Economic Evaluation of Videoconference Group Acceptance and Commitment Therapy and Behavioral Activation Therapy for Depression Versus Usual Care Among Adults With Chronic Low Back Pain Plus Comorbid Depressive Symptoms.

Chronic pain and depression are frequently comorbid conditions associated with significant health care and social costs. This study examined the cost-utility and cost-effectiveness of videoconference-based group forms of Acceptance and Commitment Therapy (ACT) and Behavioral Activation Therapy for Depression (BATD), as a complement to treatment-as-usual (TAU), for patients with chronic low back pain (CLBP) plus depressive symptoms, compared to TAU alone. A trial-based economic evaluation (n = 234) was conducted from a governmental and health care perspective with a time horizon of 12 months. Primary outcomes were the Brief Pain Inventory-Interference Scale (BPI-IS) and Quality Adjusted Life Year. Compared to TAU, ACT achieved a significant reduction in total costs (d = .47), and BATD achieved significant reductions in indirect (d = .61) and total costs (d = .63). Significant improvements in BPI-IS (d = .73 and d = .66, respectively) and Quality Adjusted Life Year scores (d = .46 and d = .28, respectively) were found in ACT and BATD compared to TAU. No significant differences in costs and outcomes were found between ACT and BATD. In the intention-to-treat analyses, from the governmental and health care perspective, no significant differences in cost reduction and incremental effects were identified in the comparison between ACT, BATD, and TAU. However, in the complete case analysis, significant incremental effects of ACT (∆BPI-IS = -1.57 and -1.39, respectively) and BATD (∆BPI-IS = -1.08 and -1.04, respectively) compared with TAU were observed. In the per-protocol analysis, only the significant incremental effects of ACT (∆BPI-IS = -1.68 and -1.43, respectively) compared to TAU were detected. In conclusion, ACT and BATD might be efficient options in the management of CLBP plus comorbid depression symptoms as compared to usual care. However, no clear difference was found in the comparison between the 2 active therapies regarding cost-effectiveness or cost-utility. PERSPECTIVE: The economic evaluation of psychological therapies for the management of complex conditions can be used in decision-making and resource allocation. This study provides evidence that ACT and BATD are more effective and involve a greater reduction in costs than usual care in the management of CLBP plus comorbid depressive symptoms. TRIAL NUMBER: NCT04140838.

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.

Experiences of patients with chronic low back pain plus comorbid depressive symptoms in a videoconference group acceptance and commitment therapy or behavioral activation treatment for depression: a qualitative study.

PURPOSE: To explore the experiences of patients with chronic low back pain (CLBP) plus comorbid depressive symptoms who received a remote synchronous videoconference group form of Acceptance and Commitment Therapy (ACT) or Behavioral Activation Treatment for Depression (BATD). METHODS: A qualitative study (IMPACT-Q) was nested within a randomized controlled trial (RCT) designed to assess the efficacy and the cost-utility/cost-effectiveness of two therapies in the management of CLBP and depression. Fifty-five patients with CLBP plus depression were selected from the RCT. Twelve focus group sessions, each approximately 60-90 min long, were audio-recorded, transcribed verbatim, and analyzed by six coders through a thematic analysis (deductive and inductive) based on a descriptive phenomenological approach. RESULTS: Patients perceived behavioral, affective, and cognitive improvements after completing group sessions. Overall, psychotherapy was perceived as a safe and non-judgmental place to express emotions and feel understood. The main barriers reported were lack of human contact and loss of social interaction. In contrast, ease of access, flexibility in the ability to connect from anywhere, avoidance of the need to travel, and savings in time and money were key facilitators to increase attendance and adherence to therapy. CONCLUSION: This study provided support for the acceptability of videoconference-delivered ACT or BATD in patients with CLBP plus comorbid depressive symptoms.

Overall, patients reported behavioral, affective, and cognitive improvements after Acceptance and Commitment Therapy and Behavioral Activation Treatment for Depression group sessions.Acceptance and Commitment Therapy and Behavioral Activation Treatment for Depression delivered via videoconference platform were perceived as a facilitator for therapy attendance rather than a barrier.The findings indicate that group therapy on videoconferencing is perceived favorably as an alternative for managing patients with chronic pain and comorbid depression.Technical and social aspects of implementing videoconferencing therapies should be improved, as well as guidelines for adequate support for patients and therapists should also be provided.

Efficacy of Videoconference Group Acceptance and Commitment Therapy (ACT) and Behavioral Activation Therapy for Depression (BATD) for Chronic Low Back Pain (CLBP) Plus Comorbid Depressive Symptoms: A Randomized Controlled Trial (IMPACT Study).

This study examined the efficacy of adding a remote, synchronous, group, videoconference-based form of acceptance and commitment therapy (ACT) or behavioral activation therapy for depression (BATD) to treatment-as-usual (TAU) in 234 patients with chronic low back pain (CLBP) plus comorbid depressive symptoms. Participants were randomly assigned to ACT, BATD, or TAU. Compared to TAU, ACT produced a significant reduction in pain interference at posttreatment (d = .64) and at follow-up (d = .73). BATD was only superior to TAU at follow-up (d = .66). A significant reduction in pain catastrophizing was reported by patients assigned to ACT and BATD at posttreatment (d = .45 and d = .59, respectively) and at follow-up (d = .59, in both) compared to TAU. Stress was significantly reduced at posttreatment by ACT in comparison to TAU (d = .69). No significant between-group differences were found in depressive or anxiety symptoms. Clinically relevant number needed to treat (NNT) values for reduction in pain interference were obtained at posttreatment (ACT vs TAU = 4) and at follow-up (ACT vs TAU = 3; BATD vs TAU = 5). In both active therapies, improvements in pain interference at follow-up were significantly related to improvements at posttreatment in psychological flexibility. These findings suggest that new forms of cognitive-behavioral therapy are clinically useful in improving pain interference and pain catastrophizing. Further research on evidence-based change processes is required to understand the therapeutic needs of patients with chronic pain and comorbid conditions. TRIAL NUMBER: NCT04140838. PERSPECTIVE: Group videoconference-based ACT and BATD showed greater efficacy than TAU for reducing pain interference and pain catastrophizing in patients with CLBP plus clinically relevant depression. Psychological flexibility appeared to be the main contributor to treatment effects for both ACT and BATD.

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.

A systematic review of cognitive behavioral therapy-based interventions for comorbid chronic pain and clinically relevant psychological distress.

Objective: Chronic pain frequently co-occurs with clinically relevant psychological distress. A systematic review was conducted to identify the efficacy of cognitive behavioral therapy-based interventions for patients with these comorbid conditions. Methods: The systematic search was carried out in Medline, PsycINFO, Web of Science, and Scopus up to March 18th, 2023. Four reviewers independently conducted screenings, extraction, and quality assessment. Results: Twelve randomized controlled trials and one non-randomized controlled trial involving 1,661 participants that examined the efficacy of Cognitive Behavioral Therapy (nine studies), Mindfulness-based Interventions (three studies), Acceptance and Commitment Therapy (one study), and Behavioral Activation Therapy for Depression (one study) were included. Compared to treatment as usual, six out of eight studies of traditional Cognitive Behavioral Therapy reported significant differences in the reduction of depressive symptoms at post-treatment (d from 1.31 to 0.18) and four out of six at follow-up (d from 0.75 to 0.26); similarly, five out of six reported significant differences in the reduction of anxiety symptoms at post-treatment (d from 1.08 to 0.19) and three out of four at follow-up (d from 1.07 to 0.27). Overall, no significant differences between traditional Cognitive Behavioral Therapy and treatment as usual were reported at post-treatment and follow-up in the studies exploring pain intensity and pain catastrophizing. Conclusion: The available evidence suggests that traditional Cognitive Behavioral Therapy may produce significant benefits for the improvement of depression, anxiety, and quality of life, but not for pain intensity and pain catastrophizing. More evidence is needed to determine the effects of MBI, ACT, and BATD. Systematic review registration: PROSPERO, CRD42021219921.

How primary and secondary appraisals of daily stressful eventsinfluence negative and positive affect / ¿Cómo la evaluación primaria y secundaria de los eventos estresantes cotidianos influyen en el afecto negativo y positivo?

The aim of this study was to evaluate the influence of primary and secondary appraisal, and of coping strategies, on daily stress, taking in-to account any possible effect of the big five personality traits. Over 10 days, a cohort of 122 people filled out an on-line diary in which they rec-orded the most important stressful event each day, their primary and sec-ondary appraisal of this, and how they coped with it. The results indicate that negative affect is influenced by a high degree of primary appraisal, lim-ited secondary appraisal and a high rate of refusal, with no significant in-fluence of personality traits. Positive affect ismainly influenced by a lower extent of primary appraisal, more secondary appraisal, and by a low rate of refusal and of social support seeking. Moreover, a low level of neuroticism was a predictor of greater positive affect. These data are discussed, high-lighting the importance of a situational assessment of stressful episodes at each moment to not only understand the effects of stress on health but al-so, to develop effective interventions.(AU)

El objetivo de este estudio fue evaluar la influencia de la evaluación primaria, secundaria y de las estrategias de afrontamiento sobre el estrés diario, teniendo en cuenta cualquier posible efecto de los cinco grandes rasgos de personalidad. Durante 10 días, una cohorte de 122 personas llenó un diario en línea en el que registraron el evento estresante más importante de cada día, su evaluación primaria y secundaria y cómo lo afrontaron. Los resultados indican que el afecto negativo está influido por una evaluación primaria alta, una evaluación secundaria limitada y una alta tasa de rechazo, sin influencia significativa de los rasgos de personalidad. El afecto positivo está influido principalmente por un menor grado de valoración primaria, una evaluación secundaria alta, por una baja tasa de rechazo y de búsqueda de apoyo social. Además, un nivel bajo de neuroticismo fue el mejor predictor del afecto positivo. Se discuten estos datos, destacando la importancia de una evaluación situacional de episodios estresantes en cada momento para no sólo comprender los efectos del estrés en la salud sino también, para desarrollar intervenciones efectivas.(AU)

Immune-inflammatory and hypothalamic-pituitary-adrenal axis biomarkers are altered in patients with non-specific low back pain: A systematic review.

This systematic review aimed to investigate immune-inflammatory and hypothalamic-pituitary-adrenal (HPA) axis biomarkers in individuals with non-specific low back pain (NSLBP) compared to healthy control. The search was performed in five databases until 4 November 2021. Two reviewers independently conducted screenings, data extraction, risk of bias, and methodological quality assessment of 14 unique studies. All studies reported the source of the fluid analyzed: nine studies used serum, two used plasma, one used serum and plasma, and two studies used salivary cortisol. We found preliminary and limited evidence (only one study for each biomarker) of increased levels in growth differentiation factor 15 (GDF-15), interleukin-23 (IL-23), transforming growth factor-beta (TGF-ß), and soluble tumor necrosis factor receptor 1 (sTNF-R1) in NSLBP. Inconsistent and limited evidence was identified for interleukin-10 (IL-10). Although C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) levels appear to increase in NSLBP, only one study per each biomarker reported statistically significant differences. Interleukin-1 beta (IL-1ß), interleukin-17 (IL-17), interferon gamma (IFN-γ), and high-sensitivity CRP (hsCRP) showed no significant differences. Regarding cortisol, one study showed a significant increase and another a significant decrease. More robust evidence between GDF-15, IL-23, TGF-ß, and sTNF-R1 with NSLBP is needed. Moreover, contrary to the findings reported in previous studies, when comparing results exclusively with healthy control, insufficient robust evidence for IL-6, TNF-α, and CRP was found in NSLBP. In addition, cortisol response (HPA-related biomarker) showed a dysregulated functioning in NSLBP, with incongruent evidence regarding its directionality. Therefore, our effort is to find adjusted evidence to conclude which immune-inflammatory and HPA axis biomarkers are altered in NSLBP and how much their levels are affected. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020176153, identifier CRD42020176153.

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.

COVID-19 and Heart Transplantation. Initial Experience in a Tertiary Hospital.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a viral infectious disease caused by the severe acute respiratory syndrome coronavirus 2 virus that is affecting the entire world population. The objective of this study was to analyze the repercussion of the disease in a group of patients at risk such as heart transplant recipients. METHODS: From February 2020 to February 2021, heart transplant recipients diagnosed with COVID-19 were consecutively included. The total number of transplant recipients in outpatient follow-up at that time was 381. Three levels of infection were determined: group A: asymptomatic patients or with trivial symptoms without the need for hospital admission (6 patients); group B: patients admitted to the hospital for respiratory symptoms (12 patients); and group C: patients with severe symptoms and need for admission to the critical care unit (2 patients). At each risk level, medical performance was different: group A: close control, no therapeutic modification; group B: reduction of calcineurin inhibitor and substitution of mycophenolate mofetil for everolimus; group C: reduction of calcineurin inhibitor and withdrawal of mycophenolate mofetil. RESULTS: The prevalence of infection in the series was 5.2%. Most patients admitted had a pathologic chest x-ray with fever, cough, dyspnea, or vomiting. The change in immunosuppression performed in patients in group 2 was well tolerated and there was no graft rejection. Antiviral treatment was little used. However, boluses of steroids and some antibiotics were used frequently. The need for supplemental oxygen was 50% in group 2 and 100% in group 3. CONCLUSIONS: A significant number of transplant recipients will be affected by COVID-19 (5.3%). Management of the infection will depend on the severity of the infection and must be based on a balance between reduction and adjustment of immunosuppression, strict control of the cardiologic situation, and treatment of the infection.

Usefulness of Immunoglobulin A in Patients With Decompensated Heart Failure: Is It a Future Marker of Congestion? Preliminary Experience.

BACKGROUND: The purpose of this study was to analyze whether the level of IgA is related to right ventricular function and systemic congestion in patients with decompensated heart failure (HF) and reduced ejection fraction (EF). METHODS: This was a consecutive prospective and observational study of hospitalized patients diagnosed with decompensated HF with reduced EF. The recruitment period lasted 2 months. In the first 24 hours after admission, clinical assessment, general laboratory tests, determination of HF biomarkers, IgA and echocardiographic study were performed. Patients were classified into 2 groups according to whether the plasma IgA level was lower (n = 11) or higher than 300 mg/dL (n = 12). RESULTS: Significant differences in IgA levels were found in the peripheral congestion variables (no congestion: 232, interquartile range [IQR], 125-310 mg/dL vs congestion: 429, IQR, 308-520 mg/dL; P = .03). There were also differences in echocardiographic parameters of right ventricular function, with a greater deterioration of right ventricular function in the group with higher IgA levels (P < .05). There was a highly significant correlation between tricuspid annulus systolic excursion values and IgA levels (P = .004). CONCLUSIONS: In decompensated HF, patients with greater clinical congestion and echocardiographic parameters of right ventricular dysfunction have higher plasma IgA levels. This study is a preliminary experience that will help to establish the basis of the cardiointestinal syndrome as a clinical picture of systemic congestion in HF.