Plasma fibroblast activation protein is decreased in acute heart failure despite cardiac tissue upregulation.

BACKGROUND: Cardiac fibroblast activation protein (FAP) has an emerging role in heart failure (HF). A paradoxical reduction in its levels in pathological conditions associated with acute processes has been observed. We aimed to identify FAP cardiac tissue expression and its relationship with the main cardiac fibrosis-related signaling pathways, and to compare plasma FAP levels in acute and chronic HF patients. METHODS: Transcriptomic changes were assessed via mRNA/ncRNA-seq in left ventricle tissue from HF patients (n = 57) and controls (n = 10). Western blotting and immunohistochemistry were used to explore FAP protein levels and localization in cardiac tissue. ELISA was performed to examine plasma FAP levels in acute HF (n = 48), chronic HF (n = 15) and control samples (n = 7). RESULTS: FAP overexpression in cardiac tissue is related to the expression of molecules directly involved in cardiac fibrosis, such as POSTN, THBS4, MFAP5, COL1A2 and COL3A1 (P < 0.001), and is directly and inversely related to pro- and antifibrotic microRNAs, respectively. The observed FAP overexpression is not reflected in plasma. Circulating FAP levels were lower in acute HF patients than in controls (P < 0.05), while chronic HF patients did not show significant changes. The clinical variables analyzed, such as functional class or etiology, do not affect plasma FAP concentrations. CONCLUSIONS: We determined that in HF cardiac tissue, FAP is related to the main cardiac fibrosis signaling pathways as well as to pro- and antifibrotic microRNAs. Additionally, an acute phase of HF decreases plasma FAP levels despite the upregulation observed in cardiac tissue and regardless of other clinical conditions.

Annual evolution of the prescription of drugs with prognostic implications in acute decompensated heart failure with reduced ejection fraction.

BACKGROUND: Quadruple therapy (renin angiotensin system inhibitors, beta-blockers, mineralocorticoid receptor antagonists and sodium/glucose cotransporter type 2 inhibitors [SGLT2i]) has become the current prognostic modifying treatment for heart failure (HF) with reduced ejection fraction (HFrEF). This study aimed to analyse the prescription´s evolution of this combination therapy, the analysis of each pharmacological group and the differences according to HF subgroups. METHODS: Retrospective analysis of consecutive patients admitted for cardiac decompensation. Inclusion period: from 1-1-2020 to 12-31-2022. Patients with left ventricular ejection fraction > 40% and deceased during admission were excluded. Finally, 602 patients were included. These were divided into: (a) de novo HF without previous heart disease (n:108), (b) de novo with previous heart disease (n:107), and (c) non-de novo (n:387). RESULTS: Over the study time, all pharmacological groups experienced an increase in drugs prescription (p < 0.001). The group with the largest prescription rate increase was SGLT2i (2020:20%, 2021:42.9%, 2022:70.4%; mean increase 47.2%). The discharge rate prescription of quadruple therapy increased progressively (2020:7.4%, 2021:21.1%, 2022:32.5%; mean increase 21.9%). The subgroup with the highest combined prescription in 2022 was de novo with previous heart disease (43.9%). CONCLUSION: The pharmacological group with the largest prescription´s rate increase was SGLT2i. The percentage of patients discharged on quadruple therapy has progressed significantly in recent years, although it remains low. The most optimised subgroup at discharge was that of de novo HF with previous heart disease.

Left atrial strain in adults after the arterial switch operation for transposition of the great arteries.

BACKGROUND: No study has focused on left atrial (LA) function assessed by echocardiography in adult patients with simple D-TGA after arterial switch operation (ASO). We aimed to describe LA strain parameters in these patients. METHODS: A prospective cohort study including 42 adult patients with simple D-TGA after ASO and 33 aged-matched controls. Phasic LA and LV global longitudinal strain (GLS) were obtained by transthoracic 2D-speckle tracking echocardiography (STE). Volumetric and functional analysis of LA and LV were also evaluated by 2D and 3D analysis. A multivariable model was performed to investigate the variables that best differentiate patients with D-TGA from healthy controls. RESULTS: LA strain parameters in D-TGA patients were within the normal range described for healthy subjects. However, the three LA strain parameters (Reservoir, Conduit, and Contraction) were lower in patients (LASr: 31.13 ± 7.67 vs. 49.71 ± 8.38; LAS cd: -22.91 ± 5.69 vs. -34.55 ± 6.54; LASct: -8.14 ± 4.93 vs. -15.15 ± 6.07, p < .001 for all three comparisons). LA volumes were similar between patients and controls. LV-GLS remained significantly lower in the D-TGA group than in controls (-17.29 ± 2.68 vs. -21.98 ± 1.84, p < .001). D-TGA patients had evidence of worse LV ejection fraction measured by the Teichholz method (63.38 ± 8.23 vs. 69.28 ± 5.92, p = .001) and 3D analysis (57.97% ± 4.16 vs. 60.67 ± 3.39, p = .011) and diastolic dysfunction as compared to healthy controls. LV-GLS and conduit LAS were the variables best differentiating patients with D-TGA from healthy controls. CONCLUSIONS: LA strain is impaired in young adults with simple D-TGA late after the ASO, probably in agreement with some degree of LV dysfunction previously described.

Novel Fibrillar and Non-Fibrillar Collagens Involved in Fibrotic Scar Formation after Myocardial Infarction.

Following myocardial infarction (MI), adverse remodeling depends on the proper formation of fibrotic scars, composed of type I and III collagen. Our objective was to pinpoint the participation of previously unreported collagens in post-infarction cardiac fibrosis. Gene (qRT-PCR) and protein (immunohistochemistry followed by morphometric analysis) expression of fibrillar (types II and XI) and non-fibrillar (types VIII and XII) collagens were determined in RNA-sequencing data from 92 mice undergoing myocardial ischemia; mice submitted to permanent (non-reperfused MI, n = 8) or transient (reperfused MI, n = 8) coronary occlusion; and eight autopsies from chronic MI patients. In the RNA-sequencing analysis of mice undergoing myocardial ischemia, increased transcriptomic expression of collagen types II, VIII, XI, and XII was reported within the first week, a tendency that persisted 21 days afterwards. In reperfused and non-reperfused experimental MI models, their gene expression was heightened 21 days post-MI induction and positively correlated with infarct size. In chronic MI patients, immunohistochemistry analysis demonstrated their presence in fibrotic scars. Functional analysis indicated that these subunits probably confer tensile strength and ensure the cohesion of interstitial components. Our data reveal that novel collagens are present in the infarcted myocardium. These data could lay the groundwork for unraveling post-MI fibrotic scar composition, which could ultimately influence patient survivorship.

Clinical profiling of patients admitted with acute heart failure: a comprehensive survival analysis.

Background: In heart failure (HF), not all episodes of decompensation are alike. The study aimed to characterize the clinical groups of decompensation and perform a survival analysis. Methods: A retrospective study was conducted on patients consecutively admitted for HF from 2018 to 2023. Patients who died during admission were excluded (final number 1,668). Four clinical types of HF were defined: low cardiac output (n:83), pulmonary congestion (n:1,044), mixed congestion (n:353), and systemic congestion (n:188). Results: The low output group showed a higher prevalence of reduced left ventricular ejection fraction (93%) and increased biventricular diameters (p < 0.01). The systemic congestion group exhibited a greater presence of tricuspid regurgitation with dilatation and right ventricular dysfunction (p:0.0001), worse renal function, and higher uric acid and CA125 levels (p:0.0001). Diuretics were more commonly used in the mixed and, especially, systemic congestion groups (p:0.0001). The probability of overall survival at 5 years was 49%, with higher survival in pulmonary congestion and lower in systemic congestion (p:0.002). Differences were also found in survival at 1 month and 1 year (p:0.0001). Conclusions: Mortality in acute HF is high. Four phenotypic profiles of decompensation differ clinically, with distinct characteristics and varying prognosis in the short, medium, and long term.

Pharmacological Considerations during Percutaneous Treatment of Heart Failure.

Heart Failure (HF) remains a global health challenge, marked by its widespread prevalence and substantial resource utilization. Although the prognosis has improved in recent decades due to the treatments implemented, it continues to generate high morbidity and mortality in the medium to long term. Interventional cardiology has emerged as a crucial player in HF management, offering a diverse array of percutaneous treatments for both acute and chronic HF. This article aimed to provide a comprehensive review of the role of percutaneous interventions in HF patients, with a primary focus on key features, clinical effectiveness, and safety outcomes. Despite the growing utilization of these interventions, there remain critical gaps in the existing body of evidence. Consequently, the need for high-quality randomized clinical trials and extensive international registries is emphasized to shed light on the specific patient populations and clinical scenarios that stand to benefit most from these innovative devices.

Alterations in Mitochondrial Oxidative Phosphorylation System: Relationship of Complex V and Cardiac Dysfunction in Human Heart Failure.

Heart failure (HF) is a disease related to bioenergetic mitochondrial abnormalities. However, the whole status of molecules involved in the oxidative phosphorylation system (OXPHOS) is unknown. Therefore, we analyzed the OXPHOS transcriptome of human cardiac tissue by RNA-seq analyses (mRNA n = 36; ncRNA n = 30) in HF patients (ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM)) and control subjects. We detected 28 altered genes in these patients, highlighting greater deregulation in ICM. Specifically, we found a general overexpression of complex V (ATP synthase) elements, among them, ATP5I (ICM, FC = 2.04; p < 0.01), ATP5MJ (ICM, FC = 1.33, p < 0.05), and ATP5IF1 (ICM, FC = 1.81; p < 0.001), which presented a significant correlation with established echocardiographic parameters of cardiac remodeling and ventricular function as follows: left ventricular end-systolic (p < 0.01) and end-diastolic (p < 0.01) diameters, and ejection fraction (p < 0.05). We also detected an increase in ATP5IF1 protein levels (ICM, FC = 1.75; p < 0.01) and alterations in the microRNA expression levels of miR-208b-3p (ICM, FC = -1.44, p < 0.001), miR-483-3p (ICM, FC = 1.37, p < 0.01), regulators of ATP5I. Therefore, we observed the deregulation of the OXPHOS transcriptome in ICM patients, highlighting the overexpression of complex V and its relationship with cardiac remodeling and function.

Practical Requirements for the Development of an Advanced Cardiorenal Unit.

BACKGROUND: Heart failure is frequently associated with kidney disease, and patients with kidney disease are at increased risk of heart failure. The co-occurrence of both entities not only significantly increases morbidity and mortality but also complicates therapy. SUMMARY: Cardiorenal syndrome often requires a broad, comprehensive, and multidisciplinary approach. As a result, a need has arisen to create specialized cardiorenal units that allow for rigorous and personalized management of this condition. Moreover, in some cases, cardiorenal syndrome is more complex, owing to an acute and critical situation that requires the concept of the cardiorenal unit to be extended toward advanced diagnostic and therapeutic positions, thus confirming the need for an advanced cardiorenal unit. The creation of these units constitutes a real challenge, necessitating a specific multilevel action plan, covering governance and management, type of patient, personnel requirements, service portfolio, care process, information systems, and other resources. Specific lines of action must be proposed for each of the relevant points in order to facilitate development of these units, together with continuous evaluation of unit activity through specific indicators, and to detect areas for improvement. KEY MESSAGES: This study addresses the conditions and organizational characteristics that enable the creation, development, and continuous improvement of advanced cardiorenal units.

Usefulness of biomarkers to predict prognosis after heart transplant.

INTRODUCTION AND OBJECTIVES: Heart transplant (HT) represents a major physiological stress, resulting in elevated levels of analytical biomarkers. This study aimed to determine whether changes in biomarker levels after HT can identify patients with a poor prognosis. METHODS: A prospective longitudinal noninterventional study was conducted in 149 consecutive patients undergoing HT from July 2017 to July 2023. Biomarkers were assessed before HT and at 6, 24, 48, 72, and 96hours after HT. The biomarkers analyzed were high-sensitivity troponin T, N-terminal pro-B-type natriuretic peptide (NT-proBNP), creatinine, and lactic acid. The primary outcome was a composite of death and severe primary graft failure (PGF). RESULTS: NT-proBNP and troponin levels remained highly elevated throughout the period and stabilized from the first 24hours post-HT. Lactate levels stabilized after the first 24hours, and creatinine from the second day onward. Exitus occurred in 23 (15%) of the patients, and severe PGF in 26 (17%). All biomarkers were significantly associated with the incidence of the combined event (P <.0001). Receiver operating characteristic curve analysis at 24hours showed significant areas under the curve (P=.0001). The greatest discriminatory power was observed for the NT-proBNP curve. A value of 10 000 pg/mL had a sensitivity of 90% and specificity of 80%. CONCLUSIONS: A significant elevation of post-HT analytical biomarkers was associated with mortality and/or severe PGF. Among the biomarkers analyzed, NT-proBNP was the most accurate in classifying patients.

Circulating long non-coding RNAs detection after heart transplantation and its accuracy in the diagnosis of acute cardiac rejection.

Long non-coding RNAs (lncRNAs) are closely implicated in biological processes and diseases with high inflammatory components. These molecules exhibit significant temporal and tissue specificity. However, the expression and function of lncRNAs have not been studied in patients after heart transplantation. Thus, we aimed to identify circulating lncRNAs in these patients and evaluate their diagnostic capacity as potential biomarkers for the non-invasive detection of acute cellular rejection (ACR). For them, we performed a transcriptomic study based on ncRNA-seq technology to detect lncRNAs in serum samples, matched to routine endomyocardial biopsies, from patients without rejection episode (0R, n = 12) and with mild (1R, n = 16) or moderate-severe (≥ 2R, n = 12) ACR. We identified 11,062 circulating lncRNAs in the serum of patients after heart transplantation. Moreover, 6 lncRNAs showed statistically significant expression when the different ACR grades were compared. Among them, AC008105.3, AC006525.1, AC011455.8, AL359220.1, and AC025279.1 had relevant diagnostic capacity for detection of ≥ 2R (AUC of 0.850 to 1.000) and 1R (AUC of 0.750 to 0.854) grades, along with high specificity and positive predictive values (≥ 83%). In addition, AL359220.1 and AC025279.1 were independent predictors for the presence of moderate-severe ACR (odds ratio = 31.132, p < 0.01 and C statistic = 0.939, p < 0.0001; odds ratio = 18.693, p < 0.05 and C statistic = 0.902, p < 0.001; respectively). In conclusion, we describe, for the first time, circulating lncRNAs after heart transplantation as potential candidates for non-invasive detection of ACR. AL359220.1 and AC025279.1 showed excellent diagnostic capability correlating with the severity episode and were strong independent predictors of rejection.

Penetrance of Dilated Cardiomyopathy in Genotype-Positive Relatives.

BACKGROUND: Disease penetrance in genotype-positive (G+) relatives of families with dilated cardiomyopathy (DCM) and the characteristics associated with DCM onset in these individuals are unknown. OBJECTIVES: This study sought to determine the penetrance of new DCM diagnosis in G+ relatives and to identify factors associated with DCM development. METHODS: The authors evaluated 779 G+ patients (age 35.8 ± 17.3 years; 459 [59%] females; 367 [47%] with variants in TTN) without DCM followed at 25 Spanish centers. RESULTS: After a median follow-up of 37.1 months (Q1-Q3: 16.3-63.8 months), 85 individuals (10.9%) developed DCM (incidence rate of 2.9 per 100 person-years; 95% CI: 2.3-3.5 per 100 person-years). DCM penetrance and age at DCM onset was different according to underlying gene group (log-rank P = 0.015 and P <0.01, respectively). In a multivariable model excluding CMR parameters, independent predictors of DCM development were: older age (HR per 1-year increase: 1.02; 95% CI: 1.0-1.04), an abnormal electrocardiogram (HR: 2.13; 95% CI: 1.38-3.29); presence of variants in motor sarcomeric genes (HR: 1.92; 95% CI: 1.05-3.50); lower left ventricular ejection fraction (HR per 1% increase: 0.86; 95% CI: 0.82-0.90) and larger left ventricular end-diastolic diameter (HR per 1-mm increase: 1.10; 95% CI: 1.06-1.13). Multivariable analysis in individuals with cardiac magnetic resonance and late gadolinium enhancement assessment (n = 360, 45%) identified late gadolinium enhancement as an additional independent predictor of DCM development (HR: 2.52; 95% CI: 1.43-4.45). CONCLUSIONS: Following a first negative screening, approximately 11% of G+ relatives developed DCM during a median follow-up of 3 years. Older age, an abnormal electrocardiogram, lower left ventricular ejection fraction, increased left ventricular end-diastolic diameter, motor sarcomeric genetic variants, and late gadolinium enhancement are associated with a higher risk of developing DCM.

Acute performance of stylet driven leads for left bundle branch area pacing: A comparison with lumenless leads.

Background: Lumenless leads (LLLs) are widely used for left bundle branch area pacing (LBBAP). Recently, stylet-driven leads (SDLs) have also been used for LBBAP. Objective: The purpose of this study was to evaluate the acute performance of SDLs during LBBAP in comparison with LLLs. Methods: Consecutive patients undergoing LBBAP for bradycardia or cardiac resynchronization therapy indications at 2 high-volume, early conduction system pacing adopters, tertiary centers were included from January 2019 to July 2023. Patients received either SDLs or LLLs at the discretion of the implanting physician. Acute performance and follow-up data of both lead types were evaluated. Results: A total of 925 LBBAP implants were included, 655 using LLLs and 270 using SDLs. Overall, LBBAP acute success was significantly higher with LLLs than SDLs (95.3% vs 85.1%, respectively; P <.001) even after the learning curve (97% vs 86%; P = .013). LLLs were implanted in more mid-basal septal positions in comparison with SDLs, which tended to be implanted in more inferior and mid-apical septal positions. Acute lead-related complications were higher with SDLs than LLLs (15.9% vs 6.1%, respectively; P <.001) with 15 cases of lead damage during implant (4.4% vs 0.5%; P <.001) but decreased with acquired experience and were comparable in the last 100 patients included in each group. Lead implant and fluoroscopy times were shorter for SDLs, with lead dislodgment occurring in 0.9% with LLLs and 1.5% with SDLs (P = .489). Conclusion: Acute lead performance proved to be different between LLLs and SDLs. A specific learning curve should be considered for SDLs even for implanters with extensive previous experience with LLLs.

Utilidad del quirófano híbrido en la extracción de dispositivos implantables: experiencia inicial de un centro / Utility of the hybrid operating room for lead extraction: initial experience in a single center

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El grosor y una expresión de miARN alterada en la grasa epicárdica se asocian con enfermedad coronaria en víctimas de muerte súbita / Thickness and an altered miRNA expression in the epicardial adipose tissue is associated with coronary heart disease in sudden death victims

Introducción y objetivos: El aumento de la grasa epicárdica (GE) es un nuevo factor de riesgo de enfermedad coronaria (EC). El estudio se propone profundizar en el papel de la GE como marcador de EC centrándose en su espesor, el perfil de expresión de los microARN (miARN) y los factores que podrían influir en ello. Métodos: Se recogieron prospectivamente 155 autopsias de víctimas de muerte súbita cardiaca por EC y 84 de controles con muerte súbita no debida a EC. En un subgrupo se analizaron el espesor de la GE y su patrón de expresión de miARN. Resultados: El grosor de GE estaba incrementado y brindaba buena precisión para discriminar a los pacientes (entre otras mediciones, área bajo la curva de la puntuación de GE, 0,718; p < 0,001). La GE de los pacientes presentó 14 miARN suprarregulados y 14 infrarregulados, y se validaron por reacción en cadena de la polimerasa en tiempo real miR-34a-3p, -34a-5p, -124-3p, -125a-5p, 628-5p, -1303 y -4286. Las proporciones de miR-34a-3p y -34a-5p en la GE de los pacientes fueron mayores que en los controles (con progresión entre la GE de coronarias sin estenosis, con estenosis estables y con placas complicadas) y solo se correlacionaron con la edad en los controles. La discreta correlación del miR-34a-5p en el hígado y la GE de los pacientes (r = 0,295; p = 0,020) aumentó llamativamente al considerar exclusivamente la GE de placas complicadas (r = 0,799; p = 0,017). Se observaron correlaciones similares con la proteína C reactiva ultrasensible y el miR-34a-5p en las muestras de GE e hígado. Conclusiones: El patrón de expresión de miARN en la GE de la EC típicamente muestra un aumento de miR-34a-3p y -34a-5p que es independiente de la edad, el grosor de la GE, las mediciones antropométricas y la presencia de lesiones coronarias subyacentes

Introduction and objectives: An increased epicardial adipose tissue (EAT) thickness has become a new risk factor for coronary heart disease (CHD). We aimed to study the role of EAT dysfunction as a CHD marker by focusing on its thickness and microRNA (miRNA) expression profile, and the potential factors possibly influencing them. Methods: One hundred and fifty-five CHD sudden cardiac death victims and 84 non-CHD-sudden death controls were prospectively enrolled at autopsy. A representative subset underwent EAT thickness measurements and EAT miRNA expression profiling. Results: Epicardial adipose tissue thickness was increased and allowed an accurate diagnosis of patient status (among other measurements, EAT score area under the curve 0.718, P < .001). Epicardial adipose tissue from patients showed 14 up- and 14 down-regulated miRNAs and miR-34a-3p, -34a-5p, -124-3p, -125a-5p, 628-5p, -1303 and -4286 were validated by quantitative real-time polymerase chain reaction. Patients exhibited higher EAT levels of miR-34a-3p and -34a-5p than controls (with a positive trend considering EAT from coronaries without stenosis, with stable stenosis and complicated plaques) and correlated with age only in controls. The mild positive correlation between liver and EAT miR-34a-5p levels in patients (r = 0.295, P = .020) dramatically increased in EAT from complicated plaques (r = 0.799, P = .017). Similar correlations were observed for high-sensitivity-C-reactive protein levels and miR-34a-5p levels both in EAT and liver extracts. Conclusions: Increased age-independent levels of miR-34a-3p and -34a-5p characterize the EAT miRNA expression profile of CHD regardless of EAT thickness, anthropometric parameters, and the presence of underlying atherosclerotic plaques

Cambios en la expresión de adrenoceptores y GRK en pacientes con insuficiencia pulmonar valvular crónica / Changes in adrenoceptor and GRK expression in patients with chronic pulmonary regurgitation

Introducción y objetivos: La insuficiencia pulmonar (IP) es una complicación frecuente tras la intervención de cardiopatías congénitas. La expresión en leucocitos mononucleares circulantes (LMC) de los adrenoceptores (ß1 y ß2) y de las cinasas (GRK2, GRK3 y GRK5) refleja los cambios neurohumorales que se producen en la insuficiencia cardiaca (IC). El objetivo principal es describir la expresión génica de dichas moléculas en LMC de pacientes con IP grave. Métodos: Estudio prospectivo que analizó la expresión de las moléculas descritas en LMC de pacientes con IP grave en comparación con controles sanos y pacientes con IC avanzada. Resultados: Se estudió a 35 pacientes con IP grave, 22 controles y 13 pacientes con IC. El análisis de comparaciones múltiples mostró que en los controles la cantidad de ARN mensajero de adrenoceptor ß2 era mayor que el que presentaban los pacientes con IP y con IC, con similar expresión en estos 2 grupos: 748,49 (intervalo, 1.703,87) frente a 402,80 (1.210,81) frente a 287,46 (685,69) (p = 0,001). Estos mismos hallazgos se obtuvieron en la expresión génica de GRK2: 760,89 (1.169,46) frente a 445,17 (1.190,69) frente a 284,09 (585,27) (p < 0,001). No hubo diferencias en la expresión de estas moléculas según las variables clínicas de los pacientes con IP. Conclusiones: El patrón de expresión génica de GRK2 y del adrenoceptor ß2 de los pacientes con IP grave, como marcadores moleculares de disfunción cardiaca, se encuentra alterado respecto a los controles y es similar al de los pacientes con IC avanzada

Introduction and objectives: Pulmonary regurgitation (PR) is a frequent complication after repair of congenital heart disease. Lymphocyte expression of adrenoceptors (ß1 and ß2) and kinases (GRK2, GRK3, and GRK5) reflects the neurohumoral changes that occur in heart failure (HF). The main objective of this study was to describe the gene expression of these molecules in circulating lymphocytes in patients with severe PR. Methods: A prospective study was conducted to analyze lymphocyte expression of these molecules in patients with severe PR and compare it with expression in healthy controls and patients with advanced HF. Results: We studied 35 patients with severe PR, 22 healthy controls, and 13 patients with HF. Multiple comparisons analysis showed that ß2-adrenoceptor gene expression levels were higher in the control group than in patients in the PR and HF groups and that expression in the latter 2 groups was similar (748.49 [rank 1703.87] vs 402.80 [rank 1210.81] vs 287.46 [rank 685.69] P = .001). Similar findings were obtained in gene expression of GRK2 (760.89 [rank 1169.46] vs 445.17 [rank 1190.69] vs 284.09 [rank 585.27] P < .001). There were no differences in expression levels of these molecules according to clinical variables in patients with PR. Conclusions: The gene expression pattern of GRK2 and ß2-adrenoceptor as molecular markers of cardiac dysfunction was altered in patients with severe PR compared with controls and was similar to expression in patients with advanced HF

Evolución de los pacientes con estenosis aórtica grave tras la indicación de intervención / Prognosis of patients with severe aortic stenosis after the decision to perform an intervention

Introducción y objetivos: Los tratamientos actuales de la estenosis aórtica (EAo) grave incluyen el implante percutáneo de válvula aórtica (TAVI) y la cirugía de sustitución valvular aórtica (SVAo). El objetivo es describir la evolución de los pacientes con EAo grave tras la indicación de intervención, las variables que influyen en su pronóstico y los determinantes de un tiempo de espera superior a 2 meses. Métodos: Subanálisis del registro IDEAS (Influencia del Diagnóstico de Estenosis Aórtica Severa) en los pacientes a los que se indicó intervención. Resultados: De 726 pacientes con EAo grave diagnosticada en enero de 2014, se indicó intervención a 300 que son el foco del presente estudio. La media de edad era 74,0 +/- 9,7 años. Se intervino a 258 pacientes (86,0%): 59 con TAVI y 199 con SVAo. Al año, 42 (14,0%) continuaban sin intervención, ya sea por seguir en espera (34) o haber fallecido (8). La mitad de los pacientes que murieron antes del procedimiento fallecieron en los primeros 100 días. El tiempo hasta la intervención fue 2,9 +/- 1,6 meses para el TAVI y 3,5 +/- 0,2 meses para la SVAo (p = 0,03). Los predictores de mortalidad independientes fueron el sexo masculino (HR = 2,6; IC95%, 1,1-6,0), la insuficiencia mitral moderada-grave (HR = 2,6; IC95%, 1,5-4,5), la movilidad reducida (HR = 4,6; IC95%, 1,7-12,6) y la falta de intervención (HR = 2,3; IC95%, 1,02-5,03). Conclusiones: Los pacientes con EAo grave en espera de intervención tienen alto riesgo de mortalidad. Hay indicadores clínicos asociados con peor pronóstico que podrían indicar la necesidad de una intervención precoz

Introduction and objectives: Current therapeutic options for severe aortic stenosis (AS) include transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR). Our aim was to describe the prognosis of patients with severe AS after the decision to perform an intervention, to study the variables influencing their prognosis, and to describe the determinants of waiting time > 2 months. Methods: Subanalysis of the IDEAS (Influence of the Severe Aortic Stenosis Diagnosis) registry in patients indicated for TAVI or SAVR. Results: Of 726 patients with severe AS diagnosed in January 2014, the decision to perform an intervention was made in 300, who were included in the present study. The mean age was 74.0 +/- 9.7 years. A total of 258 (86.0%) underwent an intervention: 59 TAVI and 199 SAVR. At the end of the year, 42 patients (14.0%) with an indication for an intervention did not receive it, either because they remained on the waiting list (34 patients) or died while waiting for the procedure (8 patients). Of the patients who died while on the waiting list, half did so in the first 100 days. The mean waiting time was 2.9 +/- 1.6 for TAVI and 3.5 +/- 0.2 months for SAVR (P = .03). The independent predictors of mortality were male sex (HR, 2.6; 95%CI, 1.1-6.0), moderate-severe mitral regurgitation (HR, 2.6; 95%CI, 1.5-4.5), reduced mobility (HR, 4.6; 95%CI, 1.7-12.6), and non intervention (HR, 2.3; 95%CI, 1.02-5.03). Conclusions: Patients with severe aortic stenosis a waiting therapeutic procedures have a high mortality risk. Some clinical indicators predict a worse prognosis and suggest the need for early intervention

CA125 como nuevo biomarcador en pacientes con circulación de Fontan / CA125: a new biomarker in patients with Fontan circulation

Introducción y objetivos Los pacientes con circulación de Fontan (CF) presentan una gran incidencia de complicaciones y ningún biomarcador estratifica el riesgo. El objetivo es analizar la asociación de biomarcadores con un perfil clínico de disfunción de la CF, incluyendo por primera vez el antígeno carbohidrato 125 (CA125), y proponer una estimación del riesgo basada en la combinación de biomarcadores. Métodos Estudio transversal de adultos con CF. Se consideró perfil clínico desfavorable el combinado de insuficiencia cardiaca, arritmias auriculares, fístulas venovenosas, enteropatía pierdeproteínas o bronquitis plástica. Se analizaron variables clínicas y analíticas, incluidos CA125, NT-proBNP, función renal y hepática y amplitud de distribución eritrocitaria (ADE). Se realizó un estudio univariado y multivariado de la relación de dichas complicaciones clínicas y curvas ROC para obtener puntos de corte. Resultados Se incluyó a 56 pacientes (media de edad, 27,4±7,8 años). El 34% tenía un perfil clínico desfavorable, con valores de CA125 significativamente mayores (30,1 frente a 12,6 UI/ml; p=0,001). LnCA125 (OR=5,1; IC95%, 1,2-22), ADE (OR=1,8; IC95%, 1,1-3.1) y FIB4 (OR=38; IC95%, 1,7-855) se asociaron con un perfil de disfunción clínica. Los puntos de corte fueron CA125 ≥ 20 U/ml, FIB4 ≥ 0,75 y ADE ≥ 14,5%, y la probabilidad de un perfil clínico desfavorable fue del 81% con 2 o más biomarcadores elevados. Conclusiones El aumento de CA125 se asocia con mayor prevalencia de complicaciones en pacientes con CF. Los valores de CA125 ≥ 20 U/ml, FIB4 ≥ 0,75 y ADE ≥ 14,5% identifican con alta probabilidad fracaso clínico de la CF. (AU)

Introduction and objectives Patients with Fontan circulation (FC) have a high incidence of clinical complications. However, no biomarker is able to accurately stratify risk. The aim of this study was to analyze the relationship between biomarkers and clinical complications, including carbohydrate antigen 125 (CA125) for the first time, and to propose a risk estimation based on a combination of biomarkers. Methods Cross-sectional study of patients with FC. The clinical endpoint was the combination of heart failure, atrial arrhythmias, veno-venous fistulae, protein-losing enteropathy, or plastic bronchitis. Demographic, clinical, and laboratory variables were analyzed, including CA125, NT-proBNP, renal and liver function, and red cell distribution width (RDW). We performed univariate and multivariate analyses of the relationship between these variables and the composite endpoint. Cutoff values were calculated by ROC curves. Results We included 56 patients (27.4±7.8 years). A total of 34% showed the composite endpoint, with significantly higher CA125 levels (30.1 IU/mL vs 12.6 IU/mL; P=.001). In the multivariate model, the biomarkers related to the endpoint were LnCA125 (OR, 5.1; 95%CI, 1.2-22), RDW (OR, 1.8; 95%CI, 1.1-3.1), and FIB4 (OR, 38, 95%CI, 1.7-855). The cutoff points were CA125 ≥ 20 U/mL, FIB4 ≥ 0.75, and RDW ≥ 14.5%, and the probability of the occurrence of the endpoint was 81% if ≥ 2 biomarkers were elevated. Conclusions CA125 elevation is associated with a higher prevalence of complications in patients with Fontan-type circulation. CA125 levels ≥ 20U/mL, FIB4 ≥ 0.75 and RDW ≥ 14.5% identify with a high probability the clinical failure of FC. (AU)

Implicaciones pronósticas de la hipo e hiperpotasemia en la insuficiencia cardíaca aguda con fracción de eyección reducida. Análisis de la mortalidad cardiovascular y reingresos hospitalarios / Prognostic implications of hypo and hyperkalaemia in acute heart failure with reduced ejection fraction. Analysis of cardiovascular mortality and hospital readmissions

Antecedentes y objetivos:Las alteraciones del potasio constituyen un problema clínico de gran magnitud en la insuficiencia cardíaca (IC) descompensada. Este estudio pretende valorar las implicaciones pronósticas de la hipo e hiperpotasemia al ingreso por IC aguda en la mortalidad cardiovascular y reingresos hospitalarios.Material y método:De enero de 2016 a junio de 2020 fueron ingresados 1.397 casos con diagnóstico de IC aguda. Se excluyeron ingresos programados para estudio, terapias electivas y pacientes con fracción de eyección del ventrículo izquierdo>40%. El estudio se realizó sobre 689 pacientes, 45 con potasio (K+)<3,5 mmol/l, 49K+>5,0mmol/l y 595K+=3,5-5,0 mmol/l. Se analizaron los antecedentes, perfil clínico basal, terapia farmacológica y niveles de potasio obtenidos al ingreso.Resultados:La mortalidad anual por hipopotasemia (K+

Background and objectives: Potassium alterations constitute a major clinical problem in decompensated heart failure (HF). This study aims to assess the prognostic implications of hypo and hyperkalaemia on admission for acute HF in cardiovascular mortality and hospital readmissions.Material and method:From January 2016 to June 2020, 1,397 cases with a diagnosis of acute HF were admitted. Admission programmed for study, elective therapies, and patients with LVEF> 40% were excluded. The study was carried out on 689 patients, 45 with K+ <3.5 mmol/L, 49K +>5.0 mmol/L and 595K+3.5-5.0 mmol/L. Medical history, baseline clinical profile, drug therapy, and potassium levels obtained upon admission were analysed.Results:Annual mortality due to hypokalaemia (K+<3.5mmol/L) was 37.8% (HR 2.4; 95% CI: 1.3-4.7; P<.007); for hyperkalaemia 40.8% (HR: 1.9; 95% CI: 0.98-3.51; P<.055). Creatinine level and age were variables associated with mortality in both the hyperkalaemic and hypokalaemic cohorts. Hospital readmissions did not show statistical association with these electrolyte disorders.Conclusions:In patients admitted for decompensated HF, both hyperkalaemia and hypokalaemia determined at admission have a negative prognostic impact on survival. Creatinine and age are other independent factors associated with mortality. The effect on the probability of hospital readmission at one year is not demonstrated in this study. (AU)