Jose Binongo

Emory University, Atlanta, Georgia, United States

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Publications (33)214.39 Total impact

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    ABSTRACT: Background: Patients with early stage lung cancer considered high risk for surgery are increasingly being treated with nonsurgical therapies. However, consensus on the classification of high risk does not exist. We compared clinical outcomes of patients considered to be high risk with those of standard-risk patients, after lung cancer surgery. Methods: A total of 490 patients from our institutional Society of Thoracic Surgeons data from 2009 to 2013 underwent resection for clinical stage I lung cancer. High-risk patients were identified by ACOSOG z4032/z4099 criteria: major: forced expiratory volume in 1 second (FEV1) 50% or less or diffusing capacity of lung for carbon monoxide (Dlco) 50% or less; and minor: (two of the following), age 75 years or more, FEV1 51% to 60%, or Dlco 51% to 60%. Demographics, perioperative outcomes, and survival between high-risk and standard-risk patients undergoing lobectomy and sublobar resection were compared. Univariate analysis was performed using the χ(2) test/Fisher's exact test and the t test/Mann-Whitney U test. Survival was studied using a Cox regression model to calculate hazard ratios, and Kaplan-Meier survival curves were drawn. Results: In all, 180 patients (37%) were classified as high risk. These patients were older than standard-risk patients (70 years versus 65 years, respectively; p < 0.0001) and had worse FEV1 (57% versus 85%, p < 0.0001), and Dlco (47% versus 77%, p < 0.0001). High-risk patients also had more smoking pack-years than standard-risk patients (46 versus 30, p < 0.0001) and a greater incidence of chronic obstructive pulmonary disease (72% versus 32%, p < 0.0001), and were more likely to undergo sublobar resection (32% versus 20%, p = 0.001). Length of stay was longer in the high-risk group (5 versus 4 days, p < 0.0001), but there was no difference in postoperative mortality (2% versus 1%, p = 0.53). Nodal upstaging occurred in 20% of high-risk patients and 21% of standard-risk patients (p = 0.79). Three-year survival was 59% for high-risk patients and 76% for standard-risk patients (p < 0.0001). Conclusions: Good clinical outcomes after surgery for early stage lung cancer can be achieved in patients classified as high risk. In our study, surgery led to upstaging in 20% of patients and acceptable 1-, 2-, and 3-year survival as compared with historical rates for nonsurgical therapies. This study suggests that empiric selection criteria may deny patients optimal oncologic therapy.
    The Annals of thoracic surgery 11/2015; DOI:10.1016/j.athoracsur.2015.08.088 · 3.85 Impact Factor
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    ABSTRACT: Background: Transfusion has been linked with increased postoperative morbidity and death after cardiac operations. The purpose of this study was to determine the associations among The Society of Thoracic Surgeons Predicted Risk of Mortality (PROM), transfusion, and postoperative outcomes in patients who underwent isolated primary valve operations. Methods: A retrospective review of the local Society of Thoracic Surgeons database of 1,575 adults undergoing isolated primary valve operations from 2003 to 2013 at a United States academic center was performed. Patients were compared by their postoperative transfusion status (NONE vs TRANS) and by PROM. Taking into account procedure type and preoperative hemoglobin, three-step multiple linear or logistic regression analyses were performed to assess (1) the influence of PROM on postoperative outcomes, (2) influence of PROM on transfusion, and (3) influence of PROM and transfusion on postoperative outcomes. Results: Of 1,575 patients studied, 1,245 (79%) received transfusions. The mean PROM was 1.2% (95% confidence interval [CI], 1.1 to 1.3) for patients in the NONE group, and was 2.7% (95% CI, 2.6 to 2.9) for the TRANS group. The correlation between PROM and total red blood cell units transfused was r = 0.31 (p < 0.0001). Patients with a PROM of 4% to 8% (odds ratio [OR], 2.10; 95% CI, 1.28 to 3.45) and exceeding 8% (OR 3.80, 95% CI, 1.35 to 10.68) were more likely to receive transfusions than the low-risk (<4%) PROM stratum. For each percentage increase in PROM, the odds of transfusion increased by 27% (95% CI, 16% to 39%), controlling for procedure type and preoperative hemoglobin. There were no 30-day deaths in the NONE group, and rates of stroke, renal failure, and mediastinitis were lower. Composite event rates increased with increasing PROM (OR, 1.39; 95% CI, 1.19 to 1.63), with TRANS patients consistently showing a higher risk of major adverse cardiac events than NONE patients (OR, 7.47; 95% CI, 2.08 to 26.80). Conclusions: Increased PROM yielded higher risks of transfusion. Postoperative outcomes were worse in patients who received a transfusion. This study suggests that the association between transfusion and clinical outcomes may be partly explained by the higher PROM among patients who ultimately received transfusions.
    The Annals of thoracic surgery 10/2015; DOI:10.1016/j.athoracsur.2015.08.001 · 3.85 Impact Factor
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    ABSTRACT: The role of robotic instruments in mitral valve (MV) surgery continues to evolve. The purpose of this study was to assess the safety, efficacy, and scope of MV surgery using a lateral endoscopic approach with robotics (LEAR) technique. From 2006 to 2013, a dedicated LEAR team performed 1,257 consecutive isolated MV procedures with or without tricuspid valve repair or atrial ablation. The procedures were performed robotically through five right-side chest ports with femoral artery or ascending aortic perfusion and balloon occlusion. Operative videos and data were recorded on all procedures and reviewed retrospectively. The mean age of all patients was 59.3 ± 20.5 years, and 8.4% (n = 105) had previous cardiac surgery. The MV repair was performed in 1,167 patients (93%). The MV replacement was performed in 88 patients (7%), and paravalvular leak repair in 2 patients. Concomitant atrial ablation was performed in 226 patients (18%), and tricuspid valve repair in 138 patients (11%). Operative mortality occurred in 11 patients (0.9%) and stroke in 9 patients (0.7%). Predischarge echocardiograms demonstrated mild or less mitral regurgitation in 98.3% of MV repair patients. At mean follow-up of 50 ± 26 months, 44 patients (3.8%) required MV reoperation. Application of the LEAR technique to all institutional isolated MV procedures increased from 46% in the first year to more than 90% in the last 3 years. Mitral valve repair or replacement, including concomitant procedures, can be performed safely and effectively using the LEAR technique. With a dedicated robotic team, the vast majority of patients with MV disorders, either isolated or with concomitant problems, can be treated using the LEAR technique. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
    The Annals of thoracic surgery 08/2015; DOI:10.1016/j.athoracsur.2015.05.068 · 3.85 Impact Factor
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    ABSTRACT: Chronic obstructive pulmonary disease (COPD) has been identified as a risk factor for morbidity and mortality after transcatheter aortic valve replacement (TAVR). We hypothesized that a portion of pulmonary dysfunction in patients with severe aortic stenosis may be of cardiac origin, and has potential to improve after TAVR. A retrospective analysis was made of consecutive TAVR patients from April 2008 to October 2014. Of patients who had pulmonary function testing and serum B-type natriuretic peptide data available before and after TAVR, 58 were found to have COPD (26 mild, 14 moderate, and 18 severe). Baseline variables and operative outcomes were explored along with changes in pulmonary function. Multiple regression analyses were performed to adjust for preoperative left ventricular ejection fraction and glomerular filtration rate. Comparison of pulmonary function testing before and after the procedure among all COPD categories showed a 10% improvement in forced vital capacity (95% confidence interval: 4% to 17%) and a 12% improvement in forced expiratory volume in 1 second (95% confidence interval: 6% to 19%). There was a 29% decrease in B-type natriuretic peptide after TAVR (95% confidence interval: -40% to -16%). An improvement of at least one COPD severity category was observed in 27% of patients with mild COPD, 64% of patients with moderate COPD, and 50% of patients with severe COPD. There was no 30-day mortality in any patient group. In patients with severe aortic stenosis, TAVR is associated with a significant improvement of pulmonary function and B-type natriuretic peptide. After TAVR, the reduction in COPD severity was most evident in patients with moderate and severe pulmonary dysfunction. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
    The Annals of thoracic surgery 08/2015; DOI:10.1016/j.athoracsur.2015.06.008 · 3.85 Impact Factor
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    ABSTRACT: A minimalist approach for transcatheter aortic valve replacement (MA-TAVR) utilizing transfemoral access under conscious sedation and transthoracic echocardiography is increasing in popularity. This relatively novel technique may necessitate a learning period to achieve proficiency in performing a successful and safe procedure. This report evaluates our MA-TAVR cohort with specific characterization between our early, midterm, and recent experience. We retrospectively reviewed 151 consecutive patients who underwent MA-TAVR with surgeons and interventionists equally as primary operator at Emory University between May 2012 and July 2014. Our institution had performed 300 TAVR procedures before implementation of MA-TAVR. Patient characteristics and early outcomes were compared using Valve Academic Research Consortium 2 definitions among 3 groups: group 1 included the first 50 patients, group 2 included patients 51 to 100, and group 3 included patients 101 to 151. Median age for all patients was 84 years and similar among groups. The majority of patients were men (56%) and the median ejection fraction for all patients was 55% (interquartile range, 38.0%-60.0%). The majority of patients were high-risk surgical candidates with a median Society of Thoracic Surgeons Predicted Risk of Mortality of 10.0% and similar among groups. The overall major stroke rate was 3.3%, major vascular complications occurred in 3% of patients, and greater-than-mild paravalvular leak rate was 7%. In-hospital mortality and morbidity were similar among all 3 groups. In a high-volume TAVR center, transition to MA-TAVR is feasible with acceptable outcomes and a diminutive procedural learning curve. We advocate for TAVR centers to actively pursue the minimalist technique with equal representation by cardiologists and surgeons. Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.
    The Journal of thoracic and cardiovascular surgery 07/2015; DOI:10.1016/j.jtcvs.2015.07.078 · 4.17 Impact Factor
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    ABSTRACT: The diagnosis of metabolic syndrome (MetS) identifies individuals at risk for developing diabetes and cardiovascular disease (CVD). African Americans (AA) have high rates of CVD and subclinical vascular disease including arterial stiffness and microvascular dysfunction but have relatively low rates of MetS. To evaluate the relationship between MetS and vascular function in a biracial cohort with the hypothesis that the diagnosis of MetS underestimates subclinical vascular disease in AA. We measured components of MetS in a community-based cohort of 951 AA and white subjects (age 48.8 ± 11 years, 47% AA, 55% female). Using digital pulse amplitude tonometry (EndoPAT), we estimated the reactive hyperemia index (RHI), a measure of microvascular endothelial function. Using applanation tonometry (Sphygmocor), central augmentation index (CAIx) and pulse wave velocity (PWV) were measured as indices of wave reflections and arterial stiffness, respectively. MetS was present in 24.0% of subjects and was associated with increased PWV (p<0.001) and CAIx (p<0.001) and trend to lower RHI (p=0.068) in both races. However, in subjects without MetS, AA had lower RHI (p<0.001), higher PWV (p=0.003) and CAIx (p=0.002) compared to white subjects. Addition of an extra MetS criterion point for AA with hypertension eliminated the racial differences in PWV and CAIx, but not RHI. Although MetS is associated with microvascular dysfunction and increased arterial stiffness in both racial groups, AA without MetS have greater vascular dysfunction compared to whites. Additional weighting for hypertension in AA attenuated the racial differences in subclinical disease associated with MetS.
    The Journal of Clinical Endocrinology and Metabolism 07/2015; DOI:10.1210/JC.2014-4344 · 6.21 Impact Factor
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    ABSTRACT: The aim of this study was to retrospectively investigate whether performing surgical atrial fibrillation (AF) ablation in conjunction with cardiac surgery (CS) increases the risk for postoperative permanent pacemaker (PPM) requirement. The 30-day risk for PPM requirement was analyzed in consecutive patients who underwent CS from January 2007 to August 27, 2013. Patients were divided into 3 groups: (1) those who underwent AF ablation concomitant with CS (AF ABL), (2) patients with any history of AF who underwent surgery who did not undergo ablation (AF NO ABL), and (3) those with no histories of AF who underwent surgery (NO AF). Logistic regression analysis was performed adjusting for age, gender, and surgery type. Of 13,453 CS patients, 353 (3%) were in the AF ABL group, 1,701 (12%) in the AF NO ABL group, and 11,399 (85%) in the NO AF group. A total of 7,651 patients (57%) underwent coronary artery bypass grafting, 4,384 (33%) underwent valve surgery, and 1,418 (10%) underwent coronary artery bypass grafting and valve surgery. The overall PPM risk was 1.6% (212 of 13,453); risk was 5.7% (20 of 353) in the AF ABL group, 3.1% (53 of 1,701) in the AF NO ABL group, and 1.2% (139 of 11,399) in the NO AF group. The unadjusted and adjusted odds of PPM were higher in the AF ABL and AF NO ABL groups than in the NO AF group (adjusted odds ratio [OR] 2.7, 95% confidence interval [CI] 1.7 to 4.4, and adjusted OR 1.7, 95% CI 1.2 to 2.4, respectively). The unadjusted OR comparing the AF ABL group and the AF NO ABL group was significant (unadjusted OR 1.9, 95% CI 1.9 to 3.2); however, the OR adjusted for surgery type, age, and gender showed a trend toward significance (adjusted OR 1.6, 95% CI 0.9 to 2.7). In conclusion, in this large cohort of patients who underwent CS, surgical AF ablation appeared to carry an increased risk for postoperative PPM implantation. Copyright © 2015 Elsevier Inc. All rights reserved.
    The American journal of cardiology 04/2015; 116(1). DOI:10.1016/j.amjcard.2015.03.046 · 3.28 Impact Factor

  • Journal of the American College of Cardiology 03/2015; 65(10):A1882. DOI:10.1016/S0735-1097(15)61882-4 · 16.50 Impact Factor

  • Journal of the American College of Cardiology 03/2015; 65(10):A1998. DOI:10.1016/S0735-1097(15)61998-2 · 16.50 Impact Factor
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    ABSTRACT: Unlike traditional beta receptor antagonists, nebivolol activates nitric oxide. We hypothesized that therapy with nebivolol compared to metoprolol would improve arterial stiffness, increase levels of circulating progenitor cells (PC) and decrease oxidative stress (OS). In a randomized, double-blind, cross-over study, 30 hypertensive subjects received either once daily nebivolol or metoprolol succinate for 3 months each. Pulse wave velocity (PWV) and augmentation index (CAIx) were measured using tonometry. Flow cytometry was used to measure circulating PC. OS was measured as plasma aminothiols. Measurements were performed at baseline, and repeated at 3 and 6 months. No significant differences were present between the levels of OS, arterial stiffness, and PC numbers during treatment with metoprolol compared to nebivolol. In subgroup analyses of beta-blocker naïve subjects (n=19), nebivolol reduced PWV significantly compared to metoprolol (-1.4±1.9 versus -0.1±2.2, p=0.005). Both nebivolol and metoprolol increased circulating levels of CD34+/CD133+ PC similarly (p=0.05), suggesting improved regenerative capacity.
    Journal of the American Society of Hypertension 12/2014; 9(3). DOI:10.1016/j.jash.2014.12.013 · 2.61 Impact Factor
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    ABSTRACT: Atherosclerotic changes associated with dyslipidemia and increased cardiovascular disease risk are believed to begin in childhood. While previous studies have linked added sugars consumption to low high-density lipoprotein (HDL), little is known about the long-term impact of this consumption. This study aims to assess the association between added sugars intake and HDL cholesterol levels during adolescence, and whether this association is modified by obesity. We used data from the National Heart Lung and Blood Institute's Growth and Health Study, a 10-year cohort study of non-Hispanic Caucasian and African-American girls (N=2379) aged 9 and 10 years at baseline recruited from 3 sites in 1987-1988 with biennial plasma lipid measurement and annual assessment of diet using a 3-day food record. Added sugars consumption was dichotomized into low (0% to <10% of total energy) and high (≥10% of total energy). In a mixed model controlling for obesity, race, physical activity, smoking, maturation stage, age, and nutritional factors, low compared with high added sugar consumption was associated with a 0.26 mg/dL greater annual increase in HDL levels (95% CI 0.48 to 0.04; P=0.02). Over the 10-year study period, the model predicted a mean increase of 2.2 mg/dL (95% CI 0.09 to 4.32; P=0.04) among low consumers, and a 0.4 mg/dL decrease (95% CI -1.32 to 0.52; P=0.4) among high consumers. Weight category did not modify this association (P=0.45). Low added sugars consumption is associated with increasing HDL cholesterol levels throughout adolescence.
    Journal of the American Heart Association 12/2014; 3(1):e000615. DOI:10.1161/JAHA.113.000615 · 4.31 Impact Factor
  • M D Kearns · J N G Binongo · D Watson · J A Alvarez · D Lodin · T R Ziegler · V Tangpricha ·
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    ABSTRACT: Background/objectives: Although single, high doses of vitamin D effectively maintain vitamin D sufficiency in several populations, no studies have evaluated healthy adults over winter, during which vitamin D status declines. This study investigated whether high-dose vitamin D3 given once to healthy adults before winter will (1) prevent the wintertime decline in vitamin D status, (2) promote vitamin D sufficiency 1 year following the dose and (3) prevent the rise of parathyroid hormone (PTH) concentrations. Subjects/methods: In this double-blind, placebo-controlled trial, we assessed plasma 25(OH)D and PTH concentrations at baseline, 5, 90 and 365 days after drug administration in 28 healthy adults. In all, >80% of subjects returned at each time point. Results: At baseline, the young, healthy participants had a mean plasma 25(OH)D concentration of 17.5±6.1 ng/ml. Only two subjects exhibited plasma 25(OH)D concentrations >30 ng/ml. At 5 days, subjects randomized to vitamin D3 had a higher mean plasma 25(OH)D concentration compared with the placebo group (39.1 vs 19.1 ng/ml, P<0.001). Plasma 25(OH)D concentrations returned to baseline at 90 and 365 days in the vitamin D3 group and remained unchanged in the placebo group. PTH and calcium concentrations were unrelated to changes in 25(OH)D levels and similar between groups over time. Conclusions: A dose of 250,000 IU of vitamin D3 given once in November resulted in a robust increase in plasma 25(OH)D after 5 days, but it was unable to sustain this increase after 90 days. A larger or more frequent dosing regimen may be needed for long-term vitamin D sufficiency.
    European Journal of Clinical Nutrition 10/2014; 69(2). DOI:10.1038/ejcn.2014.209 · 2.71 Impact Factor
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    ABSTRACT: Background: Pancreatic insufficiency is common in patients with cystic fibrosis (CF) and leads to malabsorption of fat-soluble vitamins. Multivitamins, including vitamins A, D, E, and K, are routinely prescribed to patients with CF to prevent vitamin deficiencies. Our objective was to examine the relationship between fat-soluble vitamin supplements and their impact on blood concentrations. Methods: This was a retrospective chart review of patients with CF who were treated at Emory Clinic and Emory University Hospital during 2008-2012. The amount of fat-soluble vitamin supplementation, serum markers of fat-soluble vitamin concentrations, CF transmembrane conductance regulator genotype, and other demographic information were recorded from electronic medical records. Mixed-effects models were used to investigate the trends over time of fat-soluble vitamin supplements and serum vitamin concentrations. Results: In total, 177 charts were eligible. Mean (SD) age was 26.1 (10.2) years. Ninety-two percent of patients had pancreatic insufficiency and 52% had the homozygous ΔF508 mutation. Recorded fat-soluble vitamin supplementation increased in the past 5 years (P < .001 for all). Serum 25-hydroxyvitamin D increased slightly (3% increase; P < .01); however, there were no changes in the blood concentrations of vitamins A, E, and K (P = .26-.96). Conclusions: Despite a near doubling of recorded fat-soluble vitamin supplementation over the past 5 years, there was no parallel increase in blood concentrations of these vitamins. Potential reasons include suboptimal dosages, low adherence, or ongoing issues with malabsorption.
    Nutrition in Clinical Practice 04/2014; 29(4). DOI:10.1177/0884533614530170 · 2.40 Impact Factor
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    Journal of the American College of Cardiology 04/2014; 63(12):A2079. DOI:10.1016/S0735-1097(14)62082-9 · 16.50 Impact Factor
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    ABSTRACT: Objective Redox status and inflammation are important in the pathophysiology of numerous chronic diseases. Epidemiological studies have linked vitamin D status to a number of chronic diseases. We aimed to examine the relationships between serum 25-hydroxyvitamin D (25(OH)D) and circulating thiol/disulfide redox status and biomarkers of inflammation. DesignThis was a cross-sectional study of N=693 adults (449 females, 244 males) in an apparently healthy, working cohort in Atlanta, GA. Plasma glutathione (GSH), cysteine (Cys), and their associated disulfides were determined with high performance liquid chromatography, and their redox potentials (Eh GSSG and Eh CySS) were calculated using the Nernst equation. Serum inflammatory markers included interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α, assayed on a multiplex platform; and C-reactive protein (CRP), assayed commercially. Relationships were assessed with multiple linear regression analyses. ResultsSerum 25(OH)D was positively associated with plasma GSH (β ± SE: 0.002 ± 0.0004) and negatively associated with plasma Eh GSSG (β ± SE: -0.06 ± 0.01) and Cys (β ± SE: -0.01 ± 0.003) (P<0.001 for all); statistical significance remained after adjusting for age, gender, and race, percent body fat, and traditional cardiovascular risk factors (P=0.01-0.02). The inverse relationship between serum 25(OH)D and CRP was confounded by percent body fat, and full adjustment for covariates attenuated serum 25(OH)D relationships with other inflammatory markers to non-statistical significance. Conclusions Serum 25(OH)D concentrations were independently associated with major plasma thiol/disulfide redox systems, suggesting that vitamin D status may be involved in redox-mediated pathophysiology.This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 03/2014; 81(3). DOI:10.1111/cen.12449 · 3.46 Impact Factor
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    ABSTRACT: Traditional cardiovascular risk factors lead to endothelial injury and activation of leucocytes and platelets that initiate and propagate atherosclerosis. We proposed that clopidogrel therapy in patients with stable CAD imparts a pleiotropic effect that extends beyond anti-platelet aggregation to other athero-protective processes. Forty-one subjects were randomized in a double-blind, placebo-controlled crossover study to either clopidogrel 75 mg daily or placebo for 6-weeks, and then transitioned immediately to the other treatment for an additional 6 weeks. We assessed 1) endothelial function as flow-mediated dilation of the brachial artery, 2) arterial stiffness and central augmentation index using applanation tonometry, 3) vascular function as fingertip reactive hyperemia index, 4) inflammation by measuring plasma CD40 ligand and serum high-sensitivity c-reactive protein levels, 5) oxidative stress by measuring plasma aminothiols, and 6) circulating progenitor cells, at baseline and at the end of each 6-week treatment period. Clopidogrel therapy resulted in a significant reduction in soluble CD40 ligand (p=0.03), a pro-thrombotic and pro-inflammatory molecule derived mainly from activated platelets. However, clopidogrel therapy had no effect on endothelial function, arterial stiffness, inflammatory and oxidative stress markers, or progenitor cells. Our findings suggest a solitary anti-platelet effect of clopidogrel therapy in patients with stable CAD, with no effect on other sub-clinical markers of cardiovascular disease risk.
    Journal of cardiovascular pharmacology 12/2013; 63(4). DOI:10.1097/FJC.0000000000000057 · 2.14 Impact Factor
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    ABSTRACT: IMPORTANCE Many patients with peripheral artery disease (PAD) have walking impairment despite therapy. Experimental studies in animals demonstrate improved perfusion in ischemic hind limb after mobilization of bone marrow progenitor cells (PCs), but whether this is effective in patients with PAD is unknown. OBJECTIVE To investigate whether therapy with granulocyte-macrophage colony-stimulating factor (GM-CSF) improves exercise capacity in patients with intermittent claudication. DESIGN, SETTING, AND PARTICIPANTS In a phase 2 double-blind, placebo-controlled study, 159 patients (median [SD] age, 64 [8] years; 87% male, 37% with diabetes) with intermittent claudication were enrolled at medical centers affiliated with Emory University in Atlanta, Georgia, between January 2010 and July 2012. INTERVENTIONS Participants were randomized (1:1) to received 4 weeks of subcutaneous injections of GM-CSF (leukine), 500 μg/day 3 times a week, or placebo. Both groups were encouraged to walk to claudication daily. MAIN OUTCOMES AND MEASURES The primary outcome was peak treadmill walking time (PWT) at 3 months. Secondary outcomes were PWT at 6 months and changes in circulating PC levels, ankle brachial index (ABI), and walking impairment questionnaire (WIQ) and 36-item Short-Form Health Survey (SF-36) scores. RESULTS Of the 159 patients randomized, 80 were assigned to the GM-CSF group. The mean (SD) PWT at 3 months increased in the GM-CSF group from 296 (151) seconds to 405 (248) seconds (mean change, 109 seconds [95% CI, 67 to 151]) and in the placebo group from 308 (161) seconds to 376 (182) seconds (change of 56 seconds [95% CI, 14 to 98]), but this difference was not significant (mean difference in change in PWT, 53 seconds [95% CI, -6 to 112], P = .08). At 3 months, compared with placebo, GM-CSF improved the physical functioning subscore of the SF-36 questionnaire by 11.4 (95% CI, 6.7 to 16.1) vs 4.8 (95% CI, -0.1 to 9.6), with a mean difference in change for GM-CSF vs placebo of 7.5 (95% CI, 1.0 to 14.0; P = .03). Similarly, the distance score of the WIQ improved by 12.5 (95% CI, 6.4 to 18.7) vs 4.8 (95% CI, -0.2 to 9.8) with GM-CSF compared with placebo (mean difference in change, 7.9 [95% CI, 0.2 to 15.7], P = .047). There were no significant differences in the ABI, WIQ distance and speed scores, claudication onset time, or mental or physical component scores of the SF-36 between the groups. CONCLUSIONS AND RELEVANCE Therapy with GM-CSF 3 times a week did not improve treadmill walking performance at the 3-month follow-up. The improvements in some secondary outcomes with GM-CSF suggest that it may warrant further study in patients with claudication. TRIAL REGISTRATION Identifier: NCT01041417.
    JAMA The Journal of the American Medical Association 11/2013; 310(24). DOI:10.1001/jama.2013.282540 · 35.29 Impact Factor
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    ABSTRACT: Patients with peripheral arterial disease (PAD) remain symptomatic with intermittent claudication despite therapy. Experimental studies demonstrate improved perfusion in ischemic hind-limb after mobilization of bone marrow progenitor cells (PCs). We hypothesized that therapy with granulocyte macrophage colony-stimulating factor (GM-CSF) will be safe and will improve exercise capacity by mobilizing PCs in patients with symptomatic PAD. Methods: In a Phase II double-blind, placebo-controlled study,159 patients (aged 64±8 years, 87% male, 37% diabetic) with atherosclerotic PAD and intermittent claudication were randomized (1:1) to received 4 weeks of subcutaneous injections of GM-CSF (Leukine) 500 μg/day thrice-weekly or placebo. The primary outcome was peak treadmill walking time (PWT) at 3 months. Secondary outcomes were PWT at 6 months, changes in circulating PC levels, ankle-brachial index (ABI), Walking Impairment Questionnaire, and 36-item Short-Form- Health-Survey (SF-36) scores. Results: In the intention-to-treat analysis, the primary endpoint comparing the increase in PWT from baseline to 3 months between the GM-CSF (109±21sec) and the placebo (56.2±21sec) groups had a trend toward significance, p=0.08. In the per-protocol analysis, which excluded 4 patients with protocol deviations, PWT increased by 113±20 sec in 3 months in the GM-CSF group and 44±20 in the placebo group (p=0.02), and this increase was maintained at 6 months. GM-CSF mobilized PCs with peak mobilization at 2 weeks. Subjects with a greater increase in circulating PCs (>100%) had a greater increase in PWT compared to those with <100% increase (131±29 vs. 60±17 sec, p=0.04). Compared to placebo, GM-CSF improved the physical functioning subscore of the SF-36 survey at 3 months (p=0.03). There were no significant differences in the ABI or serious adverse event rates between the groups. Conclusion: One month of thrice-weekly therapy with GM-CSF is safe and appears to improve claudication and exercise time in symptomatic patients with PAD, an effect that is sustained for 6 months. The therapeutic effect is greater in those with greater mobilization of bone marrow PCs. Therapy with GM-CSF warrants further study in patients with PAD K. Mavromatis: None. J. Binongo: None. A. Khan: None. Q. Li: None. M. Khayata: None. E. Rocco: None. R. Neuman: None. A. Morris: None. M. Topel: None. X. Zhang: None. C. Brown: None. J. Murrow: None. M. Corriere: None. S. Clement: None. S. Sher: None. K. Ashraf: None. A. Rashad: None. T. Kabbany: None. A. Ali: None. J. Oshinski: None. Y. Yoon: None. E. Waller: None. A. Quyyumi: None.
    American Heart Association, Dallas, TX; 11/2013
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    ABSTRACT: Objective Mental stress provokes myocardial ischemia in many patients with stable coronary artery disease (CAD). Mental stress-induced myocardial ischemia (MSIMI) portends a worse prognosis, independent of standard cardiac risk factors or outcome of traditional physical stress testing. Angiotensin II plays a significant role in the physiological response to stress, but its role in MSIMI remains unknown. Our aim was to evaluate whether the use of angiotensin-converting enzyme inhibitors (ACEIs) is associated with a differential effect on the incidence of MSIMI compared with ischemia during physical stress.Methods Retrospective analysis of 218 patients with stable CAD, including 110 on ACEI, was performed. 99m-Tc-sestamibi myocardial perfusion imaging was used to define ischemia during mental stress, induced by a standardized public speaking task, and during physical stress, induced by either exercise or adenosine.ResultsOverall, 40 patients (18%) developed MSIMI and 80 patients (37%) developed ischemia during physical stress. MSIMI occurred less frequently in patients receiving ACEIs (13%) compared with those not on ACEIs (24%; p = .030, adjusted odds ratio = 0.42, 95% confidence interval = 0.19-0.91). In contrast, the frequency of myocardial ischemia during physical stress testing was similar in both groups (39% versus 35% in those on and not on ACEIs, respectively); adjusted odds ratio = 0.91, 95% confidence interval = 0.48-1.73).Conclusion In this retrospective study, patients using ACEI therapy displayed less than half the risk of developing ischemia during mental stress but not physical stress. This possible beneficial effect of ACEIs on MSIMI may be contributing to their salutary effects in CAD.
    Psychosomatic Medicine 10/2013; 75(9). DOI:10.1097/PSY.0000000000000015 · 3.47 Impact Factor
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    Journal of the American College of Cardiology 03/2013; 61(10). DOI:10.1016/S0735-1097(13)62066-5 · 16.50 Impact Factor

Publication Stats

180 Citations
214.39 Total Impact Points


  • 2007-2015
    • Emory University
      • • Department of Biostatistics and Bioinformatics
      • • School of Medicine
      • • Division of Infectious Diseases
      Atlanta, Georgia, United States
  • 2010
    • Kennesaw State University
      • Department of Mathematics and Statistics
      Georgia, United States