Centro de Investigación en Red en Enfermedades Cardiovasculares

Davis B.J., Volk H., Nguyen O., Kamna D., Chen H., Barriales‐Villa R., Garcia‐Pavia P., Olivotto I., Owens A.T., Coats C.J., Abraham T.P., Solomon S.D., Maron M.S., Masri A.

Background Cardiac myosin inhibitors were recently developed to address the underlying pathophysiology of hypertrophic cardiomyopathy and to improve symptoms and quality of life. In this review, we evaluated the pharmacologic profile and clinical outcomes for mavacamten and aficamten, 2 cardiac myosin inhibitors investigated in symptomatic hypertrophic cardiomyopathy. Methods and Results Using a systematic search, 10 clinical trials with safety and efficacy data for either drug in obstructive hypertrophic cardiomyopathy (oHCM) and nonobstructive hypertrophic cardiomyopathy were included. Additionally, we included data from regulatory agencies. Both drugs demonstrated substantial benefit in reducing left ventricular outflow tract obstruction (Valsalva left ventricular outflow tract gradients improved by −45 mm Hg or better), symptom burden (placebo‐corrected New York Heart Association class improvement ≥1 of at least 30%), and cardiac biomarkers (geometric mean ratio of 0.2 for N‐terminal pro‐B‐type natriuretic peptide) while improving exercise parameters (improved placebo‐corrected peak oxygen consumption of at least 1.4 to 1.8 mL/kg per minute) in patients with oHCM. Both drugs were generally well‐tolerated, although patients on mavacamten had higher rates of treatment interruption (partly protocol‐driven, 8.7% versus 0.5%, respectively, in oHCM) due to left ventricular ejection fraction reduction, atrial fibrillation (11.5 versus 4.1 per 100 patient‐years, respectively, in oHCM), and heart failure (1.7 versus 0.0 per 100 patient‐years, respectively, in oHCM) compared with aficamten. These comparisons are limited by a shorter exposure duration to aficamten, and longer follow‐up is needed. The data in nonobstructive hypertrophic cardiomyopathy are derived from phase II trials, with phase III trials ongoing. Conclusions Mavacamten and aficamten represent effective medications for the treatment of symptomatic oHCM.

Roque A., Pizzi M.N.

Téllez L., Rincón D., Payancé A., Jaillais A., Lebray P., Rodríguez de Santiago E., Clemente A., Paradis V., Lefort B., Garrido-Lestache E., Prieto R., Iserin L., Tallegas M., Garrido E., Torres M., et. al.

Fontan-type surgery is used as a palliation for congenital heart disease with univentricular physiology but may, in the long term, lead to advanced chronic liver disease. This study assessed the accuracy of conventional non-invasive models in assessing liver fibrosis and introduces a new risk score employing non-invasive tools.

Dalmases M., Sánchez-de-la-Torre M., Martinez D., Minguez O., Vaca R., Pascual L., Aguilá M., Gracia-Lavedan E., Benitez I.D., Pinilla L., Cortijo A., Gort-Paniello C., Claret R.B., Martinez-Garcia M.Á., Mediano O., et. al.

Among all patients with hypertension, those with resistant hypertension (RH) have the highest rates of subclinical organ damage (SOD). The prevalence of obstructive sleep apnea (OSA) is high in RH patients, and it could contribute to SOD. We aimed to investigate how OSA and its treatment are related to SOD in a large cohort of RH patients.

Lorenzo M., de la Espriella R., Miñana G., Núñez G., Carratalá A., Rodríguez E., Santas E., Valls N., Villar S., Donoso V., Bayés-Genís A., Sanchis J., Núñez J.

Pérez P.C., Fernández-Herrero I., Jesús Broseta J., Ibarra-Márquez N., Blázquez-Bermejo Z., López-Azor J.C., Gordillo C.D., Marcos M.C., Bagudá J.D., Cosío M.D., García-Álvarez A., Farrero M., Delgado J.F.

Worsening renal function (WRF) is a frequent complication in acute heart failure (AHF) with a controversial prognostic value. We aimed to study the usefulness of natriuresis to evaluate WRF. We conducted an observational, prospective, multicenter study of patients with AHF who underwent a furosemide stress test. The patients were classified according to whether WRF was present or absent and according to the median natriuretic response. The main endpoint was the combination of mortality, rehospitalization due to HF, and heart transplant at 6 months of follow-up. One hundred and fifty-six patients were enrolled, and WRF occurred in 60 (38.5%). The patients were divided into 4 groups: a) 47 (30.1%) no WRF/low UNa (UNa ≤ 109 mEq/L); b) 49 (31.4%) no WRF/high UNa (UNa > 109 mEq/L); c) 31 (19.9%) WRF/low UNa and d) 29 (18.6%) WRF/high UNa. The parameters of the WRF/low UNa group showed higher clinical severity and worse diuretic and decongestive response. The development of WRF was associated with a higher risk of the combined event (HR, 1.88; 95%CI, 1.01-3.50; P = .046). When stratified by natriuretic response, WRF was associated with an increased risk of adverse events in patients with low natriuresis (HR, 2.28; 95%CI, 1.15-4.53; P = .019), but not in those with high natriuresis (HR, 1.18; 95%CI, 0.26-5.29; P = .826). Natriuresis could be a useful biomarker for interpreting and prognosticating WRF in AHF. WRF is associated with a higher risk of adverse events only in the context of low natriuresis. El empeoramiento de la función renal (EFR) es una complicación frecuente en insuficiencia cardiaca aguda (ICA) cuyo valor pronóstico es controvertido. Nuestro objetivo es estudiar la utilidad de la natriuresis en la valoración del EFR. Estudio observacional, prospectivo y multicéntrico de pacientes con ICA sometidos a una prueba de estrés con furosemida. Se clasificó a los pacientes según tuvieran EFR o no y la mediana de la respuesta natriurética. El criterio de valoración principal fue el combinado de mortalidad, rehospitalización por IC y trasplante cardiaco a los 6 meses de seguimiento. Se incluyó a 156 pacientes, 60 de ellos (38,5%) con EFR. Se dividió a los pacientes 4 grupos: a) 47 (30,1%) sin EFR/baja natriuresis (NaU ≤ 109 mEq/l); b) 49 (31,4%) sin EFR/alto NaU (NaU > 109 mEq/l); c) 31 (19,9%) con EFR/bajo NaU, y d) 29 (18,6%) con EFR/alto NaU. Los pacientes con EFR/bajo NaU mostraron parámetros clínicos de mayor gravedad y peor respuesta diurética y descongestiva. El EFR se asoció con mayor riesgo del evento combinado (HR = 1,88; IC95%, 1,01-3,50; p = 0,046). Cuando se estratificó según el NaU, el EFR se asoció con mayor riesgo de eventos adversos en pacientes con baja natriuresis (HR = 2,28; IC95%, 1,15-4,53; p = 0,019), pero no con alta natriuresis. La natriuresis podría ser un biomarcador útil para interpretar y estratificar el EFR en ICA. El EFR solo se asocia con mayor riesgo de eventos adversos en el contexto de una baja natriuresis.

García-Vega D., Cinza-Sanjurjo S., Tilves-Bellas C., Eiras S., González-Juanatey J.R.

Introduction and objectives: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1ra) reduce cardiovascular events through different mechanisms, but their association with cancer remains unclear. The aim of this study was to compare the effect of combined treatment (SGLT2i and GLP1ra) and monotherapy (SGLT2i or GLP1ra) on hospitalization and/or death from cancer in a general population and a subgroup of patients with cardiovascular disease (CVD). Methods: We conducted a nonconcurrent observational prospective study of patients prescribed SGLT2i, GLP1ra, or both. Multinomial propensity scores were performed in the entire population and in a subgroup of patients with CVD. A multivariate Cox regression analysis was used to determine the hazard ratio (HR) for age, sex, risk factors, and treatment for each outcome. Results: We included 14 709 patients (11366 with SGLT2i, 1016 with GLP1ra, and 2327 with both treatments) from treatment initiation. Diabetes was present in 97% of the patients. The subgroup with CVD included 4957 (33.7%) patients. After a median of 33 months of follow-up, the risk of adverse cancer events was similar between patients with and without CVD (3.4% or 3.7%, respectively). The main risk factors for cancer mortality were male sex and age. Combined treatment and its duration reduced the risk of cancer mortality compared with monotherapy with SGLT2i or GLP1ra in the overall population (HR, 0.2216; 95%CI, 0.1106-0.4659; P < .001; and HR, 0.1928; 95%CI, 0.071-0.5219; P = .001, respectively) and in the subgroup of patients with CVD (HR, 0.2879; 95%CI, 0.0878-0.994; P < .049; and HR, 0.1329; 95%CI, 0.024-0.6768; P = .014, respectively). Conclusions: Initiation of combined therapy (SGLT2i and GLP1ra) vs monotherapy with SGLT2i or GLP1ra was associated with a lower risk of cancer mortality, mostly in diabetic patients with or without CVD. Although clinical trials are needed, these results might be explained by the complementary mechanisms of these drugs, including their antiproliferative, anti-inflammatory, and metabolic effects. Future clinical trials and mechanistic studies will clarify the possible role of these drugs in carcinogenesis. Introducción y objetivos: Los inhibidores del cotransportador de sodio-glucosa 2 (iSGLT2) y los agonistas del receptor del péptido 1 similar al glucagón (GLP1ra) reducen los eventos cardiovasculares a través de diferentes mecanismos. Sin embargo, se necesita esclarecer su asociación con cáncer. Nuestro objetivo consiste en comparar el tratamiento combinado (SGLT2i y GLP1ra) con la monoterapia (SGLT2i o GLP1ra) en cuanto a hospitalización o muerte por cáncer en una población general y un subgrupo de pacientes con enfermedad cardiovascular (ECV). Métodos: Estudio observacional prospectivo no concurrente de pacientes a quienes se prescribió iSGLT2, GLP1ra o ambos. Se obtuvo la puntuación de propensión multinomial de toda la población y de un subgrupo de pacientes con ECV. El análisis multivariado de regresión de Cox determinó la tasa de riesgos (HR) de edad, sexo, factores de riesgo y tratamiento para cada resultado. Resultados: Se incluyó a 14.709 pacientes (11.366 con iSGLT2, 1.016 con GLP1ra y 2.327 con ambos tratamientos) desde el inicio del tratamiento. El 97% de los pacientes eran diabéticos. El subgrupo con ECV incluyó a 4.957 (33,7%) pacientes. Después de una mediana de seguimiento de 33 meses, el riesgo de eventos adversos de cáncer fue similar entre los pacientes con y sin ECV (el 3,4 y el 3,7% respectivamente). El sexo (varones) y la edad fueron los principales factores de riesgo de mortalidad por cáncer. El tratamiento combinado y su duración habían reducido el riesgo de mortalidad por cáncer con respecto a la monoterapia con iSGLT2 o GLP1ra en todas las poblaciones (HR = 0,2216; IC95%, 0,1106-0,4659; p < 0,001; y HR = 0,1928; IC95%, 0,071-0,5219; p = 0,001) y en el subgrupo de pacientes con ECV (HR = 0,2879; IC95%, 0,0878-0,994; p < 0,049; y HR = 0,1329; IC95%, 0,024-0,6768; p = 0,014). Conclusiones: El inicio del tratamiento combinado (iSGLT2 y GLP1ra) frente a monoterapia con iSGLT2 o GLP1ra se asoció con una menor tasa de riesgo de mortalidad por cáncer, principalmente en pacientes diabéticos con o sin ECV. Aunque se necesitan ensayos clínicos, los mecanismos complementarios antiproliferativos, antiinflamatorios y metabólicos de estos fármacos podrían explicar estos resultados. Futuros ensayos clínicos y estudios mecanísticos aclararán el posible papel de estos fármacos en la carcinogénesis.

Lorenzo M., Espriella R.D., Miñana G., Núñez G., Carratalá A., Rodríguez E., Santas E., Valls N., Villar S., Donoso V., Bayés-Genís A., Sanchis J., Núñez J.

Spot determination of urinary sodium (UNa+) has emerged as a useful tool for monitoring diuretic response in patients with acute heart failure (AHF). However, the evidence in outpatients is scarce. We aimed to examine the relationship between spot UNa+ levels and the risk of mortality and worsening heart failure (WHF) events in individuals with chronic HF.

Gutiérrez-Ortiz E., Cobiella J., Muñoz-Guijosa C., TELES R.C., Estévez-Loureiro R., Moñivas V., Regueiro A., Blasco-Turrión S., Mahía P., Figuereo Beltre D., Freitas P., Piñón M., Amat-Santos I.J., Julià Amill I., Nolasco T., et. al.

Transcatheter mitral valve replacement (TMVR) is an emerging treatment alternative for mitral valve (MV) disease in patients who were ineligible for surgical intervention or edge-to-edge repair. This study aimed to assess the short- and mid-term outcomes of this procedure.

Garcia-Pavia P., Kristen A.V., Drachman B., Carlsson M., Amass L., Angeli F.S., Maurer M.S.

In the pivotal Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT), tafamidis significantly reduced mortality, leading to its approval in many countries for the treatment of transthyretin amyloid cardiomyopathy (ATTR-CM). Real-world evidence on survival in patients with ATTR-CM following tafamidis treatment has not been extensively reported.

Bouzas-Mosquera A., Barbeito-Caamaño C., Martínez-Sapiña M.J., Otero-Muinelo S., Vázquez-Rodríguez J.M.

La implantación de prótesis valvulares aórticas transcatéter (TAVI) ha representado una verdadera revolución en el tratamiento de la estenosis aórtica grave y sintomática. Varios avances han propiciado un aumento significativo en el número de implantes, así como una disminución gradual de las complicaciones asociadas. Un factor clave para el éxito de la TAVI ha sido el papel desempeñado por las técnicas de imagen cardiaca no invasivas en la planificación previa al procedimiento y en la selección de candidatos. Estas técnicas permiten determinar el tipo y tamaño de la prótesis a implantar, prever los riesgos, evaluar la idoneidad del acceso vascular, supervisar el procedimiento y realizar un seguimiento después del implante. En esta revisión se analiza el papel de las técnicas de imagen no invasivas antes, durante y después de la implantación de una prótesis aórtica transcatéter. Transcatheter aortic valve implantation (TAVI) has been a true revolution in the treatment of severe symptomatic aortic stenosis. Various advances have led to an exponential growth in the number of implants and a progressive reduction in their complication rate. One key factor in the success of TAVI has been the role of non-invasive cardiac imaging techniques in pre-procedural planning and candidate selection. These techniques enable the determination of the type and size of the prosthetic valve to be implanted, prediction of risks, assessment of the suitability of vascular access, procedure monitoring, and post-implant follow-up. This review addresses the role of non-invasive imaging techniques before, during, and after transcatheter aortic valve implantation.

Knox E.C., Mateo-Rodríguez I., Daponte-Codina A., Rosell-Ortiz F., Solá-Muñoz S., Codina-Rodríguez A., Bueno H., Ruiz-Azpiazu J.I.

Background/Objectives: A systematic review was performed with the aim of analysing potential sex differences in the overall treatment of coronary heart disease (CHD). Methods: Studies published between January 2011 and November 2023 that conducted a sex-based analysis of the provision of any type of therapeutic measure to treat CHD were included. A search was performed of the Web of Science database in November 2023, resulting in 9070 articles. Study quality was examined using the Newcastle–Ottawa scale. A worksheet was produced to extract data pertaining to the title, year of publication, sample, context, study design, dependent variables, time-frame, treatment type, and outcomes reported by each article. This systematic review followed PRISMA guidelines, and the research protocol was submitted to PROSPERO (CRD42022330238). Results: A total of 80 articles presenting data representing 560.070,624 individual datapoints were selected to comprise the final sample. The main findings revealed that the majority of studies highlighted inequalities that disadvantaged females in all analysed treatment categories (pharmacological treatment, invasive interventions, rehabilitation programmes, and other treatment types). Conclusions: Despite the abundance of evidence on the need to improve healthcare provision to females with CHD, few studies examined the reasons or mechanisms underlying the inequalities identified.

Soler‐Espejo E., Marín F., López‐Gálvez R., Ramos‐Bratos M.P., Sánchez‐Villalobos M., Esteve‐Pastor M.A., Lip G.Y., Rivera‐Caravaca J.M., Roldán V.

ABSTRACTBackgroundSystemic inflammation plays a central role in atrial fibrillation (AF). The neutrophil‐to‐lymphocyte ratio (NLR) is a simple hematological index that has been shown to be associated with prognosis in different pathologies.HypothesisThe NLR is associated with an increased risk of adverse events in patients with AF.MethodsWe included a prospective cohort of AF patients who started vitamin K antagonists (VKAs) therapy between July 2016 and June 2018. NLR was assessed at baseline and classified into three categories: low (< 3), moderate (3–5), and high (> 5). During a 2‐year follow‐up period, all cardiovascular deaths, all‐cause deaths, and net clinical outcomes (NCO; either ischemic stroke/transient ischemic attack, major bleeding or all‐cause death), were recorded.ResultsA total of 1050 patients were included (51.4% women; median age 77 years). NLR was available in 936 patients: 507 (54.2%) had low NLR (< 3), 239 (25.5%) had moderate NLR (3–5), and 190 (20.3%) had high NLR (> 5). The primary endpoint was significantly increased in the high NLR category (p = 0.002 for cardiovascular death; p < 0.001 for all‐cause mortality, and p < 0.001 for NCO), with higher IRRs (all p < 0.001). Multivariate Cox regression analyses showed that high NLR was independently associated with an increased risk of cardiovascular death (aHR: 2.02; 95% CI: 1.04–3.92), all‐cause mortality (aHR: 2.51; 95% CI: 1.58–3.97), and NCO (aHR: 1.99; 95% CI: 1.37–2.87), compared to low NLR.ConclusionsIn this prospective AF cohort receiving VKAs, elevated NLR was significantly associated with an increased risk of adverse clinical outcomes. NLR has independent prognostic value beyond other classical risk factors.

Varela-Cancelo A., Barge-Caballero E., Barge-Caballero G., Couto-Mallon D., Paniagua-Martin M.J., Antunez-Ballesteros M., Enriquez-Vazquez D., Grille-Cancela Z., Muñiz J., Vazquez-Rodriguez J.M., Crespo-Leiro M.G.

García M.S., Peláez A., Punter R.M., López M.C., Carbajal C.M., Ancochea J., Bachiller J.M., Hernández A.S., Rodrigo-García M., Clemente M.G., Moreno R.M.

Abstract Background This study aimed to assess how Elexacaftor/Tezacaftor/Ivacaftor (ETI) influences lung function, Body Mass Index (BMI), Sweat Test (ST) and mental health of Cystic Fibrosis (CF) patients, emphasizing on depression and anxiety. Methods We conducted an observational, prospective, multicentre study including 108 patients over 18 years old who initiated ETI therapy between December 2019 and December 2023. Patients underwent regular evaluations, including clinical, functional, and microbiological assessments, alongside completion of quality of life, anxiety, and depression questionnaires. We evaluated whether there was a difference in anxiety and depression levels over time. Results After 12 months of treatment, significant improvements were noted in BMI, lung function (FEV1%), ST and various aspects of quality of life (CFQ-R). However, anxiety and depression levels did not differ significantly during the follow-up. When we stratified our sample by key groups, we observed that younger patients (under 28 years) and those with homozygous Phe508del mutations experienced significant higher anxiety with no differences on depression. Furthermore, anxiety and depression demonstrated a moderate correlation, strengthening over time. Conclusions Treatment with ETI establishes significant improvements in lung function, BMI, ST and quality of life in patients with CF. However, despite these positive outcomes, there were no significant changes observed in levels of anxiety and depression, except for individuals with homozygous mutation type and those younger than 28 years old, who exhibited significant higher levels of anxiety.