Borrelia burgdorferi is strong inducer of IFN-γ production by human primary NK cells.

Natural Killer (NK) cells belong to the innate lymphoid lineage and are highly present in the human skin. NK cells can produce a range of pro-inflammatory mediators, including cytokines and chemokines. The role of NK(-T) cells in the immune response towards Borrelia burgdorferi infection was studied. The production of interleukin (IL)-6, IL-1ß and interferon-gamma (IFN-γ) by human primary peripheral blood mononuclear cells (PBMCs) exposed to B. burgdorferi was assessed. Interestingly, CD56+ (NK + NK-T) cells were the only cells within the PBMC-fraction that produced IFN-γ during the first 24 h of stimulation. Within the NK(-T) cell fraction, NK cells seemed to be responsible for the IFN-γ production. Since it was previously demonstrated that both TLR2 and NOD2 receptors are involved in the recognition of B. burgdorferi, the expression of both TLR2 and NOD2 mRNA on NK cells was determined. In contrast to TLR2, NOD2 mRNA was upregulated on CD56+ (NK + NK-T) cells after Borrelia exposure. Finally, to unravel the mechanisms underlying erythema migrans (EM) development, crosstalk between CD56+ (NK + NK-T) cells and keratinocytes was investigated. CD56+ (NK + NK-T) cells activated by B. burgdorferi produced soluble mediators strongly inducing the expression of antimicrobial peptides, such as ß-defensin-2 and psoriasin in human keratinocytes. In conclusion, CD56+ (NK + NK-T) cells produced IFN-γ shortly after exposure to B. burgdorferi and released soluble mediators that were able to activate keratinocytes. These observations underscore the important role of CD56+ (NK + NK-T) cells during early host defence when Borrelia burgdorferi enters the human skin during a tick bite.

Global longitudinal strain assessment of cardiac function and extravascular lung water formation after diving using semi-closed circuit rebreather.

PURPOSE: The aim of the present investigation is to study the relationship of ventricular global longitudinal strain (GLS) and ultrasound lung comets (ULC) formation to establish a link between extravascular pulmonary water formation and cardiac contractile dysfunction. METHODS: This is a prospective observational study including 14 active military divers. The subjects performed two sea dives of 120 min each with a semi-closed SCUBA circuit at 10 m depth. Divers were examined at baseline, 15 min (D1) and 60 min (D2) after diving. The evaluation included pulmonary and cardiac echography (including speckle tracking techniques). Blood samples were drawn at baseline and after diving, assessing hs-TnT and Endothelin-1. RESULTS: ULC were detected in 9 (64.2%) and 8 (57.1%) of the subjects after D1 and D2 respectively. No differences were found in right and left ventricular GLS after both immersions (RV: Baseline: - 17.9 4.9 vs. D1: - 17.2 6.5 and D2: - 16.7 5.8 s-1; p = 0.757 and p = 0.529; LV: Baseline: - 17.0 2.3 vs. D1: - 17.4 2.1 and D2: - 16.9 2.2 s-1; p = 0.546 and p = 0.783). However, a decrease in atrial longitudinal strain parameters have been detected after diving (RA: Baseline: 35.5 9.2 vs. D1: 30.3 12.8 and D2: 30.7 13.0 s-1; p = 0.088 and p = 0.063; LA: Baseline: 39.0 10.0 vs. D1: 31.6 6.1 and D2: 32.4 10.6 s-1; p = 0.019 and p = 0.054). CONCLUSION: In the present study, no ventricular contractile dysfunction was observed. However, increase pulmonary vasoconstriction markers were present after diving.

[Psychological alterations in patients with adult celiac disease]. / Alteraciones psicológicas en pacientes con enfermedad celiaca del adulto.

UNLABELLED: Patients with recently-diagnosed adult celiac disease were evaluated with the Gastrointestinal Symptom rating Scale (GSRS) and Psychological General Well-Being Index (PGWBI) to evaluate their psychological alterations, the association between any alterations and gastrointestinal symptoms, and their outcome after starting a gluten-free diet. The patients underwent nutritional assessment and then started a gluten-free diet; they were reassessed 6 months later. Quantitative variables are expressed as the median and 25th-75th percentiles. RESULTS: We included 21 patients, 17 women and 4 mena, with a mean age of 43 years (31-47). The results of histological analysis were compatible with Marsh I lesions in 6 patients, Marsh IIIa in 6 and Marsh IIIb in 9. At baseline, 8 patients showed severe psychological distress, 4 showed moderate distress and 9 showed no distress. The GSRS score was 34 (17-43) and the PGWBI was 64 (48-87), with a significant correlation between the 2 indexes (rho=-.58, P=.006). At 6 months, 3 patients had severe psychological distress, 5 had moderate distress, 9 showed no distress and 4 showed psychological well-being. The GSRS score at 6 months was 13 (8-17) and the PGWBI was 83 (68-95) (P<.05 compared with baseline data for the 3 indicators). The 6 axes of the PGWBI showed significant improvement. At 6 months, no correlation was found between the GSRS and PGWBI. CONCLUSIONS: Patients with celiac disease have psychological alterations whose intensity is related to gastrointestinal symptoms. These symptoms improve after the start of a gluten-free diet.

Accuracy of the angiography-based quantitative flow ratio in intermediate left main coronary artery lesions and comparison with visual estimation.

BACKGROUND: Revascularization of left main coronary artery (LMCA) stenosis is mostly based on angiography. Indices based on angiography might increase accuracy of the decision, although they have been scarcely used in LMCA. The objective of this study is to study the diagnostic agreement of QFR (quantitative flow ratio) with wire-based fractional flow reserve (FFR) in LMCA lesions and to compare with visual severity assessment. METHODS: In a series of patients with invasive FFR assessment of intermediate LMCA stenoses we retrospectively compared the measured value of QFR with that of FFR and the estimate of significance from angiography. RESULTS: 107 QFR studies were included. The QFR intra-observer and inter-observer agreement was 87% and 82% respectively. The mean QFR-FFR difference was 0.047 ± 0.05 with a concordance of 90.7%, sensitivity 88.1%, specificity 92.3%, positive predictive value 88.1% and negative predictive value 92.3%. All these values were superior to those observed with the visual estimation which showed an intra- and inter-observer agreement of 73% and 72% respectively, besides 78% with the FFR value. The low diagnostic performance of the visual estimation and the acceptable performance of the QFR index measurement were observed in all subgroups analysed. CONCLUSIONS: QFR allows an acceptable estimate of the FFR obtained with intracoronary pressure guidewire in intermediate LMCA lesions, and clearly superior to the assessment based on angiography alone. The decision to revascularize patients with moderate LMCA lesions should not be based solely on the degree of angiographic stenosis.

Cost-effectiveness analysis of the SAPIEN 3 transcatheter aortic valve implant in patients with symptomatic severe aortic stenosis.

INTRODUCTION AND OBJECTIVES: Transcatheter aortic valve implant has become a widely accepted treatment for inoperable patients with aortic stenosis and patients at high surgical risk. Its indications have recently been expanded to include patients at intermediate and low surgical risk. Our aim was to evaluate the efficiency of SAPIEN 3 vs conservative medical treatment (CMT) or surgical aortic valve replacement (SAVR) in symptomatic inoperable patients at high or intermediate risk. METHODS: We conducted a cost-effectiveness analysis of SAPIEN 3 vs SAVR/CMT, using a Markov model (monthly cycles) with 8 states defined by the New York Heart Association and a time horizon of 15 years, including major complications and management after hospital discharge, from the perspective of the National Health System. Effectiveness parameters were based on the PARTNER trials. Costs related to the procedure, hospitalization, complications, and follow-up were included (euros in 2019). An annual discount rate of 3% was applied to both costs and benefits. Deterministic and probabilistic sensitivity analyses (Monte Carlo) were performed. RESULTS: Compared with SAVR (high and intermediate risk) and CMT (inoperable), SAPIEN 3 showed better clinical results in the 3 populations and lower hospital stay. Incremental cost-utility ratios (€/quality-adjusted life years gained) were 5471 (high risk), 8119 (intermediate risk) and 9948 (inoperable), respectively. In the probabilistic analysis, SAPIEN 3 was cost-effective in more than 75% of the simulations in the 3 profiles. CONCLUSIONS: In our health system, SAPIEN 3 facilitates efficient management of severe aortic stenosis in inoperable and high- and intermediate-risk patients.

[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.

Immunosuppression withdrawal improves long-term metabolic parameters, cardiovascular risk factors and renal function in liver transplant patients.

After liver transplantation, long-term immunosuppression (IS) administration is commonly complicated by renal dysfunction and cardiovascular complications. Twenty liver transplant patients on cyclosporine (CyA)-based IS were followed up prospectively after IS withdrawal. They consisted of 10 electively weaned patients and 10 either forcibly or incidentally weaned patients. Liver biochemical tests, blood pressure, serum creatinine, serum urea, serum uric acid, triglycerides, cholesterol and glucose were monitored after the start of weaning. Eight of the 20 patients (40%) were IS therapy free for a mean period of 61 +/- 39 months (range: 10-132 months). Of the remaining 12 patients, mild or moderate acute rejection occurred in six patients (30%), and mixed inflammatory portal tract infiltrate was seen in another six patients (30%). At the end of the study, mean (SD) serum creatinine had fallen by 0.28 (0.10) mg/dL (p < 0.001) in operationally tolerant (T) patients whereas the serum creatinine level increased in IS-dependent patients [+0.35 (0.35) mg/dL] (p = 0.005). In T patients, serum cholesterol, serum uric acid, fasting glucose and diastolic arterial pressure values significantly decreased. IS withdrawal can be achieved in selected liver transplant patients, and can improve not only kidney function, but also other CyA-associated side effects, such as hypercholesterolemia, hyperuricemia, hypertension and diabetes.

Positive association of anticytoskeletal endothelial cell antibodies and cardiac allograft rejection.

Using an indirect immunofluorescence method on human umbilical vein endothelial cells (HUVEC), we investigated the presence of antiendothelial cell antibodies (AECA) in 136 pre- and posttransplant serum samples sequentially collected from 31 patients during the first year after cardiac transplantation. A healthy control group was also included (n = 87). Colocalization studies demonstrated a positive staining pattern of different cytoskeletal components (cytoskeletal-antiendothelial cell antibodies, CSK-AECA) including antivimentin, antiactin, antitubulin, and anticytokeratin among heart transplanted patients. Frequency of CSK-AECA in the control group and at day 0 in the transplant group was 18.3 and 22.5%, respectively (p = NS). A progressive increase in the frequency of CSK-AECA was observed after cardiac transplantation: 13.3% at day 15; 22.2% at day 30; 53.8% at day 90, and 58% at day 360. Interestingly, rejection episodes within the first year after transplantation occurred in 83.3% of CSK-AECA-positive and in 30.7% of CSK-AECA-negative patients (p = 0.0045). The presence of antibodies was detected prior to the rejection event and was associated with a poor clinical outcome: rejection episodes occurred at a mean of 36.14 +/- 17 days after transplantation in patients with preexisting AECA and 174.25 +/- 51.9 days after de novo antibody appearance in patients with no antibodies at day 0 (p = 0.029). In conclusion, a progressive increase in the frequency of CSK-AECA was observed following cardiac transplantation; the presence of these antibodies is strongly associated and precedes the rejection episodes. Thus, CSK-AECA could be a good marker for acute graft rejection.

Association of blood pressure and its evolving changes with the survival of patients with heart failure.

OBJECTIVE: The association between low blood pressure (BP) levels and increased mortality has been established in several studies of heart failure (HF). Although many drugs administered to these patients decrease BP, the relationship between changes in BP and survival has not been investigated. Nor have previous analyses distinguished among different forms of death. We investigated the influence of baseline BP and changes in BP during a 1-year period on the survival of patients with HF, distinguishing among sudden cardiac death, nonsudden cardiac death, and noncardiac death. We also identified the possible relationship with the baseline values of and changes in other clinical and treatment variables, including pharmacologic treatments. METHOD AND RESULTS: A total of 1062 patients with chronic HF included in the Spanish National Registry of Sudden Death (mean age of 64.5 +/- 11.8 years, 72% were men, and 21% were in New York Heart Association class III with a mean left ventricular ejection fraction of 36.7% +/- 14.2%) were prospectively investigated for a mean of 1.9 +/- 0.6 years. A multivariable Cox proportional hazards model adjusting for clinical and therapeutic variables showed an independent association between low baseline systolic blood pressure (SBP) and nonsudden cardiac death (hazard ratio [HR] 0.96, 95% confidence interval [CI] 0.93-0.98), but changes in SBP during the following year did not influence survival, regardless of the baseline SBP level (P = .55). Contrariwise, baseline diastolic BP was not associated with mortality, but an increase in diastolic BP during the following year showed a borderline independent significant association with lower nonsudden cardiac death (HR 0.90, 95% CI 0.82-1.00). Treatment with angiotensin-converting enzyme inhibitors or beta-blockers at baseline was also associated with lower nonsudden cardiac mortality, as was an increase in left ventricular ejection fraction during the following year (HR 0.69, 95% CI 0.51-0.93; P = .015). CONCLUSION: Among patients with stable HF, low SBP is associated with a greater risk of nonsudden cardiac death. The change in SBP during a 1-year period has no prognostic value. Because the beneficial effects of drugs associated with increased survival (in this study, angiotensin-converting enzyme inhibitors and beta-blockers) thus seem to be independent of their effects on BP, changes in BP should probably not influence the decision to use such drugs or continue their administration.

Prognostic value of the Thrombolysis in Myocardial Infarction risk score in a unselected population with chest pain. Construction of a new predictive model.

INTRODUCTION: The Thrombolysis in Myocardial Infarction (TIMI) risk score (TRS) has proven to be a useful and simple tool for risk stratification of patients with chest pain in intermediate- and high-risk populations. There is little information on its applicability in daily clinical routine with unselected populations. AIMS: The aims of the study were to prospectively analyze the predictive value of the TRS in a heterogeneous population admitted for chest pain and to construct where possible a new modified model with a greater prognostic capacity. POPULATION AND METHODS: Seven hundred eleven consecutive patients were admitted over a 1-year period to the cardiology unit for chest pain without ST-segment elevation. Thrombolysis in Myocardial Infarction risk score variables, relevant medical history variables, in-hospital examination results, and therapy information were collected. Cardiac events at 1 and 6 months were recorded. RESULTS: Seventy-one (9.8%) patients had a compound event (myocardial infarction/revascularization/cardiac death) at 6 months. On multivariate analysis, the variables associated with cardiac events were left ventricular ejection fraction (EF) of <35% (hazard ratio [HR] = 2.9, P = .002), diabetes (HR = 1.8, P = .02), and TRS (HR = 1.3, P = .007). Events at 6 months were 2.3% for a TRS of 0/1, 4.2% for 2, 10.2% for 3, 11.0% for 4, and 18.7% for a score of more than 5. A new modified scale was constructed to include EF and diabetes as independent variables, and this yielded an increase of 44% in the combined event at 6 months per score unit increase (HR = 1.44, P = .001). The modified scale showed a greater predictive capacity than the original model. CONCLUSIONS: The TRS is an important short- and long-term prognostic predictor when applied to an unselected population consulting for chest pain. The inclusion of diabetes and EF as variables in the model increases predictive capacity at no expense to simplicity.

Value of the "Standing Test" in the Diagnosis and Evaluation of Beta-blocker Therapy Response in Long QT Syndrome.

INTRODUCTION AND OBJECTIVES: Patients with congenital long QT syndrome (LQTS) have an abnormal QT adaptation to sudden changes in heart rate provoked by standing. The present study sought to evaluate the standing test in a cohort of LQTS patients and to assess if this QT maladaptation phenomenon is ameliorated by beta-blocker therapy. METHODS: Electrographic assessments were performed at baseline and immediately after standing in 36 LQTS patients (6 LQT1 [17%], 20 LQT2 [56%], 3 LQT7 [8%], 7 unidentified-genotype patients [19%]) and 41 controls. The corrected QT interval (QTc) was measured at baseline (QTcsupine) and immediately after standing (QTcstanding); the QTc change from baseline (ΔQTc) was calculated as QTcstanding - QTcsupine. The test was repeated in 26 patients receiving beta-blocker therapy. RESULTS: Both QTcstanding and ΔQTc were significantly higher in the LQTS group than in controls (QTcstanding, 528 ± 46ms vs 420 ± 15ms, P < .0001; ΔQTc, 78 ± 40ms vs 8 ± 13ms, P < .0001). No significant differences were noted between LQT1 and LQT2 patients. Typical ST-T wave patterns appeared after standing in LQTS patients. Receiver operating characteristic curves of QTcstanding and ΔQTc showed a significant increase in diagnostic value compared with the QTcsupine (area under the curve for both, 0.99 vs 0.85; P < .001). Beta-blockers attenuated the response to standing in LQTS patients (QTcstanding, 440 ± 32ms, P < .0001; ΔQTc, 14 ± 16ms, P < .0001). CONCLUSIONS: Evaluation of the QTc after the simple maneuver of standing shows a high diagnostic performance and could be important for monitoring the effects of beta-blocker therapy in LQTS patients.

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.

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.

[Use of a coronary risk score (the TIMI Risk Score) in a non-selected patient population assessed for chest pain at an emergency department]. / Aplicación de una puntuación de riesgo coronario (TIMI Risk Score) en una población no seleccionada de pacientes que consultan por dolor torácico en un servicio de urgencias.

INTRODUCTION AND OBJECTIVES: Stratification algorithms for acute coronary syndrome enable the identification of high-risk patients who will benefit from more aggressive treatment. The TIMI Risk Score (TRS) has been shown to be useful in intermediate- and high-risk patients. However, little is known about its value in non-selected patients. Our aim was to assess the efficacy of the TRS for risk stratification in a non-selected population with chest pain. PATIENTS AND METHOD: We evaluated 1254 consecutive patients (age, 54 [19] years; 57% male) attending an emergency department for chest pain. Overall, 343 (27%) were admitted and 911 (73%) were discharged. All cardiac events during 6-month follow-up were recorded. RESULTS: Of the 911 discharged patients, 45 (5.3%) were admitted during follow-up: 9 (1.1%) underwent revascularization, 5 (0.6%) had a myocardial infarction (MI), and 2 (0.2%) died from cardiovascular disease. Patients with a high TRS had a significantly higher risk of reaching the composite endpoint of death, MI, or revascularization (relative risk per unit of TRS increase, 3.63; 95% CI, 2.20-6.00; P < .001). Of the patients who were initially admitted, 22 (6.4%) underwent revascularization, 4 (1.2%) had an MI, and 14 died (4.1%) from cardiovascular disease during follow-up. The relative risk of the composite endpoint per unit of TRS increase was 1.72 (95% CI, 1.32-2.24; P < .001). CONCLUSIONS: The TIMI risk score is useful for stratifying cardiovascular event risk in non-selected patients with chest pain. The score can identify high-risk patients who will benefit from hospital admission and early aggressive treatment.

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.

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.

Primary graft failure after heart transplantation: characteristics in a contemporary cohort and performance of the RADIAL risk score.

BACKGROUND: Primary graft failure (PGF) is the leading cause of early heart transplantation (HT) mortality. Our aim was to analyze PGF currently and explore the ability of a dedicated score for PGF risk stratification. METHODS: After applying a dedicated PGF definition, we analyzed its incidence, mortality, and associated factors in a multicenter cohort of 857 HTs performed in 2006 to 2009. We used the following criteria: recipient right (R) atrial pressure ≥ 10 mm Hg; age (A) ≥ 60 years; diabetes (D) mellitus, and inotrope (I) dependence; donor age (A) ≥ 30 years, and length (L) of ischemia ≥ 240 minutes to calculate the RADIAL score for PGF risk prediction. RESULTS: PGF incidence was 22%. The right ventricle was almost always affected, alone (45%) or as part of biventricular failure (47%). Mechanical circulatory support was used in 55%. Mortality attributable to PGF was 53% and extended through the third month after HT, but thereafter, PGF had little influence in long-term outcome. The RADIAL score was higher in PGF patients (2.78 ± 1.1 vs. 2.42 ± 1.1, p = 0.001) and stratified 3 groups with incremental PGF incidence: low risk (12.1%), intermediate risk (19.4%), and high risk (27.5%, p = 0.001). CONCLUSIONS: PGF had a strong impact, with an incidence of 22% and a mortality exceeding 50% that extends through the third post-HT month. The RADIAL score classified patients into 3 groups with incremental risk for PGF and may be useful for its prevention and early therapy.

Risk stratification of mortality in patients with heart failure and left ventricular ejection fraction >35%.

The population of patients with heart failure (HF) and mild to moderate left ventricular (LV) dysfunction is growing, and mortality remains high. There is a need for better risk stratification of patients who might benefit from primary prevention of mortality. This study aimed to evaluate the prognostic value of Holter-based parameters for predicting mortality in patients with HF with LV ejection fraction (EF) >35%. The study involved 294 patients (199 men, mean age 66 years) with HF of ischemic and nonischemic causes, New York Heart Association classes II to III, and LVEF >35%. Surface electrocardiogram and 24-hour Holter monitoring were performed at enrollment to assess traditional electrocardiographic variables, as well as heart rate variability, heart rate turbulence, and repolarization dynamics (QT/RR). Total mortality and sudden death were the primary and secondary end points. During a median 44-month follow-up, there were 43 deaths (15%). None of the traditional electrocardiographic risk parameters significantly predicted mortality. A standard deviation of all normal-to-normal RR intervals < or =86 ms, turbulence slope < or =2.5 ms/RR, and QT end/RR >0.21 at daytime were found to be independent risk predictors of mortality in multivariate analyses. The predictive score based on these 3 variables showed that patients with > or =2 abnormal risk markers were at risk of death (30% 3-year mortality rate) and sudden death (12%), similar to death rates observed in patients with LVEF < or =35%. In conclusion, increased risk of mortality and sudden death could be predicted in patients with HF with LVEF >35% by evaluating the combination of standard deviation of all normal-to-normal RR intervals, turbulence slope, and QT/RR, parameters reflecting autonomic control of the heart, baroreflex sensitivity, and repolarization dynamics.

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.