Epidemiología del eczema de contacto en España. Resultados de la Red Española de Vigilancia en Alergia de Contacto (REVAC) durante el año 2008 / Epidemiology of Contact Dermatitis in Spain. Results of the Spanish Surveillance System on Contact Allergies for the year 2008

Introducción: el estudio epidemiológico del eczema de contacto puede realizarse mediante el análisis de los datos obtenidos a partir de la experiencia clínica de las unidades de alergia cutánea. Objetivo: determinar el perfil de los pacientes que acuden a una unidad de alergia cutánea y determinar la prevalencia de sensibilizaciones más frecuente en esta población. Material y métodos: estudio observacional retrospectivo de los 5 hospitales pertenecientes a la Red Española de Vigilancia de Alergia de Contacto (REVAC) durante el año 2008. Todos los pacientes fueron estudiados mediante pruebas epicutáneas con la serie estándar española. Las frecuencias de sensibilización se han estandarizado por sexo y edad. Resultados: se recogieron datos de 1.161 pacientes. Los 5 alérgenos que presentaron positividades más frecuentemente fueron sulfato de níquel (25,88%), dicromato potásico (5,31%), cloruro de cobalto (5,10%), mezcla de fragancias (4,64%) y bálsamo del Perú (4,44%). Los alérgenos menos frecuentes fueron la mezcla de quinoleínas/clioquinol y la mezcla de lactonas sesquiterpénicas. En las mujeres la prevalencia de sensibilización al níquel fue del 35%. Conclusiones: el perfil de sensibilizaciones de España es el esperado para un país del Sur de Europa. El sulfato de níquel sigue siendo el alérgeno más prevalente, siendo especialmente importante en mujeres. La mezcla de quinoleínas/clioquinol y la mezcla de lactonas sesquiterpénicas no han mostrado rentabilidad suficiente para su permanencia en la serie española (AU)

Background: The epidemiology of contact dermatitis can be analyzed using clinical data from skin allergy units .Objectives: The aims of this study were to define the profile of patients attending a skin allergy unit and to determine the prevalence of the most common sensitizations in this population. Material and methods: Throughout 2008, a retrospective observational study was carried out in the 5 hospitals of the Spanish Surveillance System on Contact Allergies. All patients underwent skin patch tests with the Spanish standard series. The frequencies of sensitization were normalized for age and gender. Results: Data were gathered on 1161 patients. The 5 allergens that gave the most frequent positive reactions were nickel sulfate (25.88%), potassium dichromate (5.31%), cobalt chloride (5.10%), fragrance blends (4.64%), and balsam of Peru (4.44%). The least frequently detected reactions were to quinolone–clioquinol mix and sesquiterpene lactone mix. There was a 35% prevalence of sensitization to nickel among women. Conclusions: The profile of sensitizations in Spain is similar to that of other Southern European countries. Nickel sulfate continues to be the most prevalent allergen, particularly in women. The low prevalence of sensitization to quinolone–clioquinol mix and sesquiterpene lactone mix supports their exclusion of the Spanish series (AU)

Insights into the role of microRNAs in cardiac diseases: from biological signalling to therapeutic targets.

microRNAs have recently opened new pathways to explain gene expression and disease biology in many scenarios, including cardiac diseases. microRNAs are endogenous small non-coding RNAs that mediate post-transcriptional repression or messenger RNA degradation. By annealing to inexactly complementary sequences in the 3' untranslated region of the target messenger RNA, protein level is down-regulated. Several microRNAs appear to act cooperatively through multiple target sites in one gene and, conversely, most microRNAs can target several genes. miR-133 and miR-1 are specifically expressed in cardiac and skeletal muscle and control myogenesis, cardiac development, cardiac performance and cardiomyocyte hypertrophy (mainly by tuning transcription factors and other growth-related targets). They also modulate the expression of certain cardiac ion channels and related proteins with proarrhythmic effect. Besides them, other microRNAs have been shown to exert influence on the myocardial growth, the electrical balance and the angiogenesis processes that take place in the heart. Bioinformatics is a useful tool to identify potential targets of a given microRNA, although there is still substantial concern about their reliability. Experimental manipulation of microRNAs has provided a tantalizing basis to speculate that future research on microRNAs may yield important progress in the prevention of sudden cardiac death and in the treatment of cardiac heart failure. However, the final effect of the blockage of microRNAs in vivo remains unclear, since each of them can target hundreds of genes with different intensity. The era of the microRNAs in cardiovascular diseases has just started.

Prognostic value of brain natriuretic peptide in heart transplant patients.

BACKGROUND: Continuously elevated B-type natriuretic peptide B (BNP) levels are associated with adverse prognosis in heart failure, but this has been less well established in heart transplantation, where medium- to long-term studies are lacking. The purpose of this study was to determine whether BNP levels determined in the first year of transplant have prognostic implications for subsequent outcome. METHODS: A retrospective case-control study was carried out in 71 heart transplant patients with a total of 488 biopsies and BNP determinations. Determinations that might raise BNP levels (rejection, high lung pressures, renal dysfunction, depressed ventricular function and graft vascular disease) and those obtained in the first 4 months were excluded. The final analysis included 56 patients with 155 BNP determinations spread over Months 5, 7, 9 and 12. Two groups were made according to the presence of major events after the first year (death, late rejection and ventricular dysfunction associated or not with graft vascular disease): group with events: 13 patients, 37 determinations; group without events: 43 patients, 118 determinations. RESULTS: There were no differences in the clinical profile of the patients. Mean follow-up was 6 years. Mean BNP was higher in the events group for determinations at Month 5 [event: 140 (95), no events: 68 (68); p = 0.01], Month 7 [event: 174 (32), no event: 66 (65); p = 0.002], Month 9 [event: 143 (37), no event: 58 (54); p = 0.002] and Month 12 [event: 126 (55), no event: 48 (37); p = 0.001]. The receiver-operator characteristic (ROC) curve showed that a BNP value of 100 pg/ml classified patients with a sensitivity of 80% and a specificity of 75% (p = 0.0001). CONCLUSIONS: BNP values determined in the first year of transplant might help to distinguish a sub-group of patients with a higher rate of significant complications in long-term follow-up.

mTOR inhibitors: do they help preserve renal function?

BACKGROUND: Renal function deterioration is one of the main problems facing heart transplant recipients. The mammalian target of rapamycin (mTOR) inhibitors, in combination with or replacing calcineurin inhibitors, may help preserve renal function. The aim of this study was to evaluate the progression of renal function after switching the immunosuppressive regimen. PATIENTS AND METHODS: We studied 23 heart transplant recipients (5.5 +/- 4.5 years since transplantation). An mTOR inhibitor was introduced to replace cyclosporine (everolimus, 65%; sirolimus, 35%). Patient clinical characteristics and renal function were studied after switching. The statistical analysis used Student t test for paired data. RESULTS: The reason for the transplantation was ischemic cardiopathy (52%), dilated myocardiopathy (39%), or other causes (9%). Mean age at time of transplantation was 52 +/- 9 years. Comorbidities were as follows hypertension (43%), insulin-dependent diabetes (22%), hypercholesterolemia (39%), and ex-smokers (70%). The reason for the switch was increased creatinine (65%), appearance of tumors (26%), or others (8%). Previous creatinine level was 1.89 +/- 0.6 mg/dL with clearance of 61.7 +/- 23 mL/min and at the end of follow-up (mean follow-up, 11 +/- 6 months) creatinine level was 2.0 +/- 1.45 mg/dL with clearance of 68.3 +/- 35 mL/min, namely, no significant difference (P = .49 and P = .57, respectively). In the subgroup of patients who switched treatment due to renal dysfunction, initial creatinine level was 2.38 +/- 0.4 mg/dL with clearance of 42.3 +/- 10 mL/min and at the end of follow-up it was 2.28 +/- 0.2 mg/dL and 43.6 +/- 11 mL/min, respectively (P = .68 for creatinine and clearance). CONCLUSIONS: The introduction of mTOR inhibitors to the immunosuppressant regimen may be useful to delay renal functional deterioration caused by calcineurin inhibitors.

mTOR inhibitors and their secondary effects in cardiac transplant recipients: a descriptive study.

BACKGROUND: Mammalian target of rapamycin (mTOR) inhibitors are relatively new drugs in the field of cardiac transplantation (HT), hence the need for further study of their secondary effects. We described the nature and incidence of secondary effects of these drugs in a group of HT recipients. PATIENTS AND METHODS: We studied 23 HT recipients aged 52 +/- 9 years (Male: 91%, body mass index: 27 +/- 3.7, ischemic cardiopathy: 52%, dilated cardiomyopathy: 39%) who were started on an mTOR inhibitor (everolimus: 65%, sirolimus: 35%) as part of their treatment. We have described the secondary effects detected during a follow-up period of 10.7 +/- 6 months. RESULTS: The reasons for starting the drug were renal impairment (65%), tumors (26%), and others (8%). During follow-up, 17% of patients required a dose reduction and 12% required drug withdrawal: edemas: 4%, recurrent infection: 4%, and hemolytic-uremic syndrome: 4%. Drug-attributable edemas presented in 26% of patients. Thirty nine percent suffered an infection that required hospital admission, 89% of which were lung and all bacterial two patients died due to the infection). The mean time to first infection was 5 +/- 6 months. In patients who had a treatment change due to tumors, 50% experienced improvement. We did not detect alterations in cholesterol, triglycerides, creatinine, or leukocytes. There was a nonsignificant trend toward decreased hemoglobin and platelet levels (P = .07 and P = .056, respectively). CONCLUSIONS: Lung infection was the principal complication among our patients treated with mTOR inhibitors. A large percentage required dose reduction (17%) and even drug withdrawal (12%) due to secondary effects.

Does amiodarone influence early mortality in heart transplantation?

The use of amiodarone before transplantation has been linked to an increased number of complications, acute graft failures, and early mortality after a heart graft. We undertook a retrospective, descriptive, case-controlled study involving early mortality and acute graft failure. The 396 consecutive patients included 25 subjects who had been prescribed amiodarone for at least 30 days before transplantation. We excluded retransplantations, pediatric transplantations, and combined transplantations. The endpoints were early mortality and acute graft failure. No significant differences were observed in early mortality and acute graft failures. The multivariate analysis did not reveal any variable that correlated with early mortality. Our study did not support the idea that amiodarone constituted a negative predictor of early survival or acute graft failure.

Is there a correlation between brain naturietic peptide levels and echocardiographic and hemodynamic parameters in heart transplant patients?

BACKGROUND: Brain naturietic peptide (BNP) elevations have been reported in heart transplant patients both at baseline and during rejection. An association between BNP levels and certain echocardiographic and hemodynamic abnormalities has also been found in nontransplanted heart disease patients. We sought to determine whether BNP values were correlated with echocardiographic and hemodynamic parameters among a large cohort of heart transplant patients. MATERIALS AND METHODS: We studied 71 consecutive heart transplant patients, excluding combined grafts, retransplants, and pediatric cases. We performed 488 BNP determinations during catheterization and within 48 hours of echocardiography. Hemodynamic parameters included mean pulmonary artery pressure, right ventricular systolic and diastolic pressures. Doppler echocardiography parameters were wall thickness, ventricular mass, left and right ventricular end-diastolic and end-systolic diameters, isovolumic relaxation time, and mitral flow deceleration time. RESULTS: We observed significant correlations between BNP values and left ventricular size, ventricular mass, and a restrictive filling pattern. BNP levels were also significantly correlated with right ventricular size, mean pulmonary artery pressure, and right ventricular diastolic and end-diastolic pressures. CONCLUSIONS: In heart transplant patients, BNP levels positively correlated with ventricular diameters and a restrictive filling pattern. An increase in right ventricle and pulmonary artery pressures was associated with elevated BNP values.

Induction therapy with daclizumab in heart transplantation--how many doses?

UNLABELLED: Since their introduction onto the market, interleukin-2 antagonists have been increasingly used by a growing number of transplant units. Their benefits versus OKT3 appear evident, although the optimal dose remains to be established. Our objective was to establish possible differences related to the use of two versus five doses of daclizumab. MATERIALS AND METHODS: This study evaluated 81 consecutive patients treated with two bolus doses of daclizumab (1 mg/kg) on days 1 and 14 posttransplantation. We excluded retransplantations, pediatric transplantations, and combined transplantations. We compared our series to a previous trial involving the administration of a single bolus dose every 14 days (five boluses in total). Study variables included the number of graft rejections, the number of infections, and the mortality. Statistical analysis was performed using the chi square and Student's t tests. Significance was set at P < .05. RESULTS: There were no differences between groups in the baseline characteristics of the patients. The number of rejection episodes during the first year was significantly lower among the patients in our series treated with two bolus doses of daclizumab than in the series of patients treated with five bolus doses: 24 (30%) vs 17 (61%) episodes (P = .003). No significant differences were observed for mortality: the group receiving two boluses registered 10 deaths (12%) versus two (7%) in the group receiving five boluses (P = .4), or infection rate: 11 patients (40%) in the group receiving five bolus versus 31 patients (38%) in the group given two bolus doses (P = .9). CONCLUSIONS: Our results suggested that induction therapy with two doses of daclizumab was at least as effective in preventing rejection as five doses, with no negative effects on patient survival.

Influence of immunosuppression regimen on heart transplantation survival.

OBJECTIVE: To perform an analysis comparing long-term survival in heart transplant (HT) patients depending on the immunosuppressive regimen. MATERIALS AND METHODS: The study included 317 consecutive HT patients. We excluded pediatric cases, retransplants, combined transplants (lung and kidney), and immunosuppressive regimens with fewer than 10 cases. The six groups analyzed were: (1) OKT3 7 days + cyclosporine (CsA) + mycophenolate mofetil (MMF) + steroids (S); (2) OKT3 7 days + CsA + azathioprine (AZA) + S; (3) OKT3 10 days + CsA + MMF + S; (4) OKT3 10 days + CsA + AZA + S; (5) interleukin-2 (IL-2) antagonists + CsA + MMF + S; and (6) IL-2 antagonists + tacrolimus + MMF + S. Probability of survival was analyzed by Kaplan-Meier and log-rank methods. RESULTS: The groups were heterogeneous regarding the number of patients and follow-up. The baseline characteristics were similar, although there were differences in surgery times. The survivals by groups at the end of the follow-up period were: group 1: 75.8%; group 2: 51.2%; group 3: 63.6%; group 4: 25.3%; group 5: 91.2%; and group 6: 84.6%. A major reduction in survival was observed in the groups that were given induction with OKT3 monoclonal antibodies (groups 1, 2, 3, and 4), particularly when AZA was combined in the maintenance phase (groups 2 and 4) and when the induction dose was high (10-day therapy in groups 3 and 4). CONCLUSIONS: Our study suggested an association between the immunosuppressive regimen and the long-term survival of HT patients. The best results were obtained with an induction regimen based on IL-2 antagonists. On the basis of the survivals observed in this study, the maintenance combination we regard as "optimal" at this time is based on a combination of CsA, MMF, and steroids.

Evolutional changes in maintenance immunosuppression following heart transplantation.

UNLABELLED: Patients with a heart transplant (HT) may require changes in their immunosuppressive maintenance medication. The basic treatment regimen in our patients consisted of an anticalcineurin agent, an antimetabolite, and a steroid. OBJECTIVE: We undertook a descriptive study to quantify the incidence and causes of these changes and determine how they occur. MATERIALS AND METHODS: We included the 432 HT performed at our center from November 1987 to October 2005. The baseline treatment was considered to be the treatment given following HT, and the maintenance treatment was that taken at the time of data collection. Kaplan-Meier survival curves were constructed for the analysis. RESULTS: The most significant change was the switch from azathioprine to mycophenolate mofetil. The survival rate after 17 years was 66%. CONCLUSIONS: As in the international registries, there has been an evident reduction in the use of cyclosporine and more particularly of azathioprine, in favor of tacrolimus and mycophenolate mofetil, respectively. No changes in the use of steroids have been observed. These data reflect an increasingly greater use of immunosuppressive agents with reduced side effect profiles.

Variations in the frequency and type of infections in heart transplantation according to the immunosuppression regimen.

OBJECTIVE: To evaluate the frequency of infection according to the immunosuppressive regimens used in our center. MATERIALS AND METHODS: From 259 consecutive heart transplants we excluded pediatric cases, retransplants, combined transplants (lung and kidney) and immunosuppressive regimens with fewer than 10 cases. The six groups analyzed were: (1) OKT3 (7 days) + cyclosporine (CsA) + mycophenolate mofetil (MMF) + steroids (S); (2) OKT3 (7 days) + CsA + azathioprine (AZA) + S; (3) OKT3 (10 days) + CsA + MMF + S; (4) OKT3 (10 days) + CsA + AZA + S; (5) interleukin-2 (IL-2) antagonists + CsA + MMF + S; (6) IL-2 antagonists + tacrolimus + MMF + S. Infection was considered significant when it causal hospital admission or prolonged hospitalization. RESULTS: With a total mean follow-up of 54 +/- 43 months, the total percentage of infection-free patients at the end of follow-up was 45.5%. Infection-free survival was lower among patients administered induction with OKT3 antibodies for 10 days, combined with cyclosporine, either with MMF (10%, group 3) or with azathioprine (27%, group 4), compared to those given IL-2 antagonists (particularly in combination with tacrolimus and MMF-69.2%, group 6). CONCLUSIONS: The results of this study showed that infection was frequent in heart transplantation. Furthermore, induction therapy with OKT3 monoclonal antibodies was associated with an important number of infections (particularly viral infections). Comparison of the treatment groups showed that the regimen associated with fever infections included an IL-2 receptor antagonist with tacrolimus, MMF, and S.

Risk factors affecting survival in heart transplant patients.

BACKGROUND: Certain cardiovascular risk factors have been linked to morbidity and mortality in heart transplant (HT) patients. The sum of various risk factors may have a large cumulative negative effect, leading to a substantially worse prognosis and the need to consider whether HT is contraindicated. The objective of this study was to determine whether the risk factors usually available prior to HT result in an excess mortality in our setting that contraindicates transplantation. MATERIALS AND METHODS: Consecutive patients who underwent heart transplantation from November 1987 to January 2004 were included. Heart-lung transplants, retransplants, and pediatric transplants were excluded. Of the 384 patients, 89% were men. Mean age was 52 years (range, 12 to 67). Underlying disease included ischemic heart disease (52%), idiopathic dilated cardiomyopathy (36%), valvular disease (8%), and other (4%). Variables considered risk factors were obesity (BMI >25), dyslipidemia, hypertension, prior thoracic surgery, diabetes, and history of ischemic heart disease. Survival curves by number of risk factors using Kaplan-Meier and log-rank for comparison of curves. RESULTS: Overall patient survival at 1, 5, 10, and 13 years was 76%, 68%, 54%, and 47%, respectively. Survival at 10 years, if fewer than two risk factors were present, was 69%; 59% if two or three factors were present; and 37% if more than three associated risk factors were present (P = .04). CONCLUSIONS: The presence of certain risk factors in patients undergoing HT resulted in lower survival rates. The combination of various risk factors clearly worsened outcomes. However, we do not believe this should be an absolute contraindication for transplantation.

Influence of induction therapy on rejection and survival in heart transplantation.

BACKGROUND AND AIMS: Immunosuppressive therapy has undergone great changes in recent years as a result of the introduction of new drugs, presumed a prior to be more effective and better tolerated. The greatest advance seems to have been the introduction of interleukin-2 (IL-2) receptor antagonists. The objective of this study was to determine whether the use of IL-2 receptor antagonists in induction therapy has implications for the development of rejection and survival. MATERIALS AND METHODS: Three hundred sixty-five consecutive cardiac transplant patients who received induction therapy were included. Heart-lung and transplants in children under 10 years were excluded. Three groups were compared according to the induction therapy (OKT3, 10 days; OKT3, 7 days; and IL-2R antagonists). Each treatment corresponded to a time period: OKT3 10 days from June 1989 to April 1994; OKT3 7 days from May 1994 to October 2002; and IL-2R antagonists from November 2002 to May 2004. Baseline characteristics of recipient and donor, surgical times, postsurgical complications, maintenance immunosuppression, number of rejections, time (days) to first rejection, and probability of survival at 1 year were recorded. We used analysis of variance, chi(2) test, Kaplan-Meier curves, and log-rank test as appropriate. A P-value < .05 was considered significant. RESULTS: There were significant differences in the characteristics of the transplanted patients in the various time periods. Thus, recipients in the OKT3 10 day group had worse status but better donors, whereas recipients in the IL-2R antagonists group had better status but older donors with longer duration of ischemia. The incidence of acute graft failure was similar in the three groups. The number of rejection episodes in the first year was higher among the OKT3 groups (OKT3 10 days, 1.7 +/- 1.3; OKT3 7 days, 1.2 +/- 1.2; IL-2R antagonists, 1.0 +/- 1.2; P = .02) and the probability of survival at 1 year was also lower (OKT3 10 days, 74%; OKT3 7 days, 77%; IL-2R antagonists, 94%; P = .0007). CONCLUSIONS: Induction therapy with IL-2 antagonists offers important advantages over treatment with OKT3 in terms of survival, with absolute and relative risk reductions of 20% and 27%. Furthermore, it did not increase the number of rejections, although this may have been due to the greater use of MMF versus azathioprine.

Predictive factors for development of diabetes mellitus post-heart transplant.

INTRODUCTION: It is known that there is a high incidence of diabetes mellitus (DM) among heart transplant (HT) patients, which may be up to 30% at 5 years. The presence of DM has been associated with increased morbidity (infections, renal dysfunction, or graft vascular disease), and its development has been related primarily to immunosuppressive therapy. The objective of this study was to determine, in our experience, the presence of predictive variables for the development of DM following HT. METHODS: We studied 315 consecutive non-DM patients (88.6% men, mean age 51.5 years) who underwent HT in our hospital from November 1987 to May 2003, analyzing all variables that could be related to the development of DM during follow-up. Student t-test and chi(2) test were used for univariate statistical analysis and logistic regression for multivariate analysis. RESULTS: Of the 315 patients, 64 developed DM (20.3%) during a mean follow-up of 3.3 years. The univariate analysis showed that patients developing DM are older (54.9 +/- 8.7 versus 50.7 +/- 11.8 years, P = .008), have a higher body mass index (BMI) (27.3 +/- 3.8 versus 25.7 +/- 3.7, P = .003), a higher prevalence of HT (37.5% versus 23.5%, P = .023), a lower frequency of urgent HT (9.4% versus 26.2%, P = .004), are more often treated with steroids (85.9% versus 70.1%, P = .011) and tacrolimus (12.5% versus 4.4%, P = .015), and have a higher frequency of rejection episodes (71.2% versus 44.6%, P = .001). Multivariate analysis identified the following as predictive factors for the development of DM: age (OR = 1.04, P = .013), urgent HT (OR = 0.36, P = .031), treatment with tacrolimus (OR = 3.89, P = .012), and number of rejections (OR = 2.34, P = .002). CONCLUSION: In our population, age, urgent HT (which had a protective effect), treatment with tacrolimus, and number of rejections were independent predictive variables for the development of DM during follow-up.

Utility of cardiac magnetic resonance imaging for the diagnosis of heart transplant rejection.

OBJECTIVES: To assess the value of the use of cardiac MRI to detect rejection (necrosis) and its ability to discriminate it from other pathologic alterations (edema and fibrosis). MATERIALS AND METHODS: A prospective and consecutive study was designed in which cardiac MRI was performed at the same time as the scheduled endomyocardial biopsy. The study period was from 31-10-01 to 01-05-02. Ten patients with claustrophobia were excluded. Sixty-four examinations were performed in the remaining 40 patients. MRI assessment was blinded to the biopsy result. The 17 biopsies performed were insufficient (too small sample). Rejection was defined as the presence of at least 1 focus of myocyte necrosis. Technique. A high-field (1.5 T) GE CV/i magnetic resonance imaging system was used to obtain pre- and postcontrast white and black blood anatomic sequences (breathhold fast spin-echo T1-weighted images), as well as myocardial cine, perfusion and viability sequences. Variables analyzed. Ejection fraction, ventricular volumes, pericardial effusion, hypertrophy, absolute and relative myocardial intensity and uptake. Statistics. Variables were normally distributed. Student's t test was used for quantitative variables and the chi2 test for proportions. RESULTS: Mean age, 51+/-13 years. Women 5, men 35. Time since HT, 13 to 3725 days. No significant differences were found between rejection and ventricular volumes or the presence of effusion and hypertrophy. Visual estimation of myocardial perfusion and viability sequences did not detect any significant changes. Uptake showed a clear trend to increase in patients with necrosis: 34+/-21 versus 23+/-17 for relative uptake, P<.05. There were also differences in uptake when fibrosis was present: 68+/-47 versus 102+/-48 in the group without fibrosis, P <.05; but not in the presence of edema: 93+/-55 versus 94 +/- 45 for absolute uptake. CONCLUSIONS: (1) Cardiac MRI is a promising technique for diagnosis of rejection. (2) Patients with myocyte necrosis show a clear trend toward increased myocardial uptake. (3) Interstitial fibrosis is associated with decreased levels of uptake.

Radioimmunometric assay of B-type natriuretic peptide (BNP) in heart transplantation: correlation between BNP determinations and biopsy grading of rejection.

The aim of this study was to determine whether elevated brain natriuretic peptide (BNP) levels after heart transplantation are correlated with the severity of rejection by using endomyocardial biopsy (EMB) and echocardiographic parameters indicative of ventricular function of the transplanted heart. This was an observational study of 80 orthotopic heart transplant recipients (11 women and 69 men; mean age 53+/-11 years). BNP determinations were performed within 48 h of endomyocardial biopsy. The echocardiographic study and BNP determination were also performed in a group of healthy volunteers. We found significantly higher BNP mean levels in heart transplant patients than in healthy volunteers (volunteers, 16.7+/-16.2 pg.ml-1; transplant, 213.4+/-268.6 pg.ml-1; P<0.001). Transplant recipients with rejection grades 2, 3 and 4 on EMB had significantly higher BNP levels than those with rejection grades 0 and 1 (higher rejection grade, 162.5+/-168.4 pg.ml-1; lower rejection grade, 292+/-361.8 pg.ml-1; P<0.01). BNP values of patients with good left ventricular function (LVF) were significantly lower than in patients with mildly and moderately impaired LVF and patients with severely impaired LVF (good function, 199.76+/-233.6 pg.ml-1; mildly/moderately impaired LVF, 937+/-644.5 pg.ml-1; severely impaired LVF, 1038+/-491.2 pg.ml-1; P<0.001). It is concluded that BNP plasma levels are elevated in heart transplant patients compared to the normal population. The distribution of BNP levels in heart transplanted patients show a wide range. BNP elevation is greater in patients with higher rejection grades on EMB and greater impairment of left ventricular function.

Radioimmunometric assay of natriuretic peptide type-B (BNP) in heart failure.

The aim of this study was to assess the value of the radioimmunometric determination of natriuretic peptide type-B (brain natriuretic peptide, BNP) in the diagnosis and prognosis of heart failure, and to study the association between BNP and the clinical, analytical and echocardiographic variables associated with the evolution of heart failure. The study group included 169 patients (74 women and 95 men; mean, 66 years) with heart failure of different causes, admitted consecutively to our hospital. BNP levels were measured with a radioimmunometric assay (Shionora BNP Cis ) after day 3 of admission. Patients were also studied by echocardiography. A significant association between the cause of heart failure and the BNP concentration was found (patients with ischaemic disease had the highest BNP values). Systolic function was worse in patients with ischaemic disease or dilated cardiomyopathy. High BNP values were also associated with advanced functional class and male sex. Plasma creatinine correlated positively with plasma BNP. However, we found no significant association with the other clinical variables evaluated. Of the echocardiographic variables analysed, BNP correlated positively with the ventricular diameter and pulmonary artery systolic pressure, and inversely with the shortening fraction; patients with severely impaired systolic function had the highest BNP values. It can be concluded that BNP levels (by radioimmunometric assay) are increased in patients with heart failure, and increase in relation to left ventricular dysfunction and the severity of heart failure. The strong independent association of plasma BNP with the left ventricular ejection fraction, its stability and the low cost of measurement suggest that plasma BNP assay could become a routine test. BNP assay could be included as an important factor in clinical and therapeutic decision making, as it complements the information provided by other variables used in the diagnosis of heart failure.

[Refractory angina caused by subclavian-coronary steal syndrome treated with angioplasty and stent]. / Angina refractaria por robo subclavio-coronario tratada mediante angioplastia y stent.

The coronary-subclavian steal syndrome is a rare cause of recurrent myocardial ischemia in patients who have undergone left internal mammary-coronary artery bypass grafting. A significant left subclavian artery stenosis proximal to its origin, can result in an impaired or reversed flow in this graft and myocardial ischemia. We describe the case of a woman aged 76 who had undergone myocardial revascularization seven months before, and presented refractory angina with severe electrocardiographic ischemia in the left anterior descending artery territory. Arteriography confirmed this syndrome and the patient was successfully treated with percutaneous transluminal angioplasty and placement of two stents in the left subclavian artery. We review the clinical management, diagnostic methods and therapeutic options used in the subclavian-coronary steal syndrome.