Citations

Background —Although prompt treatment is a cornerstone of the management of acute myocardial infarction (AMI), prior studies have shown that one fourth of AMI patients arrive at the hospital >6 hours after symptom onset. It would be valuable to identify individuals at highest risk for late arrival, but predisposing factors have yet to be fully characterized. Methods and Results —Data from the Cooperative Cardiovascular Project, involving Medicare beneficiaries aged >65 years hospitalized between January 1994 and February 1996 with confirmed AMI, were used to identify patients who presented “late” (≥6 hours after symptom onset). Patient characteristics were tested for associations with late presentation by use of backward stepwise logistic regression. Among 102 339 subjects, 29.4% arrived late. Significant predictors of late arrival (odds ratio, 95% CI) included diabetes (1.11, 1.07 to 1.14) and a history of angina (1.32, 1.28 to 1.35), whereas prior MI (0.82, 0.79 to 0.85), prior angioplasty (0.80, 0.75 to 0.85), prior bypass surgery (0.93, 0.89 to 0.98), and cardiac arrest (0.52, 0.46 to 0.58) predicted early presentation. Additionally, initial evaluation at an outpatient clinic (2.63, 2.51 to 2.75) and daytime presentation (1.67, 1.59 to 1.72) predicted late arrival. Finally, female sex, black race, and poverty, which were evaluated with an 8-level race–sex–socioeconomic status interaction term, were also risk factors for delay. Conclusions —Delayed hospital presentation is a common problem among Medicare beneficiaries with AMI. Factors associated with delay include not only clinical and logistical issues but also race, sex, and socioeconomic characteristics. Education efforts designed to hasten AMI treatment should be directed at individuals with risk factors for late arrival.

Background —Interaction of complement with endothelial cells (ECs) underlies the development of inflammation and coagulation in disease. Assembly of the membrane attack complex (MAC) of complement on EC membrane, like stimulation with cytokines, upregulates tissue factor and cyclooxygenase-2 but does so via the intermediary action of IL-1α. We asked whether the MAC activates porcine aortic and microvascular ECs in a global manner by this mechanism and whether this mechanism is used by membrane pore-forming structures. Methods and Results —Exposure of ECs to complement caused upregulation of mRNAs for E-selectin, intracellular adhesion molecule-1, vascular cell adhesion molecule-1, Iκ-Bα, interleukin (IL)-1α, IL-1β, IL-8, and plasminogen activator inhibitor-1 over a period of 6 hours. The expression of these genes was not a primary response to stimulation, however, because IL-1 receptor antagonist inhibited expression of these genes. Activation of ECs by complement depended on the autocrine action of IL-1α, because complement-mediated EC activation was inhibited by anti–IL-1α antibodies. Melittin and mastoparan, amphiphilic pore-forming peptides like the MAC, induced E-selectin through intermediary action of IL-1. Conclusions —These findings suggest that transmembrane pore-forming proteins, as a class of molecules, activate ECs through the autocrine effects of IL-1α.

Background —The objectives of our study were to determine the frequency of supraventricular tachyarrhythmias (SVTAs) among modifications of the Fontan operation and identify risk factors for developing SVTA. Methods and Results —The population consisted of all patients who had any modification of the Fontan operation at the Mayo Clinic between 1985 and 1993. Clinically significant SVTAs were those requiring initiation or change of antiarrhythmic treatment, and they were divided into early SVTAs (<30 days after the operation) and late SVTAs (≥30 days after the operation). Clinical histories were reviewed, and health status questionnaires were sent. Four hundred ninety-nine patients had various modifications of the Fontan operation. Frequency of early SVTA was 15%. Risk factors identified by multivariate analysis for early SVTA were AV valve regurgitation, abnormal AV valve, and preoperative SVTA. Frequency of late SVTA was 6% by 1 year, 12% by 3 years, and 17% by 5 years. Risk factors for late SVTA were age at operation (<3 or ≥10 years) and systemic AV valve replacement. By univariate and multivariate analysis, the type of Fontan operation was not a significant risk factor for late SVTA when all 6 modifications were considered. However, when we analyzed the frequency of late SVTA for the 2 recently used modifications, we found a lower frequency of late SVTA in patients with atriopulmonary connection with lateral tunnel compared with those with total cavopulmonary connection. Conclusions —Postoperative SVTA continues to be a significant problem. Risk factors for SVTA are AV valve regurgitation, abnormal AV valve, preoperative SVTA, and age at operation. Frequency of SVTA does not appear to be related to type of Fontan procedure except for slightly lower frequency in patients with atriopulmonary connection with lateral tunnel compared with those with total cavopulmonary connection.

Background Transesophageal echocardiography (TEE) is the diagnostic modality of choice for visualizing the left atrial appendage (LAA). This study defined the morphology of the LAA in normal autopsy specimen hearts and considered the implications of these findings for TEE studies. Methods and Results Five hundred normal autopsy hearts were reviewed (25 male and 25 female subjects from each decade for 10 decades). LAA length, width, orifice size, and number of lobes were recorded. Number of lobes was compared between sexes with the rank sum test and regressed against age. Mean length, width, and orifice size increased with age, up to age 20 years, in both sexes. Rates were significantly different between sexes for LAA size ( P =.011) and width ( P =.006). After age 20, statistically significant but clinically insignificant age-related changes were observed. Fifty-four percent of LAAs had two lobes (range, 1 to 4), with no age or sex differences. Lobes exist in different planes of the heart. Most pectinate muscles were ≥1 mm in width. Pectinate muscles <1 mm (2.6% of cases) were seen in only the first and last decades. Conclusions Age- and sex-related differences in LAA dimensions exist. These differences and the existence of multilobed appendages are important in the accurate TEE evaluation of LAA. Because lobes exist in different planes, imaging must be done in multiple planes to visualize the entire LAA.

Background Aprotinin is a serine protease inhibitor that reduces blood loss and transfusion requirements when administered prophylactically to cardiac surgical patients. To examine the safety and dose-related efficacy of aprotinin, a prospective, multicenter, placebo-controlled trial was conducted in patients undergoing repeat coronary artery bypass graft (CABG) surgery. Methods and Results Two hundred eighty-seven patients were randomly assigned to receive either high-dose aprotinin, low-dose aprotinin, pump-prime-only aprotinin, or placebo. Drug efficacy was determined by the reduction in donor-blood transfusion up to postoperative day 12 and in postoperative thoracic-drainage volume. The percentage of patients requiring donor–red-blood-cell (RBC) transfusions in the high- and low-dose aprotinin groups was reduced compared with the pump-prime-only and placebo groups (high-dose aprotinin, 54%; low-dose aprotinin, 46%; pump-prime only, 72%; and placebo, 75%; overall P =.001). The number of units of donor RBCs transfused was significantly lower in the aprotinin-treated patients compared with placebo (high-dose aprotinin, 1.6±0.2 U; low-dose aprotinin, 1.6±0.3 U; pump-prime-only, 2.5±0.3 U; and placebo, 3.4±0.5 U; P =.0001). There was also a significant difference in total blood-product exposures among treatment groups (high-dose aprotinin, 2.2±0.4 U; low-dose aprotinin, 3.4±0.9 U; pump-prime-only, 5.1±0.9 U; placebo, 10.3±1.4 U). There were no differences among treatment groups for the incidence of perioperative myocardial infarction (MI). Conclusions This study demonstrates that high- and low-dose aprotinin significantly reduces the requirement for donor-blood transfusion in repeat CABG patients without increasing the risk for perioperative MI.

Background The purpose of this study was to identify the predictors and sequelae of distal embolization from a multicenter, randomized trial of saphenous vein graft intervention. The CAVEAT-II trial demonstrated that saphenous vein graft directional coronary atherectomy (DCA) was associated with greater angiographic success and less need for repeat intervention compared with percutaneous transluminal coronary angioplasty (PTCA) but at the cost of more acute complications—notably distal embolization. Methods and Results In CAVEAT-II, 305 patients were randomly assigned to DCA (149 patients) or PTCA (156 patients) for lesions with >60% diameter stenosis in vein grafts ≥3 mm in diameter. Distal embolization occurred in 20 patients (13.4%) assigned to DCA and 8 patients (5.1%) assigned to PTCA ( P =.011). Independent predictors of distal embolization were use of DCA (71% in distal embolization patients versus 47% in patients without distal embolization, P =.011) and presence of thrombus (39% in distal embolization patients versus 14% in patients without distal embolization, P <.00). In-hospital adverse events were more frequent after distal embolization: 71% versus 20%, odds ratio plus (95% confidence intervals) 9.87 (4.65, 20.94). At 12-month follow-up, adverse event rates were also higher in patients with distal embolization (odds ratio, 3.05 [1.95, 4.76]). Conclusions In this first prospective multicenter trial of saphenous vein graft intervention, distal embolization was more common after DCA than PTCA and in lesions containing thrombus. It also was associated with worse in-hospital and 12-month outcomes. The risk and sequelae of distal embolization should be considered when choosing a treatment strategy for vein graft disease.

SummaryBackgroundThe extent to which potentially curative therapies are used in patients with hepatocellular cancer (HCC) and their related outcomes are unknown in the US.AimTo determine the rate and outcomes of potentially curative treatment in patients with HCC.MethodsEleven US centers followed patients with HCC between 2001 and 2007. We determined rates of liver transplantation, surgical resection, or tumour ablation during follow‐up, examined differences in adjusted survival of patients receiving these treatments, and determined the factors associated with receipt of potentially curative treatment.ResultsOf the 267 patients, 76 (28%) patients had early HCC, defined as Child A or B cirrhosis, with a solitary HCC or ≤3 nodules, each ≤3 cm. Of these, 53 (69.7%) received curative treatment. Thirty six percent of patients with non‐early HCC received curative treatment. Compared to patients with non‐early HCC who did not receive curative treatment, patients with early HCC and curative treatment had the best survival [hazard ratio, HR = 0.19 (95% CI, 0.08–0.42)] followed by patients with advanced HCC who received curative treatment [HR = 0.37 (95% CI, 0.22–0.64)]. Baseline performance status was significantly associated with receipt of curative treatment as well as survival after adjusting for demographics, clinical characteristics, and HCC stage.ConclusionsIn this multicenter database, most of the patients with early HCC received potentially curative treatment. However, only 28% of patients had early HCC. One‐third of patients with non‐early HCC also underwent curative therapy. Potentially curative treatment improved survival and this effect was seen in patients with early as well as non‐early HCC.

Abstract Rationale The immune response in sepsis is characterized by overt immune dysfunction. Studies indicate immunostimulation represents a viable therapy for patients. One study suggests a potentially protective role for interleukin 5 (IL-5) in sepsis; however, the loss of eosinophils in this disease presents a paradox. Objectives To assess the protective and eosinophil-independent effects of IL-5 in sepsis. Methods We assessed the effects of IL-5 administration on survival, bacterial burden, and cytokine production after polymicrobial sepsis. In addition, we examined the effects on macrophage phagocytosis and survival using fluorescence microscopy and flow cytometry. Measurements and Main Results Loss of IL-5 increased mortality and tissue damage in the lung, IL-6 and IL-10 production, and bacterial burden during sepsis. Therapeutic administration of IL-5 improved mortality in sepsis. Interestingly, IL-5 administration resulted in neutrophil recruitment in vivo. IL-5 overexpression in the absence of eosinophils resulted in decreased mortality from sepsis and increased circulating neutrophils and monocytes, suggesting their importance in the protective effects of IL-5. Furthermore, novel data demonstrate IL-5 receptor expression on neutrophils and monocytes in sepsis. IL-5 augmented cytokine secretion, activation, phagocytosis, and survival of macrophages. Importantly, macrophage depletion before the onset of sepsis eliminated IL-5–mediated protection. The protective effects of IL-5 were confirmed in humans, where IL-5 levels were elevated in patients with sepsis. Moreover, neutrophils and monocytes from patients expressed the IL-5 receptor. Conclusions Taken together, these data support a novel role for IL-5 on noneosinophilic myeloid populations, and suggest treatment with IL-5 may be a viable therapy for sepsis.