Emir Veledar

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.

Effect of PCI on Quality of Life in Patients with Stable Coronary Disease

BACKGROUND It has not been clearly established whether percutaneous coronary intervention (PCI) can provide an incremental benefit in quality of life over that provided by optimal medical therapy among patients with chronic coronary artery disease. METHODS We randomly assigned 2287 patients with stable coronary disease to PCI plus optimal medical therapy or to optimal medical therapy alone. We assessed angina-specific health status (with the use of the Seattle Angina Questionnaire) and overall physical and mental function (with the use of the RAND 36-item health survey [RAND-36]). RESULTS At baseline, 22% of the patients were free of angina. At 3 months, 53% of the patients in the PCI group and 42% in the medical-therapy group were angina-free (P<0.001). Baseline mean (+/-SD) Seattle Angina Questionnaire scores (which range from 0 to 100, with higher scores indicating better health status) were 66+/-25 for physical limitations, 54+/-32 for angina stability, 69+/-26 for angina frequency, 87+/-16 for treatment satisfaction, and 51+/-25 for quality of life. By 3 months, these scores had increased in the PCI group, as compared with the medical-therapy group, to 76+/-24 versus 72+/-23 for physical limitation (P=0.004), 77+/-28 versus 73+/-27 for angina stability (P=0.002), 85+/-22 versus 80+/-23 for angina frequency (P<0.001), 92+/-12 versus 90+/-14 for treatment satisfaction (P<0.001), and 73+/-22 versus 68+/-23 for quality of life (P<0.001). In general, patients had an incremental benefit from PCI for 6 to 24 months; patients with more severe angina had a greater benefit from PCI. Similar incremental benefits from PCI were seen in some but not all RAND-36 domains. By 36 months, there was no significant difference in health status between the treatment groups. CONCLUSIONS Among patients with stable angina, both those treated with PCI and those treated with optimal medical therapy alone had marked improvements in health status during follow-up. The PCI group had small, but significant, incremental benefits that disappeared by 36 months. (ClinicalTrials.gov number, NCT00007657.)

Comparative Effectiveness of Exercise Electrocardiography With or Without Myocardial Perfusion Single Photon Emission Computed Tomography in Women With Suspected Coronary Artery Disease Results From the What Is the Optimal Method for Ischemia Evaluation in Women (WOMEN) Trial

Background— There is a paucity of randomized trials regarding diagnostic testing in women with suspected coronary artery disease (CAD). It remains unclear whether the addition of myocardial perfusion imaging (MPI) to the standard ECG exercise treadmill test (ETT) provides incremental information to improve clinical decision making in women with suspected CAD. Methods and Results— We randomized symptomatic women with suspected CAD, an interpretable ECG, and ≥5 metabolic equivalents on the Duke Activity Status Index to 1 of 2 diagnostic strategies: ETT or exercise MPI. The primary end point was 2-year incidence of major adverse cardiac events, defined as CAD death or hospitalization for an acute coronary syndrome or heart failure. A total of 824 women were randomized to ETT or exercise MPI. For women randomized to ETT, ECG results were normal in 64%, indeterminate in 16%, and abnormal in 20%. By comparison, the exercise MPI results were normal in 91%, mildly abnormal in 3%, and moderate to severely abnormal in 6%. At 2 years, there was no difference in major adverse cardiac events (98.0% for ETT and 97.7% for MPI; P=0.59). Compared with ETT, index testing costs were higher for exercise MPI (P<0.001), whereas downstream procedural costs were slightly lower (P=0.0008). Overall, the cumulative diagnostic cost savings was 48% for ETT compared with exercise MPI (P<0.001). Conclusions— In low-risk, exercising women, a diagnostic strategy that uses ETT versus exercise MPI yields similar 2-year posttest outcomes while providing significant diagnostic cost savings. The ETT with selective follow-up testing should be considered as the initial diagnostic strategy in symptomatic women with suspected CAD. Clinical Trial Registration— http://www.clinicaltrials.gov. Unique identifier: NCT00282711.

Prognostic Value of Stress Myocardial Perfusion Positron Emission Tomography: Results From a Multicenter Observational Registry

OBJECTIVES The primary objective of this multicenter registry was to study the prognostic value of positron emission tomography (PET) myocardial perfusion imaging (MPI) and the improved classification of risk in a large cohort of patients with suspected or known coronary artery disease (CAD). BACKGROUND Limited prognostic data are available for MPI with PET. METHODS A total of 7,061 patients from 4 centers underwent a clinically indicated rest/stress rubidium-82 PET MPI, with a median follow-up of 2.2 years. The primary outcome of this study was cardiac death (n = 169), and the secondary outcome was all-cause death (n = 570). Net reclassification improvement (NRI) and integrated discrimination analyses were performed. RESULTS Risk-adjusted hazard of cardiac death increased with each 10% myocardium abnormal with mildly, moderately, or severely abnormal stress PET (hazard ratio [HR]: 2.3 [95% CI: 1.4 to 3.8; p = 0.001], HR: 4.2 [95% CI: 2.3 to 7.5; p < 0.001], and HR: 4.9 [95% CI: 2.5 to 9.6; p < 0.0001], respectively [normal MPI: referent]). Addition of percent myocardium ischemic and percent myocardium scarred to clinical information (age, female sex, body mass index, history of hypertension, diabetes, dyslipidemia, smoking, angina, beta-blocker use, prior revascularization, and resting heart rate) improved the model performance (C-statistic 0.805 [95% CI: 0.772 to 0.838] to 0.839 [95% CI: 0.809 to 0.869]) and risk reclassification for cardiac death (NRI 0.116 [95% CI: 0.021 to 0.210]), with smaller improvements in risk assessment for all-cause death. CONCLUSIONS In patients with known or suspected CAD, the extent and severity of ischemia and scar on PET MPI provided powerful and incremental risk estimates of cardiac death and all-cause death compared with traditional coronary risk factors.

The Impact of Pruritus on Quality of Life The Skin Equivalent of Pain

OBJECTIVE To compare the impact of chronic pruritus and chronic pain on quality of life (QoL) using directly elicited health utility scores. DESIGN Cross-sectional study. SETTING Convenience sample of patients attending the Emory Dermatology Clinic, Emory Spine Center, and Emory Center for Pain Management, Atlanta, Georgia. PARTICIPANTS Adult men and women (aged ≥ 18 years) experiencing chronic pain or pruritus for 6 weeks or more. MAIN OUTCOME MEASURES The mean utility score of patients with chronic pruritus was compared with that of patients with chronic pain. A regression analysis was performed to determine the impact of the primary predictor variable-symptom type-on the primary outcome variable-mean utility score (a metric representing the impact on QoL). RESULTS The study included 73 patients with chronic pruritus and 138 patients with chronic pain. The mean (SD) utility among patients with pruritus was 0.87 (0.27) compared with 0.77 (0.31) for patients with pain (P < .01). After symptom severity, duration, and demographic factors were controlled for, only symptom severity (0.03 [P < .05]) and single marital status (-0.12 [P = .02]), but not symptom type (P = .43), remained significant predictors of the mean symptom utility score. CONCLUSIONS Chronic pruritus has a substantial impact on QoL, one that may be comparable to that of pain. The severity of symptoms and the use of support networks are the main factors that determine the degree to which patients are affected by their symptoms. Addressing support networks in addition to developing new therapies may improve the QoL of itchy patients.

Alterations in Cortical Thickness and White Matter Integrity in Mild Cognitive Impairment Measured by Whole Brain Cortical Thickness Mapping and Diffusion Tensor Imaging

BACKGROUND AND PURPOSE: Mild cognitive impairment (MCI) is a risk factor for Alzheimer disease and can be difficult to diagnose because of the subtlety of symptoms. This study attempted to examine gray matter (GM) and white matter (WM) changes with cortical thickness analysis and diffusion tensor imaging (DTI) in patients with MCI and demographically matched comparison subjects to test these measurements as possible imaging markers for diagnosis. MATERIALS AND METHODS: Subjects with amnestic MCI (n = 10; age, 72.2 ± 7.1 years) and normal cognition (n = 10; age, 70.1 ± 7.7 years) underwent DTI and T1-weighted MR imaging at 3T. Fractional anisotropy (FA), apparent diffusion coefficient (ADC), and cortical thickness were measured and compared between the MCI and control groups. We evaluated the diagnostic accuracy of 2 methods, either in combination or separately, using binary logistic regression and nonparametric statistical analyses for sensitivity, specificity, and accuracy. RESULTS: Decreased FA and increased ADC in WM regions of the frontal and temporal lobes and corpus callosum (CC) were observed in patients with MCI. Cortical thickness was decreased in GM regions of the frontal, temporal, and parietal lobes in patients with MCI. Changes in WM and cortical thickness seemed to be more pronounced in the left hemisphere compared with the right hemisphere. Furthermore, the combination of cortical thickness and DTI measurements in the left temporal areas improved the accuracy of differentiating MCI patients from control subjects compared with either measure alone. CONCLUSIONS: DTI and cortical thickness analyses may both serve as imaging markers to differentiate MCI from normal aging. Combined use of these 2 methods may improve the accuracy of MCI diagnosis.

Adherence to the Mediterranean Diet Is Inversely Associated With Circulating Interleukin-6 Among Middle-Aged Men: A Twin Study

Background— The Mediterranean diet is protective against cardiovascular disease; a proposed mechanism is through a reduction in systemic inflammation. It is unknown to what extent the association between the Mediterranean diet and inflammation is due to genetic or other familial factors. Methods and Results— We administered the Willett food frequency questionnaire to 345 middle-aged male twins and assessed adherence to the Mediterranean diet using a published adherence score. Fasting plasma levels of interleukin-6, C-reactive protein, and known cardiovascular risk factors were measured. Mixed-effect regression analyses were used to examine the relationship between diet score and inflammatory biomarkers after accounting for known cardiovascular risk factors. Adherence to the Mediterranean diet was associated with reduced levels of interleukin-6 (P<0.001) but not C-reactive protein (P=0.10) after adjustment for total energy intake, other nutritional factors, known cardiovascular risk factors, and use of supplements and medications. When the overall association of adherence to the diet with interleukin-6 levels was partitioned into between- and within-pair effects, the between-pair effect was not significant (P=0.9) and the within-pair effect was highly significant (P<0.0001). A 1-unit within-pair absolute difference in the diet score was associated with a 9% (95% CI, 4.5 to 13.6) lower interleukin-6 level. Conclusions— Shared environmental and genetic factors are unlikely to play a major role in the association between adherence to the Mediterranean diet and systemic inflammation. These results support the hypothesis that reduced inflammation is an important mechanism linking Mediterranean diet to reduced cardiovascular risk.

Post-traumatic stress disorder and incidence of coronary heart disease: a twin study.

OBJECTIVES The aim of this study was to determine whether post-traumatic stress disorder (PTSD) is associated with coronary heart disease (CHD) using a prospective twin study design and objective measures of CHD. BACKGROUND It has long been hypothesized that PTSD increases the risk of CHD, but empirical evidence using objective measures is limited. METHODS We conducted a prospective study of middle-aged male twins from the Vietnam Era Twin Registry. Among twin pairs without self-reported CHD at baseline, we selected pairs discordant for a lifetime history of PTSD, pairs discordant for a lifetime history of major depression, and pairs without either condition. All underwent a clinic visit after a median follow-up of 13 years. Outcomes included clinical events (myocardial infarction, other hospitalizations for CHD and coronary revascularization) and quantitative measures of myocardial perfusion by [(13)N] ammonia positron emission tomography, including a stress total severity score and coronary flow reserve. RESULTS A total of 562 twins (281 pairs) with a mean age of 42.6 years at baseline were included in this study. The incidence of CHD was more than double in twins with PTSD (22.6%) than in those without PTSD (8.9%; p < 0.001). The association remained robust after adjusting for lifestyle factors, other risk factors for CHD, and major depression (odds ratio: 2.2; 95% confidence interval: 1.2 to 4.1). Stress total severity score was significantly higher (+95%, p = 0.001) and coronary flow reserve was lower (-0.21, p = 0.02) in twins with PTSD than in those without PTSD, denoting worse myocardial perfusion. Associations were only mildly attenuated in 117 twin pairs discordant for PTSD. CONCLUSIONS Among Vietnam-era veterans, PTSD is a risk factor for CHD.

Cost-effectiveness of targeting patients undergoing cardiac surgery for therapy with intravenous amiodarone to prevent atrial fibrillation ☆

OBJECTIVES This study evaluated the cost-effectiveness of administering prophylactic intravenous (IV) amiodarone therapy to patients undergoing cardiac surgery according to their predicted risk of postoperative atrial fibrillation. BACKGROUND Atrial fibrillation (AF) is a common complication of cardiovascular surgery that is associated with a significant increase in hospitalization costs. Intravenous amiodarone has been shown to decrease the incidence of postoperative AF. METHODS All 8,709 patients who underwent coronary artery bypass grafting (CABG), 1,217 patients who underwent valve replacement and 624 patients who underwent CABG and valve replacement procedures (CABG + valve) from January 1, 1994, to June 30, 1999, at Emory University Hospitals were studied. Models predicting the risk of AF were developed using logistic regression; linear regression was used to estimate the influence of AF on hospitalization costs. Cost-effectiveness was evaluated for patient subsets identified according to their predicted risk of AF. RESULTS Postoperative AF rates were 17.7% for CABG, 24.6% for valve and 33.8% for CABG + valve. Using 5,000 dollars as an acceptable cost per episode of atrial fibrillation averted, prophylactic IV amiodarone in CABG patients was not found to be cost-effective. Therapy would be recommended for roughly 5% of valve patients with a predicted risk of atrial fibrillation >45%, and roughly two thirds of CABG + valve patients who have a predicted risk of >30%. CONCLUSIONS Cost-effectiveness of prophylactic IV amiodarone varies according to type of surgery and the predicted risk of atrial fibrillation. Older patients undergoing valve replacement, particularly those with a history of chronic obstructive pulmonary disease, and those undergoing concomitant CABG are likely to be the most appropriate candidates for IV amiodarone therapy in the perioperative period.

Cost-Effectiveness of Percutaneous Coronary Intervention in Optimally Treated Stable Coronary Patients

Background—The COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive druG Evaluations) trial compared the effect of percutaneous coronary intervention (PCI) plus optimal medical therapy with optimal medical therapy alone on cardiovascular events in 2287 patients with stable coronary disease. After 4.6 years, there was no difference in the primary end point of death or myocardial infarction, although PCI improved quality of life. The present study evaluated the relative cost and cost-effectiveness of PCI in the COURAGE trial. Methods and Results—Resource use was assessed by diagnosis-related group for hospitalizations and by current procedural terminology code for outpatient visits and tests and then converted to costs by use of 2004 Medicare payments. Medication costs were assessed with the Red Book average wholesale price. Life expectancy beyond the trial was estimated from Framingham survival data. Utilities were assessed by the standard gamble method. The incremental cost-effectiveness ratio was expressed as cost per life-year and cost per quality-adjusted life-year gained. The added cost of PCI was approximately