Explore the vast range of titles available.

Prior trials comparing a strategy of optimal medical therapy with or without revascularization have not shown that revascularization reduces cardiovascular events in patients with stable ischemic heart disease (SIHD). However, those trials only included participants in whom coronary anatomy was known prior to randomization and did not include sufficient numbers of participants with significant ischemia. It remains unknown whether a routine invasive approach offers incremental value over a conservative approach with catheterization reserved for failure of medical therapy in patients with moderate or severe ischemia. The ISCHEMIA trial is a National Heart, Lung, and Blood Institute supported trial, designed to compare an initial invasive or conservative treatment strategy for managing SIHD patients with moderate or severe ischemia on stress testing. Five thousand one-hundred seventy-nine participants have been randomized. Key exclusion criteria included estimated glomerular filtration rate (eGFR) <30 mL/min, recent myocardial infarction (MI), left ventricular ejection fraction <35%, left main stenosis >50%, or unacceptable angina at baseline. Most enrolled participants with normal renal function first underwent blinded coronary computed tomography angiography (CCTA) to exclude those with left main coronary artery disease (CAD) and without obstructive CAD. All randomized participants receive secondary prevention that includes lifestyle advice and pharmacologic interventions referred to as optimal medical therapy (OMT). Participants randomized to the invasive strategy underwent routine cardiac catheterization followed by revascularization with percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery, when feasible, as selected by the local Heart Team to achieve optimal revascularization. Participants randomized to the conservative strategy undergo cardiac catheterization only for failure of OMT. The primary endpoint is a composite of cardiovascular (CV) death, nonfatal myocardial infarction (MI), hospitalization for unstable angina, hospitalization for heart failure, or resuscitated cardiac arrest. Assuming the primary endpoint will occur in 16% of the conservative group within 4 years, estimated power exceeds 80% to detect an 18.5% reduction in the primary endpoint. Major secondary endpoints include the composite of CV death and nonfatal MI, net clinical benefit (primary and secondary endpoints combined with stroke), angina-related symptoms and disease-specific quality of life, as well as a cost-effectiveness assessment in North American participants. Ancillary studies of patients with advanced chronic kidney disease and those with documented ischemia and non-obstructive coronary artery disease are being conducted concurrently. ISCHEMIA will provide new scientific evidence regarding whether an invasive management strategy improves clinical outcomes when added to optimal medical therapy in patients with SIHD and moderate or severe ischemia.

Arginine contains the guanidinium group and thus has structural similarity to ligands of imidazoline and α-2 adrenoceptors (α-2 AR). Therefore, we investigated the possibility that exogenous arginine may act as a ligand for these receptors in human umbilical vein endothelial cells and activate intracellular nitric oxide (NO) synthesis. Idazoxan, a mixed antagonist of imidazoline and α-2 adrenoceptors, partly inhibited L-arginine-initiated NO formation as measured by a Griess reaction. Rauwolscine, a highly specific antagonist of α-2 AR, at very low concentrations completely inhibited NO formation. Like L-arginine, agmatine (decarboxylated arginine) also activated NO synthesis, however, at much lower concentrations. We found that dexmedetomidine, a specific agonist of α-2 AR was very potent in activating cellular NO, thus indicating a possible role for α-2 AR in L-arginine-mediated NO synthesis. D-arginine also activated NO production and could be inhibited by imidazoline and α-2 AR antagonists, thus indicating nonsubstrate actions of arginine. Pertussis toxin, an inhibitor of G proteins, attenuated L-arginine-mediated NO synthesis, thus indicating mediation via G proteins. L-type Ca²⁺ channel blocker nifedipine and phospholipase C inhibitor U73122 inhibited NO formation and thus implicated participation of a second messenger pathway. Finally, in isolated rat gracilis vessels, rauwolscine completely inhibited the L-arginine-initiated vessel relaxation. Taken together, these data provide evidence for binding of arginine to membrane receptor(s), leading to the activation of endothelial NO synthase (eNOS) NO production through a second messenger pathway. These findings provide a previously unrecognized mechanistic explanation for the beneficial effects of L-arginine in the cardiovascular system and thus provide new potential avenues for therapeutic development.

Although hemodynamic monitoring is often performed after coronary artery bypass grafting (CABG), the role of monitoring postoperative central venous pressure (CVP) measurement as a predictor of clinical outcomes is unknown. As such, this study tests the hypothesis that postoperative CVP is predictive of operative mortality or renal failure. This is an observational cohort study of detailed clinical data from 2390 randomly selected patients undergoing high-risk CABG or CABG/valve at 55 hospitals participating in the Society of Thoracic Surgeons' National Cardiac Surgery Database 2004-2005. Eligible patients underwent elective/urgent CABG with an ejection fraction less than 40% or elective/urgent CABG at 65 years or older with diabetes or a glomerular filtration rate less than 60 mL/min per 1.73 m2. The exposure of interest is CVP monitoring in the intensive care unit after adult cardiac surgery. The primary outcome measure was correlation between postoperative CVP and inhospital/30-day mortality and renal failure, assessed as a continuous variable, both unadjusted and after adjusting for important clinical factors using logistic regression modeling. Mean age was 72 years, 54% of patients had diabetes mellitus, 49% were urgent procedures, and mean cardiopulmonary bypass time was 105 minutes. Patients' CVP 6 hours postoperation was strongly associated with inhospital and 30-day mortality: odds ratio (OR) of 1.5 (95% confidence interval [CI], 1.23-1.87) for every 5-mm Hg increase in CVP; P < .0001. This association remained significant after risk adjustment: adjusted OR of 1.44 (95% CI, 1.10-1.89); P < .01. A model adjusting for cardiac index also revealed increased incidence of mortality or renal failure: adjusted OR of 1.5 (95% CI, 1.28-1.86) for every 5-mm Hg increase in CVP; P < .0001. Patients' CVP at 6 hours after CABG surgery was highly predictive of operative mortality or renal failure, independent of cardiac index and other important clinical variables. Future studies will need to assess whether interventions guided by postoperative CVP can improve patient outcomes.

Edifoligide, an E2F transcription factor decoy, does not prevent vein graft failure or adverse clinical outcomes at 1 year in patients undergoing coronary artery bypass grafting (CABG). We compared the 5-year clinical outcomes of patients in PREVENT IV treated with edifoligide and placebo to identify predictors of long-term clinical outcomes. A total of 3,014 patients undergoing CABG with at least 2 planned vein grafts were enrolled. Kaplan-Meier curves were generated to compare the long-term effects of edifoligide and placebo. A Cox proportional hazards model was constructed to identify factors associated with 5-year post-CABG outcomes. The main outcome measures were death, myocardial infarction (MI), repeat revascularization, and rehospitalization through 5 years. Five-year follow-up was complete in 2,865 patients (95.1%). At 5 years, patients randomized to edifoligide and placebo had similar rates of death (11.7% and 10.7%, respectively), MI (2.3% and 3.2%), revascularization (14.1% and 13.9%), and rehospitalization (61.6% and 62.5%). The composite outcome of death, MI, or revascularization occurred at similar frequency in patients assigned to edifoligide and placebo (26.3% and 25.5%, respectively; hazard ratio 1.03 [95% CI 0.89-1.18], P = .721). Factors associated with death, MI, or revascularization at 5 years included peripheral and/or cerebrovascular disease, time on cardiopulmonary bypass, lung disease, diabetes mellitus, and congestive heart failure. Up to a quarter of patients undergoing CABG will have a major cardiac event or repeat revascularization procedure within 5 years of surgery. Edifoligide does not affect outcomes after CABG; however, common identifiable baseline and procedural risk factors are associated with long-term outcomes after CABG.

Although irreversible reaction of NO with the oxyheme of hemoglobin (producing nitrate and methemoglobin) is extremely rapid, it has been proposed that, under normoxic conditions, NO binds preferentially to the minority deoxyheme to subsequently form S-nitrosohemoglobin (SNOHb). Thus, the primary reaction would be conservation, rather than consumption, of nitrogen oxide. Data supporting this conclusion were generated by using addition of a small volume of a concentrated aqueous solution of NO to a normoxic hemoglobin solution. Under these conditions, however, extremely rapid reactions can occur before mixing. We have thus compared bolus NO addition to NO generated homogeneously throughout solution by using NO donors, a more physiologically relevant condition. With bolus addition, multiple hemoglobin species are formed (as judged by visible spectroscopy) as well as both nitrite and nitrate. With donor, only nitrate and methemoglobin are formed, stoichiometric with the amount of NO liberated from the donor. Studies with increasing hemoglobin concentrations reveal that the nitrite-forming reaction (which may be NO autoxidation under these conditions) competes with reaction with hemoglobin. SNOHb formation is detectable with either bolus or donor; however, the amounts formed are much smaller than the amount of NO added (less than 1%). We conclude that the reaction of NO with hemoglobin under normoxic conditions results in consumption, rather than conservation, of NO.

There is limited information about the association between diabetes, its treatment, and long-term angiographic and clinical outcomes in patients undergoing coronary artery bypass graft surgery (CABG). We evaluated the association of diabetes and its treatment with 1-year angiographic graft failure and 5-year clinical outcomes in patients undergoing CABG. Using data from 3,014 patients in PREVENT IV, we analyzed angiographic and clinical outcomes in patients with and without diabetes and among those who did and did not receive insulin before CABG. Logistic regression and Cox proportional hazards models were used to adjust for differences in baseline variables. Overall, 1,139 (37.8%) patients had diabetes. Of these, 305 (26.8%) received insulin. One-year rates of vein graft failure were similar in patients with and without diabetes but, among diabetics, tended to be higher in patients who received insulin compared with those who did not. At 5 years, rates of death, myocardial infarction, or revascularization were higher among patients with compared with those without diabetes (adjusted hazard ratio 1.57; 95% CI 1.26-1.96; P < .001) and, among diabetics, higher among those who received insulin (adjusted hazard ratio 1.15; 95% CI 1.02-1.30; P = .02). Patients with diabetes had similar rates of vein graft failure but worse clinical outcomes than patients without diabetes. Patients who received insulin had significantly worse clinical outcomes than patients who did not receive insulin. Further studies to better understand the mechanism behind these findings and to improve the outcomes of patients with insulin-requiring diabetes undergoing CABG surgery are warranted.

Dual antiplatelet therapy with both aspirin and clopidogrel is increasingly used after coronary artery bypass grafting (CABG); however, little is known about the safety or efficacy. We sought to determine the relationship between postoperative clopidogrel and clinical and angiographic outcomes following CABG. We evaluated 3,014 patients from PREVENT IV who underwent CABG at 107 US sites. Postoperative antiplatelet therapy was left to physician discretion. Risk-adjusted angiographic and clinical outcomes were compared in patients taking and not taking clopidogrel 30 days post-CABG. At 30 days, 633 (21 %) patients were taking clopidogrel. Clopidogrel users were more likely to have peripheral vascular (15 vs. 11 %) and cerebrovascular disease (17 vs. 11 %), prior myocardial infarction (MI) (46 vs. 41 %), and off-pump surgery (33 vs. 18 %). Clopidogrel use was associated with statistically insignificant higher graft failure (adjusted odds ratio 1.3; 95 % confidence interval [CI] [1.0, 1.7]; P  = 0.05). At 5-year follow-up, clopidogrel use was associated with similar composite rates of death, MI, or revascularization (27 vs. 24 %; adjusted hazard ratio 1.1; 95 % CI [0.9, 1.4]; P  = 0.38) compared with those not using clopidogrel. There was an interaction between use of cardiopulmonary bypass and clopidogrel with a trend toward lower 5-year clinical events with clopidogrel in patients undergoing off-pump CABG. In this observational analysis, clopidogrel use was not associated with better 5-year outcomes following CABG. There may be better outcomes with clopidogrel among patients having off-pump surgery. Adequately powered randomized clinical trials are needed to determine the role of dual antiplatelet therapy after CABG.

This clinical trial compared mitral-valve repair with replacement for severe ischemic mitral regurgitation. There were no significant between-group differences in left ventricular remodeling and clinical outcomes, but replacement was associated with more durable correction. Functional ischemic mitral regurgitation affects 1.6 million to 2.8 million patients in the United States and is associated with a doubling in mortality among patients with mild or greater degrees of mitral regurgitation after myocardial infarction. 1 – 3 Ischemic mitral regurgitation is a consequence of adverse left ventricular remodeling after myocardial injury with enlargement of the left ventricular chamber and mitral annulus, apical and lateral migration of the papillary muscles, leaflet tethering, and reduced closing forces. These processes lead to malcoaptation of the leaflets and variable degrees of mitral regurgitation that can fluctuate dynamically as a function of volume status, afterload, . . .

The appropriate use of vasoactive cardiovascular drugs in high-risk coronary artery bypass grafting (CABG) patients has not been well characterized. We performed a detailed chart analysis on 2,390 randomly selected patients undergoing CABG between January 2004 and June 2005 at 55 hospitals participating in the Society of Thoracic Surgeons' National Adult Cardiac Surgery Database. Patients were eligible if they had elective/urgent CABG with an ejection fraction (EF) <40%, or if they had an elective or urgent CABG at ≥65 years with diabetes, or a glomerular filtration rate <60 mL/min per 1.73 m 2. Logistic regression modeling was used to determine predictors of and provide risk-adjusted frequencies of postoperative vasoactive therapies. Vasoactive therapy was used in 90% of patients. Inotropes/vasopressors were used in 28% (668), vasodilators in 18% (430), and the combination in 43% (1,037). Predictors of any inotrope use were preoperative atrial fibrillation (odds ratio [OR] 1.48), other arrhythmia (OR 2.09), EF (OR 1.09 per 5-unit decrease), severe mitral regurgitation (OR 2.56), 3-vessel coronary artery disease (OR 1.35), New York Heart Association class IV (1.38), on-pump (OR 1.86), other procedure (OR 2.51), and peripheral vascular disease (OR 1.28) (all OR P < .05). Hospital-level risk-adjusted rates of any inotrope use varied significantly from 100% to 35% ( P < .01) and vasodilator rates varied from 100% to 10% ( P < .01). There is marked hospital variation in the use of vasoactive therapies in high-risk CABG patients in clinical practice, indicating an important area for further research to better clarify best practice.

Endoscopic vein-graft harvesting is often used in coronary-artery bypass grafting (CABG) to prevent postoperative wound complications. However, in this study, which had a 3-year follow-up, endoscopic harvesting was associated with a higher rate of graft failure and adverse clinical outcomes. Although this is not a randomized study, it calls into question the use of endoscopic vein-graft harvesting in CABG. Endoscopic vein-graft harvesting is often used in coronary-artery bypass grafting (CABG) to prevent postoperative wound complications. However, in this study, endoscopic harvesting was associated with a higher rate of graft failure and adverse clinical outcomes. Coronary-artery bypass grafting (CABG) is one of the most commonly performed surgical procedures and improves the clinical outcomes in appropriately selected patients. 1 , 2 Despite increased use of an arterial conduit, the greater saphenous vein remains the conduit that is used most often in CABG. 1 Traditionally, the saphenous vein is harvested under direct vision (open harvesting) with the help of linear incisions along the course of the vein. This approach is associated with discomfort and the risk of complications, including edema, hematoma, delayed healing, cellulitis, and wound dehiscence. 3 – 7 Endoscopic vein-graft harvesting, a procedure that was developed to eliminate the need . . .