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.

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)

CA125: a new biomarker in patients with Fontan circulation.

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.

Spatiotemporal Complexity of Vena Contracta and Mitral Regurgitation Grading Using Three-Dimensional Echocardiographic Analysis.

BACKGROUND: Spatiotemporal complexity of the color Doppler vena contracta challenging the assumption of a circular and constant orifice may lead to mitral regurgitation (MR) grading inconsistencies. Using 3D transesophageal echocardiography, we characterized spatiotemporal vena contracta complexity and its impact on MR severity grading. METHODS: In 192 patients with suspected moderate or severe MR (100 primary MR [PMR]; 92 secondary MR [SMR]), we performed three-dimensional vena contracta area (VCA) quantification using single-frame (midsystolic or VCAmid, maximum or VCAmax) and multiframe (VCAmean) methods, as well as measures of orifice shape (shape index) and systolic variation of VCA. Vena contracta complexity and intermethod discrepancies were analyzed and correlated with functional class and pulmonary vein flow (PVF) patterns and with cardiac magnetic resonance (CMR) in a subset of cases (n = 20). RESULTS: The vena contracta was noncircular (shape index > 1.5) in 90% of patients. Severe noncircularity (shape index > 3) was more prevalent in SMR than in PMR (32.4% vs 14.6%). Variations of the VCA were more prominent in SMR than in PMR. VCAmid showed a low grading agreement with VCAmax (62%) and high grading agreement with VCAmean (83.3%). Pulmonary vein flow systolic reversal was associated with MR severity by VCA in SMR but not in PMR. VCAmid and VCAmean showed a stronger association with systolic flow reversal than VCAmax (area under the curve, 0.88, 0.86, and 0.79, respectively). In the subset of patients with CMR quantification, severe MR by VCAmax was graded as nonsevere by CMR more frequently compared with VCAmid and VCAmean. CONCLUSIONS: Highly prevalent spatiotemporal vena contracta complexity features in MR challenge the assumption of a circular and constant orifice. VCAmid seems the best single-frame approximation to multiframe quantification, and VCAmax may lead to severity overestimation.

Cardiac Allograft Rejection Induces Changes in Nucleocytoplasmic Transport: RANGAP1 as a Potential Non-Invasive Biomarker.

The non-invasive diagnosis of acute cellular rejection (ACR) is a major challenge. We performed a molecular study analyzing the predictive capacity of serum RanGTPase AP1 (RANGAP1) for diagnosing ACR during the first year after heart transplantation (HT). We included the serum samples of 75 consecutive HT patients, extracted after clinical stability, to determine the RANGAP1 levels through ELISA. In addition, various clinical, analytical, and echocardiographic variables, as well as endomyocardial biopsy results, were collected. RANGAP1 levels were higher in patients who developed ACR (median 63.15 ng/mL; (inter-quartile range (IQR), 36.61-105.69) vs. 35.33 ng/mL (IQR, 19.18-64.59); p = 0.02). Receiver operating characteristic (ROC) curve analysis confirmed that RANGAP1 differentiated between patients with and without ACR (area under curve (AUC), 0.70; p = 0.02), and a RANGAP1 level exceeding the cut-off point (≥90 ng/mL) was identified as a risk factor for the development of ACR (OR, 6.8; p = 0.006). Two independent predictors of ACR identified in this study were higher RANGAP1 and N-terminal pro-brain natriuretic peptide levels. The analysis of the ROC curve of the model showed a significant AUC of 0.77, p = 0.001. Our findings suggest that RANGAP1 quantification facilitates risk prediction for the occurrence of ACR and could be considered as a novel non-invasive biomarker of ACR.

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)

Impact of intravenous ferric carboxymaltose on heart failure with preserved and reduced ejection fraction.

AIMS: Heart failure (HF) is a proinflammatory disease often associated with the onset of iron deficiency (ID). ID alters mitochondrial function, reducing the generation of cellular energy in skeletal muscle and cardiomyocytes. This study aimed to analyse the response of patients with HF to intravenous iron administration according to the type of HF: preserved ejection fraction (HFpEF) or reduced ejection fraction (HFrEF). METHODS AND RESULTS: We conducted a retrospective, single-centre study of 565 consecutive outpatients diagnosed with HF, recruited over 5 years, who were given intravenous ferric carboxymaltose (FCM) for the treatment of ID [defined as ferritin < 100 µg/L or ferritin 100-300 µg/L with transferrin saturation (TSAT) < 20%]. Clinical, laboratory, and echocardiographic parameters were analysed before and after administration. After FCM administration, overall ferritin, TSAT, and haemoglobin levels increased up to 5-fold, 1.6-fold, and 1.1-fold, respectively, relative to baseline values in HF patients with reduced and preserved ejection fraction (P < 0.0001), with a greater increase in ferritin and TSAT in HFpEF patients. The left ventricular ejection fraction of the overall series improved by 8 percentage points in both types of HF (from 40% to 48%, P < 0.0001). The percentage of patients with normalization of right ventricular function increased by 6.9 points (from 74.1% to 81%) in HFpEF patients and by 6.4 points (from 53% to 59.4%) in the HFrEF subgroup (P < 0.0001). New York Heart Association functional status slightly improved, from a median of 2.4 (interquartile range, IQR: 2-2.7) to 1.9 (IQR: 1.5-2.5; P < 0.0001) after FCM in both types of HF. No changes were noted in plasma levels of liver enzymes, creatinine, or natriuretic peptide (P > 0.05). CONCLUSIONS: Intravenous iron administration appeared to improve ejection fraction and cardiac functional status in outpatients with ID and HF with both preserved and reduced ejection fraction.

Plasma Levels of SERCA2a as a Noninvasive Biomarker of Primary Graft Dysfunction After Heart Transplantation.

BACKGROUND: Noninvasive detection of primary graft dysfunction (PGD) remains a major challenge. SERCA2a plays an important role in cardiac homeostasis and its dysregulation has been associated with ventricular dysfunction and rejection. This study aimed to determine the potential utility of plasma levels of SERCA2a as a biomarker of PGD. METHODS: One hundred thirty-five plasma samples were collected from adult recipients 2-6 hours before heart transplantation (HT). Plasma concentrations of SERCA2a were determined using a specific sandwich ELISA. Variables related to the recipient, the donor, and the periprocedural were collected to determine a multivariate predictive model of PGD. RESULTS: Levels of SERCA2a were decreased in patients who developed PGD (median 0.430 ng/mL [interquartile range, 0.260-0.945] versus 0.830 ng/mL [interquartile range, 0.582-1.052]; P = 0.001). Receiver operating characteristic curve analysis revealed that SERCA2a discriminated between patients with and without PGD (AUC = 0.682; P = 0.001), and a cutoff point ≥ 0.60 ng/mL was a protective independent predictor of PGD (odds ratio 0.215 [P = 0.004]). Three independent predictors of PGD in this study were reduced levels of pre-HT SERCA2a, increased bilirubin levels, and short-term mechanical circulatory support bridge to transplantation. The analysis of the receiver operating characteristic curve of the model obtained a significant AUC 0.788, P = 0.0001. CONCLUSIONS: Our findings suggest that assessment of SERCA2a plasma levels may improve risk prediction for the occurrence of PGD and could be considered as a novel noninvasive biomarker in patients undergoing HT.

[Prognostic implications of hypo and hyperkalaemia in acute heart failure with reduced ejection fraction. Analysis of cardiovascular mortality and hospital readmissions]. / 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.

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.

Value of SERCA2a as a Biomarker for the Identification of Patients with Heart Failure Requiring Circulatory Support.

BACKGROUND: Heart failure (HF) alters the nucleo-cytoplasmic transport of cardiomyocytes and reduces SERCA2a levels, essential for intracellular calcium homeostasis. We consider in this study whether the molecules involved in these processes can differentiate those patients with advanced HF and the need for mechanical circulatory support (MCS) as a bridge to recovery or urgent heart transplantation from those who are clinically stable and who are transplanted in an elective code. MATERIAL AND METHOD: Blood samples from 29 patients with advanced HF were analysed by ELISA, and the plasma levels of Importin5, Nucleoporin153 kDa, RanGTPase-Activating Protein 1 and sarcoplasmic reticulum Ca2+ ATPase were compared between patients requiring MCS and those patients without a MCS need prior to heart transplantation. RESULTS: SERCA2a showed significantly lower levels in patients who had MCS compared to those who did not require it (0.501 ± 0.530 ng/mL vs. 1.123 ± 0.661 ng/mL; p = 0.01). A SERCA2a cut-off point of 0.84 ng/mL (AUC 0.812 ± 0.085, 95% CI: 0.646-0.979; p = 0.004) provided a 92% sensitivity, 62% specificity, 91% negative predictive value and 67% positive predictive value. CONCLUSIONS: In this cohort, patients with advanced HF and a need for MCS have shown significantly lower levels of SERCA2a as compared to stable patients without a need for MCS prior to heart transplantation. This is a small study with preliminary findings, and larger-powered dedicated studies are required to confirm and validate these results.

Alterations in the Nucleocytoplasmic Transport in Heart Transplant Rejection.

BACKGROUND: Nucleocytoplasmic transport is a crucial process for cell function. Previous studies have observed alterations in different molecules involved in it, relating them to ventricular function. However, there are no published data evaluating possible differences in the expression of these molecules in heart transplantation (HT) recipients. Our objective is to evaluate whether its levels are related to the appearance of cellular rejection (CR) during the first year after HT. METHODS: A prospective clinical cohort that included patients undergoing HT between January 2017 and January 2019 (n = 46). Blood samples for the analysis of importin 5 (IMP5), nucleoporin 153 (Nup153); RAN-GTPaseAP1 (RanGAP1), and sarcoplasmic reticulum calcium ATPase (ATP-aseCaTransp) were collected approximately 2 months post-HT. The levels obtained were correlated with the incidence of at least moderate CR during the first year of follow-up. RESULTS: Results showed that 17.39% of the patients had at least moderate CR during the first year of follow-up. Higher levels of IMP5, Nup153, and RanGAP1 were observed in this group. This difference was statistically significant in the case of Nup153 and RanGAP1 (15.94 ± 14.00 vs 28.62 ± 23.61, P = .048; 21.95 ± 15.97 vs 40.90 ± 27.16, P = .026, respectively); there was an opposite trend in the ATP-aseCaTransp case. CONCLUSION: Patients with at least a moderate degree of CR during follow-up showed higher serum levels of IMP5, Nup153, and RanGAP1. The prognostic usefulness of the determination of these biomarkers and whether their elevation during follow-up would facilitate early, noninvasive identification of patients with CR remains to be clarified.