- Relationship Between Preventability of Death After Coronary Artery Bypass Graft Surgery and All-Cause Risk-Adjusted Mortality Rates
- Reduction in Myocardial Ischemia/Reperfusion Injury in Group X Secretory Phospholipase A2–Deficient Mice
- Nitrite Anion Provides Potent Cytoprotective and Antiapoptotic Effects as Adjunctive Therapy to Reperfusion for Acute Myocardial Infarction
- Diagnostic Errors in Pediatric Echocardiography: Development of Taxonomy and Identification of Risk Factors
- Lipids, Apolipoproteins, and Their Ratios in Relation to Cardiovascular Events With Statin Treatment
- Ambrisentan for the Treatment of Pulmonary Arterial Hypertension: Results of the Ambrisentan in Pulmonary Arterial Hypertension, Randomized, Double-Blind, Placebo-Controlled, Multicenter, Efficacy (ARIES) Study 1 and 2
- Circulating Endothelial Progenitor Cells in Patients With Eisenmenger Syndrome and Idiopathic Pulmonary Arterial Hypertension
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Relationship Between Preventability of Death After Coronary Artery Bypass Graft Surgery and All-Cause Risk-Adjusted Mortality Rates
In this study, we conducted a large, population-based, retrospective audit (using implicit review) of randomly selected deaths after cardiac surgery over a 2-year period in Ontario, Canada, and showed that 32% of the deaths were judged by experienced surgeons as being potentially preventable, even though the crude mortality rates were already fairly low (≈2%). Our study showed that preventable deaths occurred at all hospitals in Ontario and that the relative proportions of deaths were similar, even though the risk-adjusted all-cause mortality rates varied significantly across hospitals. Our study has important implications for the field of quality improvement because it demonstrates that opportunities exist for improving death rates at all hospitals, even in a region with relatively high institutional volumes where institution-level cardiac surgery report cards have been published for more than a decade. Our results suggest that a need for quality improvement exists at all hospitals as opposed to only outlier hospitals, the traditional outcome from the report card movement. The findings of the study represent a significant paradigm shift in our thinking about how to improve quality with report cards. To the best of our knowledge, this study includes the largest and most comprehensive audit of cardiac surgical deaths that has ever been undertaken in any jurisdiction. Our identification that most deaths occur as a result of problems in the operating room suite and/or intensive care unit and the reasons why these deaths occurred should be of interest to all those interested in further lowering the death rates for these complex operations. See p 2969.
Reduction in Myocardial Ischemia/Reperfusion Injury in Group X Secretory Phospholipase A2–Deficient Mice
Various types of phospholipases A2 (PLA2s) have long been thought to have a crucial role in the pathogenesis of myocardial ischemia/reperfusion injury. However, the precise subtype of PLA2 in these phenomena remains undetermined because most of the previous studies used pharmacological inhibitors that were not necessarily specific for individual PLA2 enzymes. Among the human secretory PLA2s (sPLA2s), sPLA2-X has the most potent hydrolyzing activity toward phosphatidylcholine and elicits a marked release of arachidonic acid. In this study, we generated mice that lack sPLA2-X, and we found that sPLA2-X–deficient mice showed a reduction in myocardial ischemia/reperfusion injury and that neutrophils functions were suppressed in sPLA2-X–deficient mice. The suppressed cytotoxic activities of neutrophils were at least partly related to the reduction of myocardial ischemia/reperfusion injury in sPLA2-X–deficient mice. This study of sPLA2-X–deficient mice strongly suggests that sPLA2-X is causally related to myocardial ischemia/reperfusion injury. Moreover, the present study shows that systemic administration of sPLA2-X inhibitor suppressed myocardial ischemia/reperfusion injury in wild-type mice. Thus, sPLA2-X inhibition may have therapeutic value in acute myocardial infarction. In addition, the inhibition of sPLA2-X might be therapeutically useful for neutrophil-mediated injury and inflammation in other organs. See p 2977.
Nitrite Anion Provides Potent Cytoprotective and Antiapoptotic Effects as Adjunctive Therapy to Reperfusion for Acute Myocardial Infarction
Although current therapies directed at reestablishing blood flow and limiting ischemia are efficacious in the treatment of acute myocardial infarction, intrinsic and practical delays between symptom presentation and intervention compromise the amount of myocardial salvage. Adjunctive pharmacological therapies that improve the amount of myocardial salvage after emergent percutaneous reperfusion of an acute myocardial infarction could have substantial beneficial impact on cardiac function and possibly prognosis. The present study in a canine model of acute myocardial infarction indicates that intravenous nitrite (not to be confused with nitroglycerin) significantly reduces infarct size when the nitrite is administered intravenously during the second hour (n=9) or last 5 minutes (n=9) of a 2-hour coronary occlusion compared with a saline-treated group (n=9). The mechanism of myocardial protection appears independent of the time/ischemia severity integral because the brief 5-minute infusion of nitrite during the end of a 2-hour occlusion reduced infarct size and apoptosis almost as much as a 60-minute infusion, and the short infusion caused virtually no hemodynamic perturbations. Nitrite has significant potential as adjunctive therapy to enhance the efficacy of reperfusion therapy for acute myocardial infarction. See p 2986.
Diagnostic Errors in Pediatric Echocardiography: Development of Taxonomy and Identification of Risk Factors
Echocardiography is the first line of investigation among patients with congenital heart disease; timely treatment depends on accurate diagnosis. Inaccurate diagnoses place children with congenital heart disease at risk for adverse outcomes. Despite increased interest in complications within pediatric cardiology, the domain of imaging-related diagnostic errors has received little attention. We developed a new taxonomy for diagnostic errors within pediatric echocardiography that categorizes errors by severity, preventability, and primary contributor. Our objectives were to examine its findings when applied to diagnostic error cases and to identify risk factors for preventable or possibly preventable diagnostic errors. Diagnostic errors were identified at a high-volume academic pediatric cardiac center from December 2004 to August 2007. Demographic, clinical, and situational variables were collected from these cases and controls. Among the diagnostic error cases identified, 70% affected clinical management or the patient was at risk of or experienced an adverse event. One third of the errors were preventable and 46% were possibly preventable; 69% of preventable errors were of moderate severity or greater. Multivariate analysis identified the following risk factors for preventable or possibly preventable echocardiography diagnostic errors: rare or very rare diagnoses (odds ratio [OR], 9.2; P<0.001), study location in the recovery room (OR, 7.9; P<0.001), moderate anatomic complexity (OR, 3.5; P=0.004), and patient weight <5 kg (OR, 3.5; P=0.031). A diagnostic error taxonomy and knowledge of risk factors can assist in identifying and prioritizing targets for quality improvement initiatives that aim to decrease diagnostic error in pediatric echocardiography. See p 2995.
Lipids, Apolipoproteins, and Their Ratios in Relation to Cardiovascular Events With Statin Treatment
In guidelines for cardiovascular disease risk management, low-density lipoprotein (LDL) cholesterol is the principal target of lipid-lowering therapy; however, recent evidence has suggested more appropriate targets, including non–high-density lipoprotein (HDL) cholesterol, apolipoprotein B, and ratios of proatherogenic to antiatherogenic lipoprotein parameters (total/HDL cholesterol, LDL/HDL cholesterol, and apolipoprotein B/A-I). To assess whether these parameters are indeed more appropriate treatment targets, we compared the relationships of levels of these parameters with the occurrence of cardiovascular events using data from 2 prospective, randomized clinical trials, the Treating to New Targets (TNT; n=10 001) and Incremental Decrease in End Points through Aggressive Lipid Lowering (IDEAL; n=8888) trials. In these studies, patients with established coronary heart disease were assigned to usual-dose or high-dose statin treatment and followed up for a median of 4.9 and 4.8 years, respectively. The present post hoc analysis demonstrated non-HDL cholesterol and apolipoprotein B to be more closely related to cardiovascular outcome than LDL cholesterol. A comparison of non-HDL cholesterol versus apolipoprotein B revealed no significant difference. Moreover, it became clear that total/HDL cholesterol and apolipoprotein B/A-I were more closely associated with outcome than any of the individual lipoprotein parameters. Among all study variables, the apolipoprotein B/A-I ratio was the best determinant of residual risk. This outcome, as well as the fact that non-HDL cholesterol and apolipoprotein B can be measured reliably under nonfasting conditions, supports the use of these parameters as a target of lipid-lowering therapy. Implementation of the ratios as treatment targets awaits final confirmation that any increase in the antiatherogenic lipoprotein is associated with risk reduction. See p 3002.
Ambrisentan for the Treatment of Pulmonary Arterial Hypertension: Results of the Ambrisentan in Pulmonary Arterial Hypertension, Randomized, Double-Blind, Placebo-Controlled, Multicenter, Efficacy (ARIES) Study 1 and 2
Pulmonary arterial hypertension is a progressive disease characterized by an elevated pulmonary vascular resistance leading to right ventricular failure and premature death. Current therapies approved for the treatment of pulmonary arterial hypertension in North America and/or Europe include prostacyclin analogues administered by intravenous, inhaled, and subcutaneous routes; the oral endothelin receptor antagonists bosentan and sitaxsentan; and the oral phosphodiesterase type 5 inhibitor sildenafil. Although these agents are efficacious, each has safety-, tolerability-, or drug delivery–related adverse effects. The data of the Ambrisentan in Pulmonary Arterial Hypertension, Randomized, Double-Blind, Placebo-Controlled, Multicenter, Efficacy Study 1 and 2 (ARIES-1 and ARIES-2) trials show that the once-daily oral active A-selective endothelin receptor antagonist ambrisentan is effective in improving exercise capacity, functional class, and clinical outcome of patients with symptomatic pulmonary arterial hypertension. Remarkably, no elevation of serum aminotransferases concentrations >3 times the upper normal limits was observed in the ambrisentan-treated patients. The favorable efficacy-to-safety profile of ambrisentan may offer potential advantages over the currently approved treatment options. See p 3010.
Circulating Endothelial Progenitor Cells in Patients With Eisenmenger Syndrome and Idiopathic Pulmonary Arterial Hypertension
Impaired endothelial homeostasis underlies the pathophysiology of pulmonary arterial hypertension (PAH). We speculated that PAH patients are deficient in circulating endothelial progenitor cells (EPCs), potentially contributing to endothelial dysfunction and disease progression. Forty-one patients with Eisenmenger syndrome (13 with Down syndrome), 55 with idiopathic PAH, and 47 healthy control subjects were recruited. The number of EPCs was low in Eisenmenger patients compared with healthy control subjects, and those with Down syndrome displayed even fewer EPCs. Reductions in EPC numbers correlated with functional class, 6-minute walk distance, and plasma brain-type natriuretic peptide levels. Idiopathic PAH patients had reduced numbers of EPCs, and the number of circulating EPCs correlated with invasive hemodynamic parameters in this cohort. Levels of immune inflammatory markers, cGMP, stable nitric oxide oxidation products, and asymmetric dimethylarginine were abnormal in patients with PAH and related to numbers of EPCs. Within the idiopathic PAH population, treatment with the phosphodiesterase inhibitor sildenafil was associated with a dose-dependent rise in EPC numbers, resulting in levels consistently above those found with other therapies. In conclusion, circulating EPC numbers are reduced in 2 well-characterized forms of PAH, which also exhibit raised levels of inflammatory mediators. Sildenafil treatment may represent a pharmacological means of increasing circulating EPC numbers long-term. See p 3020.
- Lipids, Apolipoproteins, and Their Ratios in Relation to Cardiovascular Events With Statin Treatment
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