Impact of the New Definition of Pulmonary Hypertension on the Prevalence of Primary Graft Dysfunction in Lung Transplant Recipients.

BACKGROUND & AIM: Pulmonary hypertension (PH) secondary to lung disease (Group-3 PH) is the second leading cause of PH. The role of PH as a risk factor for primary graft dysfunction (PGD) following lung transplant (LT) is controversial. OBJECTIVE: To assess the impact that the new definition of PH had on the prevalence of PH in patients with advanced lung disease-candidate for LT, and its association with the occurrence of PGD. METHOD: A retrospective study was performed in all patients undergoing cardiac catheterisation referred for consideration as candidates to LT in a centre between 1 January 2017 and 31 December 2022. The baseline and haemodynamic characteristics of patients were analysed, along with the occurrence of PGD and post-transplant course in those who ultimately underwent transplantation. RESULTS: A total of 396 patients were included. Based on the new 2022 European Society of Cardiology/European Respiratory Society definitions, as many as 70.7% of patients met PH criteria. Since the introduction of the 2022 definition, a significant reduction was observed in the frequency of severe Group-3 PH (41.1% vs 10.3%; p<0.001), with respect to the 2015 definition. As many as 236 patients underwent transplantation. None of the variables associated with PH was identified as a risk factor for PGD. CONCLUSION: The new classification did not have any impact on the prevalence of PGD after transplantation. These results exclude that any significant differences exist in the baseline characteristics or post-transplant course of patients with Group-3 PH vs unclassified PH.

[Pulmonary Embolism]. / Tromboembolia de pulmón.

Pulmonary embolism (PE), the most severe form of presentation of venous thromboembolic disease (VTE), currently represents a foremost healthcare issue due to its high impact in terms of morbidity, mortality, costs, and resource consumption. Early mortality associated with PE is primarily due to hemodynamic instability, exacerbation of pre-existing conditions, or major complications of antithrombotic therapies. Beyond the risk of death, there are relevant complications related to PE, such as bleedings, VTE recurrences, and persistence of residual respiratory symptoms; the latter complication related to PE is mainly characterized by two entities, chronic thromboembolic pulmonary hypertension and chronic thromboembolic disease. Significant scientific advances made in recent years have allowed for the improvement of both diagnostic and therapeutic management of the disease, as outlined in this document through a series of relevant issues about PE that are answered with the most up-to-date scientific evidence.

Simplified risk stratification based on cardiopulmonary exercise test: A Spanish two-center experience.

A simplified 4-strata risk stratification approach based on three variables is widespread in pulmonary arterial hypertension (PAH) at follow-up. This study aimed to assess the impact of replacing the 6-min walk test (6MWT) with the peak 02 uptake evaluated by the cardiopulmonary exercise test (CPET) on risk stratification by this scale. We included 180 prevalent patients with PAH from two reference hospitals in Spain, followed up between 2006 and 2022. Patients were included if all the variables of interest were available within a 3-month period on the Spanish Registry of Pulmonary Arterial Hypertension (REHAP): functional class (FC); NT-proBNP; 6MWT; and CPET. The original 4-strata model (NT-proBNP, 6MWT, FC) identified most patients at low or intermediate-low risk (36.7% and 51.1%, respectively). Notably, the modified scale (NT-proBNP, CPET, FC) improved the identification of patients at intermediate-high risk up to 18.9%, and at high risk up to 1.1% in comparison with the previous 12.2% and 0.0% in the original scale. This new model increased the number of patients correctly classified into higher-risk strata (positive NRI of 0.06), as well as classified more patients without events in lower-risk strata (negative NRI of 0.04). The proposed score showed a slightly superior prognostic capacity compared with the original model (Harrel's C-index 0.717 vs. 0.709). Using O2 uptake instead of distance walked in the 6MWT improves the identification of high-risk patients using the 4-strata scale. This change could have relevant prognostic implications and lead to changes in the specific treatment of PAH.

The impact of time from ILD diagnosis to referral to the transplant center on the probability of inclusion in the transplant waiting list.

BACKGROUND: Lung transplant is a therapeutic option for patients with progressive interstitial lung disease (ILD). OBJECTIVES: The objective of this study was to determine whether time from ILD diagnosis to referral to a transplant center influences the probability of being included in the transplant waiting list. METHODS: We performed a retrospective cohort study including all ILD patients evaluated as lung transplantation (LT) candidates at a lung transplant center between 01/01/2017 and 31/12/2022. The primary endpoint was the probability of being included in the lung transplant waiting list according to the time elapsed from diagnosis to referral to the transplant center. RESULTS: A total of 843 lung transplant requests were received, of which 367 (43.5%) were associated with ILD. Thirteen patients were excluded because they did not attend the first visit, whereas another 11 were excluded because some information was missing. As a result, our final sample was composed of 343 patients. The median time from diagnosis to referral was 29.4 (10.9 - 61.1) months. The overall probability of inclusion in the waiting list was 29.7%. By time from diagnosis to referral, the probability of inclusion in the waiting list was 48.1% for the patients referred 〈 6 months from diagnosis; 27.5% for patients referred 6 to 24 months from diagnosis; and 25.8% for patients referred 〉 24 months from diagnosis (p = 0.007). CONCLUSIONS: Early referral to a lung transplant center seemed to increase the probability of being included in the lung transplant waiting list. Further research is needed in this topic.

Hipertensión pulmonar tromboembólica crónica en España: una década de cambio / Chronic thromboembolic pulmonary hypertension in Spain: a decade of change

Introducción y objetivos El tratamiento de la hipertensión pulmonar tromboembólica crónica (HTPTEC) ha evolucionado en la última década. Sin embargo, apenas se dispone de información sobre el impacto de estos logros en la población general a escala nacional. Este estudio se diseñó para describir las características de los pacientes con HTPTEC en España en la última década. Métodos Se recogieron prospectivamente datos epidemiológicos, clínicos y pronósticos de los pacientes con HTPTEC consecutivos incluidos en el registro español REHAP desde el 1 de enero de 2007 al 31 de diciembre de 2018. Se evaluaron las diferencias entre diferentes periodos de tiempo, estableciendo 2013 como fecha de referencia para el análisis. Se calculó la puntuación de propensión para la intervención mediante un modelo multivariable de regresión logística. Resultados Se incluyó a 1.019 pacientes; se remitió a 659 (64,4%) a un centro nacional de referencia en HTPTEC. Del total, se seleccionó a 350 (34,3%) para cirugía y a 97 (9,6%) para tratamiento percutáneo. Entre los pacientes diagnosticados entre 2007 y 2012 hubo más frecuencia de muerte que entre los diagnosticados de 2013 en adelante (HR=1,83; IC95%, 1,07-3,15; p=0,027). En el grupo de pacientes ajustado por el modelo de puntuación de propensión, las resistencias vasculares pulmonares basales y la distancia recorrida en el test de 6 min de marcha también fueron determinantes del pronóstico (respectivamente, HR=1,24; IC95%, 1,15-1,33; p=0,011, y HR=0,93; IC95%, 0,90-0,97; p=0,001). Las tasas de supervivencia de los pacientes que se sometieron a un procedimiento intervencionista (trombendarterectomía pulmonar o angioplastia con balón de arterias pulmonares) resultaron llamativamente altas. Conclusiones Durante la última década, el diagnóstico y el pronóstico de la HTPTEC han mejorado de manera considerable. La gravedad de la enfermedad al diagnóstico determinó el perfil de riesgo. ... (AU)

Introduction and objectives Chronic thromboembolic pulmonary hypertension (CTEPH) treatment has evolved in the last decade. However, there is scarce information on the long-term impact of this progress in a real-life population at a national level. This study was designed to analyze the characteristics of CTEPH patients in Spain over the last decade. Methods We prospectively collected epidemiological, clinical, and prognostic data from CTEPH patients consecutively included in the Spanish REHAP registry from January 1, 2007, to December 31, 2018. We evaluated differences over time, establishing 2013 as the reference date for analysis. Propensity scores for interventional treatment were calculated using a multivariable logistic regression model. Results A total of 1019 patients were included; 659 (64.4%) were evaluated at a national CTEPH center. Overall, 350 patients (34.3%) were selected for surgery and 97 (9.6%) for percutaneous treatment. Patients diagnosed between 2007 and 2012 died more frequently than those diagnosed from 2013 onward (HR, 1.83; 95%CI, 1.07-3.15; P=.027). Within the subgroup of patients adjusted by propensity score, baseline pulmonary vascular resistance and the 6-minute walk test distance also determined the outcome (HR, 1.24; 95%CI, 1.15-1.33; P=.011; and HR, 0.93; 95%CI, 0.90-0.97; P=.001, respectively). High survival rates were found in patients who underwent an invasive procedure (pulmonary endarterectomy or balloon pulmonary angioplasty). Conclusions CTEPH diagnosis and prognosis have consistently improved in the last decade. Baseline disease severity determines the risk profile. Patients who undergo pulmonary endarterectomy or balloon pulmonary angioplasty have better outcomes. (AU)

Expresividad variable de una mutación fundadora en el gen EIF2AK4 en pacientes con enfermedad venooclusiva pulmonar hereditaria. Impacto en la supervivencia / Variable expressivity of a founder mutation in the EIF2AK4 gene in hereditary pulmonary veno-occlusive disease and its impact on survival

Introducción y objetivos: La enfermedad venooclusiva pulmonar (EVOP) hereditaria se relaciona con mutaciones bialélicas en EIF2AK4 y se ha descrito una mutación fundadora en pacientes ibéricos de etnia gitana con EVOP familiar. Los objetivos son la caracterización fenotípica y el análisis de supervivencia de pacientes ibéricos de etnia gitana con EVOP familiar portadores de la mutación fundadora p.Pro1115Leu en EIF2AK4, según su tolerancia clínica a vasodilatadores pulmonares (VDP). Estudio genético familiar y análisis de factores socioculturales de la etnia con potencial impacto en la propagación de la enfermedad. Métodos: Estudio observacional de pacientes de etnia gitana con EVOP familiar incluidos en el Registro Español de Hipertensión Arterial Pulmonar. Se realizó estudio genético de EIF2AK4 a casos afectados y familiares (noviembre 2011-julio 2016) y estudio histopatológico pulmonar en caso de trasplante pulmonar o fallecimiento. Los pacientes se clasificaron en tolerantes y no tolerantes a VDP, comparando sus características basales y la supervivencia libre de fallecimiento o el trasplante. Resultados: Se estudió a 18 pacientes (9 casos índice y 9 familiares afectados). Se halló la mutación fundadora en homocigosis en EIF2AK4 en todos ellos y en 2 familiares sanos, y en heterocigosis en el 34,2% de familiares sanos. Se observó elevada consanguineidad, edad joven de reproducción con multiparidad y pronóstico sombrío de nuestra cohorte existiendo diferencias significativas entre pacientes tolerantes y no tolerantes. Conclusiones: Se describen 2 fenotipos de EVOP hereditaria en etnia gitana según tolerancia a VDP e histología pulmonar, con impacto pronóstico y distribución familiar. Destacamos el papel de la consanguineidad en la propagación de la enfermedad y una alta rentabilidad del cribado genético familiar (AU)

Introduction and objectives: Hereditary pulmonary veno-occlusive disease (PVOD) has been associated with biallelic mutations in EIF2AK4 with the recent discovery of a founder mutation in Iberian Romani patients with familial PVOD. The aims of this study were phenotypical characterization and survival analysis of Iberian Romani patients with familial PVOD carrying the founder p.Pro1115Leu mutation in EIF2AK4, according to their tolerance to pulmonary vasodilators (PVD). Familial genetic screening was conducted, as well as assessment of sociocultural determinants with a potential influence on disease course. Methods: Observational study of Romani patients with familial PVOD included in the Spanish Registry of Pulmonary Arterial Hypertension. Genetic screening of EIF2AK4 was performed in index cases and relatives between November 2011 and July 2016 and histological pulmonary examination was carried out in patients who received a lung transplant or died. The patients were divided into 2 groups depending on their tolerance to PVD, with comparison of baseline characteristics and survival free of death or lung transplant. Results: Eighteen Romani patients were included: 9 index cases and 9 relatives. The biallelic founder mutation in EIF2AK4 was found in all affected cases and 2 unaffected relatives. Family screening showed 34.2% of healthy heterozygotes, high consanguinity, young age at childbirth, and frequent multiparity. Prognosis was bleak, with significant differences depending on tolerance to PVD. Conclusions: We describe 2 phenotypes of hereditary PVOD depending on tolerance to PVD, with prognostic impact and familial distribution. Consanguinity may have a negative impact on the transmission of PVOD, with familial genetic screening showing high effectiveness (AU)