G.B. John Mancini

Optimal Medical Therapy With or Without Percutaneous Coronary Intervention to Reduce Ischemic Burden Results From the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) Trial Nuclear Substudy

Background— Extent and severity of myocardial ischemia are determinants of risk for patients with coronary artery disease, and ischemia reduction is an important therapeutic goal. The Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) nuclear substudy compared the effectiveness of percutaneous coronary intervention (PCI) for ischemia reduction added to optimal medical therapy (OMT) with the use of myocardial perfusion single photon emission computed tomography (MPS). Methods and Results— Of the 2287 COURAGE patients, 314 were enrolled in this substudy of serial rest/stress MPS performed before treatment and 6 to 18 months (mean=374±50 days) after randomization using paired exercise (n=84) or vasodilator stress (n=230). A blinded core laboratory analyzed quantitative MPS measures of percent ischemic myocardium. Moderate to severe ischemia encumbered ≥10% myocardium. The primary end point was ≥5% reduction in ischemic myocardium at follow-up. Treatment groups had similar baseline characteristics. At follow-up, the reduction in ischemic myocardium was greater with PCI+OMT (−2.7%; 95% confidence interval, −1.7%, −3.8%) than with OMT (−0.5%; 95% confidence interval, −1.6%, 0.6%; P<0.0001). More PCI+OMT patients exhibited significant ischemia reduction (33% versus 19%; P=0.0004), especially patients with moderate to severe pretreatment ischemia (78% versus 52%; P=0.007). Patients with ischemia reduction had lower unadjusted risk for death or myocardial infarction (P=0.037 [risk-adjusted P=0.26]), particularly if baseline ischemia was moderate to severe (P=0.001 [risk-adjusted P=0.08]). Death or myocardial infarction rates ranged from 0% to 39% for patients with no residual ischemia to ≥10% residual ischemia on follow-up MPS (P=0.002 [risk-adjusted P=0.09]). Conclusions— In COURAGE patients who underwent serial MPS, adding PCI to OMT resulted in greater reduction in ischemia compared with OMT alone. Our findings suggest a treatment target of ≥5% ischemia reduction with OMT with or without coronary revascularization.

Angiotensin-Converting Enzyme Inhibition With Quinapril Improves Endothelial Vasomotor Dysfunction in Patients With Coronary Artery Disease

Background Angiotensin-converting enzyme (ACE) inhibitors may exert some of their benefits in the therapy of hypertension, congestive heart failure, and acute myocardial infarction by their improvement of endothelial dysfunction. TREND (Trial on Reversing ENdothelial Dysfunction) investigated whether quinapril might improve endothelial dysfunction in normotensive patients with coronary artery disease and no heart failure, cardiomyopathy, or major lipid abnormalities so that confounding variables that affect endothelial dysfunction could be minimized. Methods and Results Using a double-blind, randomized, placebo-controlled design, we measured the effects of quinapril (40 mg daily) on coronary artery diameter responses to acetylcholine using quantitative coronary angiography. The primary response variable was the net change in the acetylcholine-provoked constriction of target segments between the baseline (prerandomization) and 6-month follow-up angiograms. The constrictive responses to acetylcholine were c...

Angiotensin-Converting Enzyme Inhibition With Quinapril Improves Endothelial Vasomotor Dysfunction in Patients With Coronary Artery Disease The TREND (Trial on Reversing ENdothelial Dysfunction) Study

BACKGROUND Angiotensin-converting enzyme (ACE) inhibitors may exert some of their benefits in the therapy of hypertension, congestive heart failure, and acute myocardial infarction by their improvement of endothelial dysfunction. TREND (Trial on Reversing ENdothelial Dysfunction) investigated whether quinapril might improve endothelial dysfunction in normotensive patients with coronary artery disease and no heart failure, cardiomyopathy, or major lipid abnormalities so that confounding variables that affect endothelial dysfunction could be minimized. METHODS AND RESULTS Using a double-blind, randomized, placebo-controlled design, we measured the effects of quinapril (40 mg daily) on coronary artery diameter responses to acetylcholine using quantitative coronary angiography. The primary response variable was the net change in the acetylcholine-provoked constriction of target segments between the baseline (prerandomization) and 6-month follow-up angiograms. The constrictive responses to acetylcholine were comparable in the placebo (n = 54) and quinapril (n = 51) groups at baseline. After 6 months, only the quinapril group showed significant net improvement in response to incremental concentrations of acetylcholine (4.5 +/- 3.0% [mean +/- SEM] versus -0.1 +/- 2.8% at 10(-6) mol/L and 12.1 +/- 3.0% versus -0.8 +/- 2.9% at 10(-4) mol/L, quinapril versus placebo, respectively; overall P = .002). CONCLUSIONS TREND shows that ACE inhibition with quinapril improved endothelial dysfunction in patients who were normotensive and who did not have severe hyperlipidemia or evidence of heart failure. These benefits of ACE inhibition are likely due to attenuation of the contractile effects and superoxide-generating effects of angiotensin II and to enhancement of endothelial cell release of nitric oxide secondary to diminished breakdown of bradykinin.

Effect of Amlodipine on the Progression of Atherosclerosis and the Occurrence of Clinical Events

BackgroundThe results of angiographic studies have suggested that calcium channel–blocking agents may prevent new coronary lesion formation, the progression of minimal lesions, or both. Methods and ResultsThe Prospective Randomized Evaluation of the Vascular Effects of Norvasc Trial (PREVENT) was a multicenter, randomized, placebo-controlled, double-masked clinical trial designed to test whether amlodipine would slow the progression of early coronary atherosclerosis in 825 patients with angiographically documented coronary artery disease. The primary outcome was the average 36-month angiographic change in mean minimal diameters of segments with a baseline diameter stenosis of 30%. A secondary hypothesis was whether amlodipine would reduce the rate of atherosclerosis in the carotid arteries as assessed with B-mode ultrasonography, which measured intimal-medial thicknesses (IMT). The rates of clinical events were also monitored. The placebo and amlodipine groups had nearly identical average 36-month reductions in the minimal diameter: 0.084 versus 0.095 mm, respectively (P =0.38). In contrast, amlodipine had a significant effect in slowing the 36-month progression of carotid artery atherosclerosis: the placebo group experienced a 0.033-mm increase in IMT, whereas there was a 0.0126-mm decrease in the amlodipine group (P =0.007). There was no treatment difference in the rates of all-cause mortality or major cardiovascular events, although amlodipine use was associated with fewer cases of unstable angina and coronary revascularization. ConclusionsAmlodipine has no demonstrable effect on angiographic progression of coronary atherosclerosis or the risk of major cardiovascular events but is associated with fewer hospitalizations for unstable angina and revascularization.

2012 Update of the Canadian Cardiovascular Society Guidelines for the Diagnosis and Treatment of Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult

Many developments have occurred since the publication of the widely-used 2009 Canadian Cardiovascular Society (CCS) Dyslipidemia guidelines. Here, we present an updated version of the guidelines, incorporating new recommendations based on recent findings and harmonizing CCS guidelines with those from other Societies. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used, per present standards of the CCS. The total cardiovascular disease Framingham Risk Score (FRS), modified for a family history of premature coronary disease, is recommended for risk assessment. Low-density lipoprotein cholesterol remains the primary target of therapy. However, non-high density lipoprotein cholesterol has been added to apolipoprotein B as an alternate target. There is an increased emphasis on treatment of higher risk patients, including those with chronic kidney disease and high risk hypertension. The primary panel has recommended a judicious use of secondary testing for subjects in whom the need for statin therapy is unclear. Expanded information on health behaviours is presented and is the backbone of risk reduction in all subjects. Finally, a systematic approach to statin intolerance is advocated to maximize appropriate use of lipid-lowering therapy. This document presents the recommendations and principal conclusions of this process. Along with associated Supplementary Material that can be accessed online, this document will be part of a program of knowledge translation. The goal is to increase the appropriate use of evidence-based cardiovascular disease event risk assessment in the management of dyslipidemia as a fundamental means of reducing global risk in the Canadian population.

Estimated Radiation Dose Reduction Using Adaptive Statistical Iterative Reconstruction in Coronary CT Angiography: The ERASIR Study

OBJECTIVE The objective of our study was to assess the impact of Adaptive Statistical Iterative Reconstruction (ASIR) on radiation dose and study quality for coronary CT angiography (CTA). SUBJECTS AND METHODS We prospectively evaluated 574 consecutive patients undergoing coronary CTA at three centers. Comparisons were performed between consecutive groups initially using filtered back projection (FBP) (n = 331) and subsequently ASIR (n = 243) with regard to patient and scan characteristics, radiation dose, and diagnostic study quality. RESULTS There was no difference between groups in the use of prospective gating, tube voltage, or scan length. The examinations performed using ASIR had a lower median tube current than those obtained using FBP (median [interquartile range], 450 mA [350-600] vs 650 mA [531-750], respectively; p < 0.001). There was a 44% reduction in the median radiation dose between the FBP and ASIR cohorts (4.1 mSv [2.3-5.2] vs 2.3 mSv [1.9-3.5]; p < 0.001). After adjustment for scan settings, ASIR was associated with a 27% reduction in radiation dose compared with FBP (95% CI, 21-32%; p < 0.001). Despite the reduced current, ASIR was not associated with a difference in adjusted signal, noise, or signal-to-noise ratio (p = not significant). No differences existed between FBP and ASIR for interpretability per coronary artery (98.5% vs 99.3%, respectively; p = 0.12) or per patient (96.1% vs 97.1%, p = 0.65). CONCLUSION. ASIR enabled reduced tube current and lower radiation dose in comparison with FBP, with preserved signal, noise, and study interpretability, in a large multicenter cohort. ASIR represents a new technique to reduce radiation dose in coronary CTA studies.

Adaptive Statistical Iterative Reconstruction: Assessment of Image Noise and Image Quality in Coronary CT Angiography

OBJECTIVE The purpose of our study was to determine the effect of Adaptive Statistical Iterative Reconstruction (ASIR) on cardiac CT angiography (CTA) signal, noise, and image quality. MATERIALS AND METHODS We evaluated 62 consecutive patients at three sites who underwent clinically indicated cardiac CTA using an ASIR-capable 64-MDCT scanner and a low-dose cardiac CTA technique. Studies were reconstructed using filtered back projection (FBP), ASIR-FBP composites using 20-80% ASIR, and 100% ASIR. The signal and noise were measured in the aortic root and each of the four coronary arteries. Two blinded readers graded image quality on a 5-point Likert scale and determined the proportion of interpretable segments. All segments were included for analysis regardless of size. RESULTS In comparison with FBP (0% ASIR), the use of 20%, 40%, 60%, 80%, and 100% ASIR resulted in reduced image noise between groups (-7%, -17%, -26%, -35%, and -43%, respectively; p < 0.001) without difference in signal (p = 0.60). There were significant differences between groups (0%, 20%, 40%, 60%, 80%, and 100% ASIR) in the Likert scores (1.5, 2.1, 3.7, 3.8, 2.0, and 1.1, respectively; p < 0.001) and proportion of interpretable segments (88.7%, 89.3%, 90.5%, 90.4%, 88.0%, and 87.3%, respectively; p < 0.001). Reconstruction using 40% and 60% ASIR had the highest Likert scores and largest proportion of interpretable segments. In comparison with FBP, each was associated with higher Likert scores and increased interpretable segments (p < 0.001 for all). CONCLUSION ASIR resulted in noise reduction and significantly impacted image quality. When using a low tube current technique, cardiac CTA reconstruction using 40% or 60% ASIR significantly improved image quality and the proportion of interpretable segments compared with FBP reconstruction.

Reduction in cardiovascular events during pravastatin therapy : Pooled analysis of clinical events of the pravastatin atherosclerosis intervention program

BACKGROUND It has been documented that the HMG coenzyme A reductase inhibitors, or statins, can decrease cardiovascular events and mortality in patients with clinical coronary disease and moderately to severely elevated lipid levels. Additional data are required to demonstrate a reduction of vascular events in coronary patients with less than severely elevated lipid levels and in subgroups of this population. METHODS AND RESULTS Clinical data from four atherosclerosis regression trials that evaluated pravastatin were pooled for a predetermined analysis of the effect of that agent on the risk of coronary events. All trials were double-masked, placebo-controlled designs that used pravastatin as monotherapy for 2 to 3 years. The 1981 participants in the trials had evidence of atherosclerosis and mildly to moderately elevated lipid levels. For fatal or nonfatal myocardial infarction, there was a 62% reduction in events attributable to pravastatin (P = .001). This effect was evident in younger and older patients, men and women, and patients with and without histories of hypertension and prior infarction. There was a 46% reduction in all-cause mortality (P = .17), which, although not statistically significant, is consistent with the results of other statin trials. There also was a 62% reduction in the risk of fatal or nonfatal stroke (P = .054). CONCLUSIONS These pooled results provide strong evidence that pravastatin reduces the risk of cardiovascular events in patients with atherosclerotic disease and mildly to moderately elevated lipid levels. The benefit for reducing myocardial infarction is evident in older and younger patients, men and women, and patients with and without histories of hypertension and prior infarction.

SCCT guidelines for the interpretation and reporting of coronary CT angiography: A report of the Society of Cardiovascular Computed Tomography Guidelines Committee

Jonathon Leipsic MD, FSCCT Co-Chair*, Suhny Abbara MD, FSCCT, Stephan Achenbach MD, FSCCT, Ricardo Cury MD, FSCCT, James P. Earls MD, FSCCT, GB John Mancini MD, Koen Nieman MD, PhD, Gianluca Pontone MD, Gilbert L. Raff MD, FSCCT Co-Chair University of British Columbia, Vancouver, Canada University of Texas Southwestern Medical Center, Dallas, Texas University of Erlangen, Erlangen, Germany Baptist Cardiac and Vascular Institute, Miami, Florida Fairfax Radiological Consultants, PC, Fairfax, Virginia University of British Columbia, Vancouver, Canada Erasmus MC, Rotterdam, Netherlands Centro Cardiologico Monzino, Milan, Italy William Beaumont Hospital, Royal Oak, Michigan

Spontaneous Coronary Artery Dissection Association With Predisposing Arteriopathies and Precipitating Stressors and Cardiovascular Outcomes

Background—Nonatherosclerotic spontaneous coronary artery dissection (NA-SCAD) is underdiagnosed and an important cause of myocardial infarction in young women. The frequency of predisposing and precipitating conditions and cardiovascular outcomes remains poorly described. Methods and Results—Patients with NA-SCAD prospectively evaluated (retrospectively or prospectively identified) at Vancouver General Hospital were included. Angiographic SCAD diagnosis was confirmed by 2 experienced interventional cardiologists and categorized as type 1 (multiple lumen), 2 (diffuse stenosis), or 3 (mimic atherosclerosis). Fibromuscular dysplasia screening of renal, iliac, and cerebrovascular arteries were performed with angiography or computed tomographic angiography/MR angiography. Baseline, predisposing and precipitating conditions, angiographic, revascularization, in-hospital, and long-term events were recorded. We prospectively evaluated 168 patients with NA-SCAD. Average age was 52.1±9.2 years, 92.3% were women (62.3% postmenopausal). All presented with myocardial infarction. ECG showed ST-segment elevation in 26.1%, and 3.6% had ventricular tachycardia/ventricular fibrillation arrest. Fibromuscular dysplasia was diagnosed in 72.0%. Precipitating emotional or physical stress was reported in 56.5%. Majority had type 2 angiographic SCAD (67.0%), only 29.1% had type 1, and 3.9% had type 3. The majority (134/168) were initially treated conservatively. Overall, 6 of 168 patients had coronary artery bypass surgery and 33 of 168 had percutaneous coronary intervention in-hospital. Of those treated conservatively (n=134), 3 required revascularization for SCAD extension, and all 79 who had repeat angiogram ≥26 days later had spontaneous healing. Two-year major adverse cardiac events were 16.9% (retrospectively identified group) and 10.4% (prospectively identified group). Recurrent SCAD occurred in 13.1%. Conclusions—Majority of patients with NA-SCAD had fibromuscular dysplasia and type 2 angiographic SCAD. Conservative therapy was associated with spontaneous healing. NA-SCAD survivors are at risk for recurrent cardiovascular events, including recurrent SCAD.