Biomarcadores y variables clínicas asociadas a la insuficiencia cardiaca avanzada con asistencia circulatoria tipo ECMO en pacientes a los que se realiza un trasplante cardiaco en código urgente. Análisis descriptivo e implicaciones pronósticas

La utilización de oxigenador de membrana extracorpórea (ECMO) como puente a trasplante cardiaco en código urgente (TCU) se ha asociado en numerosos trabajos con un incremento de la mortalidad postoperatoria, aunque datos más recientes indican que con una adecuada selección de pacientes y un protocolo de donación de órganos en el que se priorice a los pacientes de máxima urgencia, el pronóstico puede ser similar al trasplante cardiaco electivo (TCE). Sin embargo, existe menos información acerca de la repercusión del empleo de ECMO pre-trasplante cardiaco (TC) sobre otras complicaciones típicas en el post-TC, tales como el fallo primario del injerto (FPI), el rechazo agudo del injerto (RAI) y la infección, sobre todo valoradas de forma conjunta. El objetivo del presente estudio es conocer si el empleo del ECMO antes del TC se asocia a una respuesta inflamatoria sistémica diferenciada que conlleve un aumento de las complicaciones a corto plazo. Para ello, se estudiaron 3 cohortes según el tipo de TC: pacientes crónicos y ambulatorios con insuficiencia cardiaca avanzada en los que se realizaba TCE; pacientes en shock cardiogénico que precisaban de asistencia circulatoria tipo ECMO como puente directo al TCU, y pacientes críticos que requirieron TCU y pudieron precisar de inótropos, vasopresores y ventilación mecánica, pero que no necesitaron la colocación de asistencia mecánica pre-TC. Se definió un período temporal de 50 días como referencia para identificar las complicaciones a corto plazo. A fin de fenotipar el sustrato fisiopatológico subyacente, se seleccionaron 80 pacientes en los que se llevó a cabo una determinación de 6 biomarcadores en muestras extraídas inmediatamente antes del TC. El principal resultado del estudio es que la incidencia del objetivo primario compuesto a 50 días post-TC de FPI, RAI e infección que motiva ingreso hospitalario, no difirió entre el grupo de ECMO y las cohortes de TCE y TCU. Considerando los eventos de forma individual, no existieron diferencias en la tasa de FPI ni RAI, pero sí un mayor número de infecciones precoces en el grupo de ECMO. A medio plazo, a partir de los 50 días y hasta el año post-TC, los eventos de infección, RAI y mortalidad son prácticamente superponibles entre los 3 grupos de estudio. La elevación de algunos de los biomarcadores se asocia a la aparición del objetivo primario compuesto, y a su vez varios biomarcadores se encuentran más altos en el grupo de ECMO que en TCU o TCE. Sin embargo, la capacidad discriminativa y la elección de potenciales puntos de corte es subóptima, con áreas bajo la curva inferiores a 0,660. En el análisis de regresión logística multivariable, los predictores del objetivo primario compuesto fueron la necesidad de tratamiento inotrópico en el receptor, el antecedente de cirugía cardiaca previa en el receptor, la existencia de hipertensión arterial basal en el receptor, el grupo sanguíneo B del donante y la serología de toxoplasma negativa del donante

Soluble Transferrin Receptor as Iron Deficiency Biomarker: Impact on Exercise Capacity in Heart Failure Patients

The soluble transferrin receptor (sTfR) is a marker of tissue iron status, which could indicate an increased iron demand at the tissue level. The impact of sTfR levels on functional capacity and quality of life (QoL) in non-anemic heart failure (HF) patients with otherwise normal systemic iron status has not been evaluated. We conducted an observational, prospective, cohort study of 1236 patients with chronic HF. We selected patients with normal hemoglobin levels and normal systemic iron status. Tissue iron deficiency (ID) was defined as levels of sTfR > 75th percentile (1.63 mg per L). The primary endpoints were the distance walked in the 6 min walking test (6MWT) and the overall summary score (OSS) of the Minnesota Living with Heart Failure Questionnaire (MLHFQ). The final study cohort consisted of 215 patients. Overall QoL was significantly worse (51 +/- 27 vs. 39 +/- 20, p-value = 0.006, respectively), and the 6 MWT distance was significantly worse in patients with tissue ID when compared to patients without tissue ID (206 +/- 179 m vs. 314 +/- 155, p-value < 0.0001, respectively). Higher sTfR levels, indicating increased iron demand, were associated with a shorter distance in the 6 MWT (standardized beta = -0.249, p < 0.001) and a higher MLHFQ OSS (standardized fi = 0.183, p-value = 0.008). In this study, we show that in patients with normal systemic iron parameters, higher levels of sTfR are strongly associated with an impaired submaximal exercise capacity and with worse QoL

Short-term changes in klotho and FGF23 in heart failure with reduced ejection fraction—a substudy of the DAPA-VO2 study

The klotho and fibroblast growth factor 23 (FGF-23) pathway is implicated in cardiovascular pathophysiology. This substudy aimed to assess the changes in klotho and FGF-23 levels 1-month after dapagliflozin in patients with stable heart failure and reduced ejection fraction (HFrEF). The study included 29 patients (32.2% of the total), with 14 assigned to the placebo group and 15 to the dapagliflozin, as part of the double-blind, randomized clinical trial [DAPA-VO2 (NCT04197635)]. Blood samples were collected at baseline and after 30 days, and Klotho and FGF-23 levels were measured using ELISA Kits. Between-treatment changes (raw data) were analyzed by using the Mann-Whitney test and expressed as median (p25%–p75%). Linear regression models were utilized to analyze changes in the logarithm (log) of klotho and FGF-23. The median age was 68.3 years (60.8–72.1), with 79.3% male and 81.5% classified as NYHA II. The baseline medians of left ventricular ejection fraction, glomerular filtration rate, NT-proBNP, klotho, and FGF-23 were 35.8% (30.5–37.8), 67.4 ml/min/1.73 m2 (50.7–82.8), 1,285 pg/ml (898–2,305), 623.4 pg/ml (533.5–736.6), and 72.6 RU/ml (62.6–96.1), respectively. The baseline mean peak oxygen uptake was 13.1 ± 4.0 ml/kg/min. Compared to placebo, patients on dapagliflozin showed a significant median increase of klotho [Δ+29.5, (12.9–37.2); p = 0.009] and a non-significant decrease of FGF-23 [Δ−4.6, (−1.7 to −5.4); p = 0.051]. A significant increase in log-klotho (p = 0.011) and a decrease in log-FGF-23 (p = 0.040) were found in the inferential analysis. In conclusion, in patients with stable HFrEF, dapagliflozin led to a short-term increase in klotho and a decrease in FGF-23

Comparison of 1-year outcome in patients with severe aorta stenosis treated conservatively or by aortic valve replacement or by percutaneous transcatheter aortic valve implantation (data from a multicenter Spanish registry)

The factors that influence decision making in severe aortic stenosis (AS) are unknown. Our aim was to assess, in patients with severe AS, the determinants of management and prognosis in a multicenter registry that enrolled all consecutive adults with severe AS during a 1-month period. One-year follow-up was obtained in all patients and included vital status and aortic valve intervention (aortic valve replacement [AVR] and transcatheter aortic valve implantation [TAVI]). A total of 726 patients were included, mean age was 77.3 ± 10.6 years, and 377 were women (51.8%). The most common management was conservative therapy in 468 (64.5%) followed by AVR in 199 (27.4%) and TAVI in 59 (8.1%). The strongest association with aortic valve intervention was patient management in a tertiary hospital with cardiac surgery (odds ratio 2.7, 95% confidence interval 1.8 to 4.1, p <0.001). The 2 main reasons to choose conservative management were the absence of significant symptoms (136% to 29.1%) and the presence of co-morbidity (128% to 27.4%). During 1-year follow-up, 132 patients died (18.2%). The main causes of death were heart failure (60% to 45.5%) and noncardiac diseases (46% to 34.9%). One-year survival for patients treated conservatively, with TAVI, and with AVR was 76.3%, 94.9%, and 92.5%, respectively, p <0.001. One-year survival of patients treated conservatively in the absence of significant symptoms was 97.1%. In conclusion, most patients with severe AS are treated conservatively. The outcome in asymptomatic patients managed conservatively was acceptable. Management in tertiary hospitals is associated with valve intervention. One-year survival was similar with both interventional strategies