Variabilidad interhospitalaria en la prescripción tras un síndrome coronario agudo: hallazgos del estudio ACDC / Interhospital variability in drug prescription after acute coronary syndrome: insights from the acdc study

Introducción y objetivos: Analizar la tasa de pacientes ingresados por síndrome coronario agudo que recibieron al alta conjuntamente ácido acetilsalicílico, estatinas e inhibidores de la enzima de conversión de la angiotensina, la variabilidad entre hospitales en dicha prescripción y el pronóstico asociado a esta. Métodos: Se estimó la variabilidad entre hospitales en la prescripción con el coeficiente de correlación intraclase y la odds ratio mediana ajustada (análisis jerárquico). El riesgo de muerte o infarto a 2 años se estimó mediante modelos de Cox. Resultados: De un total de 917 pacientes, 489 (53,3%) tenían prescritos los 3 fármacos, sin apenas variación entre hipertensos y diabéticos (56,8%). Se observó una alta variabilidad entre centros en la prescripción (23-77% de los pacientes). La hipertensión (odds ratio = 1,93; intervalo de confianza del 95%, 1,42-2,61), la fracción de eyección < 45% (odds ratio = 2,2; intervalo de confianza del 95%, 1,44-3,37), la inclusión en el ensayo clínico (odds ratio = 1,89; intervalo de confianza del 95%, 1,24-2,88) y la insuficiencia renal (odds ratio = 0,53; intervalo de confianza del 95%, 0,29-0,94) se asociaron con la prescripción. En el análisis ajustado persistió una variabilidad residual (coeficiente de correlación intraclase 0,046 [intervalo de credibilidad del 95%, 0,007 a 0,192]; odds ratio mediana =1,46 [intervalo credibilidad del 95%, 1,16-2,32]). No se verificó un mayor riesgo de eventos durante el seguimiento (hazard ratio = 0,81; intervalo de confianza del 95%, 0,55-1,18; p = 0,27). Conclusiones: Tras un síndrome coronario agudo, en casi la mitad de los pacientes no se prescribieron los tres fármacos al alta. La prescripción fue variable entre centros y posiblemente relacionada con hábitos asistenciales diferentes (AU)

Introduction and objectives: To analyze the rate of patients admitted for acute coronary syndrome who concomitantly received acetylsalicylic acid, statins, and angiotensin-converting enzyme inhibitors at discharge, and to analyze interhospital variability in the prescription of these drugs and its potential prognostic impact. Methods: Interhospital variability in drug prescription was estimated using the intraclass correlation coefficient and median odds ratio (hierarchical analysis). Cox regression analysis was used to estimate the risk of death or myocardial infarction associated with prescription of all 3 agents at 2-years of follow-up. Results: In total, 489 (53.3%) of 917 patients were prescribed all 3 agents. The rate was similar in patients with hypertension and diabetes (56.8%). There was significant variability among centers in the prescription of the 3 drugs at discharge (from 23% to 77% of patients). Hypertension (odds ratio = 1.93; 95% confidence interval, 1.42-2.61), ejection fraction < 45% (odds ratio = 2.2; 95% confidence interval, 1.44-3.37), being in a clinical trial (odds ratio = 1.89; 95% confidence interval, 1.24-2.88), and renal failure (odds ratio = 0.53; 95% confidence interval, 0.29-0.94) were associated with prescription of the 3 drugs. After adjustment for these factors, residual variability persisted (intraclass correlation coefficient 0.046 [95% credibility interval, 0.007 to 0.192]; median odds ratio = 1.46 [95% credibility interval, 1.16-2.32]). There was no clear association between the prescription of all 3 drugs and the risk of events during follow-up (hazard ratio = 0.81, 95% confidence interval, 0.55-1.18;P = .27). Conclusions: The prescription rate for acetylsalicylic acid, angiotensin-converting enzyme inhibitors, and statins after acute coronary syndrome is suboptimal, varies among centers, and is possibly related to different health care approaches (AU)

Interhospital Variability in Drug Prescription After Acute Coronary Syndrome: Insights From the ACDC Study.

INTRODUCTION AND OBJECTIVES: To analyze the rate of patients admitted for acute coronary syndrome who concomitantly received acetylsalicylic acid, statins, and angiotensin-converting enzyme inhibitors at discharge, and to analyze interhospital variability in the prescription of these drugs and its potential prognostic impact. METHODS: Interhospital variability in drug prescription was estimated using the intraclass correlation coefficient and median odds ratio (hierarchical analysis). Cox regression analysis was used to estimate the risk of death or myocardial infarction associated with prescription of all 3 agents at 2-years of follow-up. RESULTS: In total, 489 (53.3%) of 917 patients were prescribed all 3 agents. The rate was similar in patients with hypertension and diabetes (56.8%). There was significant variability among centers in the prescription of the 3 drugs at discharge (from 23% to 77% of patients). Hypertension (odds ratio=1.93; 95% confidence interval, 1.42-2.61), ejection fraction < 45% (odds ratio=2.2; 95% confidence interval, 1.44-3.37), being in a clinical trial (odds ratio=1.89; 95% confidence interval, 1.24-2.88), and renal failure (odds ratio=0.53; 95% confidence interval, 0.29-0.94) were associated with prescription of the 3 drugs. After adjustment for these factors, residual variability persisted (intraclass correlation coefficient 0.046 [95% credibility interval, 0.007 to 0.192]; median odds ratio=1.46 [95% credibility interval, 1.16-2.32]). There was no clear association between the prescription of all 3 drugs and the risk of events during follow-up (hazard ratio=0.81, 95% confidence interval, 0.55-1.18; P=.27). CONCLUSIONS: The prescription rate for acetylsalicylic acid, angiotensin-converting enzyme inhibitors, and statins after acute coronary syndrome is suboptimal, varies among centers, and is possibly related to different health care approaches.

Role of novel DSP_p.Q986X genetic variation in arrhythmogenic right ventricular cardiomyopathy.

INTRODUCTION: Arrhythmogenic right ventricular cardiomyopathy is an inherited disease characterized by a progressive myocardium fibrofatty replacement. This abnormality disrupts electrical transmission causing ventricular arrhythmias and sudden cardiac death. This genetic disease is transmitted mainly with an autosomal dominant pattern. Our aim was to identify the genetic defect responsible for the pathology in a Spanish family, and to perform its phenotype connotations. MATERIAL AND METHODS: A total of 15 individuals in a three-generation Spanish family were screened after the sudden cardiac death of one family member. All they underwent a complete physical examination, 12-lead electrocardiogram, 2-dimensional echocardiography, magnetic resonance imaging, exercise stress test, 24-h Holter and genetic testing. RESULTS: Autopsy revealed the presence of biventricular arrhythmogenic dysplasia in deceased member. Six family members showed clinical symptoms but only three of them fulfilled definite diagnostic criteria of the disease. Genetic analysis showed a novel nonsense genetic variation in nine family members. All family members with clinical symptoms carried the genetic variation. CONCLUSIONS: Genetic testing in families affected by arrhythmogenic right ventricular cardiomyopathy helps to identify the genetic cause responsible for the disease. The incomplete penetrance and variable phenotypic expression highlights the need of comprehensive genetic analysis and further phenotype implications of genetics to clarify the pathophysiology of the disease.

Miocardiopatía arritmogénica con afectación predominante del ventrículo izquierdo por una mutación nueva «sin sentido» en desmoplaquina / Left dominant arrhythmogenic cardiomyopathy caused by a novel nonsense mutation in desmoplakin

La miocardiopatía arritmogénica predominantemente izquierda (MCAI) presenta características fenotípicas y genotípicas reflejadas en la familia española de cinco miembros que aquí describimos. Durante un catarro, un joven presentó una taquicardia ventricular con origen ventricular izquierdo y realce tardío en dicha localización. Su ECG basal mostró bajos voltajes, retraso en la activación terminal del QRS (cara inferior y V4-V6) y trastorno de la conducción auriculoventricular. Su biopsia endomiocárdica evidenció pérdida miocitaria y fibrosis. Aunque inicialmente fue catalogado de miocarditis, la evaluación familiar fue decisiva para sospechar una MCAI. El estudio genético identificó una mutación nueva en desmoplaquina tipo «sin sentido» (Q1866X) congruente con la presencia de una desmoplaquina truncada en muestras de piel de los afectados (AU)

Left dominant arrhythmogenic cardiomyopathy (LDAC) exhibits characteristic phenotypic and genetic features which were found in the five Spanish family members described in this study. Triggered by a cold, a young man presented with a ventricular tachycardia of left ventricular origin and left ventricular late gadolinium enhancement. His resting ECG showed low potentials, delayed ventricular depolarization (inferior and V4-V6 leads) and atrioventricular conduction disturbances. His endomyocardial biopsy revealed myocyte loss with interstitial fibrosis. Despite the initial diagnosis of myocarditis, familial screening was pivotal in confirming the diagnosis of LDAC. A novel nonsense mutation in the desmoplakin gene (Q1866X) and the truncated protein which it produces were observed in skin samples (AU)

[Left dominant arrhythmogenic cardiomyopathy caused by a novel nonsense mutation in desmoplakin]. / Miocardiopatía arritmogénica con afectación predominante del ventrículo izquierdo por una mutación nueva «sin sentido¼ en desmoplaquina.

Left dominant arrhythmogenic cardiomyopathy (LDAC) exhibits characteristic phenotypic and genetic features which were found in the five Spanish family members described in this study. Triggered by a cold, a young man presented with a ventricular tachycardia of left ventricular origin and left ventricular late gadolinium enhancement. His resting ECG showed low potentials, delayed ventricular depolarization (inferior and V4-V6 leads) and atrioventricular conduction disturbances. His endomyocardial biopsy revealed myocyte loss with interstitial fibrosis. Despite the initial diagnosis of myocarditis, familial screening was pivotal in confirming the diagnosis of LDAC. A novel nonsense mutation in the desmoplakin gene (Q1866X) and the truncated protein which it produces were observed in skin samples.

Dosis repetidas de daclizumab para retrasar la instauración del inhibidor de la calcineurina en pacientes con trasplante cardiaco y disfunción renal postoperatoria / Repeated Daclizumab administration to delay the introduction of calcineurin inhibitors in heart transplant patients with postoperative renal dysfunction

El daclizumab es un antagonista del receptor de la IL-2 usado como terapia de inducción en el trasplante cardiaco con pocos efectos secundarios y baja tasa de infecciones. La insuficiencia renal postoperatoria tras un trasplante cardiaco es frecuente y potencialmente grave. La introducción de los inhibidores de la calcineurina en el postoperatorio puede agravar esta situación. Presentamos 6 casos de pacientes sometidos a trasplante cardiaco y que desarrollaron insuficiencia renal postoperatoria. En todos ellos se administró daclizumab de forma semanal para evitar la introducción del inhibidor de la calcineurina y permitir la recuperación renal. Una vez mejorada la función renal, se introdujo el inhibidor de la calcineurina. En todos los casos se recuperó la función renal y la tasa de complicaciones fue baja. La administración de dosis repetidas de daclizumab en pacientes con insuficiencia renal tras un trasplante cardiaco puede ser una alternativa para evitar el uso de inhibidores de la calcineurina y permitir así la recuperación de la función renal(AU)

Daclizumab is an interleukin-2 receptor antagonist which is used for induction therapy in heart transplant patients. It has few side effects and is associated with a low infection rate. Postoperative renal failure after heart transplantation is common and potentially fatal. The administration of calcineurin inhibitors in the postoperative period can aggravate the situation. We report the cases of six patients who underwent heart transplantation and developed acute renal failure in the immediate postoperative period. All were administered daclizumab weekly to avoid the introduction of calcineurin inhibitors and to facilitate recovery of renal function. Calcineurin inhibitors were introduced only once renal function had improved. Renal function recovered in all cases and there was a low complication rate. The administration of repeated doses of daclizumab to patients who experience acute postoperative renal failure after heart transplantation may provide an alternative therapeutic approach that enables calcineurin inhibitors to be avoided and, consequently, renal function to recover(AU)

Repeated daclizumab administration to delay the introduction of calcineurin inhibitors in heart transplant patients with postoperative renal dysfunction.

Daclizumab is an interleukin-2 receptor antagonist which is used for induction therapy in heart transplant patients. It has few side effects and is associated with a low infection rate. Postoperative renal failure after heart transplantation is common and potentially fatal. The administration of calcineurin inhibitors in the postoperative period can aggravate the situation. We report the cases of six patients who underwent heart transplantation and developed acute renal failure in the immediate postoperative period. All were administered daclizumab weekly to avoid the introduction of calcineurin inhibitors and to facilitate recovery of renal function. Calcineurin inhibitors were introduced only once renal function had improved. Renal function recovered in all cases and there was a low complication rate. The administration of repeated doses of daclizumab to patients who experience acute postoperative renal failure after heart transplantation may provide an alternative therapeutic approach that enables calcineurin inhibitors to be avoided and, consequently, renal function to recover.

A prospective randomized study comparing cyclosporine versus tacrolimus combined with daclizumab, mycophenolate mofetil, and steroids in heart transplantation.

BACKGROUND: Cyclosporine (CsA) and tacrolimus (Tac) in heart transplantation (HTx) have been compared but with certain drawbacks. We compared both drugs in a prospective analysis with medium-term follow-up. METHODS: Hundred and six patients were randomized to receive CsA or Tac (53 per group). Target levels of CsA were 200-300 ng/mL in the first six months and 100-200 ng/mL thereafter. Tac levels were 10-15 and 5-10 ng/mL, respectively. We also used daclizumab as induction and mycophenolate mofetil (MMF) and steroids as maintenance therapy. RESULTS: Baseline characteristics were similar. Survival (CsA 88.7% vs. Tac 81.1%; p = 0.493) was similar. There was a tendency for longer time to first rejection with CsA (93 ± 110 vs. 55 ± 81 d; p = 0.122). There were more rejection-free patients with Tac (39 vs. 28%; p = 0.233). CsA patients suffered more viral infections (0.41 ± 0.58 vs. 0.11 ± 0.31; p = 0.003). CsA patients developed hypertension often (64 vs. 43%; p = 0.032). Tac patients suffered more gastrointestinal complications (16 vs. 6%; p = 0.042). Renal function and the development of diabetes, dyslipidemia, or neurological complications was similar. CONCLUSIONS: Tac patients showed a tendency for longer time to first rejection, and there were more rejection-free patients with Tac and suffered fewer viral infections. Tac patients developed less hypertension and needed less drugs for its control. Renal function was similar in both groups.

Prognostic value of glomerular filtration rate 1 year after heart transplantation.

INTRODUCTION AND OBJECTIVES: The development of renal failure is one of the most important problems after heart transplantation (HT), but the wide range of definitions means that estimates of its prevalence vary considerably. Furthermore, its impact on mortality has not been adequately studied. The objective was to investigate the relationship between the glomerular filtration rate (GFR) 1 year after transplantation and mortality during follow-up. METHODS: The GFR was determined in 316 patients still living 1 year after transplantation using the abbreviated Modification of Diet in Renal Disease Study formula. Patients were divided into three groups according to GFR (i.e. <30, 30-59 and > or =60 mL/min per 1.73 m2) and pretransplant variables and rejection and infection rates within the first year were analyzed. The association between GFR at 1 year and mortality during follow-up was evaluated and reasons for the association were examined. RESULTS: There was no difference in the number of rejections or infections in the first year between the three groups. During a mean follow-up period of 6.3 years, 74% of patients with a GFR <30 mL/min per 1.73 m2 died, compared with 24% and 30% of those with a GFR > or =60 and 30-59 mL/min per 1.73 m2, respectively. Survival analysis (i.e. Cox regression analysis) demonstrated a significant difference between patients with a GFR <30 mL/min per 1.73 m2 and other patients (P< .001). A very low GFR at 1 year was the only independent predictor that remained statistically significant on multivariate analysis (hazard ratio =2.87; 95% confidence interval, 1.52-5.41). CONCLUSIONS: Severe renal dysfunction at 1 year was an independent predictor of long-term all-cause mortality in heart transplant patients.

Valor pronóstico de la tasa de filtración glomerular al año del trasplante cardiaco / Prognostic value of glomerular filtration rate 1 year after heart transplantation

Introducción y objetivos. Uno de los problemas más relevantes tras el trasplante cardiaco es el desarrollo de insuficiencia renal. La heterogeneidad en su definición hace que la estimación de su prevalencia sea variable. Por otro lado, su impacto en la mortalidad no ha sido suficientemente estudiado. El objetivo fue evaluar la relación entre la tasa de filtración glomerular al año (TFG) y la mortalidad en el seguimiento. Métodos. Se analizó la TFG de 316 pacientes vivos al año del trasplante mediante la fórmula abreviada Modification of Diet in Renal Disease Study. Se clasificaron en tres grupos según su TFG ( < 30, 30-59 y ≥ 60 ml/ min/1,73 m2, respectivamente) y se analizaron variables antes del trasplante, tasa de rechazo e infección durante el primer año. Se evaluó la relación entre la TFG al año y la mortalidad en el seguimiento y se revisaron sus causas. Resultados. No hubo diferencias en el número de rechazos ni infecciones durante el primer año en los tres grupos. En el seguimiento medio (6,3 años) falleció el 74% de los pacientes con TFG < 30, frente al 24% y al 30% de aquellos con TFG ≥ 60 y 30-59, respectivamente. El análisis de supervivencia (regresión de Cox) mostró diferencias estadísticamente significativas entre aquellos con TFG < 30 y el resto (p < 0,001). La TFG gravemente disminuida al año se mantuvo como el único predictor independiente en el análisis multivariable (hazard ratio = 2,87; intervalo de confianza del 95%, 1,52-5,41). Conclusiones. La disfunción grave de la función renal al año es un predictor independiente de mortalidad por todas las causas a largo plazo en el paciente con trasplante cardiaco (AU)

Introduction and objectives. The development of renal failure is one of the most important problems after heart transplantation (HT), but the wide range of definitions means that estimates of its prevalence vary considerably. Furthermore, its impact on mortality has not been adequately studied. The objective was to investigate the relationship between the glomerular filtration rate (GFR) 1 year after transplantation and mortality during follow-up. Methods. The GFR was determined in 316 patients still living 1 year after transplantation using the abbreviated Modification of Diet in Renal Disease Study formula. Patients were divided into three groups according to GFR (i.e. <30 30-59 and 8805 60 ml min per 1 73 m2 pretransplant variables rejection infection rates within the first year were analyzed association between gfr at mortality during follow-up was evaluated reasons for examined results there no difference in number of rejections or infections three groups a mean period 6 3 years 74 patients with <30 ml min per 1 73 m2 died compared with 24 and 30 of those a gfr 8805 60 30-59 respectively survival analysis i e cox regression demonstrated significant difference between patients <30 ml min per 1 73 m2 and other patients p <.001). A very low GFR at 1 year was the only independent predictor that remained statistically significant on multivariate analysis (hazard ratio =2.87; 95% confidence interval, 1.52-5.41). Conclusions. Severe renal dysfunction at 1 year was an independent predictor of long-term all-cause mortality in heart transplant patients (AU)

Predictors of renal dysfunction at 1 year in heart transplant patients.

BACKGROUND: Renal dysfunction (RD) is one of the most significant long-term complications of heart transplantation (HT). Although RD is generally attributed to a direct effect of calcineurin inhibitors, it is more probable that multiple factors contribute to its development. The aim of this study was to search for predictor variables of RD at 1 year after HT. METHODS: Three hundred sixteen consecutive HT patients were evaluated. The relationship between RD at 1 year (glomerular filtration rate <60 mL/min/1.73 m2), and pretransplant and 1-year follow-up variables was analyzed. RESULTS: At 1 year following HT, 181 patients (57%) had a glomerular filtration rate of <60 mL/min/1.73 m2. On multivariate analysis, pretransplant serum creatinine values (odds ratio [OR] 5.106, 95% confidence interval [CI]: 2.35-11.09, P=0.0001) and cytomegalovirus (CMV) infection (OR 2.04, 95% CI: 1.08-3.83, P=0.027) were significant predictors of RD, and diabetes mellitus was almost significant (OR 1.65, 95% CI: 0.98-2.76, P=0.055). Variables protective against RD were induction therapy with interleukin-2 receptor antagonists versus muromonab-CD3 (OR 0.389, 95% CI: 0.24-0.61, P=0.0001), maintenance treatment with mycophenolate mofetil versus azathioprine (OR 0.42, 95% CI: 0.26-0.68, P=0.0001), and CMV antiviral prophylaxis (OR 0.38, 95% CI: 0.17-0.68, P=0.021). CONCLUSIONS: Fifty-seven percent of HT patients had RD at 1 year posttransplant. RD was associated with pretransplant serum creatinine values, CMV infection, and diabetes mellitus. Induction with interleukin-2 receptor antagonists, treatment with mycophenolate mofetil, and antiviral prophylaxis for CMV infection all helped maintain renal function in this cohort of HT patients.