Factors related to early readmissions after acute heart failure: a nested case-control study.

AIMS: To describe the main characteristics of patients who were readmitted to hospital within 1 month after an index episode for acute decompensated heart failure (ADHF). METHODS AND RESULTS: This is a nested case-control study in the ReIC cohort, cases being consecutive patients readmitted after hospitalization for an episode of ADHF and matched controls selected from those who were not readmitted. We collected clinical data and also patient-reported outcome measures, including dyspnea, Minnesota Living with Heart Failure Questionnaire (MLHFQ), Tilburg Frailty Indicator (TFI) and Hospital Anxiety and Depression Scale scores, as well as symptoms during a transition period of 1 month after discharge. We created a multivariable conditional logistic regression model. Despite cases consulted more than controls, there were no statistically significant differences in changes in treatment during this first month. Patients with chronic decompensated heart failure were 2.25 [1.25, 4.05] more likely to be readmitted than de novo patients. Previous diagnosis of arrhythmia and time since diagnosis ≥ 3 years, worsening in dyspnea, and changes in MLWHF and TFI scores were significant in the final model. CONCLUSION: We present a model with explanatory variables for readmission in the short term for ADHF. Our study shows that in addition to variables classically related to readmission, there are others related to the presence of residual congestion, quality of life and frailty that are determining factors for readmission for heart failure in the first month after discharge. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03300791. First registration: 03/10/2017.

Neumonitis secundaria a reactivación del Virus Varicela Zoster en un paciente con trasplante cardiaco / No disponible

Presentamos el caso de un hombre de 50 años, trasplantado cardiaco, que ingresó en nuestro hospital con un cuadro de insuficiencia respiratoria aguda 24 h. después de recibir tratamiento ambulatorio con corticoides endovenoso por episodio de rechazo celular agudo. Presentaba lesiones maculosas en piel de perineo, abdomen y tórax, por lo que fue tratado con antivirales ante la sospecha de neumonía por virus de varicela. Se confirmó el diagnóstico mediante PCR para virus de varicela zoster en muestras de aspirado bronco-alveolar obtenidas por fibrobroncoscopia. Exponemos las formas de presentación de varicela en pacientes inmunocomprometidos y cómo debe ser tenida en cuenta como diagnóstico diferencial en este tipo de pacientes (AU)

A 50 years old male was admitted to our hospital because of acute respiratory insufficiency requiring mechanical ventilation. Four months earlier he had undergone heart transplantation. Three days before admission he received ivcorticosteroids as therapy for an episode of acute cellular rejection. Twelve hours after admission, a maculopapulous rash appeared on the trunk, arms and legs. A positive PCR for varicella virus DNA in the bronchoalveolar lavage confirmed the diagnosis of varicella pneumonitis. The patient received iv aciclovir and the pneumonitis resolved within 2 weeks. The clinical presentation of varicella infection inheart-transplanted patients is discussed (AU)

Benefit of Neoral C2 monitoring in de novo cardiac transplant recipients receiving basiliximab induction.

BACKGROUND: For cyclosporine (CsA), 2-hr postdose level (C2) is the best single time point predictor of the area under the curve and a critical measure for effective dosing. The therapeutic CsA microemulsion (Neoral) C2 range in de novo heart transplant patients remains to be determined. PURPOSE: The purpose of this study was to determine the efficacy of CsA C2 monitoring in de novo heart transplant patients receiving basiliximab induction. METHODS: This prospective, multicenter, randomized study enrolled 87 adult heart transplant recipients stratified according to 4 to 6 hrs posttransplant serum creatinine less than or equal to 170 micromol/L (cohort A) or more than 170 micromol/L (cohort B). Patients in cohort A were randomized into three C2 ranges (A1: "high" n=25, 1600-1800 ng/mL; A2: "intermediate" n=27, 1400-1600 ng/mL; and A3: "low" n=24, 1200-1400 ng/mL). Patients in cohort B were randomized into intermediate (n=5) and low C2 (n=6). Target ranges were progressively lowered after 1 month. Immunosuppression included basiliximab, Neoral, mycophenolate mofetil, and corticosteroids. Endpoints were acute rejection and renal function. RESULTS: The incidence of acute rejection at 12 months was 44% in group A1, 41% in group A2, 33% in group A3, and 27% in cohort B. Pretransplant and 12-month creatinine clearance (mL/min) were group A1, 72+/-25 and 64+/-24; group A2, 81+/-32 and 68+/-25; group A3, 91+/-28 and 86+/-26; and cohort B, 62+/-28 and 79+/-37. CONCLUSION: These results suggest that C2 monitoring is safe in de novo heart transplant patients. A low Neoral C2 range in combination with basiliximab induction resulted in preserved renal function without increased risk of acute rejection.

[Treatment of atrial fibrillation at different levels of health care]. / Tratamiento de la fibrilación auricular en los distintos niveles asistenciales de un área sanitaria.

BACKGROUND AND OBJECTIVE: Atrial fibrillation is managed in multiple settings by different specialists. We sought to analyze treatment and compliance of the prevailing guidelines of patients with atrial fibrillation attended at different levels of health care and to quantify interventions to correct treatment inadequacies. PATIENTS AND METHOD: We included all adult patients with atrial fibrillation who presented during a 14 day-period to different levels of health care of a tertiary hospital and a related primary care clinic (family physician, cardiologist, emergency department, hospitalization). In all of them, clinical and epidemiological data in relation to atrial fibrillation, and all data referring to treatment and compliance of guidelines, were recorded prospectively. RESULTS: 293 patients were included. Clinical and epidemiological data were similar in the different settings. A great diversity in atrial fibrillation treatment was observed. In 30 and 33% of the patients, antiarrhythmic and antithrombotic treatment, respectively, did not meet the recommendations of the prevailing guidelines. The adequacy was inferior in primary care. The adequacy percentages increased slightly after the medical attention (2 and 3% respectively, p non significant) with no differences in this increase between the different settings. CONCLUSIONS: There are no epidemiological differences between patients with atrial fibrillation treated at different levels of health care. An important number of patients do not follow the recommendations of the prevailing guidelines. There is a clear medical abstention in incorrectly treated cases.

Tratamiento de la fibrilación auricular en los distintos niveles asistenciales de un área sanitaria / Treatment of atrial fibrillation at different levels of health care

Fundamento y objetivo: La fibrilación auricular se trata en múltiples niveles asistenciales por distintos especialistas. El objetivo del estudio fue analizar el tratamiento de esta arritmia y su adecuación a las guías clínicas vigentes en los distintos niveles de atención sanitaria, así como cuantificar las intervenciones correctoras en los mismos niveles cuando el tratamiento era inadecuado. Pacientes y método: Se incluyó a todos los pacientes adultos con fibrilación auricular (FA) que consultaron a los distintos niveles de atención sanitaria de un hospital de tercer nivel y de un centro de atención primaria (CAP) relacionado (CAP, cardiólogo ambulatorio, urgencias, hospitalización) durante 14 días consecutivos. En todos ellos se registraron las características clínico-epidemiológicas, los datos referentes al tratamiento de la fibrilación auricular y su adecuación a las guías clínicas vigentes antes y después de la visita. Resultados: Se incluyó a 293 pacientes. Las características clínico-epidemiológicas fueron similares entre los distintos niveles asistenciales. Se objetivó una gran variabilidad en el tratamiento de la FA. En un 30 y un 33% de los pacientes el tratamiento antiarrítmico y antitrombótico, respectivamente, no se adecuaba a las recomendaciones de las guías clínicas vigentes. La adecuación fue inferior en las consultas del médico de familia. Estos porcentajes de adecuación se incrementaron mínimamente tras la visita (el 2 y el 3%, respectivamente; p no significativas), sin diferencias en este incremento entre los distintos niveles asistenciales. Conclusiones: No hay diferencias epidemiológicas entre los pacientes con fibrilación auricular tratados en los distintos niveles de la atención sanitaria. Un porcentaje importante de los pacientes no siguen las recomendaciones de las guías clínicas vigentes. Hay un claro nihilismo médico ante los pacientes con FA incorrectamente tratados

Background and objective: Atrial fibrillation is managed in multiple settings by different specialists. We sought to analyze treatment and compliance of the prevailing guidelines of patients with atrial fibrillation attended at different levels of health care and to quantify interventions to correct treatment inadequacies. Patients and method: We included all adult patients with atrial fibrillation who presented during a 14 day-period to different levels of health care of a tertiary hospital and a related primary care clinic (family physician, cardiologist, emergency department, hospitalization). In all of them, clinical and epidemiological data in relation to atrial fibrillation, and all data referring to treatment and compliance of guidelines, were recorded prospectively. Results: 293 patients were included. Clinical and epidemiological data were similar in the different settings. A great diversity in atrial fibrillation treatment was observed. In 30 and 33% of the patients, antiarrhythmic and antithrombotic treatment, respectively, did not meet the recommendations of the prevailing guidelines. The adequacy was inferior in primary care. The adequacy percentages increased slightly after the medical attention (2 and 3% respectively, p non significant) with no differences in this increase between the different settings. Conclusions: There are no epidemiological differences between patients with atrial fibrillation treated at different levels of health care. An important number of patients do not follow the recommendations of the prevailing guidelines. There is a clear medical abstention in incorrectly treated cases

Increased expression of the renin-angiotensin system and mast cell density but not of angiotensin-converting enzyme II in late stages of human heart failure.

BACKGROUND: The activation of the renin-angiotensin system (RAS) contributes to the progression of left ventricular dysfunction. A novel human homologue of the angiotensin-converting enzyme (ACE), named ACE2, has been described but its role in human heart failure (HF) has not been elucidated. Besides, there is controversy as to whether the major angiotensin II-forming-activity in heart is ACE or chymase released from mast cells. Furthermore, long-term blockade of nitric oxide (NO) synthesis has been shown to increase ACE activity. To assess the locally activated vasoactive mediators that may contribute to the ventricular deterioration process, we sought to simultaneously analyze their expression in failing hearts. METHODS: We analyzed left ventricular biopsies from 30 patients with heart failure undergoing heart transplantation and 12 organ donors. The mRNA levels of ACE, ACE2, chymase and endothelial nitric oxide synthase (eNOS), were quantified by real-time polymerase chain reaction and mast cell density was assessed by immunohistochemistry. The mRNA levels of the atrial natriuretic peptide (ANP) and the brain natriuretic peptide (BNP) were also quantified as controls. RESULTS: There was higher ACE and chymase mRNA expression and mast cell density in failing than in control myocardium and no changes in ACE2 expression were detected. eNOS mRNA levels were lower in failing hearts. Both ANP and BNP expression were higher in pathological than in control samples. CONCLUSIONS: These data document a decompensation of vasoactive systems that may contribute to the progressive impairment of the myocardial function in HF. On the other hand, ACE2 mRNA expression is not altered in human end-stage HF.

[Impaired endothelium-dependent forearm vasodilation in idiopathic dilated cardiomyopathy is related to severe left ventricular dysfunction and elevated serum tumor necrosis factor levels]. / La disfunción endotelial periférica en la miocardiopatía dilatada idiopática se asocia con mayor disfunción ventricular y concentraciones plasmáticas elevadas de factor de necrosis tumoral.

INTRODUCTION AND OBJECTIVES: Endothelial dysfunction has been found in patients with idiopathic dilated cardiomyopathy (IDC), but its mechanism remains unknown. Our aim was to investigate whether forearm endothelium-dependent vasoreactivity correlates with cardiac disease severity or neurohormonal activation. PATIENTS AND METHOD: We studied 23 patients with IDC and 10 healthy sex- and age-matched controls using brachial artery ultrasound to assess flow-mediated dilation (FMD) and nitroglycerin-induced vasodilation (NIV). In the IDC group, we determined plasma neurohormone and cytokine levels at the same time. RESULTS: FMD was significantly less in the IDC group compared with the control group [--0.06 (2.8)% vs 4.4 (4.6)%, respectively; P<.01], whereas NIV was similar in both groups [15.0 (6.4)% vs 14.0 (7.4)%, respectively; P=NS]. FMD was significantly less in patients with poorer left ventricular (LV) function and more severe LV dilatation, and in those with a higher tumor necrosis factor-alpha (TNF-alpha) level. NIV was similar in all patient subgroups. There was a significant inverse correlation between the TNF-alpha plasma level and FMD (r=-0.75; P<.01). No correlation was found between the plasma levels of other neurohormones and FMD. CONCLUSIONS: FMD, but not NIV, was impaired in patients with IDC compared with control subjects. In patients, there were significant associations between FMD impairment and the severity of LV dilatation, the severity of LV systolic dysfunction, and the plasma TNF-alpha level. The strongest correlation was observed between TNF-alpha plasma level and FMD. These data suggest that TNF-alpha may be implicated in endothelial dysfunction in patients with IDC.

La disfunción endotelial periférica en la miocardiopatía dilatada idiopática se asocia con mayor disfunción ventricular y concentraciones plasmáticas elevadas de factor de necrosis tumoral / Impaired endothelium - Dependent forearm vasodilation in idiopathic dilated cardiomyopathy is related to severe left ventricular dysfunction and elevated serum tumor necrosis factor levels

Introducción y objetivos. La miocardiopatia dilatada idiopática (MCDI) se asocia con disfunción endotelial, aunque se desconoce el mecanismo que la produce. Nuestro objetivo fue estudiar si la vasodilatación dependiente del endotelio (VED) analizada en la arteria humeral se correlaciona con la severidad de la insuficiencia cardíaca o el grado de activación neurohormonal. Pacientes y método. Se estudió a 23 pacientes con MCDI y a 10 sujetos sanos de edad y sexo similares. La VED y la vasodilatación secundaria a nitroglicerina (VD-NTG) se analizaron mediante eco-Doppler de la arteria humeral. También se determinaron las concentraciones de neurohormonas y citocinas en los pacientes con MCDI. Resultados. En los pacientes con MCDI se observó una reducción de la VED en comparación con el grupo control (­-0,06 ± 2,8 frente a 4,4 ± 4,6%, respectivamente, p < 0,01), mientras que la VD-NTG fue similar en ambos grupos (15,0 ± 6,4 frente a 14,0 ± 7,4%, respectivamente; p = NS). La VED fue significativamente menor en los pacientes con peor función ventricular y mayor dilatación ventricular, y también en los que presentaban concentraciones de factor de necrosis tumoral (TNF-α) más elevados. No se observaron diferencias significativas en cuanto a la VD-NTG entre los diferentes subgrupos. Se observó una correlación inversa significativa entre los valores plasmáticos de TNF-α y la VED (r = -­0,75; p < 0,01). Conclusiones. En comparación con el grupo control, los pacientes con MCDI tienen una reducción de la VED y conservan la VD-NTG. La disfunción ventricular severa, el mayor grado de dilatación ventricular y las concentraciones plasmáticas elevadas de TNF-α se asocian con una peor VED, pero la mayor correlación se observó entre los valores de TNF-α y la VED. Estos datos sugieren que el TNF-α puede estar implicado en la aparición de disfunción endotelial en la MCDI (AU)

Introduction and objectives. Endothelial dysfunction has been found in patients with idiopathic dilated cardiomyopathy (IDC), but its mechanism remains unknown. Our aim was to investigate whether forearm endothelium-dependent vasoreactivity correlates with cardiac disease severity or neurohormonal activation. Patients and method. We studied 23 patients with IDC and 10 healthy sex- and age-matched controls using brachial artery ultrasound to assess flow-mediated dilation (FMD) and nitroglycerin-induced vasodilation (NIV). In the IDC group, we determined plasma neurohormone and cytokine levels at the same time. Results. FMD was significantly less in the IDC group compared with the control group [­-0.06 (2.8)% vs 4.4 (4.6)%, respectively; P<.01], whereas NIV was similar in both groups [15.0 (6.4)% vs 14.0 (7.4)%, respectively; P=NS]. FMD was significantly less in patients with poorer left ventricular (LV) function and more severe LV dilatation, and in those with a higher tumor necrosis factor-α (TNF-α) level. NIV was similar in all patient subgroups. There was a significant inverse correlation between the TNF-α plasma level and FMD (r=­0.75; P<.01). No correlation was found between the plasma levels of other neurohormones and FMD. Conclusions. FMD, but not NIV, was impaired in patients with IDC compared with control subjects. In patients, there were significant associations between FMD impairment and the severity of LV dilatation, the severity of LV systolic dysfunction, and the plasma TNF-α level. The strongest correlation was observed between TNF-α plasma level and FMD. These data suggest that TNF-α may be implicated in endothelial dysfunction in patients with IDC (AU)

Epitope mapping of mitochondrial adenine nucleotide translocase-1 in idiopathic dilated cardiomyopathy.

Mitochondrial adenine nucleotide translocase (ANT) is a specific target for the autoantibody response in idiopathic dilated cardiomyopathy (IDCM). We have undertaken an epitope analysis of ANT in IDCM by immunoblot with recombinant GST-ANT fusion proteins and with cellulose-bound decapeptides of human ANT1. Forty-five patients with IDCM, 17 patients with ischemic left ventricle dysfunction (LVD) and 20 controls were analyzed for circulating antibodies against ANT (AAb-ANT). Sixteen of the 45 (36%) IDCM patients showed AAb-ANT above controls. In immunoblots, AAb-ANT detected purified bovine heart ANT and GST-ANT1 and GST-ANT2 isoforms and, less frequently, the GST-ANT3 isoform. A construct lacking the last 146 amino acids did not react with AAb-ANT, indicating that the main epitopes are in the C-terminal 146 amino acids. Immunodetection of decapeptides covering this region shows that AAb-ANT detects at least three epitopes, demonstrating that ANT is the primary target of AAb-ANT. The most significant epitopes belong to the M2 and M3 hydrophilic loops of ANT suggesting that apart from being essential for its activity, these loops are highly immunogenic.

[Prognostic value of cytokines and neurohormones in severe heart failure]. / Valor pronóstico de los niveles de citocinas y neurohormonas en la insuficiencia cardíaca severa.

BACKGROUND AND OBJECTIVES: The screening of candidates for heart transplantation continues to present difficulties. High plasma levels of cytokines and neurohormones have been associated with a poor prognosis in heart failure but their usefulness for identifying candidates for heart transplantation is still not established. METHODS: In 83 patients (59 11 years old), with systolic left ventricular dysfunction and New York Heart Association functional class III-IV, we assessed levels of aldosterone, atrial natriuretic peptide, plasma renin activity, angiotensin II, norepinephrine, endothelin, interleukin-6 and tumor necrosis factor-alpha. RESULTS: Over the following year, 13 patients died and 26 received heart transplantation. Mean ejection fraction was 23 6%, end-diastolic and end-systolic diameters were 73 10 and 60 10 mm, respectively. Univariate analysis identified the following variables to be associated with poor prognosis: angiotensin II (p = 0.001), norepinephrine (p = 0.003), plasma renin activity (p = 0.02), systolic blood pressure (p = 0.006), end-diastolic diameter (p = 0.02) and end-systolic diameter (p = 0.04). Multivariate regression analysis identified the following variables to be independent predictors of death or need for heart transplantation: a low cardiac index (p = 0.007), plasma angiotensin II (p = 0.001) and pulmonary capillary wedge pressure (p = 0.04) The sensitivity and specificity of angiotensin II for predicting poor outcome was only moderate according to interpretation of the receiver operating curves. CONCLUSIONS: Although plasma angiotensin II was the best neurohormone for identifying patients with severe heart failure and the worst prognosis, its sensitivity and specificity for predicting death or the need for heart transplantation was limited. The decision to transplant should continue to be based on clinical and hemodynamic parameters.

Valor pronóstico de los niveles de citocinas y neurohormonas en la insuficiencia cardíaca severa / Prognostic value of cytokines and neurohormones in severe heart failure

Introducción y objetivos. La selección de pacientes candidatos a trasplante cardíaco sigue siendo un problema difícil. Los valores elevados de citocinas y neurohormonas se han asociado a peor pronóstico en la insuficiencia cardíaca, pero su utilidad para seleccionar pacientes candidatos a trasplante cardíaco es todavía incierta. Métodos. Se analizaron los valores plasmáticos de aldosterona, factor natriurético auricular, actividad de la renina plasmática, angiotensina II, noradrenalina, endotelina, interleucina 6 y factor de necrosis tumoral alfa, en 83 pacientes con insuficiencia cardíaca severa en clase funcional III-IV de la NYHA. Resultados. Durante el seguimiento, 13 pacientes fallecieron y 26 precisaron un trasplante cardíaco. La fracción de eyección fue del 23 ñ 6 por ciento y los diámetros telediastólico y telesistólico de 73 ñ 10 y de 60 ñ 10 mm, respectivamente. El análisis univariado identificó los valores de angiotensina II (p = 0,001), noradrenalina (p = 0,003), actividad de la renina plasmática (p = 0,02), presión arterial sistólica (p = 0,006) y los diámetros telediastólico (p = 0,02) y telesistólico (p = 0,04) como factores asociados a un peor pronóstico. El análisis de regresión multivariado identificó el índice cardíaco (p = 0,007), los títulos de angiotensina II (p = 0,001) y la presión capilar pulmonar (p = 0,04) como predictores independientes de muerte o necesidad de trasplante cardíaco. La sensibilidad y especificidad de la angiotensina II, representadas mediante las curvas ROC, para identificar a los pacientes con peor pronóstico fueron sólo moderadas. Conclusiones. La angiotensina II fue la neurohormona más eficaz para identificar a los pacientes con insuficiencia cardíaca severa y peor pronóstico. No obstante, la sensibilidad y la especificidad para detectar mayor mortalidad o necesidad de trasplante cardíaco fueron sólo moderadas. La decisión de indicar trasplante cardíaco debe seguir basándose en datos clínicos y hemodinámicos (AU)