Efficacy and safety of hypertonic saline therapy in ambulatory patients with heart failure: The SALT-HF trial.

AIMS: Combination of hypertonic saline solution (HSS) with intravenous loop diuretics has been suggested to improve diuretic response in patients hospitalized for heart failure (HF). The efficacy and safety of this approach in the ambulatory setting remain unexplored. METHODS AND RESULTS: In this multicentre, double-blind, randomized study, we allocated ambulatory patients with worsening heart failure (WHF) to a 1-h infusion of intravenous furosemide (ivFurosemide)-HSS versus ivFurosemide. The primary endpoint was the volume of diuresis at 3 h. Secondary endpoints included 3-h natriuresis and weight variation, 7-day congestion data, kidney function and electrolytes, and 30-day clinical events. Overall, 167 participants (median age: 81 years, 30.5% female) were randomized across 13 sites between December 2020 and March 2023. There were no differences in 3-h diuresis between treatments (ivFurosemide-HSS: 1099 ml vs. ivFurosemide: 1103 ml, p = 0.963), 3-h natriuresis (∆ +2.642 mEq/L, p = 0.559), or 3-h weight (∆ +0.012 kg, p = 0.920). Patients in the ivFurosemide-HSS arm experienced significant weight decrease at 7 days (Δ -0.586 kg, p = 0.048). There were no between-treatment differences in clinical congestion score, biomarkers, inferior vena cava diameter, or the presence of lung ultrasound B-lines. At 30 days, 26.5% of the patients in the ivFurosemide-HSS group versus 33.3% in the ivFurosemide group experienced WHF (hazard ratio 0.76, p = 0.330). The incidence of death from any cause or HF hospitalization was 6% of patients in the ivFurosemide-HSS group and 8.3% of patients in the ivFurosemide group (hazard ratio 0.69, p = 0.521). The incidence of worsening kidney function or metabolic derangements was not significantly different in the two arms. CONCLUSIONS: A single infusion of ivFurosemide-HSS did not improve 3-h diuresis or congestion parameters in patients with ambulatory WHF. This therapy showed an appropriate safety profile.

Molecular Analysis of BMPR2, TBX4, and KCNK3 and Genotype-Phenotype Correlations in Spanish Patients and Families With Idiopathic and Hereditary Pulmonary Arterial Hypertension.

INTRODUCTION AND OBJECTIVES: Recent advances in genetics have led to the discovery of new genes associated with pulmonary arterial hypertension, such as TBX4 and KCNK3. The phenotype and prognosis associated with these new genes have been scarcely described and their role in the Spanish population is unknown. The aim of this study was to characterize the genetics of a Spanish cohort of patients with idiopathic and hereditary pulmonary arterial hypertension and to describe the phenotype and prognostic factors associated with BMPR2 and the new genes (KCNK3 and TBX4). METHODS: A total of 165 adult patients were screened for BMPR2, KCNK3, and TBX4 mutations, 143 with idiopathic pulmonary arterial hypertension and 22 with hereditary pulmonary arterial hypertension. Baseline characteristics and survival were compared among the different subgroups and predictors of poor outcomes were analyzed. We also performed family screening. RESULTS: The genetic study identified a possibly associated mutation in 11.10% of the idiopathic cases (n = 16) and in 68.18% of the hereditary cases (n = 15). There were 19 mutations in BMPR2, 4 in TBX4, and 3 in KCNK3. The forms associated with TBX4 showed the highest survival rate (P < .01). Advanced functional class at diagnosis was the only factor associated with poor outcomes in the hereditary forms. In the family screening, 37.5% of relatives tested positive. CONCLUSIONS: The genetics of pulmonary arterial hypertension in the Spanish population may differ from other populations, with a lower proportion of BMPR2 causative mutations. In our cohort, TBX4-related forms of pulmonary arterial hypertension showed a more benign course and late diagnosis was the only predictor of adverse outcomes in the hereditary forms of the disease.

High incidence of bloodstream infection due to gram-negative bacilli in patients with pulmonary hypertension receiving intravenous treprostinil.

INTRODUCTION: An excessive risk for bacteremia has recently been reported in patients with pulmonary arterial hypertension (PAH) treated with intravenous treprostinil. We aimed to assess this association in a cohort of patients from a Spanish referral center. PATIENTS AND METHODS: We performed a retrospective cohort study that included 55 patients diagnosed with PAH who received a continuous intravenous infusion of a prostanoid (epoprostenol or treprostinil) for ≥1month at our center between January 1991 and December 2011. The risk factors associated with the incidence of bacteremia were analyzed with the log-rank test. RESULTS: After a total follow-up of 64,453 treatment days, we found 12 episodes of bacteremia: Staphylococcus aureus (5 episodes), non-fermenting gram-negative bacilli (4 episodes), other gram-positive cocci (2 episodes), and Enterobacter cloacae (one episode). The incidence of bacteremia was 0.118 episodes per 1,000 treatment days in patients receiving epoprostenol versus 0.938 episodes per 1,000 treatment-days in patients receiving treprostinil (P=.0037). All episodes of bacteremia due to Gram-negative bacilli were diagnosed in patients on treprostinil. In the univariate analysis the treatment with intravenous treprostinil was associated with the incidence of bacteremia (hazard ratio: 4.09; 95% confidence interval: 1.24-14.53), although the low number of events prevented us from performing a multivariate analysis. CONCLUSIONS: Therapy with intravenous treprostinil is associated with a higher risk for bacteremia, especially due to non-fermenting Gram-negative bacilli. This association should be taken in consideration when choosing empirical antibiotic therapy for patients with PAH and sepsis.

Análisis de los genes BMPR2, TBX4 y KCNK3 y correlación genotipo-fenotipo en pacientes y familias españolas con hipertensión arterial pulmonar / Molecular analysis of BMPR2, TBX4, and KCNK3and Genotype-Phenotype correlations in spanish patients and families with idiopathic and hereditary pulmonary arterial hypertension

Introducción y objetivos: Avances recientes en genética han permitido el descubrimiento de nuevos genes relacionados con la hipertensión arterial pulmonar, como TBX4 y KCNK3. El fenotipo y el pronóstico asociado a ellos se han detallado escasamente y se desconoce su papel en la población española. El objetivo de este estudio es caracterizar genotípicamente una cohorte española de pacientes con hipertensión arterial pulmonar idiopática y hereditaria, describiendo el fenotipo y los factores pronósticos asociados a BMPR2 y a los nuevos genes (KCNK3 y TBX4). Métodos: Se seleccionó a 165 pacientes adultos con hipertensión arterial pulmonar: 143 con hipertensión arterial pulmonar idiopática y 22 con hipertensión arterial pulmonar familiar. Se compararon las características basales y la supervivencia libre de eventos entre los distintos subgrupos, se analizaron los factores predictores de mal pronóstico y se llevó a cabo el cribado familiar. Resultados: El estudio genético fue positivo en 16 pacientes con hipertensión arterial pulmonar idiopática (11,10%) y 15 con hipertensión arterial pulmonar familiar (68,18%), y se hallaron 19 mutaciones en BMPR2, 4 en TBX4 y 3 en KCNK3. Se observó mayor supervivencia libre de eventos en las formas asociadas a TBX4 (p < 0,01). El diagnóstico en clases funcionales avanzadas fue el único factor pronóstico en las formas heredables. El cribado de familiares fue positivo en el 37,5%. Conclusiones: En la población española con hipertensión arterial pulmonar puede existir un sustrato genético diferente, con menor proporción de mutaciones en BMPR2. A la vista de nuestros resultados, las formas asociadas a TBX4 podrían conllevar un fenotipo más benigno, y el diagnóstico tardío sería un factor de mal pronóstico en las formas heredables de la enfermedad (AU)

Introduction and objectives: Recent advances in genetics have led to the discovery of new genes associated with pulmonary arterial hypertension, such as TBX4 and KCNK3. The phenotype and prognosis associated with these new genes have been scarcely described and their role in the Spanish population is unknown. The aim of this study was to characterize the genetics of a Spanish cohort of patients with idiopathic and hereditary pulmonary arterial hypertension and to describe the phenotype and prognostic factors associated with BMPR2 and the new genes (KCNK3 and TBX4). Methods: A total of 165 adult patients were screened for BMPR2, KCNK3, and TBX4 mutations, 143 with idiopathic pulmonary arterial hypertension and 22 with hereditary pulmonary arterial hypertension. Baseline characteristics and survival were compared among the different subgroups and predictors of poor outcomes were analyzed. We also performed family screening. Results: The genetic study identified a possibly associated mutation in 11.10% of the idiopathic cases (n = 16) and in 68.18% of the hereditary cases (n = 15). There were 19 mutations in BMPR2, 4 in TBX4, and 3 in KCNK3. The forms associated with TBX4 showed the highest survival rate (P < .01). Advanced functional class at diagnosis was the only factor associated with poor outcomes in the hereditary forms. In the family screening, 37.5% of relatives tested positive. Conclusions: The genetics of pulmonary arterial hypertension in the Spanish population may differ from other populations, with a lower proportion of BMPR2 causative mutations. In our cohort, TBX4-related forms of pulmonary arterial hypertension showed a more benign course and late diagnosis was the only predictor of adverse outcomes in the hereditary forms of the disease (AU)

Alta incidencia de bacteriemia por bacilos gramnegativos en pacientes con hipertensión pulmonar tratados con treprostinil por vía intravenosa / High Incidence of Bloodstream Infection Due to Gram-negative Bacilli in Patients With Pulmonary Hypertension Receiving Intravenous Treprostinil

Introducción: Recientemente se ha comunicado un exceso de riesgo de bacteriemia en pacientes con hipertensión arterial pulmonar (HAP) que reciben tratamiento con treprostinil intravenoso. Pretendemos evaluar esta asociación en una unidad de referencia española. Pacientes y método: Estudio de cohortes retrospectivo con inclusión de 55 pacientes con HAP seguidos en nuestro centro y que recibieron tratamiento mediante perfusión intravenosa continua con un prostanoide (epoprostenol o treprostinil) durante ≥1mes entre enero de 1991 y diciembre de 2011. Analizamos mediante el test de log-rank los factores asociados a la incidencia de bacteriemia. Resultados: Tras un seguimiento total de 64.453 días se documentaron 12 episodios de bacteriemia: Staphylococcus aureus (5 episodios), bacilos gramnegativos (BGN) no fermentadores (4 episodios), otros cocos grampositivos (2 episodios) y Enterobacter cloacae (un episodio). La incidencia de bacteriemia fue de 0,118 episodios por 1.000 días de tratamiento con epoprostenol, frente a 0,938 episodios por 1.000 días de tratamiento con treprostinil (p=0,0037). Todos los casos de bacteriemia por BGN tuvieron lugar en pacientes que recibían treprostinil. En el análisis univariante el tratamiento con treprostinil se asoció a la incidencia de bacteriemia (hazard ratio: 4,09; intervalo de confianza del 95%: 1,24-14,53), si bien el limitado número de eventos impidió la realización de un modelo multivariante. Conclusiones: El tratamiento con treprostinil intravenoso conlleva un mayor riesgo de bacteriemia, especialmente por BGN no fermentadores. Esta asociación debe ser tenida en cuenta en la elección del tratamiento antibiótico empírico en pacientes con HAP y sepsis(AU)

Introduction: An excessive risk for bacteremia has recently been reported in patients with pulmonary arterial hypertension (PAH) treated with intravenous treprostinil. We aimed to assess this association in a cohort of patients from a Spanish referral center. Patients and methods: We performed a retrospective cohort study that included 55 patients diagnosed with PAH who received a continuous intravenous infusion of a prostanoid (epoprostenol or treprostinil) for ≥1month at our center between January 1991 and December 2011. The risk factors associated with the incidence of bacteremia were analyzed with the log-rank test. Results: After a total follow-up of 64,453 treatment days, we found 12 episodes of bacteremia: Staphylococcus aureus (5 episodes), non-fermenting gram-negative bacilli (4 episodes), other gram-positive cocci (2 episodes), and Enterobacter cloacae (one episode). The incidence of bacteremia was 0.118 episodes per 1,000 treatment days in patients receiving epoprostenol versus 0.938 episodes per 1,000 treatment-days in patients receiving treprostinil (P=.0037). All episodes of bacteremia due to Gram-negative bacilli were diagnosed in patients on treprostinil. In the univariate analysis the treatment with intravenous treprostinil was associated with the incidence of bacteremia (hazard ratio: 4.09; 95% confidence interval: 1.24-14.53), although the low number of events prevented us from performing a multivariate analysis. Conclusions: Therapy with intravenous treprostinil is associated with a higher risk for bacteremia, especially due to non-fermenting Gram-negative bacilli. This association should be taken in consideration when choosing empirical antibiotic therapy for patients with PAH and sepsis(AU)

Aneurisma coronario de rápido crecimiento y pericarditis purulenta por Streptococcus pneumoniae: ¿asociación casual o causal? / A rapidly growing coronary aneurysm and purulent pericarditis due to : coincidence or consequence?

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