess disease progression by quantitative angiography. RESULTS The culprit lesion was located in a vein graft in 51 patients, an ungrafted coronary artery in 17 and a grafted artery (proximal and distal to the site of graft insertion) in 9 and was of undetermined site in the remaining 18. The proportion of grafts accounting for acute disease increased to 85% with CABG > or = 5 years. Total occlusion occurred in 25 vein grafts and 4 ungrafted coronary arteries (49% vs. 24%, p = 0.02). Intravessel thrombus was found in 18 culprit vein grafts but in only 2 ungrafted coronary arteries (37% vs. 12%, p = 0.04). Both intravessel thrombus and total occlusion were demonstrated in six culprit vein grafts but in none of the ungrafted coronary arteries (12% vs. 0%, p = NS). The prevalence of total occlusion and thrombus was not influenced by trial medication, streptokinase or placebo. CONCLUSIONS Unstable angina in patients with previous CABG is most often due to graft disease and is associated with more frequent thrombi that are more refractory to medical therapy.

Restenosis and progression of coronary atherosclerosis after coronary angioplasty

The relation between restenosis and progression of atherosclerosis in other coronary segments after angioplasty was studied in 98 consecutive patients with 110 coronary stenoses successfully treated with angioplasty. At early angiographic restudy (5 +/- 2 months after angioplasty) 37 patients (38%) had restenosis (defined as a stenosis greater than or equal to 50% of the luminal diameter or loss of greater than or equal to 50% of the gain achieved by angioplasty); progression of atherosclerosis was observed in 4 patients with and 7 without restenosis (13 versus 11%, p = NS). Ninety of the 98 patients underwent a late angiographic restudy a mean of 34 +/- 11 months after angioplasty. Late restenosis was found in one patient. Progression of coronary artery disease (defined as a greater than or equal to 20% decrease in the diameter of a vessel initially narrowed by greater than or equal to 50% or a greater than or equal to 30% decrease when the initial stenosis was less than 50%) was examined in relation to restenosis in 85 of the 90 patients. It occurred in 9 of 27 patients with and 22 of 58 patients without restenosis (33 versus 38%, p = NS). Restenosis developed more rapidly than did progression of disease. Diameter stenosis increased from 35 +/- 8 to 73 +/- 11% at the early restudy in lesions with restenosis; in lesions with disease progression it increased from 9 +/- 18 to 20 +/- 28% (p less than 0.001) at the early restudy to 53 +/- 21% (p less than 0.001) at the late restudy.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulmonary Arterial Hypertension in Patients With Transcatheter Closure of Secundum Atrial Septal Defects A Longitudinal Study

Background—Pulmonary arterial hypertension (PAH) may develop in patients with atrial septal defects (ASD); however, little is known about associated risk factors and its evolution after transcatheter ASD closure. Methods and Results—We conducted a cohort study on 215 adults with attempted transcatheter ASD closure from 1999 to 2006. Patients were classified according to baseline systolic pulmonary artery pressures as having no (I, <40 mm; Hg), mild (II, 40 to 49 mm; Hg), moderate (III, 50 to 59 mm; Hg), or severe (IV, ≥60 mm; Hg) PAH. Independent predictors of moderate or severe PAH were older age (odds ratio [OR], 1.10 per year; P<0.0001), larger ASD (OR, 1.13 per millimeter; P=0.0052), female sex (OR, 3.9; P=0.0313), and at least moderate tricuspid regurgitation (OR, 3.6; P=0.0043). At 15 (interquartile range, 8 to 43) months post–ASD closure, patients with higher baseline pressures were more likely to experience a ≥5-mm; Hg decrease (33.7%, 73.9%, 79.2%, and 100.0% in groups I to IV, P<0.0001), with a larger magnitude of reduction (0, 8, 17, and 22 mm; Hg; P<0.0001). However, normalization of pressures (<40 mm; Hg) occurred less frequently in patients with more advanced PAH (90.2%, 71.7%, 66.7%, and 23.5%, P<0.0001). Among patients with moderate or severe PAH, independent predictors of normalization were lower baseline pressures (OR, 0.91 per mm; Hg; P=0.0418) and no more than mild tricuspid regurgitation (OR, 0.14; P=0.0420). Conclusion—In adults with ASDs, severity of PAH is modulated by age, sex, defect size, and degree of tricuspid regurgitation. Patients with moderate or severe PAH may benefit from substantial reductions in pulmonary artery pressures after transcatheter ASD closure, although the PAH values remain elevated in a sizeable proportion.

Intravenous diltiazem in acute myocardial infarction. Diltiazem as adjunctive therapy to activase (DATA) trial.

OBJECTIVES This study was defined as a pilot investigation of the usefulness and safety of intravenous diltiazem as adjunctive therapy to tissue plasminogen activator in acute myocardial infarction, followed by oral therapy for 4 weeks. BACKGROUND Experimental studies have documented that calcium antagonists protect the myocardial cell against the damage caused by coronary artery occlusion and reperfusion, yet no benefits have been conclusively demonstrated in acute myocardial infarction (AMI) in humans. METHODS In this pilot study, 59 patients with an AMI treated with tissue-type plasminogen activator (t-PA) were randomized, double blinded, to intravenous diltiazem or placebo for 48 h, followed by oral therapy for 4 weeks. The primary objective was to detect an effect on indices of regional left ventricular function and perfusion. Patients were also closely monitored for clinical events, coronary artery patency and indices of infarct size and of left ventricular function. RESULTS Creatine kinase elevation, Q wave score, global and regional left ventricular function and coronary artery patency at 48 h were not significantly different between the diltiazem and placebo groups. A greater improvement observed in regional perfusion and function with diltiazem was likely explained by initial larger defects. Diltiazem, compared to placebo, reduced the rate of death, reinfarction or recurrent ischemia at 35 days from 41% to 13% (p=0.027) and prevented the need for an urgent intervention. The rate of death or myocardial infarction was reduced by 65% (p=0.15). These benefits could not be explained by differences in baseline characteristics such as age, site and extent of infarction, time of inclusion or concomitant therapy. Heart rate and blood pressure were reduced throughout the study with active diltiazem treatment. Side effects of diltiazem were bradycardia and hypotension that required transient or permanent discontinuation of the study drug in 27% of patients, vs. 17% of patients with placebo. CONCLUSIONS A protective effect for clinical events related to early postinfarction ischemia and reinfarction was suggested in this study, with diltiazem administered intravenously with t-PA followed by oral therapy for 1 month, with no effect on coronary artery patency and left ventricular function and perfusion.

Outcome of children with atrial septal defect considered too small for surgical closure

There are few studies providing information on the natural course of hemodynamically insignificant atrial septal defect (ASD). To review the outcome of patients with secundum ASD, we retrospectively reviewed the charts of patients who had initially not been considered for surgical closure after age 1 year, and who had either a follow-up of at least 10 years or documented closure. Thirty patients, 22 females and 8 males, fulfilled our inclusion criteria. Mean age at diagnosis was 1.3 year and mean follow-up duration was 11.5 years. Seventeen patients had spontaneous closure of the ASD at a mean age of 8.4 years. There were 7 asymptomatic patients whose ASD was still patent at the last visit (mean age 14.1 years, mean follow-up 13.2), with defect dimensions on echocardiography ranging from 1 to 6 mm. The remaining 6 patients were considered to require surgical closure on the basis of an apparent increase in size of the ASD and secondary clinical and hemodynamic manifestations. These results (1) confirm that not all secundum ASDs need to be treated surgically because they can still spontaneously close past the age of 5, and (2) suggest that in a minority of cases the size of the defect could increase.

Adult congenital heart disease: a growing epidemic.

Medical and surgical breakthroughs in the care of children born with heart defects have generated a growing population of adult survivors and spawned a new subspecialty of cardiology: adult congenital heart disease. The prevalence of adult congenital heart disease is escalating at a rampant rate, outpacing the relatively static prevalence of pediatric congenital heart disease, because adults now surpass children in numbers by a ratio of 2:1. As such, congenital heart disease can no longer be considered primarily a pediatric specialty. Most congenital heart defects are not curable and require lifelong specialized care. Health care systems worldwide are challenged to meet the unique needs of this increasingly complex patient population, including the development of supraregional centres of excellence to provide comprehensive and multidisciplinary specialized care. In this review, we explore the incidence and prevalence of congenital heart disease and their changing patterns, address organization and delivery of care, highlight the importance of appropriate training and dedicated research, summarize the high burden of health care resource utilization, and provide an overview of common issues encountered in adults with congenital heart disease.