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1.  Long-Term Outcomes of Hospitalized Patients with a Non-Acute Coronary Syndrome Diagnosis and an Elevated Cardiac Troponin Level 
The American journal of medicine  2011;124(7):630-635.
Cardiac troponin levels help risk-stratify patients presenting with an acute coronary syndrome (ACS). Although they may be elevated in patients presenting with Non-ACS conditions, specific diagnoses and long-term outcomes within that cohort are unclear.
Methods and Results
Using the Veterans Affairs (VA) centralized databases, we identified all hospitalized patients in 2006 who had a troponin assay obtained during their initial reference hospitalization. Based on ICD-9 diagnostic codes, primary diagnoses were categorized as either ACS or Non-ACS conditions. Of a total of 21,668 patients with an elevated troponin level who were discharged from the hospital, 12,400 (57.2%) had a Non-ACS condition. Among that cohort, the most common diagnostic category involved the cardiovascular system and congestive heart failure (N=1661) and chronic coronary artery disease (N=1648) accounted for the major classifications. At one-year following hospital discharge, mortality in patients with a Non-ACS condition was 22.8% and was higher than the ACS cohort (Odds Ratio=1.39; 95%CI: 1.30–1.49). Despite the high prevalence of cardiovascular diseases in patients with a Non-ACS diagnosis, utilization of cardiac imaging within 90 days of hospitalization was low compared with ACS patients (Odds Ratio=0.25; 95%CI: 0.23–0.27).
Hospitalized patients with an elevated troponin level most often have a primary diagnosis that is not an acute coronary syndrome. Their long-term survival is poor and justifies novel diagnostic or therapeutic strategy-based studies to target the highest risk subsets prior to hospital discharge.
PMCID: PMC3771399  PMID: 21601821
outcomes; troponins; non-ACS diagnosis; cardiac imaging; coronary artery disease
2.  Uncoupling Protein-2 Expression and Effects on Mitochondrial Membrane Potential and Oxidant Stress in Heart Tissue 
Translational Research  2011;159(5):383-390.
Myocardial uncoupling protein (UCP)-2 is increased with chronic peroxisome proliferator-activated receptor γ (PPARγ) stimulation but the effect on membrane potential and superoxide is unclear. Wild type (WT) and UCP-2 knock-out (KO) mice were given a 3-week diet of control (C) or the PPAR γ agonist pioglitazone (50 μg/gram-chow per day) (PIO). In isolated mitochondria, UCP-2 content by Western blots, membrane potential (ΔΨm) by tetraphenylphosphonium (TPP) and relative superoxide levels by dihydroethidium (DHE) were measured. Oxygen respiration was determined at baseline and following 10 minutes anoxia-reoxygenation. PIO induced a 2-fold increase in UCP-2 and nuclear-bound PGC1α in WT mice with no UCP-2 expression in KO mice. Mitochondrial ΔΨm from WT mice on C and PIO diets was −166±4 mv and −147±6 mV respectively (P<0.05) and were lower than UCP-2 KO mice on C and PIO (−180±4 and −180±4 mv respectively; P<0.05). Maximal complex III inhibitable superoxide from WT mice on C and PIO diets was 22.5±1.3 and 17.8±1.1 AU respectively (P<0.05) and were lower than UCP-2 KO on C and PIO (32.9±2.3 and 29.2±1.9 AU respectively; P<0.05). Post-anoxia, the respiratory control index (RCI) in mitochondria from WT mice with and without PIO was 2.5±0.3 and 2.4±0.2 respectively and exceeded that of UCP-2 KO mice on C and PIO (1.2±0.1 and 1.4±0.1 respectively (P<0.05). In summary, chronic PPARγ stimulation leads to depolarization of the inner membrane and reduced superoxide of isolated heart mitochondria, which was critically dependent upon increased expression of UCP-2. UCP-2 expression affords resistance to brief anoxia-reoxygenation.
PMCID: PMC3328031  PMID: 22500511
3.  Variation of mortality after coronary artery bypass surgery in relation to hour, day and month of the procedure 
Mortality and complications after percutaneous coronary intervention is higher when performed after regular duty hours due to challenging patient characteristics, inferior processes of care and limited resources. Since these challenges are also encountered during coronary artery bypass graft (CABG) surgery that is performed after regular work hours, we assessed whether hour and day of procedure influenced mortality after CABG.
We studied 4,714 consecutive patients who underwent CABG at the Minneapolis Veterans Administration (VA) Medical Center between 1987 and 2009. We compared postoperative (30-day) mortality rates in relation to hour and day in which the operation was performed.
Operations performed on weekends and after 4 PM had higher risk patients (p < 0.0001) and were more likely to be emergent (p < 0.0001), require intra-aortic balloon pump support (p < 0.0001) and result in postoperative complications (p < 0.0001) compared to those at regular work hours. Mortality was significantly higher when CABG was performed on weekends compared to weekdays (9.4% versus 2.5%; odds ratio (OR) 4.1, 95% confidence interval (CI) 1.6 to 10.4, p = 0.003), and after 4 PM compared to between 7 AM-4 PM (6.2% versus 2.2%; OR 2.9, 95% CI 1 to 8, p = 0.049). In multivariable analysis, when adjusted for the urgency of the operation and the VA estimated mortality risk score, these associations were no longer statistically significant.
Mortality after CABG is higher when surgery is performed on the weekends and after 4 PM. These variations in mortality were related to higher patient risk, and urgency of the operation rather than external factors.
PMCID: PMC3206827  PMID: 22014242
coronary artery bypass surgery; mortality
5.  Interpreting troponin elevations: do we need multiple diagnoses? 
European Heart Journal  2008;30(2):135-138.
PMCID: PMC2639109  PMID: 19043078
Myocardial infarction; Troponin
6.  Utility of nuclear stress imaging for detecting coronary artery bypass graft disease 
The value of Single Photon Emission Computed Tomography stress myocardial perfusion imaging (SPECT-MPI) for detecting graft disease after coronary artery bypass surgery (CABG) has not been studied prospectively in an unselected cohort.
Radial Artery Versus Saphenous Vein Graft Study is a Veterans Affairs Cooperative Study to determine graft patency rates after CABG surgery. Seventy-nine participants agreed to SPECT-MPI within 24 hours of their coronary angiogram, one-year after CABG. The choice of the stress protocol was made at the discretion of the nuclear radiologist and was either a symptom-limited exercise test (n = 68) or an adenosine infusion (n = 11). The SPECT-MPI results were interpreted independent of the angiographic results and estimates of sensitivity, specificity and accuracy were based on the prediction of a graft stenosis of ≥70% on coronary angiogram.
A significant stenosis was present in 38 (48%) of 79 patients and 56 (22%) of 251 grafts. In those stress tests with an optimal exercise heart rate response (>80% maximum predicted heart rate) (n = 26) sensitivity, specificity and accuracy of SPECT-MPI for predicting the graft stenosis was 77%, 69% and 73% respectively. With adenosine (n = 11) it was 75%, 57% and 64%, respectively. Among participants with a suboptimal exercise heart rate response, the sensitivity of SPECT-MPI for predicting a graft stenosis was <50%. The accuracy of SPECT-MPI for detecting graft disease did not vary significantly with ischemic territory.
Under optimal stress conditions, SPECT-MPI has a good sensitivity and accuracy for detecting graft disease in an unselected patient population 1 year post-CABG.
PMCID: PMC3469356  PMID: 22862805
Coronary artery bypass grafts; CABG; Coronary artery imaging; Cardiac catheterization/intervention
7.  Dose dependent effect of statins on postoperative atrial fibrillation after cardiac surgery among patients treated with beta blockers 
Previous studies on the effects of Statins in preventing atrial fibrillation (AF) after cardiac surgery have shown conflicting results. Whether statins prevent AF in patients treated with postoperative beta blockers and whether the statin-effect is dose related are unknown.
We retrospectively studied 1936 consecutive patients who underwent coronary artery bypass graft (CABG) (n = 1493) or valve surgery (n = 443) at the Minneapolis Veterans Affairs Medical Center. All patients were in sinus rhythm before the surgery. Postoperative beta blockers were administered routinely (92% within 24 hours postoperatively).
Mean age was 66+10 years and 68% of the patients were taking Statins. Postoperative AF occurred in 588 (30%) patients and led to longer length of stay in the intensive care unit versus those without AF (5.1+7.6 days versus 2.5+2.3 days, p < 0.0001). Patients with a past history of AF had a 5 times higher risk of postoperative AF (odds ratio 5.1; 95% confidence interval 3.4 to 7.7; p < 0.0001). AF occurred in 31% of patients taking statins versus 29% of the others (p = 0.49). In multivariable analysis, statins were not associated with AF (odds ratio (OR) 0.93, 95% confidence interval (CI) 0.7 to 1.2; p = 0.59). However, in a subgroup analysis, the patients treated with Simvastatin >20 mg daily had a 36% reduction in the risk of postoperative AF (OR 0.64, 95% CI 0.43 to 0.6; p = 0.03) in comparison to those taking lower dosages.
Among cardiac surgery patients treated with postoperative beta blockers Statin treatment reduces the incidence of postoperative AF when used at higher dosages
PMCID: PMC2777853  PMID: 19889221

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