Risk stratification, prognosis, and survival in a pulmonary arterial hypertension cohort in Latin America. A multicenter study.

BACKGROUND: Pulmonary arterial hypertension (PAH) guidelines suggest that achieving a low-risk profile should be the treatment goal. Our aim was to assess a risk assessment strategy based on three non-invasive variables from the ESC/ERS 2015 guidelines in a Latin American cohort. METHODS: 92 incident patients (mean [SD] age 47, 77% female, 53% idiopathic PAH) were included in this retrospective, multicenter study. Patients were stratified at baseline and at early follow-up, within the first year, using three non-invasive variables (WHO functional class, 6-minute walking distance, BNP/NT-proBNP) from the ESC/ERS 2015 risk assessment instrument. Median (IQR) follow-up was 3.11 years (3.01 years). RESULTS: At baseline assessment, 25% of patients were at low risk, 61.9% at intermediate-risk, and 13% at high-risk. At early follow-up (median 9.5 months), 56.5% of patients were at low-risk, 40.2% at intermediate-risk, and 3.2% at high-risk (p<0.001 vs. baseline). According to risk stratification at early follow-up, one, three and five-year overall survival was 100% in the low-risk group (no deaths at five-year follow-up), and 100%, 84% (95% CI: 72-98%), and 66% (95% CI: 48-90%) respectively in the intermediate-risk group, p = 0.0003. Mortality in the high-risk patients at early follow-up was 1/3 (33.3%). One, three, and five-year event-free survival (death or transplant or first hospitalization due to worsening PAH) based on early follow-up risk assessment was higher in the low-risk group, p = 0.0003. CONCLUSION: Our study validates a risk assessment strategy based on three non-invasive variables and confirms that early achievement of a low-risk profile should be the treatment goal.

La T3 baja marcaría peor evolución en pacientes internados por insuficiencia cardíaca descompensada / Low T3 Would Indicate Adverse Outcomes for Inpatients with Decompensated Heart Failure

RESUMEN Introducción: El síndrome de T3 baja se asocia con niveles elevados de interleucinas y citoquinas circulantes, lo que refuerza la hipótesis de una estrecha relación entre el sistema neuroendocrino y ciertos mecanismos inflamatorios e inmunológicos, involucrados en la insuficiencia cardíaca. Objetivo: Evaluar la evolución de pacientes ingresados por insuficiencia cardíaca descompensada según niveles de T3 al ingreso, y eventos durante la hospitalización y en el seguimiento. Material y métodos: Estudio prospectivo, observacional, analítico de 524 pacientes internados por primera vez con diagnóstico de insuficiencia cardíaca descompensada. Se evaluó la mortalidad intrahospitalaria, y al seguimiento y readmisiones de acuerdo con niveles de T3 normal o disminuida al ingreso. Se excluyeron 91 pacientes con distiroidismo conocido, hipotiroidismo o hipertiroidismo, cirugía tiroidea previa, sepsis o síndrome coronario agudo. Se realizó un análisis de subgrupo de pacientes según recibieran crónicamente amiodarona y se evaluaron variables pronosticas. Resultados: De 433 pacientes analizados, el 40,0% presentaban bajos niveles de T3 (BT3). La edad, albúmina, TFG y edad mayor de 75 años, fueron predictores independientes de BT3. Si bien se observó un aumento en ambos grupos en la adecuación de tratamientos recomendados por las guías, el grupo de BT3 mostró significativamente tasas menores de estos con respecto a aquellos con T3 normal (BT3 vs. NT3: betabloqueantes 81,5% vs. 89,4%, p = 0,02; IECA/ARAII 78,5% vs. 87,9% p <0,001; antialdosterónicos 29,2% vs. 40,5% p = 0,019). La mortalidad hospitalaria fue mayor en BT3 (5,8% vs. 1,5%) sin diferencias en readmisiones o mortalidad en el seguimiento. Del subgrupo de pacientes sin amiodarona al ingreso (353), 37,8% tenían BT3. Se halló que los pacientes de este subgrupo presentaron diferencias significativas en cuanto a mortalidad intrahospitalaria y mortalidad en seguimiento (5,3% en BT3 vs. 0,9% NT3; p = 0,03 y 40,2% vs. 26,6%; p = 0,023), respectivamente. Conclusiones: Los pacientes ingresados por insuficiencia cardíaca descompensada con T3 baja al ingreso representarían un subgrupo de pacientes con enfermedad más grave y peor pronóstico durante la internación.

ABSTRACT Background: Low T3 syndrome is associated with elevated circulating levels of cytokines and interleukins, reinforcing the hypothesis of a close relation between the neuroendocrine system and certain inflammatory and immunological mechanisms involved in heart failure. Objective: To assess the progress of patients admitted for decompensated heart failure according to T3 levels on admission, and events during hospitalization and follow-up. Materials and methods: It was a prospective, observational, analytical study of 524 patients hospitalized for the first time with a diagnosis of decompensated heart failure. In-hospital and follow-up mortality and readmissions were evaluated according to normal or low T3 levels on admission. Ninety-one patients with known dysthyroidism, hypo or hyperthyroidism, previous thyroid surgery, sepsis or acute coronary syndrome were excluded. A subgroup analysis of patients receiving chronic amiodarone therapy was conducted, and prognostic variables were evaluated. Results: Of the 433 patients analyzed, 40.0% had low T3 (LT3) levels. Age, albumin level, age >75 years, and glomerular filtration rate (GFR) were independent predictors of LT3. While adaptation of guideline-recommended treatments increased in both groups, treatment rates in the LT3 group were significantly lower than those in the normal T3 (NT3) group (LT3 vs. NT3: Betablockers 81.5% vs. 89.4%, p=0.02; ACEI/ARA II 78.5% vs. 87.9%, p=0.001; anti-aldosterone agents 29.2% vs. 40.5%; p=0.019). Hospital mortality was higher in the LT3 group (5.8 vs. 1.5%), with no difference in rehospitalizations or mortality rates at follow-up. Of the subgroup of patients without amiodarone on admission (353), 37.8% had LT3. Patients in this subgroup were found to have significant differences in follow-up and in-hospital mortality (5.3% in LT3 vs. 0.9% in NT3, p=0.03, and 40.2% vs. 26.6%, p=0.023) respectively. Conclusions: Decompensated heart failure patients with LT3 on admission would represent a subgroup with more severe disease and worse prognosis during hospitalization.

Hipertensión pulmonar grave reversible asociada al uso de dasatinib en un paciente con leucemia mieloide crónica

La hipertensión arterial pulmonar (HAP) es una enfermedad rara caracterizada por un incremento progresivo de las resistencias vasculares pulmonares que lleva a la falla cardíaca derecha y muerte prematura. La enfermedad puede ser idiopática o asociada a otras condiciones como la hipertensión portal, el virus de la inmunodeficiencia humana, las enfermedades del tejido conectivo, las cardiopatías congénitas con cortocircuitos de izquierda a derecha o asociadas a diferentes toxinas o drogas. Se han realizado avances en el tratamiento farmacológico enfocados en el remodelado de la vasculatura pulmonar. En este sentido, se encuentran en evaluación los inhibidores de la tirosina kinasa (ITK). El imatinib es un ITK selectivo aprobado para el tratamiento de la leucemia mieloide crónica (LMC) que ha demostrado beneficios en el tratamiento de la HAP en estudios de fase II. Paradójicamente, el ITK dasatinib, también aprobado para el tratamiento de la LMC, ha sido asociado a HAP, falla ventricular derecha y a derrame pleural, lo que sugiere la posibilidad de un efecto adverso a nivel pulmonar vinculado con esta droga.(AU)

Pulmonary arterial hypertension is a rare disease that is characterized by a progressive increase in vascular pulmonary resistance, chronic right ventricle failure and premature death. Pulmonary arterial hypertension can be either idiopathic or associated to other conditions such as portal hypertension, human immunodeficiency virus, connective tissue diseases, congenital systemic-to-pulmonary shunts or associated to different drugs/toxins. Encouraging progress has been made by targeting the main vasoproliferative aspects of the disease. Tyrosine kinase inhibitors (TKI) are promising emerging therapeutics. Imatinib, a selective TKI approved for the treatment of chronic myeloid leukaemia, has demonstrated some efficacy in treating pulmonary arterial hypertension in a phase II study. However, the TKI dasatinib, also approved for therapy of chronic myeloid leukaemia, has been linked to reversible pulmonary arterial hypertension and right ventricular failure, with pleural effusion, suggesting the possibility of drug-related pulmonary arterial hypertension.(AU)

Hipertensión pulmonar grave reversible asociada al uso de dasatinib en un paciente con leucemia mieloide crónica / Reversible Severe Pulmonary Arterial Hypertension Associated to Dasatinib in a Chronic Myeloid Leukaemia Patient

La hipertensión arterial pulmonar (HAP) es una enfermedad rara caracterizada por un incremento progresivo de las resistencias vasculares pulmonares que lleva a la falla cardíaca derecha y muerte prematura. La enfermedad puede ser idiopática o asociada a otras condiciones como la hipertensión portal, el virus de la inmunodeficiencia humana, las enfermedades del tejido conectivo, las cardiopatías congénitas con cortocircuitos de izquierda a derecha o asociadas a diferentes toxinas o drogas. Se han realizado avances en el tratamiento farmacológico enfocados en el remodelado de la vasculatura pulmonar. En este sentido, se encuentran en evaluación los inhibidores de la tirosina kinasa (ITK). El imatinib es un ITK selectivo aprobado para el tratamiento de la leucemia mieloide crónica (LMC) que ha demostrado beneficios en el tratamiento de la HAP en estudios de fase II. Paradójicamente, el ITK dasatinib, también aprobado para el tratamiento de la LMC, ha sido asociado a HAP, falla ventricular derecha y a derrame pleural, lo que sugiere la posibilidad de un efecto adverso a nivel pulmonar vinculado con esta droga.

Pulmonary arterial hypertension is a rare disease that is characterized by a progressive increase in vascular pulmonary resistance, chronic right ventricle failure and premature death. Pulmonary arterial hypertension can be either idiopathic or associated to other conditions such as portal hypertension, human immunodeficiency virus, connective tissue diseases, congenital systemic-to-pulmonary shunts or associated to different drugs/toxins. Encouraging progress has been made by targeting the main vasoproliferative aspects of the disease. Tyrosine kinase inhibitors (TKI) are promising emerging therapeutics. Imatinib, a selective TKI approved for the treatment of chronic myeloid leukaemia, has demonstrated some efficacy in treating pulmonary arterial hypertension in a phase II study. However, the TKI dasatinib, also approved for therapy of chronic myeloid leukaemia, has been linked to reversible pulmonary arterial hypertension and right ventricular failure, with pleural effusion, suggesting the possibility of drug-related pulmonary arterial hypertension.