Clinical and economic outcomes of multivessel coronary stenting compared with bypass surgery: a single-center US experience

Background Randomized trials comparing multivessel stenting with coronary artery bypass surgery (CABG) have demonstrated similar rates of death and myocardial infarction but higher rates of repeat revascularization after stenting. The impact of these alternative strategies on overall medical care costs is uncertain, particularly within the US health care system. Methods We performed a retrospective, matched cohort study to compare the clinical and economic outcomes of multivessel stenting and bypass surgery. The stent group consisted of 100 consecutive patients who underwent stenting of ≥2 major native coronary arteries at our institution. The CABG group consisted of 200 patients who underwent nonemergent isolated bypass surgery during the same time frame, matched (2:1) for age, sex, ejection fraction, diabetes mellitus, and extent of coronary disease. Detailed clinical follow-up and resource utilization data were collected for a minimum of 2 years. Total costs were calculated by use of year 2000 unit prices. Results Over a median follow up period of 2.8 years, there were no significant differences in all-cause mortality rates (3.0% vs 3.0%), Q-wave myocardial infarction (5.1% vs 4.0%), or the composite of death or myocardial infarction (7.1% vs 7.0%) between the stent and CABG groups (P = not significant for all comparisons). However, at 2-year follow up, patients with stents were more likely to require ≥1 repeat revascularization procedure (32.0% vs 4.5%, P < .001). The initial cost of multivessel stenting was 43% less than the cost of CABG ($11,810 vs $20,574, P < .001) and remained 27% less ($17,634 vs $24,288, P = .005) at 2 years. Conclusions Multivessel stenting and CABG result in comparable risks of death and myocardial infarction. Despite a higher rate of repeat revascularization, multivessel stenting was significantly less costly than CABG through the first 2 years of follow-up. (Am Heart J 2003;145:334-42.)     

Heterogeneity of microvascular dysfunction in women with chest pain not attributable to coronary artery disease: implications for clinical practice

Background Women with chest pain in the absence of obstructive coronary artery disease (CAD) frequently have coronary microvascular dysfunction and inducible myocardial ischemia. Microvascular dysfunction is commonly diagnosed by demonstrating abnormal flow reserve in a single coronary artery during angiography. Therefore, diagnostic accuracy is dependent on homogeneity of microvascular dysfunction in the myocardium. Methods In the Women's Ischemia Syndrome Evaluation (WISE), 34 women with chest pain and no significant CAD and 9 female control subjects underwent ¹³N-NH₃ positron emission tomography to measure adenosine-induced changes in myocardial perfusion (ie, coronary flow reserve [CFR]). Flow reserve was correlated among the left anterior descending (LAD), circumflex (LCx), and right (RCA) coronary artery distributions. Results The mean CFR in the LAD, LCx, and RCA was 2.85 ± 1.35, 2.58 ± 0.94, and 3.24 ± 1.42, respectively. Concordance in the classification of microvascular function as normal (CFR ≥2.5) versus abnormal was present in the LAD and RCA, LAD and LCx, and RCA and LCx distributions in only 71.8%, 66.7%, and 61.6% of patients, respectively. There was a modest degree of correlation of CFR between the LAD and RCA (r = 0.79, P < .001), LAD and LCx (r = 0.61, P < .001), and LCx and RCA (r = 0.57, P < .001). Comparison of CFR in the 3 coronary arteries simultaneously in all patients demonstrated that the LCx had values that were significantly lower than the RCA and LAD distributions. Conclusion Substantial discordance of classification of microvascular function among coronary artery distributions in women with chest pain and no CAD suggests that microvascular dysfunction is distributed heterogeneously in the myocardium. Assessment of CFR in a single coronary artery during cardiac catheterization may not provide an accurate assessment of the coronary microcirculation in women with chest pain not attributable to CAD. (Am Heart J 2003;145:628-35.)     

Angiographic changes in saphenous vein grafts are predictors of clinical outcomes

Background Previous studies have suggested that angiographic evidence of disease progression in coronary arteries increases the risk of subsequent coronary clinical events. This study ascertained whether patients enrolled in the Post Coronary Artery Bypass Graft Clinical Trial (POST CABG) who had substantial progression of atherosclerosis in ≥1 saphenous vein grafts (on the basis of assessment of baseline and follow-up angiograms obtained 4-5 years after study entry), but who had not reported clinical symptoms before follow-up angiography, were at a higher risk of subsequent events than patients who did not have substantial progression of atherosclerosis (decrease ≥0.6 mm in lumen diameter at site of greatest change from baseline). Methods All 1351 patients enrolled in the trial underwent baseline angiography; only the 961 patients who had follow-up angiography and no coronary events before the follow-up study were included in this analysis. The clinical center staff contacted patients to ascertain the events that had occurred after follow-up angiography (approximately 3.4 years later). Results Sixty-nine patients had died; 870 patients or relatives were interviewed, and 22 patients could not be contacted. Univariable estimates of relative risk associated with substantial progression ranged from 2.2 (P < .001) for cardiovascular death or nonfatal myocardial infarction to 3.3 (P < .001) for revascularization. Multivariable and univariable estimates of risk were similar. Conclusions The findings provide evidence that patients who had substantial progression of atherosclerosis in vein grafts are at an increased risk for subsequent coronary events and suggest that angiographic changes in vein grafts are appropriate surrogate measures for clinical outcomes. (Am Heart J 2003;145:262-9.)     

Angiopoietin-like protein 4 significantly predicts future cardiovascular events in coronary patients

Background: Angiopoietin-like protein 4 (ANGPTL4) has been associated with cardiometabolic disorders including dyslipidemia and atherosclerosis in animal studies; in humans, however, its impact on metabolic traits and cardiovascular risk remains unclear. Methods: We examined the association of plasma ANGPTL4 levels with the metabolic syndrome (harmonized consensus definition), with angiographically determined coronary artery disease (CAD), and with the risk of future cardiovascular events in a cohort of 490 patients undergoing coronary angiography for the evaluation of stable CAD. In addition, we investigated the influence of the tagging single nucleotide polymorphisms (SNPs) rs4076317, rs2278236, rs1044250, and rs11672433 as well as variant rs116843064 (E40K) of the ANGPTL4 gene on cardiovascular risk in a larger sample of 983 angiographied coronary patients including the above mentioned 490 subjects. Results: Plasma ANGPTL4 was significantly higher in patients with the metabolic syndrome than in subjects without the metabolic syndrome (26.0 ± 19.4 ng/ml vs. 22.2 ± 19.7 ng/ml; p = 0.008). No significant association was found between ANGPTL4 and angiographically characterized coronary atherosclerosis. Prospectively, however, plasma ANGPTL4 significantly predicted future cardiovascular events both univariately (HR1.45 [1.16–1.82], p = 0.001) and after adjustment for standard cardiovascular risk factors (1.26 [1.01–1.58]; p = 0.045). Concordantly, rs4076317, rs2278236, and rs1044250 significantly affected the risk of future cardiovascular events (adjusted HRs 0.70 [0.54–0.90]; p = 0.005, 0.76 [0.61–0.94]; p = 0.012, and 1.30 [1.03–1.62]; p = 0.025, respectively). Conclusions: We conclude that plasma ANGPTL4 levels as well as ANGPTL4 variants significantly predict cardiovascular events independently of conventional cardiovascular risk factors.     

Prognostic value of a negative stress echocardiographic study in diabetic patients

Background Diabetic patients have increased cardiovascular morbidity and mortality. We compared the long-term prognostic value of a negative, nonischemic stress echocardiogram in patients with and without diabetes. Methods Two hundred thirty-six consecutive subjects who had stress echocardiography and who were negative for inducible ischemia were included in the study. Baseline cardiac risk factors and cardiac events (cardiac death, nonfatal myocardial infarction, and coronary revascularization) were identified. Results Follow-up was obtained in 233 subjects for a mean duration of 25 months. There were 144 nondiabetic and 89 diabetic patients. At baseline, the diabetic group had a significantly higher incidence of hypertension, hyperlipidemia, and history of coronary artery disease but had a lower incidence of smoking (P < .05). Diabetic patients had a significantly higher incidence of cardiac events (19% vs 9.7%, P = .03) and worse event-free survival (P = .03). There were more nonfatal myocardial infarctions in the diabetic group (6.7% vs 1.4%, P < .05) and a trend toward a higher proportion of hard events (myocardial infarction and cardiac death) in diabetic patients (12.4% vs 5.6%, P = .11). The hard event rate per year of follow-up was 2.7% in nondiabetic and 6.0% in diabetic patients. In diabetic patients, a history of coronary artery disease was the only predictor of cardiac events (R = 0.18, P < .05). Conclusion Compared with nondiabetic patients, diabetic patients with negative stress echocardiograms are at greater risk for cardiac events. This appears to be due to a higher prevalence of established coronary disease in diabetic patients. (Am Heart J 2002;143:163-8.)     

Serum glucose and lipid levels in adult congenital heart disease patients

Atherosclerosis has been correlated with known cardiovascular risk factors such as serum glucose or lipid levels. Because congenital heart disease patients tend to survive until adulthood, atherosclerosis has also become a matter of concern in these patients. One hundred fifty-eight congenital heart disease patients and 152 patients selected at random from the population were studied and compared to determine serum glucose, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein cholesterol, and triglycerides levels. Both groups had similar socioeconomic status levels and the same environmental influences. Significant differences were seen between congenital heart disease patients and the control group, after sex, age, and body mass index adjustment, in fasting plasma glucose (97.7 [94.2-101.2] vs 86.9 [83.2-90.7], P < .001), total cholesterol (171.5 [165.7-177.3] vs 199.8 [90.7-206.0], P < .001), LDL cholesterol (103.9 [98.8-108.8] vs 123.8 [118.5-129.1], P < .001), and high-density lipoprotein cholesterol (48.1 [46.2-50.0] vs 54.2 [52.1-56.2], P < .001) levels. Nonsignificant differences were seen in triglycerides concentrations. Those patients with ventricular septal defect, coarctation of the aorta, and cyanosis had the lowest total cholesterol and LDL cholesterol concentrations. Congenital heart disease patients have lower plasma cholesterol concentrations and higher serum glucose levels than noncongenital ones.     

Influence of Coronary Anatomy and SYNTAX Score on the Variations in Revascularization Strategies for Patients With Multivessel Disease

Background

The Variation in Revascularization Practice in Ontario (VRPO) project helped describe variations in revascularization across Ontario. Coronary anatomy was the most important predictor of revascularization strategy. We conducted a novel angiographic substudy of the VRPO cohort to: (1) validate “real-world” coronary angiographic reporting in the province of Ontario; and (2) understand the relationship between variability in revascularization and coronary anatomy complexity.

Methods

Seventeen hundred eighty-seven angiograms from 17 cardiac centres were randomly sampled from the VRPO cohort. The core lab assessment involved blinded interpretation of each angiographic film. A comparison of agreement in coronary anatomy and treatment strategy between abstracted chart data from the VRPO study and blinded film review was undertaken. Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) scores were calculated for all patients with multivessel disease.

Results

The weighted κ statistic for coronary anatomy was 0.75 (95% confidence interval, 0.72-0.77), suggesting substantial agreement between abstracted chart data and blinded film review. The weighted κ for revascularization strategy was 0.51 (95% confidence interval, 0.47-0.54) suggesting only moderate agreement. There were no significant differences in the mean/median SYNTAX scores across all 4 percutaneous coronary intervention: coronary artery bypass graft (CABG) groups.

Conclusions

Abstracted chart data in the VRPO project provides a valid assessment of coronary anatomy and furthermore serves as validation of “real-world” coronary angiographic reporting in the province of Ontario. The uniform distribution of coronary complexity across centres in Ontario, with respect to the SYNTAX score, suggests the variation of percutaneous coronary intervention: CABG ratio is not related to a difference in coronary anatomy complexity across sites, but rather a difference in management strategies for the same anatomy.     

Inhospital outcome of acute myocardial infarction in patients with prior coronary artery bypass surgery

Objectives Our goals were to compare the characteristics of patients with and without prior coronary artery bypass graft (CABG) presenting with acute myocardial infarction (MI) with or without ST elevation/left bundle branch block (LBBB), and to evaluate the effect of ST shift on inhospital mortality. Methods and Results Using the National Registry of Myocardial Infarction-3 Registry, we identified 112,697 patients with acute MI without exclusion criteria. Of these, 15,936 (14.1%) had prior CABG. Patients with prior CABG had more adverse characteristics and were less likely to have ST elevation/LBBB than patients without prior CABG. The unadjusted mortality for ST elevation/LBBB patients was higher in patients with prior CABG versus without (16.2% vs 14.1%, P = .0001), whereas in patients without ST elevation/LBBB, prior CABG conferred a lower unadjusted mortality versus without (10.1% vs 12.4%, P = .0001). Adjusting for baseline differences, prior CABG was weakly associated with inhospital mortality in ST elevation/LBBB patients (odds ratio [OR], 1.11, 95% CI 1.00-1.23), but not in patients without ST elevation/LBBB (OR 0.99, 95% CI 0.92-1.07). Conclusion Acute MI patients with prior CABG are more likely to present without ST elevation/LBBB than patients without prior CABG. Prior CABG was weakly associated with inhospital mortality in patients with ST elevation/LBBB, but not in patients without these electrocardiographic findings. This suggests the differences in absolute mortality rates between patients presenting with MI with and without a history of prior CABG are largely caused by differences in baseline characteristics and presentation. (Am Heart J 2002;144:463-9.)     

Hepatocyte growth factor as a potential predictor of the presence of atherosclerotic aorto-iliac artery disease

Background Hepatocyte growth factor (HGF), a member of the endothelial-specific growth factors with the greatest mitogenic activity, may play a role in the protection and/or repair of vascular endothelial cells injured by atherosclerosis. As a result, plasma HGF concentration may increase in response to endothelial cell damage. To test this hypothesis, we measured plasma concentrations of HGF in patients with or without aorto-iliac artery atherosclerotic disease. Methods One hundred ten consecutive patients who underwent coronary angiography were enrolled in this study. Abdominal aortography was performed after coronary arteriography to determine whether aorto-iliac artery atherosclerotic disease was present. Peripheral venous blood samples were obtained to measure the plasma HGF concentration. Results Aortography revealed aorto-iliac atherosclerotic disease in 35 patients (32%). The plasma HGF concentration was significantly higher in patients with arteriosclerotic lesions (0.35 ± 0.11 ng/mL) than in patients without atherosclerotic lesions (0.27 ± 0.09 ng/mL, P = .0002). On the basis of multiple logistic regression analysis of the relationships between coronary risk factors, age, sex, severity of coronary artery disease, plasma HGF concentration, and the presence of arteriosclerotic lesions, plasma HGF concentration (P = .0005) and age (P = .035) were found to predict independently the presence of aorto-iliac arteriosclerosis. Conclusion Plasma HGF concentration can be used to predict the presence of arteriosclerotic lesions in the region from the abdominal aorta to the femoral arteries. (Am Heart J 2002;143:272-6.)     

Home-based versus hospital-based exercise programs in patients with coronary artery disease: effects on coronary vasomotion

Background In a randomized study, we recently documented that a vigorous, hospital-based exercise training (ET) program improves coronary endothelial function in coronary artery disease. The aim of this consecutive study was to assess whether a home-based exercise program with reduced average training duration can sustain previously achieved effects on coronary endothelial function.Methods Nineteen patients with coronary endothelial dysfunction documented by acetylcholine-induced vasoconstriction were randomly assigned to a training group (n = 10) or a control group (n = 9). After 4 weeks of inhospital training (60 min of bicycle ergometry per day), all training patients were enrolled in a 5-month home-based program of 20 minutes' ergometry training per day and 1 group training session per week. At baseline, after 4 weeks and 6 months, endothelium-mediated vasodilation was assessed by quantitative coronary angiography after intracoronary infusions of acetylcholine. Average peak velocity (APV) was measured with a Doppler wire. Coronary blood flow (CBF) was calculated by multiplying vascular cross-sectional area and APV.Results CBF increased in response to 7.2 μg/min acetylcholine, from 27% ± 11% at the beginning of the study to 110% ± 24% after 4 weeks (P < .01 vs control group). After 6 months, the increase in CBF was lower versus inhospital training (67% ± 18%, P < .05 vs 4 weeks). Changes in APV between 1 and 6 months correlated with daily training durations (r = 0.65, P = .03).Conclusions Home-based ET sustained part of the effects of hospital-based ET on endothelium-dependent vasodilation in coronary artery disease. However, acetylcholine-induced increases in CBF were lower after home-based ET, suggesting a relation between daily training duration and improvement of coronary vasomotion. (Am Heart J 2003;145:e3.)     

Relationship between vascular dysfunction in peripheral arteries and ischemic episodes during daily life in patients with ischemic heart disease and hypercholesterolemia

Background It is well established that endothelial dysfunction is present in patients with ischemic heart disease and hypercholesterolemia. Some of these patients will have signs of transient myocardial ischemia during Holter monitoring. We sought to describe the correlation between daily life ischemia and signs of endothelial dysfunction as assessed by means of brachial vasoreactivity. Methods We included in the study 131 patients with documented ischemic heart disease and a serum cholesterol level of ≥5 mmol/L before the institution of lipid-lowering treatment and dietary intervention. Results Satisfactory 48-hour Holter recordings and ultrasound scans of the brachial artery were obtained in 119 patients. During 5712 hours of ambulatory monitoring, 181 episodes of transient ST-segment depression with a mean duration of 52 ± 66 minutes were recorded in 31 patients. The mean percentage dilatation of the brachial artery after occlusion was 4.38% ± 5.66%; after nitroglycerin administration, it was 13.86% ± 7.06%. By means of Spearman correlation analysis, the number of ischemic episodes and degree of flow-mediated vasodilatation and nitroglycerin-mediated vasodilatation were significantly negatively correlated (r = −0.249, P = .006 and r = −0.302, P = .02, respectively). In a linear regression model, the presence of ischemic episodes was a significant predictor of impaired flow-mediated vasodilatation (β = −3.31, P < .01), even after the adjustment for vessel size and classic cardiovascular risk factors. Conclusions These results indicate a significant relationship between ischemic episodes and vascular dysfunction in patients with ischemic heart disease and hypercholesterolemia and may justify an aggressive preventive therapy targeted directly at the endothelium. (Am Heart J 2002;144:108-14.)     

Effect of 300- and 450-mg clopidogrel loading doses on membrane and soluble P-selectin in patients undergoing coronary stent implantation

Background After coronary artery stent implantation patients are treated with the adenosine diphosphatase (ADP) receptor antagonist clopidogrel to prevent subacute stent thromboses. Today these patients initially receive a loading dose of 300 mg of clopidogrel to accelerate the complete drug effect. In the current study we investigated whether a higher loading dose can shorten the time until the maximum platelet inhibitory effect of clopidogrel is achieved. Methods P-selectin expression of nonstimulated and ADP-stimulated platelets was flow cytometrically measured before the clopidogrel loading dose and on 3 consecutive days in 52 patients with coronary artery disease: 21 patients in group 1 received 300 mg of clopidogrel after stent implantation and 11 patients in group 2 received the higher 450-mg clopidogrel loading dose followed by a daily dose of 75 mg of clopidogrel for both groups. The control group consisted of 20 patients who were monitored over 2 days before coronary intervention. Soluble P-selectin levels in plasma were determined by an enzyme-linked immunosorbent assay. Results Inducible P-selectin expression on ADP-stimulated platelets was significantly reduced (P = .05) on days 1 and 2 in patient group 2 (450-mg loading dose) compared with group 1 (300-mg loading dose). No influence of clopidogrel on the P-selectin levels in plasma was observed. Conclusions In our study the application of 450 mg of clopidogrel as the loading dose in patients undergoing coronary stenting shortens the period until the maximum effect of the ADP receptor antagonist is achieved and thus may lead to a more successful prevention of subacute coronary stent thromboses. (Am Heart J 2002;143:118-23.)     

Peripheral endothelium-dependent flow-mediated vasodilatation is associated with left ventricular mass in older persons with hypertension

Background Increased left ventricular (LV) mass is associated with greater cardiovascular disease risk. Recent studies have also shown an association of increased LV mass with attenuated endothelium-dependent coronary flow reserve. Less is known about the association between LV mass and endothelium-dependent flow-mediated dilatation (FMD) in peripheral arteries, a noninvasive measure of endothelial function. Methods Sixty-two subjects with untreated mild hypertension, aged 55 to 75 years and otherwise healthy, were examined. Resting blood pressure was obtained by the average of 4 to 5 visits, each at least 1 week apart. LV mass was determined from magnetic resonance imaging and was indexed by body surface area, height and height^2.7. Body composition was assessed with dual energy x-ray absorptiometry. FMD was measured as the percent change of brachial artery diameter during reactive hyperemia by use of high-resolution ultrasound. Results Median LV mass index was 63 g/m² (interquartile range, 58-73). In bivariate analysis, LV mass was correlated to lean body mass (r = 0.63, P < .001), diastolic blood pressure (r = 0.35, P < .01), and FMD (r = −0.27, P < .05). In multivariate analysis, 44% of the variance in log-LV mass was explained by lean body mass. An additional 6% of the variance was explained by FMD (P < .05). For each 1% point decrease in FMD, LV mass increased by 1.1%. Conclusions In addition to the expected influences of body size, impairment of brachial artery FMD was independently related to LV mass in elderly subjects with mild hypertension who did not yet have LV hypertrophy. Whether mild hypertension is the common mechanism linking LV mass and endothelial function has yet to be determined. (Am Heart J 2002;144:39-44.)     

Electron beam tomography and angiography: sex differences

Background We sought to study a large cohort of symptomatic women to determine the clinical use of electron beam tomography (EBT), with evaluation of the sensitivity and specificity of obstructive coronary disease and the differences between premenopausal and postmenopausal cohorts. Methods Patients who underwent angiography for evaluation of coronary artery disease (CAD) and EBT within 3 months were enrolled. Receiver operating characteristic curves were used to establish relationships between EBT calcium scores and angiographic disease. Results We studied 1120 symptomatic patients, 387 women and 733 men. We found no significant differences with respect to sensitivity for obstructive disease (96% in men and women). However, women had a significantly higher specificity (46% in men versus 57% in women; P = .01). The area under the curves for coronary calcium score predicting angiographic disease was 0.85 for all patients and 0.84 in women. Evaluation of scores on the basis of age revealed a 14.4-year lag between men and women. One hundred thirty-five women had negative EBT study results (score, zero; no calcium present), with 6 with single-vessel disease and 129 with normal coronaries or nonobstructive disease only (negative predictive value, 96%). Conclusion EBT may have a great value in evaluation of women with possible CAD. The high sensitivity and high negative predictive value may serve as the basis for a new diagnostic approach to filter symptomatic women with suspected CAD before coronary angiography. (Am Heart J 2002;143:877-82.)     

Large brachial artery diameter is associated with angiographic coronary artery disease in women

Background Noninvasive methods are needed for the identification of women at highest risk for coronary artery disease (CAD) who might benefit most from aggressive preventive therapy. Identification of brachial artery atherosclerosis, which correlates with coronary artery atherosclerosis, may be useful to estimate or stratify CAD risk. Because atherosclerosis disrupts the arterial architecture that regulates vessel size, we hypothesized that noninvasively measured large brachial artery diameter is a manifestation of atherosclerosis that is associated with angiographic CAD in women with chest pain. Methods We examined 376 women (mean age, 57.1 years) with chest pain in the National Heart, Lung, and Blood Institute's Women's Ischemia Syndrome Evaluation study who underwent B-mode ultrasound scan measurement of brachial artery diameter at rest and during hyperemic stress (to quantify flow-mediated dilation), quantitative coronary angiography, and risk factor assessment. Results Large resting brachial artery diameter was associated with significant angiographic CAD (3.90 ± 0.79 mm vs 3.52 ± 0.59 mm in women with CAD vs no CAD; P < .001). Impaired flow-mediated dilation, which correlated with resting diameter (r = −0.17; P = .001), was weakly associated with significant CAD (2.74% ± 7.11% vs 4.48% ± 9.52% in CAD vs no CAD; P = .046). After adjustment for age, body size, and CAD risk factors, women with large resting brachial artery diameters (>4.1 mm) had 3.6-fold increased odds (95% confidence interval, 1.8 to 7.1; P < .001) of significant angiographic CAD compared with those with small brachial arteries (≤3.6 mm). Conclusion Large resting brachial artery diameter is an independent predictor of significant CAD in women with chest pain. Therefore, a simple ultrasonographic technique may be useful in the identification of women with chest pain who are at increased risk for CAD. (Am Heart J 2002;143:802-7.)     

Implantation of CD133 Stem Cells in Patients Undergoing Coronary Bypass Surgery: IMPACT-CABG Pilot Trial

Background

The Implantation of Autologous CD133⁺ Stem Cells in Patients Undergoing CABG (IMPACT-CABG) trial is investigating the feasibility, safety, and efficacy of intramyocardial injections of autologous CD133⁺ stem cells during coronary artery bypass grafting (CABG) in patients with chronic ischemic cardiomyopathy. We are reporting the results of the first 5 open-label patients.

Methods

Bone marrow was harvested from iliac crests and stem cells were isolated using the CliniMACS CD133⁺ Reagent System (Miltenyi Biotec, GmbH, Bergisch Gladbach, Germany). Patients received CABG, followed by CD133⁺ cellular injection in the revascularized hypokinetic myocardium.

Results

Five males New York Heart Association (NYHA) class III patients aged 64 ± 10 years were treated. Immunomagnetic cell processing allowed an average of 100 ± 48-fold enrichment in CD133⁺ cells, with 92 ± 11% recovery after selection. Mean number of CD133⁺ cells injected was 8.4 ± 1.2 million. There were no protocol-related complications during the 18-month follow-up and all patients improved to NYHA class I. Six-month echocardiography showed no significant improvement in left ventricular ejection fraction (34 ± 2% at baseline vs 38 ± 12%: P = 0.50). However, cardiac magnetic resonance showed that systolic wall thickening increased from 15.0 ± 10.5% to 29.0 ± 22.1% (P = 0.01). In addition, mean segmental wall thickness also improved in comparison with baseline (10.7 ± 2.7% to 12.1 ± 4.8%; P < 0.01).

Conclusions

This work represents the first Canadian experience with CD133⁺ stem cells for the treatment of chronic ischemic cardiomyopathy. These results demonstrate the initial safety and feasibility of the IMPACT-CABG pilot trial. Subsequent patients are now being randomized to receive either CD133⁺ stem cell or placebo.     

Impact of renal function on morbidity and mortality after percutaneous aortocoronary saphenous vein graft intervention

Background Percutaneous coronary intervention in patients with chronic renal insufficiency (CRI) and native coronary artery disease is often problematic, marred by increased morbidity and mortality rates and a high incidence of restenosis and revascularization. However, little is known about the effect of CRI in patients who have undergone prior coronary artery bypass graft surgery and then undergo saphenous vein graft (SVG) intervention. Methods We analyzed the inhospital and 1-year outcomes of 1265 consecutive patients with normal renal function and varying degrees of renal insufficiency who underwent percutaneous SVG intervention and divided them into 4 groups on the basis of the calculated creatinine clearance (CrCl): group 1, CrCl ≥70 mL per minute (n = 626); group 2, CrCl 50 to 69 mL per minute (n = 357); group 3, CrCl 30 to 49 mL per minute (n = 228); and group 4, CrCl <30 mL per minute (n = 54). Patients undergoing dialysis replacement therapy were excluded from the study. Results Patients with lower CrCl more often were older, female, had diabetes mellitus, and had worse left ventricular function. Angiographic baseline characteristics were comparable among the 4 groups. Overall immediate procedural success was similar for all groups. Patients with a low CrCl had significantly higher inhospital overall and cardiac mortality rates (P < .001), including a significantly higher incidence of myocardial infarction, vascular complications, pulmonary edema, and renal function deterioration. At 1-year follow-up, the overall mortality rates remained significantly higher in patients with decreased CrCl, with an incremental rise in overall mortality rate associated with lower renal function (P < .001). Conclusions This study suggests that renal function is a primary determinate of short- and long-term survival in patients undergoing percutaneous SVG intervention and that there is a clear relationship between CrCl and cardiovascular outcome. (Am Heart J 2003;145:529-34.)     

Impact of body iron status on myocardial perfusion, left ventricular function, and angiographic morphologic features in patients with hypercholesterolemia

Background Previous studies have shown that the effects of iron stores on atherogenesis through promotion of free radical formation and low-density lipoprotein (LDL) oxidation largely depend on the state of hypercholesterolemia (HCL) in animal models. A synergistic association of serum ferritin and LDL cholesterol with the risk of myocardial infarction has also been observed in humans. Methods We sought to assess the relationship of serum iron parameters to myocardial perfusion and wall motion abnormalities and to the extent of angiographic coronary artery disease (CAD) in patients with HCL. Sixty-eight male patients (mean age 58 ± 9 years) with hypercholesterolemia (LDL cholesterol >130 mg/dL) who had never been treated and 52 normocholesterolemic male subjects of similar age underwent coronary angiography and exercise technetium-99m sestamibi gated single-photon emission computed tomography imaging within 10 days. Results Serum ferritin had a significant correlation with the perfusion index (r = 0.70, P < .001), the reversibility index (r = 0.68, P < .01), and the wall motion index (r = 0.54, P < .05), whereas a relatively weak correlation was observed between total iron binding capacity and perfusion index (inversely) (r = −0.59, P < .01) in patients with HCL. Iron parameters were not associated with either perfusion or wall motion indices in the normocholesterolemic group. Stepwise multiple regression analysis confirmed these results. Ferritin was a strong determinant of perfusion in patients with HCL only (β = .55, P = .002). Iron parameters were not related to the angiographic extent of CAD as defined by angiographic vessel or extent score in either group. Conclusions Our data suggest that increased iron stores are closely associated with a greater extent and severity of perfusion and functional abnormalities but not with the angiographic extent of CAD in patients with HCL. Enhanced iron-mediated oxidative stress and LDL peroxidation may contribute to the hypercholesterolemia-related endothelial dysfunction and cause further impairment of myocardial perfusion and wall motion. (Am Heart J 2002;143:257-64.)     

Prognostic significance of coronary artery calcium in asymptomatic subjects with usual cardiovascular risk

Background Coronary calcium detected noninvasively is an attractive way to diagnose atherosclerosis before the development of symptoms. This study examines the prognostic value of coronary calcium in asymptomatic subjects with usual cardiovascular risk. Methods and Results In 425 asymptomatic subjects, 229 men (aged 45.1 ± 14 years) and 196 women (aged 42.7 ± 13 years), coronary calcium presence was studied by digital cinefluoroscopy. The majority (76%) had no or at most one risk factor. Subjects were followed up for 58.4 ± 12.7 months for cardiac events. Coronary calcium was present in 76 of 425 (17.9%) subjects. Cardiac events were observed in 21 subjects: 2 cardiac deaths, 7 acute myocardial infarctions, 3 coronary artery bypass grafts, 3 coronary angioplasty procedures, 3 events of unstable angina, and 10 events of stable angina pectoris. Survival curve analysis showed significant differences in all the studied end points between subjects with and those without calcium. Coronary calcium was an independent predictor of all events (3.6-fold increase, P < .008), cardiac death/myocardial infarction/revascularization (13.9-fold increase, P < .02), and stable angina (7.4-fold increase, P < .007). However, calcium did not independently predict cardiac death/myocardial infarction or acute coronary syndromes. Conclusions Coronary calcium in asymptomatic subjects with usual cardiovascular risk adds significant incremental information to risk factors information for the development of symptomatic coronary artery disease. (Am Heart J 2003;145:542-8.)     

Influence of left ventricular size and hemodynamics on the systolic longitudinal myocardial Doppler velocity response to stress

Background Systolic myocardial Doppler velocity accurately identifies coronary artery disease. However, these velocities may be affected by age, hemodynamic responses to stress, and left ventricular cavity size. We sought to examine the influences of these variables on myocardial velocity during dobutamine stress in patients with normal wall motion. Methods One hundred seventy-nine consecutive patients with normal dobutamine echocardiograms were studied. Color myocardial tissue Doppler data were obtained at rest and peak stress, and peak systolic myocardial velocity (PSV) was measured in all basal and midventricular segments. Velocities at rest and peak stress were compared with left ventricular diastolic and systolic volumes, blood pressure, heart rate, and age by Pearson correlation and interdecile analysis by use of analysis of variance. Results The only clinical variable correlating with velocity was age; PSV showed only mild correlation with age at rest (r² = 0.01, P = .001) and peak stress (r² = 0.02, P = .001), but the normal peak velocity was significantly different between the extremes of age (<44 years and >74 years). There was very weak correlation of PSV with systolic and diastolic blood pressure (r² < 0.01), heart rate (r² < 0.01), systemic vascular resistance (r² = 0.08), and left ventricular volumes (r² < 0.01). Conclusions Peak systolic velocity during dobutamine stress is relatively independent of hemodynamic factors and left ventricular cavity size. The extremes of age may influence peak systolic Doppler velocities. These results suggest that peak systolic velocity may be a robust quantitative measure during dobutamine echocardiography across most patient subgroups. (Am Heart J 2002;143:169-75.)