Use of antiplatelet drugs after cardiac operations.

Unfortunately, venous bypass grafts still have a prominent role in operative coronary revascularization (coronary artery bypass graft [CABG]). Venous grafts develop pathologically occlusive disease that limits the effectiveness of CABG, and antiplatelet drugs following operation may limit this problem. The types and indications of antiplatelet drugs following CABG generate some controversy in the recent literature. This review surveys relevant evidence about the use of antiplatelet drugs following CABG to identify the controversial issues, define appropriate questions, and attempt to provide evidence-based interventions that may be helpful in limiting graft occlusion after CABG. Evidence suggests that, in most CABG patients, dual antiplatelet drugs (aspirin and clopidogrel), given after operation, minimizes early (within 1 year) graft failure and improves intermediate-term outcomes, better than single antiplatelet therapy with aspirin alone. There are gaps in the knowledge base that supports this contention, and future clinical trials will likely augment or alter this recommendation.

Identification of patients with postoperative complications who are at risk for failure to rescue.

IMPORTANCE: A minority of patients who experience postoperative complications die (failure to rescue). Understanding the preoperative factors that lead to failure to rescue helps surgeons predict and avoid operative mortality. OBJECTIVE: To provide a mechanism for identifying a high-risk group of patients with postoperative complications who are at a substantially increased risk for failure to rescue. DESIGN, SETTING, AND PATIENTS: Observational study evaluating failure to rescue in patients entered into the American College of Surgeons National Surgical Quality Improvement Program database. The large sample of surgical patients included in this study underwent a wide range of operations during a 5-year period in more than 200 acute care hospitals. We examined and identified patients at high risk for failure to rescue using propensity stratification. We also developed a risk-scoring system that allowed preoperative identification of patients at the highest risk for failure to rescue. MAIN OUTCOMES AND MEASURES: Risk-scoring system that predicts failure to rescue. RESULTS: Of the 1,956,002 database patients, there were 207,236 patients who developed serious postoperative complications. Deaths occurred in 21,731 patients with serious complications (10.5% failure to rescue). Stratification of patients into quintiles, according to their propensity for developing serious complications, found that 90% of operative deaths occurred in the highest-risk quintile, usually within a week of developing the initial complication. A risk-scoring system for failure to rescue, based on regression-derived variable odds ratios, predicted patients in the highest-risk quintile with good predictive accuracy. Only 31.8% of failure-to-rescue patients had a single postoperative complication. Perioperative deaths increased exponentially as the number of complications per patient increased. Patients with complications who had surgical residents involved in their care had reduced rates of failure to rescue compared with patients without resident involvement. CONCLUSIONS AND RELEVANCE: Twenty percent of high-risk patients account for 90% of failure to rescue (Pareto principle). More than two-thirds of patients with failure to rescue have multiple complications. On average, a few days elapse before death following a complication. A risk-scoring system based on preoperative variables predicts patients in the highest-risk category of failure to rescue with good accuracy. In high-risk patients who develop complications, our results suggest that early intervention, preferably in a high-level intensive care facility with a surgical training program, offers the best chance to reduce failure-to-rescue rates.

X-linked inhibitor of apoptosis protein-mediated attenuation of apoptosis, using a novel cardiac-enhanced adeno-associated viral vector.

Successful amelioration of cardiac dysfunction and heart failure through gene therapy approaches will require a transgene effective at attenuating myocardial injury, and subsequent remodeling, using an efficient and safe delivery vehicle. Our laboratory has established a well-curated, high-quality repository of human myocardial tissues that we use as a discovery engine to identify putative therapeutic transgene targets, as well as to better understand the molecular basis of human heart failure. By using this rare resource we were able to examine age- and sex-matched left ventricular samples from (1) end-stage failing human hearts and (2) nonfailing human hearts and were able to identify the X-linked inhibitor of apoptosis protein (XIAP) as a novel target for treating cardiac dysfunction. We demonstrate that XIAP is diminished in failing human hearts, indicating that this potent inhibitor of apoptosis may be central in protecting the human heart from cellular injury culminating in heart failure. Efforts to ameliorate heart failure through delivery of XIAP compelled the design of a novel adeno-associated viral (AAV) vector, termed SASTG, that achieves highly efficient transduction in mouse heart and in cultured neonatal rat cardiomyocytes. Increased XIAP expression achieved with the SASTG vector inhibits caspase-3/7 activity in neonatal cardiomyocytes after induction of apoptosis through three common cardiac stresses: protein kinase C-γ inhibition, hypoxia, or ß-adrenergic receptor agonist. These studies demonstrate the potential benefit of XIAP to correct heart failure after highly efficient delivery to the heart with the rationally designed SASTG AAV vector.