Prognostic Value and Kinetics of Soluble Neprilysin in Acute Heart Failure: A Pilot Study.

OBJECTIVES: This study sought to examine the prognostic value of the soluble form of neprilysin (sNEP) in acute heart failure (AHF) and sNEP kinetics during hospital admission. BACKGROUND: sNEP was recently identified in chronic heart failure (HF) and was associated with cardiovascular outcomes. METHODS: A total of 350 patients (53% women, mean 72.6 ± 10.7 years of age) were included in the study. Primary endpoints were composites of cardiovascular death or HF hospitalizations at short-term (2 months) and long-term (mean: 1.8 ± 1.2 years) follow-up. sNEP was measured using an ad hoc-modified enzyme-linked immunosorbent assay, and its prognostic value was assessed using Cox regression analyses. In a subgroup of patients, sNEP was measured both at admission and at discharge (n = 92). RESULTS: Median admission sNEP concentrations were 0.67 ng/ml (Q1 to Q3: 0.37 to 1.29), and sNEP was significantly associated, in age-adjusted Cox regression analyses, with the composite endpoint at short-term (hazard ratio [HR]: 1.29; 95% confidence interval [CI]: 1.04 to 1.61; p = 0.02) and long-term (HR: 1.23; 95% CI: 1.01 to 1.05; p = 0.003) follow-up. In multivariate Cox analyses that included clinical variables and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) concentration, sNEP concentration at admission showed a clear trend toward significance for the composite endpoint at 2 months (HR: 1.22; 95% CI: 0.97 to 1.53; p = 0.09) and remained significant at the end of follow-up (HR: 1.21; 95% CI: 1.04 to 1.40; p = 0.01). At discharge, sNEP levels decreased from 0.70 to 0.52 ng/ml (p = 0.06). CONCLUSIONS: Admission sNEP concentration was associated with short- and long-term outcomes in AHF, and dynamic sNEP concentrations were observed during hospital admission. These preliminary data may be hypothesis-generating for the use of NEP inhibitors in AHF.

[Emergency care of patients with upper gastrointestinal bleeding in regional hospitals in Catalonia]. / Asistencia urgente a los pacientes con hemorragia digestiva alta en los hospitales comarcales catalanes.

OBJECTIVE: To evaluate the resources available in Catalan regional hospitals for the emergency care of upper gastrointestinal hemorrhage. METHODS: We analyzed a survey sent to 32 hospitals on the availability, composition and resources of a duty endoscopy service for the year 2009. RESULTS: Responses were obtained from 24 centers, covering 3,954,000 inhabitants. Duty endoscopists were available in 12 hospitals. A total of 1,483,000 inhabitants were unable to access a duty endoscopist in the referral center. Centers with duty endoscopists had more beds and had a larger catchment area. Duty services were composed of 4.5 endoscopists (range 2-11), covering 82.1 (33.2-182.5) duty shifts/year. Seventeen centers reported 1,571 episodes (51%, range: 3-280, 39.68/100,000 inhabitants). Centers with a duty service reported a greater number of cases (76 vs. 43, p=0.047). Centers without this service referred a greater number of patients (147 vs. 17, p=0.001). Patients in the emergency department were under the care of the internal medicine department in four centers, the surgery department in 14 centers and under the care of both departments in six. Admitted patients were under the care of the gastroenterology department in only six hospitals. The most widely used procedures were ligation of varicose bleeding and injection therapies in non-varicose bleeding. Twenty-one percent of centers did not perform combined treatment. CONCLUSIONS: A significant proportion of the population does not have access to a duty endoscopist in referral centers. Duty shifts represent significant workload in regional hospitals. Coordination among health professionals and centers would allow the efficient application of therapeutic resources and a duty endoscopy service to be established in centers lacking this resource.

Influence of induction therapy, immunosuppressive regimen and anti-viral prophylaxis on development of lymphomas after heart transplantation: data from the Spanish Post-Heart Transplant Tumour Registry.

BACKGROUND: Lymphoma after heart transplantation (HT) has been associated with induction therapy and herpesvirus infection. It is not known whether anti-viral agents administered immediately after HT can reduce the incidence of lymphoma. METHODS: This study was a retrospective review of 3,393 patients who underwent HT in Spain between 1984 and December 2003. Variables examined included development of lymphoma and, as possible risk factors, recipient gender and age, induction therapies (anti-thymocyte globulin, OKT3 and anti-interleukin-2 receptor antibodies) and anti-viral prophylaxis (acyclovir or ganciclovir). To study the effect of evolving treatment strategy, three HT eras were considered: 1984 to 1995; 1996 to 2000; and 2001 to 2003. RESULTS: Induction therapy was employed in >60% of HTs, and anti-viral prophylaxis in >50%. There were 62 cases of lymphoma (3.1 per 1,000 person-years, 95% confidence interval: 2.4 to 4.0). Univariate analyses showed no influence of gender, age at transplant, HT era, pre-HT smoking or the immunosuppressive maintenance drugs used in the first 3 months post-HT. The induction agent anti-thymocyte globulin (ATG) was associated with increased risk of lymphoma, and prophylaxis with acyclovir with decreased risk of lymphoma. Multivariate analyses (controlling for age group, gender, pre-HT smoking and immunosuppression in the first 3 months with mycophenolate mofetil and/or tacrolimus) showed that induction increased the risk of lymphoma if anti-viral prophylaxis was not used (regardless of induction agent and anti-viral agent), but did not increase the risk if anti-viral prophylaxis was used. CONCLUSIONS: Induction therapies with ATG or OKT3 do or do not increase the risk of lymphoma depending on whether anti-viral prophylaxis with acyclovir or ganciclovir is or is not employed, respectively.

The predictive value of soluble major histocompatibility complex class I chain-related molecule A (MICA) levels on heart allograft rejection.

BACKGROUND: Recently the presence of a soluble form of major histocompatibility complex class I chain-related molecule A (sMICA) has been detected in the sera of patients with tumors. Shedding of sMICA by tumor cells downregulates NKG2D-mediated antitumor immunity. The aim of this investigation was to study the possible involvement of sMICA in the allograft acceptance after heart transplantation (HTX). METHODS: We monitored the levels of sMICA by specific enzyme-linked immunosorbent assay (ELISA) in a total of 146 serum samples obtained from 34 heart transplantation patients followed up during the first year post-HTX. RESULTS: The persistence of sMICA expression was correlated with the clinical evolution of these patients. sMICA was detected in the serum of 21 of 34 patients (61.70%) between 15 and 20 days after implantation and was practically absent in pretransplant serum samples. Twenty of these 21 patients (95.24%) with sMICA did not experience episodes of severe rejection during this period (P = 0.0001), whereas sMICA was practically absent in patients with manifestations of severe acute rejection. The longitudinal study of these patients revealed that the presence of sMICA was consistently maintained in 75% of the patients with good graft status during the period of observation. CONCLUSION: This has led us to believe that the presence of levels of sMICA during the first year post-HTX may contribute to allograft acceptance. Additionally, functional studies indicate that sMICA downregulates NKG2D surface expression, which may lead to a functional impairment of cell-mediated cytolysis. These data suggest a significant correlation between the presence of sMICA and a lower incidence of rejection.

Preoperative statin therapy and troponin T predict early complications of coronary artery surgery.

BACKGROUND: Pretreatment with statins reduces early ischemic events after percutaneous coronary interventions, primarily in patients with a high level of inflammation markers. We sought to examine the association between preoperative statin therapy, systemic inflammation, and myocardial ischemia with the occurrence of early cardiac complications after coronary artery bypass grafting surgery. METHODS: One hundred forty-one consecutive patients who underwent coronary artery bypass grafting surgery from two university tertiary hospitals were stratified according to their preoperative status of statin therapy (87 treated and 54 nontreated). Preoperative blood samples were collected for measurement of lipid parameters, C-reactive protein, interleukin-6, and troponin T. The evaluated primary endpoint was a composite of death and myocardial infarction at 30 days. RESULTS: Patients undergoing preoperative statin therapy showed a reduced incidence of death (2.3% versus 13.0%, p = 0.012), myocardial infarction (5.7% versus 18.5%, p = 0.017), and primary combined endpoint (8.0% versus 22.2%, p = 0.017). In the multivariate model, preoperative troponin T greater than 0.01 ng/mL (odds ratio 6.85, p = 0.001) and nonstatin therapy (odds ratio 4.2, p = 0.01) predicted a higher risk of primary endpoint. Statins showed a significant interaction with troponin T status and benefited primarily those patients with positive troponin T. Among 19 patients with troponin T greater than 0.01 ng/mL, the primary endpoint occurred in all 6 nonstatin-treated patients, but it occurred in only 1 of 13 statin-treated patients (p < 0.001). Neither C-reactive protein nor interleukin-6 predicted early complications, nor did they interact with statin therapy (p = not significant). CONCLUSIONS: Preoperative statin therapy reduces early complications and offers additional protection in patients with positive troponin T status, regardless of inflammatory markers.

Statins and postoperative risk of atrial fibrillation following coronary artery bypass grafting.

Atrial fibrillation (AF) is a common complication after coronary artery bypass grafting. Atrial remodeling has been observed in AF and has been associated with the development of this arrhythmia. Because 3-hydroxy-3-methylglutaryl coenzyme A inhibitors (statins) have been demonstrated to modify remodeling, we hypothesized a protective role of statins against postoperative AF. We also hypothesized that extracellular matrix turnover and brain natriuretic peptide (BNP) might be related to such atrial remodeling. We studied 234 consecutive patients who underwent coronary artery bypass grafting (173 men; 65 +/- 9 years of age) in whom the occurrence of postoperative AF was monitored. In a subgroup of 66 patients, we measured plasma levels of matrix metalloproteinase-1 (MMP-1), its inhibitor, tissue inhibitor matrix metalloproteinase-1 (TIMP-1; as indexes of extracellular matrix remodeling), and N-terminus pro-BNP (related to left ventricular function) at baseline and at 24 hours after surgery. Of 234 patients, 66 (28.2%) developed postoperative AF. In multivariate analysis, previous AF was related to an increase in the development of AF (odds ratio 11.92, 95% confidence interval 2.37 to 59.98, p = 0.026), whereas statin use was related to a decrease in arrhythmia (odds ratio 0.52, 95% confidence interval 0.28 to 0.96, p = 0.038). A higher TIMP-1/MMP-1 ratio at 24 hours after surgery was present in those who did not develop postoperative AF (p = 0.043). Statin use was associated with increased TIMP-1 levels and TIMP-1/MMP-1 ratio (p = 0.027 and 0.036, respectively). No significant relations to N-terminus pro-BNP were seen. In conclusion, previous AF and nonuse of statins are significantly associated with AF after coronary artery bypass grafting. Statin use may be protective against AF after coronary artery bypass grafting, possibly due to alterations in the extracellular matrix and remodeling after coronary artery bypass grafting.

Successful biventricular assistance after heart transplantation.

We present a successful use of biventricular pneumatic assistance during seven days allowing the recovery from a severe primary graft failure that occurred in the operating room. Suboptimal donors are associated with higher rates of immediate graft failure; however proper use of mechanical assistance can help to recover graft function.