Coronary Artery Disease: O'Connor CM

Becker RC, Meade TW, Berger PB, Ezekowitz M, O'Connor CM, Vorchheimer DA, Guyatt GH, Mark DB, Harrington RA, Anonymous00140. · Duke Cardiovascular Thrombosis Center, Duke Clinical Research Institute, 2400 Pratt Street, Durham, NC 27705, USA. · Chest. · Pubmed #18574278 links to  free full text

Abstract: The following chapter devoted to antithrombotic therapy for chronic coronary artery disease (CAD) is part of the Antithrombotic and Thrombolytic Therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Grade 1 recommendations are strong and indicate that the benefits do or do not outweigh risks, burden, and costs. Grade 2 suggests that individual patient values may lead to different choices (for a full understanding of the grading see the "Grades of Recommendation" chapter by Guyatt et al in this supplement, CHEST 2008; 133[suppl]:123S-131S). Among the key recommendations in this chapter are the following: for patients with non-ST-segment elevation (NSTE)-acute coronary syndrome (ACS) we recommend daily oral aspirin (75-100 mg) [Grade 1A]. For patients with an aspirin allergy, we recommend clopidogrel, 75 mg/d (Grade 1A). For patients who have received clopidogrel and are scheduled for coronary bypass surgery, we suggest discontinuing clopidogrel for 5 days prior to the scheduled surgery (Grade 2A). For patients after myocardial infarction, after ACS, and those with stable CAD and patients after percutaneous coronary intervention (PCI), we recommend daily aspirin (75-100 mg) as indefinite therapy (Grade 1A). We recommend clopidogrel in combination with aspirin for patients experiencing ST-segment elevation (STE) and NSTE-ACS (Grade 1A). For patients with contraindications to aspirin, we recommend clopidogrel as monotherapy (Grade 1A). For long-term treatment after PCI in patients who receive antithrombotic agents such as clopidogrel or warfarin, we recommend aspirin (75 to 100 mg/d) [Grade 1B]. For patients who undergo bare metal stent placement, we recommend the combination of aspirin and clopidogrel for at least 4 weeks (Grade 1A). We recommend that patients receiving drug-eluting stents (DES) receive aspirin (325 mg/d for 3 months followed by 75-100 mg/d) and clopidogrel 75 mg/d for a minimum of 12 months (Grade 2B). For primary prevention in patients with moderate risk for a coronary event, we recommend aspirin, 75-100 mg/d, over either no antithrombotic therapy or vitamin K antagonist (Grade 1A).

Harrington RA, Becker RC, Ezekowitz M, Meade TW, O'Connor CM, Vorchheimer DA, Guyatt GH. · Duke Clinical Research Institute, 2400 Pratt St, Durham, NC 27705, USA. · Chest. · Pubmed #15383483 links to  free full text

Abstract: This chapter about antithrombotic therapy for coronary artery disease (CAD) is part of the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy: Evidence Based Guidelines. Grade 1 recommendations are strong and indicate that the benefits do, or do not, outweigh risks, burden, and costs. Grade 2 suggests that individual patients' values may lead to different choices (for a full understanding of the grading see Guyatt et al, CHEST 2004; 126:179S-187S). Among the key recommendations in this chapter are the following: For patients presenting with non-ST-segment elevation (NSTE) acute coronary syndrome (ACS), we recommend immediate and then daily oral aspirin (Grade 1A). For patients with an aspirin allergy, we recommend immediate treatment with clopidogrel, 300-mg bolus po, followed by 75 mg/d indefinitely (Grade 1A). In all NSTE ACS patients in whom diagnostic catheterization will be delayed or when coronary bypass surgery will not occur until > 5 days, we recommend clopidogrel as bolus therapy (300 mg), followed by 75 mg/d for 9 to 12 months in addition to aspirin (Grade 1A). In NSTE ACS patients in whom angiography will take place within 24 h, we suggest beginning clopidogrel after the coronary anatomy has been determined (Grade 2A). For patients who have received clopidogrel and are scheduled for coronary bypass surgery, we recommend discontinuing clopidogrel for 5 days prior to the scheduled surgery (Grade 2A). In moderate- to high-risk patients presenting with NSTE ACS, we recommend either eptifibatide or tirofiban for initial (early) treatment in addition to treatment with aspirin and heparin (Grade 1A). For the acute treatment of NSTE ACS, we recommend low molecular weight heparins over unfractionated heparin (UFH) [Grade 1B] and UFH over no heparin therapy use with antiplatelet therapies (Grade 1A). We recommend against the direct thrombin inhibitors as routine initial antithrombin therapy (Grade 1B). For patients after myocardial infarction, after ACS, and with stable CAD, we recommend aspirin in doses from 75 to 325 mg as initial therapy and in doses of 75 to 162 mg as indefinite therapy (Grade 1A). For patients with contraindications to aspirin, we recommend long-term clopidogrel (Grade 1A). For primary prevention in patients with at least moderate risk for a coronary event, we recommend aspirin, 75 to 162 mg/d, over either no antithrombotic therapy or vitamin K antagonist (VKA) [Grade 2A]; for patients at particularly high risk of events in whom the international normalized ratio (INR) can be monitored without difficulty, we suggest low-dose VKA (target INR, 1.5) [Grade 2A].

O'Connor CM, Joynt KE. · No affiliation provided · J Am Coll Cardiol. · Pubmed #15120810 No free full text.

This publication has no abstract.

Phillips HR, O'Connor CM, Rogers J. · Duke University Medical Center, Durham, NC 27710, USA. · Am Heart J. · Pubmed #17394905 No free full text.

Abstract: Coronary artery disease is the most common underlying cause of heart failure, yet there is little consensus on the role of revascularization in the management of patients with ischemic cardiomyopathy. The concept of recovery of dysfunctional but viable myocardium forms the pathophysiologic basis for the benefit of revascularization. Data from observational studies suggest that patients with coronary disease and left ventricular dysfunction may have improved outcomes after surgical revascularization or percutaneous coronary intervention (PCI) compared to medical treatment. Viability testing may be useful in selecting a population of patients who will receive differential benefit. In the clinical management of patients with heart failure, clinicians face challenging decisions about whether to recommend revascularization especially in patients who do not have angina. As data from randomized trials are awaited, PCI and coronary artery bypass grafting may be considered as complimentary revascularization approaches. Registry data suggest a benefit of coronary artery bypass grafting over PCI in patients with reduced ejection fraction; however, in patients with focal disease and comorbidities including previous surgery, PCI is reasonable, especially if complete revascularization is possible.

Bourque JM, Velazquez EJ, Borges-Neto S, Shaw LK, Whellan DJ, O'Connor CM. · Division of Cardiology, Department of Internal Medicine, Duke University Medical Center, Durham, NC 27710, USA. · Am Heart J. · Pubmed #12766731 No free full text.

Abstract: BACKGROUND: Ischemic heart failure is a significant source of morbidity and mortality, yet it has an unclear treatment strategy. The assessment of viable myocardium by nuclear imaging studies has shown promise in predicting improvements in ejection fraction and symptoms. However, the relationship of viability to long-term mortality has not been fully established. METHODS: A number of studies have addressed long-term mortality with nuclear viability imaging in patients with impaired left ventricular function and significant coronary artery disease. These studies were analyzed to determine differences in design, results, trends, and limitations. They were then evaluated by use of qualitative criteria established for prognostic studies. RESULTS: Fourteen studies met our criteria. Although the conclusions differed, it appears that patients with viability who undergo revascularization have the highest survival rate, whereas patients with viability who are treated medically have a much lower survival rate. Patients without viability have an intermediate survival rate, regardless of treatment. Several limitations were identified, including a lack of randomization, small sample size, inadequate follow-up, and extensive study protocol and design differences. CONCLUSIONS: The use of viability testing in patients with heart failure and significant coronary artery disease has shown promise in predicting the long-term mortality rate with treatment allocation. However, there is a need for further study involving larger cohorts with a randomized design, longer periods of follow-up, improved study designs, and identification of referral bias and viability prevalence.

Jiang W, Krishnan RR, O'Connor CM. · Department of Psychiatry, Duke University Medical Center, Durham, North Carolina 27707, USA. · CNS Drugs. · Pubmed #11825102 No free full text.

Abstract: Over several decades, a large body of evidence has emerged to suggest that depressive disorder is a risk factor for heart diseases, both aetiologically and prognostically. Several large, prospective, longitudinal studies have examined the relationship between depression and the development of coronary artery disease (CAD); they reveal that the relationship is significant and independent of conventional risk factors. Prognostic studies have shown that depression is associated with two to three times higher mortality after myocardial infarction, unstable angina or coronary artery bypass grafting, and in patients with stable CAD compared with such patients without depression. Depression also has been found to increase mortality and morbidity in patients with heart failure, regardless of its aetiology. Such adverse associations persist after adjustment for conventional prognostic risk factors. Despite all of these findings, depressed patients with heart disease are less likely to be recognised clinically as being depressed than those patients who have depression but no heart disease. The very limited evidence available from pharmacological clinical trials raises concern about the safety of antidepressants in CAD and heart failure. In addition, no research has addressed whether the treatment of depression in patients with heart disease will improve their prognosis.

Kong DF, Blazing MA, O'Connor CM. · Department of Medicine, Duke University Medical Center, Durham, N.C., USA. · Hosp Pract (Minneap). · Pubmed #10780184 No free full text.

Abstract: Acute coronary syndromes is a new term that encompasses the many permutations of acute ischemic heart disease. Management guidelines can help steer clinicians through diagnosis and facilitate rational selection of therapy from the myriad of available treatments.

Del Carlo CH, O'Connor CM. · Duke Clinical Research Institute, Duke University Medical Center, Durham, NC 27710, USA. · Am Heart J. · Pubmed #10502209 No free full text.

Abstract: BACKGROUND: We sought to assess the release of cardiac troponins in congestive heart failure (CHF). METHODS AND RESULTS: We performed a computer-assisted search of the English language literature (MEDLINE database) followed by a manual search of the reference list of pertinent articles retrieved. Studies evaluating the release of cardiac troponins (T and I) in patients with CHF were screened for review. Studies investigating cardiac troponins in patients with ischemic coronary syndromes that reported the rate of CHF were also selected. Available data on the release of cardiac troponins in ischemic and nonischemic CHF were summarized. Possible mechanisms of cell death in the progression to end-stage CHF were discussed. CONCLUSIONS: Cardiac troponins were detected in patients with advanced CHF. These markers correlated with the severity of CHF and suggest an association with worse prognosis. Possible mechanisms for the release of cardiac troponins T and I in advanced CHF may include the following: ventricular remodeling, presence of coronary artery disease in CHF, abnormalities of coronary microcirculation, and reduced coronary reserve. Further studies will be necessary to elucidate the actual mechanism and determine the clinical significance of cardiac troponins in CHF.

Gurbel PA, O'Connor CM, Cummings CC, Serebruany VL. · Center for Thrombosis Research, Sinai Hospital of Baltimore, 2401 West Belvedere Avenue, Schapiro Research Building-R202, Baltimore, MD 21215, USA. · Pharmacol Res. · Pubmed #10433868 No free full text.

Abstract: Ticlopidine has become an established therapy in patients with stroke, and during stenting in patients with coronary artery disease. Clopidogrel, another thienopyridine, is a safe and promising alternative, that irreversibly inhibits ADP-induced platelet aggregation, and reduces formation of both arterial and venous thrombi. In a recent, large, well-controlled trial (CAPRIE), clopidogrel has been shown to be superior to aspirin in terms of prevention of ischaemic stroke, myocardial infarction and death in patients with atherosclerotic vascular disease. Clopidogrel provides a safe opportunity to enhance reperfusion when administered during stent placement, by protecting platelets from excessive activation. However, the ability of clopidogrel to be superior to ticlopidine in terms of its antiplatelet properties in the clinical setting of coronary stenting, is unknown. The effects of clopidogrel versus ticlopidine on platelet and endothelial function are yet to be determined and may strongly affect the outcome, benefits, and complications following coronary stent placement. Further clinical trials, well-designed, and carefully conducted, should elucidate possible benefits of clopidogrel during coronary interventions, especially in conjunction with new and aggressive reperfusion techniques. The benefits of clopidogrel in an expanding array of clinical conditions, including myocardial infarction, may be directly related to platelet inhibition. Moreover, marginal clinical benefits, and recently reported severe bleeding events in some patients after oral platelet glycoprotein IIb/IIIa therapy, may advance clopidogrel as a safe, and efficient alternative during coronary interventions. This review summarises the latest, and often confusing data on the effects of thienopyridines on certain haemostatic characteristics in interventional cardiology. 1999 Academic Press.

Kong DF, Blazing MA, O'Connor CM. · Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA. · Cardiol Clin. · Pubmed #10384824 No free full text.

Abstract: Worldwide, UA represents a significant allocation of resources. UA represents a syndrome where not only do many therapies exist, but considerable clinical trial evidence has accumulated. Universal application of effective practice patterns is warranted if we are to successfully reduce the burden of UA. Economic analyses cannot resolve many of the underlying societal issues that affect decision making. Often, the acceptability of an economic burden is dependent on the willingness of both individuals and society to pay. In an interesting study, Chestnut et al evaluated the willingness of 50 patients to pay for avoiding a worsening of their angina symptoms. On average, the patients were willing to pay between $210 and $499 to avoid four to eight additional angina episodes each month. The "rule of rescue" suggests that society is often willing to pay large sums of money to save those in extreme need, such as the 55-year-old man rushed to the emergency department clutching his chest. Only recently has attention been paid to how much this disease entity costs us. Whereas the 1980s and 1990s saw a focus on costs, the next century will increasingly focus on value--obtaining the best health outcome for the dollars spent. Debate has shifted, at least in part, from purely financial costs to medical effectiveness and outcomes management. Continuing assessments of value of interventions and application of evidence based-management strategies permit rational selection of therapy and allow us best to bear the burden of UA.

O'Connor CM, Dunne MW, Pfeffer MA, Muhlestein JB, Yao L, Gupta S, Benner RJ, Fisher MR, Cook TD, Anonymous00270. · Duke University, Durham NC, USA. · JAMA. · Pubmed #13129985 links to  free full text

Abstract: CONTEXT: Several lines of evidence have implied an association between Chlamydia pneumoniae infection and atherogenesis. OBJECTIVE: To determine the effect of 12 weeks of antibiotic therapy on coronary heart disease events in patients with stable coronary artery disease and known C pneumoniae exposure. DESIGN, SETTING, AND PARTICIPANTS: Randomized, placebo-controlled trial of 7747 adults with previous myocardial infarction that had occurred at least 6 weeks previously (median, 2.6 years) and a C pneumoniae IgG titer of 1:16 or more. Patients were recruited from 271 clinical practices in North America, Europe, Argentina, and India, from October 10, 1997, to July 22, 2001. INTERVENTION: The patients received either azithromycin (600 mg/d for 3 days during week 1, then 600 mg/wk during weeks 2-12; n = 3879) or placebo (n = 3868). MAIN OUTCOME MEASURES: The primary event was the first occurrence of death from any cause, nonfatal reinfarction, coronary revascularization, or hospitalization for angina. Patients were followed up until 1038 events accrued. RESULTS: After a median of 14 months of follow-up, there was no significant risk reduction in the likelihood of a primary event with azithromycin vs placebo (7% [95% confidence interval, -5% to 17%], P =.23). Analysis of hazard ratios suggested early benefits of azithromycin on the primary event and on death or reinfarction, but these decreased over time. There were no significant risk reductions for any of the components of the primary end point including death (8%), recurrent myocardial infarction (7%), revascularization procedures (5%), or hospitalizations for angina (-1%). Adverse events related to study drug were reported by 13.2% of those randomized to receive azithromycin, predominantly a result of diarrhea, compared with 4.6% randomized to receive placebo, and resulted in discontinuation of drug in 1.6% of those taking azithromycin and 0.4% taking placebo. CONCLUSION: Among stable patients with previous myocardial infarction and with evidence of C pneumoniae exposure, a 3-month course of azithromycin did not significantly reduce the clinical sequelae of coronary heart disease.

Serebruany VL, Glassman AH, Malinin AI, Nemeroff CB, Musselman DL, van Zyl LT, Finkel MS, Krishnan KR, Gaffney M, Harrison W, Califf RM, O'Connor CM, Anonymous00209. · Sinai Center for Thrombosis Research, Johns Hopkins University, Baltimore, MD 21215, USA. · Circulation. · Pubmed #12912814 links to  free full text

Abstract: BACKGROUND: Depression after acute coronary syndromes (ACSs) has been identified as an independent risk factor for subsequent cardiac death. Enhanced platelet activation has been hypothesized to represent 1 of the mechanisms underlying this association. Selective serotonin reuptake inhibitors (SSRIs) are known to inhibit platelet activity. Whether treatment of depressed post-ACS patients with SSRIs alters platelet function was not known. Accordingly, we serially assessed the release of established platelet/endothelial biomarkers in patients treated with sertraline vs placebo in the Sertraline AntiDepressant Heart Attack Randomized Trial (SADHART). METHODS AND RESULTS: Plasma samples (baseline, week 6, and week 16) were collected from patients randomized to sertraline (n=28) or placebo (n=36). Anticoagulants, aspirin, and ADP-receptor inhibitors were permitted in this study. Platelet factor 4, beta-thromboglobulin (betaTG), platelet/endothelial cell adhesion molecule-1, P-selectin, thromboxane B2, 6-ketoprostaglandin F1a, vascular cell adhesion molecule-1, and E-selectin were measured by ELISA. Treatment with sertraline was associated with substantially less release of platelet/endothelial biomarkers than was treatment with placebo. These differences attained statistical significance for betaTG (P=0.03) at weeks 6 and 16 and for P-selectin (P=0.04) at week 16. Repeated-measures ANOVA revealed a significant advantage for sertraline vs placebo for diminishing E-selectin and betaTG concentrations across the entire treatment period. CONCLUSIONS: Treatment with sertraline in depressed post-ACS patients is associated with reductions in platelet/endothelial activation despite coadministration of widespread antiplatelet regimens including aspirin and clopidogrel. The antiplatelet and endothelium-protective properties of SSRIs might represent an attractive additional advantage in patients with depression and comorbid coronary artery and/or cerebrovascular disease.

Gurbel PA, Bliden KP, Hiatt BL, O'Connor CM. · Sinai Center for Thrombosis Research, Hoffberger Bldg, Suite 56, 2401 W Belvedere Ave, Baltimore, Md 21215, USA. · Circulation. · Pubmed #12796140 links to  free full text

Abstract: BACKGROUND: Clopidogrel is administered to prevent stent thrombosis; however, the uniformity of platelet inhibition after treatment and the influence of pretreatment reactivity on drug response have not been described. METHODS AND RESULTS: Platelet aggregation (5 and 20 micromol/L ADP), the activation of glycoprotein IIb/IIIa (PAC-1 antibody), and the expression of P-selectin were measured in patients undergoing elective coronary stenting (n=96) at baseline and at 2 hours, 24 hours, 5 days, and 30 days after stenting. All patients received aspirin (325 mg). Clopidogrel (300 mg) was administered in the catheterization laboratory and followed by 75 mg daily. There was marked interindividual variability in drug response as measured by all markers that showed a normal distribution. Resistance, defined as baseline aggregation (%) minus posttreatment aggregation (%) < or =10% by 5 micromol/L ADP, was present in 31% and 15% of patients at 5 and 30 days, respectively. Patients with the highest pretreatment platelet reactivity remained the most reactive at 24 hours after treatment (P<0.0001). CONCLUSIONS: Interindividual variability in the platelet inhibitory response from clopidogrel occurs in patients undergoing elective coronary stenting. Patients with high pretreatment reactivity are least protected. Alternative pharmacological strategies and the association of adverse ischemic events should be investigated in these patients.

Flaherty JD, Rossi JS, Fonarow GC, Nunez E, Stough WG, Abraham WT, Albert NM, Greenberg BH, O'Connor CM, Yancy CW, Young JB, Davidson CJ, Gheorghiade M. · Northwestern University, Chicago, IL, USA. · Am Heart J. · Pubmed #19464412 No free full text.

Abstract: BACKGROUND: Most patients hospitalized for acute heart failure syndromes (AHFS) carry a diagnosis of coronary artery disease (CAD), but coronary angiography is infrequently performed. This purpose of this study was to determine the influence of coronary angiography on use of therapeutics and early postdischarge outcomes in patients with AHFS. METHODS: The Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure program enrolled 48,612 patients admitted with AHFS at 259 academic and community hospitals throughout the United States Inhospital treatments and outcomes were tracked in all patients and postdischarge outcomes in a prespecified 10% sample. Outcome data were prospectively collected and analyzed according to whether coronary angiography was performed during the index hospitalization and whether a patient had CAD. RESULTS: Overall, 8.7% of all patients underwent inhospital angiography. Among patients with CAD who underwent angiography, 27.5% underwent inhospital myocardial revascularization. At the time of discharge, patients with CAD who underwent angiography were significantly more likely to be receiving aspirin (68.9% vs 50.3%, P < .0001), statins (56.6% vs 40.6%, P < .0001), beta-blockers (78.6% vs 67.5%, P < .0001), and angiotensin-converting enzyme inhibitors (64.9% vs 51.5%, P < .0001). In patients with AHFS and CAD, the use of inhospital angiography was associated with significantly lower mortality and rehospitalization risk in the first 60 to 90 days post hospital discharge after adjustment for multiple comorbidities and patient factors: mortality (HR 0.31 [95% CI 0.14-0.70], P = .004) and death or rehospitalization (OR 0.65 [95% CI 0.50-0.86], P = .003). There were no significant differences in any of these outcomes in patients with AHFS and a nonischemic etiology based the performance of inhospital angiography. CONCLUSIONS: The performance of inhospital angiography on patients with AHFS and CAD is associated with an increased use of aspirin, statins, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors and myocardial revascularization. This corresponded with significantly lower rates of death, rehospitalization, and death or rehospitalization at 60 to 90 days post discharge.

Jones RH, Velazquez EJ, Michler RE, Sopko G, Oh JK, O'Connor CM, Hill JA, Menicanti L, Sadowski Z, Desvigne-Nickens P, Rouleau JL, Lee KL, Anonymous00116. · Duke Clinical Research Institute, Duke University Medical Center, Durham, NC 27710, USA. · N Engl J Med. · Pubmed #19329820 No free full text.

Abstract: BACKGROUND: Surgical ventricular reconstruction is a specific procedure designed to reduce left ventricular volume in patients with heart failure caused by coronary artery disease. We conducted a trial to address the question of whether surgical ventricular reconstruction added to coronary-artery bypass grafting (CABG) would decrease the rate of death or hospitalization for cardiac causes, as compared with CABG alone. METHODS: Between September 2002 and January 2006, a total of 1000 patients with an ejection fraction of 35% or less, coronary artery disease that was amenable to CABG, and dominant anterior left ventricular dysfunction that was amenable to surgical ventricular reconstruction were randomly assigned to undergo either CABG alone (499 patients) or CABG with surgical ventricular reconstruction (501 patients). The primary outcome was a composite of death from any cause and hospitalization for cardiac causes. The median follow-up was 48 months. RESULTS: Surgical ventricular reconstruction reduced the end-systolic volume index by 19%, as compared with a reduction of 6% with CABG alone. Cardiac symptoms and exercise tolerance improved from baseline to a similar degree in the two study groups. However, no significant difference was observed in the primary outcome, which occurred in 292 patients (59%) who were assigned to undergo CABG alone and in 289 patients (58%) who were assigned to undergo CABG with surgical ventricular reconstruction (hazard ratio for the combined approach, 0.99; 95% confidence interval, 0.84 to 1.17; P=0.90). CONCLUSIONS: Adding surgical ventricular reconstruction to CABG reduced the left ventricular volume, as compared with CABG alone. However, this anatomical change was not associated with a greater improvement in symptoms or exercise tolerance or with a reduction in the rate of death or hospitalization for cardiac causes. (ClinicalTrials.gov number, NCT00023595.)

Mehta RH, Rogers JG, Hasselblad V, Tasissa G, Binanay C, Califf RM, O'Connor CM, Anonymous00066. · Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina, USA. · Am J Cardiol. · Pubmed #19101234 No free full text.

Abstract: The association of weight loss achieved through various decongestive strategies with clinical outcomes in patients with acute decompensated heart failure (HF) is not well described. The aim of this study was to determine the relation between weight change during hospitalization and subsequent clinical events in patients with decompensated HF. Data from 433 patients hospitalized with advanced HF enrolled in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial were evaluated. The influence of change in weight during hospitalization to clinical outcomes (days alive out of the hospital in the first 6 months; death; death or rehospitalization; and death, rehospitalization, or cardiac transplantation) was evaluated. On average, patients lost approximately 3.6 kg during hospitalization. When categorized into 3 weight loss tertiles, those in the highest tertile were more likely to be older, women, and smokers, with higher body weights, previous percutaneous coronary interventions, baseline heart rates, and brain natriuretic peptide and blood urea nitrogen values but lower ejection fractions and peak oxygen consumption. No significant differences were observed between weight change and any in-hospital or follow-up events (days well: hazard ratio 0.995, 95% confidence interval 0.975 to 1.016; 180-day death: hazard ratio 1.012, 95% confidence interval 0.969 to 1.057; death or rehospitalization at 180 days: hazard ratio 1.014, 95% confidence interval 0.990 to 1.038). In conclusion, weight loss in patients with acute decompensated HF during hospitalization was not related to clinical end points. These data challenge the merit of using weight as a surrogate end point for more important clinical events (i.e., death and/or rehospitalization) in patients with HF in the design of treatment strategies for novel therapeutic agents in randomized controlled clinical trials.

Rossi JS, Flaherty JD, Fonarow GC, Nunez E, Gattis Stough W, Abraham WT, Albert NM, Greenberg BH, O'Connor CM, Yancy CW, Young JB, Davidson CJ, Gheorghiade M. · Northwestern University, Chicago, Illinois, United States. · Eur J Heart Fail. · Pubmed #19006680 No free full text.

Abstract: BACKGROUND: Coronary artery disease (CAD) is frequent among patients hospitalized with acute heart failure syndromes (AHFS). AIMS: To describe the influence of coronary revascularization status on survival in patients with AHFS. METHODS AND RESULTS: OPTIMIZE-HF enrolled 48,612 patients with AHFS from 259 U.S. hospitals. In-hospital data were obtained for all patients and post-discharge 60-90 day follow-up in a pre-specified 10% sample. CAD was associated with higher in-hospital (3.7% vs. 2.9%, OR 1.14, 95% CI 1.00-1.31) and post-discharge mortality (9.2% vs. 6.9%, HR 1.37, 95% CI 1.03-1.81) compared to no CAD. Post-discharge, patients with CAD who were not revascularized had higher mortality compared to patients without CAD (10.6% vs. 6.9%, HR 1.56, 95% CI 1.15-2.11). This association was similar in patients with left ventricular systolic dysfunction (EF <40%, adjusted HR 1.52, 95% CI 0.98-2.35) and preserved systolic function (EF > or =40%, adjusted HR1.58, 95% CI 1.05-2.39). Patients with CAD who were revascularized had similar mortality to patients without CAD (HR 1.06, 95% CI 0.62-1.80 for PSF, HR 1.13, 95% CI 0.71-1.80 for LVSD). CONCLUSIONS: In AHFS, patients with CAD have a higher 60-90 day post-discharge mortality compared to no-CAD patients. However, patients with CAD who are revascularized appear to have similar post-discharge mortality when compared to the no-CAD group. This suggests that revascularization status may confer a survival advantage in this high risk population.

Hammill BG, Curtis LH, Bennett-Guerrero E, O'Connor CM, Jollis JG, Schulman KA, Hernandez AF. · Center for Clinical and Genetic Economics, Duke Clinical Research Institute, Durham, North Carolina, USA. · Anesthesiology. · Pubmed #18362586 links to  free full text

Abstract: BACKGROUND: Changes in the demographics and epidemiology of patients with cardiovascular comorbidities who undergo major noncardiac surgery require an updated assessment of which patients are at greater risk of mortality or readmission. The authors evaluated short-term outcomes among patients with heart failure, coronary artery disease (CAD), or neither who underwent major noncardiac surgery. METHODS: Patients were aged 65 and older, had Medicare fee-for-service coverage, and underwent 1 of 13 major noncardiac procedures from 2000 through 2004, excluding patients with end-stage renal disease and patients who did not have at least 1 yr of Medicare fee-for-service eligibility before surgery. Main outcome measures were operative mortality and 30-day all-cause readmission. RESULTS: Of 159,327 procedures, 18% were performed in patients with heart failure and 34% were performed in patients with CAD. Adjusted hazard ratios of mortality and readmission for patients with heart failure, compared with patients with neither heart failure nor CAD, were 1.63 (95% confidence interval, 1.52-1.74) and 1.51 (95% confidence interval, 1.45-1.58), respectively. Adjusted hazard ratios of mortality and readmission for patients with CAD, compared with patients with neither heart failure nor CAD, were 1.08 (95% confidence interval, 1.01-1.16) and 1.16 (95% confidence interval, 1.12-1.20), respectively. These effects were statistically significant. Patients with heart failure were at significantly higher risk for both outcomes compared with patients with CAD. CONCLUSIONS: Elderly patients with heart failure who undergo major surgical procedures have substantially higher risks of operative mortality and hospital readmission than other patients, including those with coronary disease, admitted for the same procedures. Improvements in perioperative care are needed for the growing population of patients with heart failure undergoing major noncardiac surgery.

Velazquez EJ, Lee KL, O'Connor CM, Oh JK, Bonow RO, Pohost GM, Feldman AM, Mark DB, Panza JA, Sopko G, Rouleau JL, Jones RH, Anonymous00315. · Division of Cardiovascular Medicine, Department of Medicine, Duke University Medical Center, Durham, NC; Duke Clinical Research Institute, Durham, NC, USA. · J Thorac Cardiovasc Surg. · Pubmed #18023680 No free full text.

Abstract: OBJECTIVES: The rationale and design of the Surgical Treatment for Ischemic Heart Failure trial is described. Before the Surgical Treatment for Ischemic Heart Failure trial, less than 1000 patients with ischemic cardiomyopathy had been studied in randomized comparisons of medical therapy versus coronary artery bypass grafting. Trial data reflect how these therapies were delivered more than 20 years ago and do not indicate the relative benefits of medical therapy versus coronary artery bypass grafting in contemporary practice. METHODS: Randomization of consenting patients with heart failure, left ventricular ejection fraction of 0.35 or less, and coronary artery disease is based on whether patients are judged by attending physicians to be candidates only for coronary artery bypass grafting or can be treated with medical therapy without coronary artery bypass grafting. Patients eligible for surgical ventricular reconstruction because of significant anterior wall akinesis or dyskinesis but ineligible for medical therapy are randomly assigned to coronary artery bypass grafting with or without surgical ventricular reconstruction. Patients eligible for medical therapy are randomly assigned between medical therapy only and medical therapy with coronary artery bypass grafting. Patients eligible for all 3 are randomly assigned evenly to medical therapy only, medical therapy and coronary artery bypass grafting, or medical therapy and coronary artery bypass grafting and surgical ventricular reconstruction. Major substudies will examine quality of life, cost-effectiveness, changes in left ventricular volumes, effect of myocardial viability, selected biomarkers, and selected polymorphisms on treatment differences. RESULTS: Enrollment is now complete in both STICH hypotheses. Follow-up will continue until sufficient end points are available to address both hypotheses with at least 90% power. The primary outcome of hypothesis 2 is expected to be reported in 2009. The primary outcome of hypothesis 1 is expected to be reported in 2011. CONCLUSIONS: The Surgical Treatment for Ischemic Heart Failure trial is a National Heart, Lung, and Blood Institute-funded multicenter international randomized trial addressing 2 specific primary hypotheses: (1) coronary artery bypass grafting with intensive medical therapy improves long-term survival compared with survival with medical therapy alone, and (2) in patients with anterior left ventricular dysfunction, surgical ventricular reconstruction to a more normal left ventricular size plus coronary artery bypass grafting improves survival free of subsequent hospitalization for cardiac cause when compared with that with coronary artery bypass grafting alone.

Bourque JM, Velazquez EJ, Tuttle RH, Shaw LK, O'Connor CM, Borges-Neto S. · Division of Cardiology, Department of Internal Medicine, Duke University Health System, Durham, NC, USA. · J Nucl Cardiol. · Pubmed #17386378 No free full text.

Abstract: BACKGROUND: Left ventricular ejection fraction (LVEF) is a significant predictor of morbidity and death. The nuclear summed rest score (SRS) measures myocardial perfusion defects and provides prognostic information, but its effects on long-term outcomes are not fully established. Moreover, information regarding the potential interaction between these 2 covariates is limited. The purpose of this study was to determine whether the mortality risk associated with LVEF is the same across all values of SRS in a population undergoing evaluation for ischemic heart disease. METHODS AND RESULTS: We examined 3,187 patients who underwent cardiac catheterization and perfusion single photon emission computed tomography imaging with a maximum follow-up of 8.1 years and median follow-up of 3.1 years. Cox proportional hazards modeling showed that increasing nuclear SRS and decreasing LVEF were independently associated with a higher long-term mortality rate, with a clinically significant interaction between them (P = .032). Patients with a normal LVEF and a high SRS (greater perfusion abnormality) have a prognosis similar to those with a reduced LVEF. CONCLUSIONS: Resting perfusion studies provide prognostic information for long-term survival and significantly impact the interpretation of mortality risk associated with changes in LVEF. Patient prognostication, risk stratification, and future research using these variables should take this interaction into account.

Whellan DJ, Tuttle RH, Velazquez EJ, Shaw LK, Jollis JG, Ellis W, O'Connor CM, Califf RM, Borges-Neto S. · Department of Medicine, Jefferson Medical College, Philadelphia, PA 19107, USA. · Am Heart J. · Pubmed #16875920 No free full text.

Abstract: BACKGROUND: Because coronary artery disease (CAD) is a prevalent comorbidity in patients with low ejection function (EF), a number of patients with heart failure undergo diagnostic cardiac catheterization. The objective of this study was to develop a model to assist clinicians in determining the likelihood of CAD before cardiac catheterization. METHODS: This study was a retrospective analysis using the Duke Databank for Cardiovascular Disease. From the databank, 2054 patients who underwent cardiac catheterization between 1992 and 2002 that was preceded by echocardiography with an EF of < 45% were identified. The patients' median age was 63 years, and the median EF was 30%. Patients were considered to have significant CAD if any major epicardial vessel had > or = 75% stenosis. A multivariable model of CAD was generated using stepwise logistic regression. We included demographic, clinical, electrocardiographic, and echocardiographic parameters, including segmental wall motion abnormality. RESULTS: Of the patients who met the criteria, 1184 (58%) had significant CAD and 870 (42%) did not. Significant predictors of CAD, in the order of their ability to predict significant CAD, included history of myocardial infarction, age, diabetes mellitus, Q wave on electrocardiogram, male sex, and segmental wall motion abnormality (all P < .0001). The area under the receiver operating characteristic curve was 0.865. CONCLUSIONS: By using baseline demographic and clinical characteristics, we developed a highly discriminatory diagnostic model for predicting CAD in patients with heart failure. Given the high prevalence of patients without CAD in this cohort, accurate baseline assessment of patients with left ventricular dysfunction for CAD might avoid unnecessary invasive procedures.

Aguilar D, Fisher MR, O'Connor CM, Dunne MW, Muhlestein JB, Yao L, Gupta S, Benner RJ, Cook TD, Edwards D, Pfeffer MA, Anonymous00224. · Cardiology Division, Baylor College of Medicine, Houston, TX 77030, USA. · Am Heart J. · Pubmed #16875914 No free full text.

Abstract: BACKGROUND: The prognosis associated with metabolic syndrome and high-sensitivity C-reactive protein (hs-CRP) in patients with stable coronary artery disease has not been well established. METHODS: The WIZARD study was to determine the effects of 12 weeks of antibiotic therapy on coronary heart disease events in patients with stable coronary artery disease and known Chlamydia pneumoniae exposure. Baseline metabolic risk factors were available for 3319 patients enrolled from 1997 to 1998. The primary outcome was the first occurrence of death, recurrent myocardial infarction, coronary revascularization procedure, or hospitalization for angina. RESULTS: Of the 3319 subjects, 825 patients experienced the primary outcome during the mean follow-up of 37 months. For the composite outcome, there was an increased hazard ratio (HR) for metabolic syndrome (HR 1.40, 95% CI 1.22-1.61) (unadjusted) and for hs-CRP (HR 1.60, 95% CI 1.38-1.85) (unadjusted). Both the metabolic syndrome and hs-CRP indicated, in a multivariable model including age and sex, an increased HR for the primary outcome (metabolic syndrome: HR 1.33, 95% CI 1.15-1.53; hs-CRP: HR 1.52, 95% CI 1.30-1.76). CONCLUSIONS: Although related, the presence of the metabolic syndrome and increased levels of hs-CRP were associated with increased risk of adverse cardiovascular outcomes.

Xiong GL, Jiang W, Clare R, Shaw LK, Smith PK, Mahaffey KW, O'Connor CM, Krishnan KR, Newby LK. · Department of Internal Medicine, Duke University Medical Center, Durham, North Carolina, USA. · Am J Cardiol. · Pubmed #16784918 No free full text.

Abstract: Depression is increasingly recognized as an independent prognostic risk factor in patients with coronary artery disease and coronary artery bypass grafting (CABG). The use of selective serotonin reuptake inhibitors (SSRIs) for depression in patients with cardiac disease is becoming more prevalent. We examined the long-term outcomes of patients on SSRIs before CABG. We prospectively examined collected data in the Duke Databank for Cardiovascular Disease from January 1, 1999 to December 31, 2003. The median and maximum follow-up periods were 3 and 6 years, respectively. We screened patients who underwent CABG (n = 5,364) and excluded those who underwent simultaneous CABG and valvular surgery (n = 570). SSRI antidepressants included fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, escitalopram, venlafaxine, and clomipramine, and their use was determined from the inpatient pharmacy records during the index hospitalization. Outcomes included event-free survival from all-cause mortality, rehospitalization, and a composite end point of all-cause mortality or rehospitalization. Of 4,794 CABG-only patients, 246 (5.1%) took SSRIs before CABG. The SSRI group had a higher prevalence of diabetes, hypercholesterolemia, hypertension, cerebrovascular disease, peripheral vascular disease, and previous cardiovascular intervention. After adjustment for baseline differences, patients on SSRIs before CABG had increased risks of mortality, rehospitalization, and the composite end point (hazard ratio 1.61, 95% confidence interval 1.17 to 2.21, p = 0.003; hazard ratio 1.52, 95% confidence interval 1.30 to 1.77, p <0.0001; and hazard ratio 1.46, 95% confidence interval 1.26 to 1.70, p <0.0001, respectively). In conclusion, SSRI use before CABG was associated with a higher risk of long-term post-CABG mortality and rehospitalization. The explanation behind these findings requires further research.

Thomas KL, East MA, Velazquez EJ, Tuttle RH, Shaw LK, O'Connor CM, Peterson ED. · The Duke University Medical Center, Durham, North Carolina, USA. · Am J Cardiol. · Pubmed #16188524 No free full text.

Abstract: Previous studies have shown that blacks have worse long-term outcomes than whites who have systolic heart failure. The reasons for these racial differences remain unclear. We investigated the effect of race and etiology of heart failure on outcomes of patients who had left ventricular (LV) systolic dysfunction. We studied records of 1,977 patients (27% black) who underwent cardiac catheterization who had New York Heart Association class II to IV symptoms and a LV ejection fraction <40%. Adjusted Cox's proportional hazards regression models were examined for the end points of mortality, rehospitalization, and a composite of the 2. Black versus white patients were younger (median age 56 vs 63 years, p <0.01), more often were women (49% vs 33%, p <0.01), had diabetes (37% vs 31%, p = 0.02), and hypertension (75% vs 56%, p <0.01). Black patients were less likely to have significant coronary artery disease by angiography (41% vs 69%, p <0.01). Race was not an independent predictor of mortality (hazard ratio 1.09, 95% confidence interval 0.93 to 1.28, p = 0.27). After adjusted survival curves were stratified by race and etiology, the estimates indicated that among those patients who had nonischemic LV dysfunction, blacks appeared to have worse survival than whites. Thus, we found no racial differences in the long-term mortality risk of patients who had symptomatic LV systolic dysfunction. In conclusion, after stratifying by ischemic and nonischemic etiologies, we found decreased survival in blacks who had a nonischemic etiology compared with whites. There were no racial differences in rehospitalization between patients who had ischemic LV systolic dysfunction and those who did not.

Gheorghiade M, Gattis Stough W, Adams KF, Jaffe AS, Hasselblad V, O'Connor CM. · Division of Cardiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA. · Am J Cardiol. · Pubmed #16181819 No free full text.

Abstract: Acute heart failure syndromes (AHFS) are related to several diseases affecting not only the heart but also the kidneys and blood vessels. Emerging evidence indicates that myocardial injury may also play a role in the pathophysiology of AHFS, as suggested by increased levels of markers of injury, such as cardiac troponin (cTn). Although cTn is a known prognostic marker, the release of cTn during hospitalization has not been evaluated prospectively with serial measures. We prospectively evaluated patterns of cTn release by conducting serial measures of cTnI and cTnT in patients hospitalized for AHFS. This study enrolled 51 patients with AHFS who were admitted with worsening heart failure (HF) and a history of coronary artery disease (CAD) in whom an acute coronary event was not suspected. Levels of cTnI and cTnT were measured at 8, 32, 56, and 80 hours after study entry. At baseline, 73.9% of patients had detectable cTnI, and 43.5% had detectable cTnT levels. The median concentrations of cTnI and cTnT were unchanged from 0 to 32 hours, increased from 32 to 56 hours, then either plateaued (cTnT) or decreased to baseline (cTnI). Of the 26 patients who had no detectable cTn levels at baseline, 2 (7.7%) developed detectable cTnT and 5 (41.7%) developed detectable cTnI release during hospitalization. Detectable levels of cTn at baseline were related to short-term clinical events. In this study of patients with CAD in whom an acute coronary event was not suspected, most had detectable levels of cTn present at admission, and some patients developed cTn release during hospitalization. Because cTn release may be a marker for myocardial injury, this study raises the possibility that injury occurred in most patients admitted with AHFS. Therefore, the goal of therapy for AHFS should be not only to improve symptoms and hemodynamics but also to salvage myocardium. Accordingly, therapies for AHFS that are aimed at improving hemodynamics may affect long-term prognosis by either injuring or salvaging myocardium.