Empleo de un score semicuantitativo en la valoración de la congestión pulmonar: prevalencia e implicaciones en el manejo diurético tras el alta por insuficiencia cardiaca / Semi-quantitative pulmonary congestion score: prevalence and diuretic management implications after heart failure discharge

Introducción La congestión persistente tras el alta por insuficiencia cardiaca (IC) se asocia a mayor riesgo de reingresos, siendo necesaria su valoración de forma precisa. Material y métodos Un total de 82 pacientes incluidos tras el alta por IC con el objetivo de caracterizar de forma sencilla y semicuantitativa el grado de congestión pulmonar y sus cambios, describiendo la relación entre dichos hallazgos y el manejo diurético. Resultados En la visita postalta, pese a la ausencia de congestión clínica en la mayoría de pacientes, la mitad presentaba algún grado de congestión pulmonar por ecografía. Tras valoración ecográfica y clínica en esta visita inicial se bajó el diurético en 50 pacientes (60%), se mantuvo igual en 16 (20%) y se aumentó en el resto. En los 45 pacientes sin congestión ecográfica, la bajada de diuréticos se intentó en el 80% siendo exitosa esta estrategia en la mayoría de ellos. Conclusiones La ecografía pulmonar, usando métodos de cuantificación sencillos, permite su incorporación real a nuestra práctica clínica ayudándonos en la toma de decisiones. (AU)

Introduction Persistent congestion after heart failure (HF) discharge is associated with a higher risk of readmissions. Material and methods Eighty-two patients included after HF discharge. The aim of the study was to characterize semiquantitatively the degree of pulmonary congestion and its changes, describing the relationship between these findings and diuretic management. Results On the first visit, despite the absence of clinical congestion in the majority of patients, half of the had some degree of pulmonary congestion by ultrasound. After global assessment in this initial visit (clinical and ultrasound) the diuretic was lowered in 50 patients (60%), kept the same in 16 (20%) and it was increased in the rest. In the 45 patients without ultrasound congestion, diuretic reduction was attempted in 80%, being this strategy successful in the majority of them. Conclusions Lung ultrasound, using simple quantification methods, allows its real incorporation into clinical practice, helping us in the decision making process. (AU)

Semi-quantitative pulmonary congestion score: prevalence and diuretic management implications after heart failure discharge.

INTRODUCTION: Persistent congestion after heart failure (HF) discharge is associated with a higher risk of readmissions. MATERIAL AND METHODS: eighty-two patients included after HF discharge. The aim of the study was to characterize semiquantitatively the degree of pulmonary congestion and its changes, describing the relationship between these findings and diuretic management. RESULTS: On the first visit, despite the absence of clinical congestion in the majority of patients, half of the had some degree of pulmonary congestion by ultrasound. After global assessment in this initial visit (clinical and ultrasound) the diuretic was lowered in 50 patients (60%), kept the same in 16 (20%) and it was increased in the rest. In the 45 patients without ultrasound congestion, diuretic reduction was attempted in 80%, being this strategy successful in the majority of them. CONCLUSIONS: Lung ultrasound, using simple quantification methods, allows its real incorporation into clinical practice, helping us in the decision making process.

Early Initiation of Sacubitril/Valsartan in Patients With Acute Heart Failure and Renal Dysfunction: An Analysis of the TRANSITION Study.

BACKGROUND: Treatment of patients with heart failure with reduced ejection fraction (HFrEF) and renal dysfunction (RD) is challenging owing to the risk of further deterioration in renal function, especially after acute decompensated HF (ADHF). METHODS AND RESULTS: We assessed the effect of RD (estimated glomerular filtration rate of ≥30 to <60 mL/min/1.73 m2) on initiation, up-titration, and tolerability of sacubitril/valsartan in hemodynamically stabilized patients with HFrEF admitted for ADHF (RD, n = 476; non-RD, n = 483). At week 10, the target dose of sacubitril/valsartan (97/103 mg twice daily) was achieved by 42% patients in RD subgroup vs 54% in non-RD patients (P < .001). Sacubitril/valsartan was associated with greater estimated glomerular filtration rate improvements in RD subgroup than non-RD (change from baseline least squares mean 4.1 mL/min/1.73 m2, 95% confidence interval 2.2-6.1, P < .001). Cardiac biomarkers improved significantly in both subgroups; however, compared with the RD subgroup, the improvement was greater in those without RD (N-terminal pro-brain natriuretic peptide, -28.6% vs -44.8%, high-sensitivity troponin T -20.3% vs -33.9%) (P < .001). Patients in the RD subgroup compared with those without RD experienced higher rates of hyperkalemia (16.3% vs 6.5%, P < .001), investigator-reported cardiac failure (9.7% vs 5.6%, P = .029), and renal impairment (6.4% vs 2.1%, P = .002). CONCLUSIONS: Most patients with HFrEF and concomitant RD hospitalized for ADHF tolerated early initiation of sacubitril/valsartan and showed significant improvements in estimated glomerular filtration rate and cardiac biomarkers. CLINICAL TRIAL REGISTRATION: NCT02661217.

Colchicine anti-inflammatory therapy for non-intensive care unit hospitalized COVID-19 patients: results from a pilot open-label, randomized controlled clinical trial.

Systemic inflammation is a hallmark of severe coronavirus disease-19 (COVID-19). Anti-inflammatory therapy is considered crucial to modulate the hyperinflammatory response (cytokine storm) in hospitalized COVID-19 patients. There is currently no specific, conclusively proven, cost-efficient, and worldwide available anti-inflammatory therapy available to treat COVID-19 patients with cytokine storm. The present study aimed to investigate the treatment benefit of oral colchicine for hospitalized COVID-19 patients with suspected cytokine storm. Colchicine is an approved drug and possesses multiple anti-inflammatory mechanisms. This was a pilot, open-label randomized controlled clinical trial comparing standard of care (SOC) plus oral colchicine (colchicine arm) vs. SOC alone (control arm) in non-ICU hospitalized COVID-19 patients with suspected cytokine storm. Colchicine treatment was initiated within first 48 hours of admission delivered at 1.5 mg loading dose, followed by 0.5 mg b.i.d. for next 6 days and 0.5 mg q.d. for the second week. A total of 96 patients were randomly allocated to the colchicine (n=48) and control groups (n=48). Both colchicine and control group patients experienced similar clinical outcomes by day 14 of hospitalization. Treatment outcome by day 14 in colchicine vs control arm: recovered and discharged alive: 36 (75.0%) vs. 37 (77.1%), remain admitted after 14-days: 4 (8.3%) vs. 5 (10.4%), ICU transferred: 4 (8.3%) vs. 3 (6.3%), and mortality: 4 (8.3%) vs. 3 (6.3%). The speed of improvement of COVID-19 acute symptoms including shortness of breath, fever, cough, the need of supplementary oxygen, and oxygen saturation level, was almost identical in the two groups. Length of hospitalization was on average 1.5 day shorter in the colchicine group. There was no evidence for a difference between the two groups in the follow-up serum levels of inflammatory biomarkers including C-reactive protein (CRP), D-dimer, lactate dehydrogenase (LDH), ferritin, interleukin-6 (IL-6), high-sensitivity troponin T (hs-TnT) and N-terminal pro b-type natriuretic peptide (NT pro-BNP). According to the results of our study, oral colchicine does not appear to show clinical benefits in non-ICU hospitalized COVID-19 patients with suspected cytokine storm. It is possible that the anti-inflammatory pathways of colchicine are not crucially involved in the pathogenesis of COVID-19.

Evolución de los pacientes con insuficiencia cardiaca aguda secundaria a infarto agudo de miocardio tratados con ventilación mecánica no invasiva / Outcome of patients with acute heart failure secondary to acute myocardial infarction treated with noninvasive mechanical ventilation

Introducción y objetivos: La ventilación no invasiva (VNI) es capaz de reducir la necesidad de intubación endotraqueal y la mortalidad de los pacientes con insuficiencia cardiaca aguda (ICA). Sin embargo, de muchos de los ensayos clínicos se ha excluido a los pacientes con ICA secundaria a síndrome coronario agudo o infarto agudo de miocardio (SCA-IAM). El objetivo de este estudio es comparar la efectividad de la VNI entre pacientes con ICA desencadenada por SCA-IAM y por otras causas. Métodos: Estudio prospectivo de cohortes, durante un periodo de 20 años, de todos los pacientes con ICA tratados con VNI ingresados en una unidad de cuidados intensivos. Se agrupó a los pacientes por la presencia o ausencia de SCA-IAM como causante del evento de ICA. Se definió el fracaso de la VNI por la necesidad de intubación endotraqueal o muerte. Resultados: Se analizó a 1.009 pacientes, 403 (40%) con SCA-IAM y 606 (60%) con otras etiologías. La VNI fracasó en 61 casos (15,1%) del grupo de SCA-IAM y 64 (10,6%) del grupo sin SCA-IAM (p=0,031), sin diferencias en la mortalidad hospitalaria (el 16,6 y el 14,9%; p=0,478). Conclusiones: El SCA-IAM como causa desencadenante de la ICA no influye en el pronóstico de los pacientes con insuficiencia respiratoria aguda que precisan asistencia respiratoria no invasiva (AU)

Introduction and objectives: Noninvasive ventilation (NIV) has been shown to reduce the rate of endotracheal intubation and mortality in patients with acute heart failure (AHF). However, patients with AHF secondary to acute coronary syndrome/acute myocardial infarction (ACS-AMI) have been excluded from many clinical trials. The purpose of this study was to compare the effectiveness of NIV between patients with AHF triggered by ACS-AMI and by other etiologies. Methods: Prospective cohort study of all patients with AHF treated with NIV admitted to the intensive care unit for a period of 20 years. Patients were divided according to whether they had ACS-AMI as the cause of the AHF episode. NIV failure was defined as the need for endotracheal intubation or death. Results: A total of 1009 patients were analyzed, 403 (40%) showed ACS-AMI and 606 (60%) other etiologies. NIV failure occurred in 61 (15.1%) in the ACS-AMI group and in 64 (10.6%) in the other group (P=.031), without differences in in-hospital mortality (16.6% and 14.9%, respectively; P=.478). Conclusions: The presence of ACS-AMI as the triggering cause of AHF did not influence patients with acute respiratory failure requiring noninvasive respiratory support (AU)

Tocilizumab therapy for severely-ill COVID-19 pneumonia patients: a single-centre retrospective study.

Systemic hyperinflammation is a hallmark of severe coronavirus disease-2019 (COVID-19). Tocilizumab (TCZ) (an interleukin-6 receptor blocker) therapy is currently used as an anti-inflammatory intervention alongside corticosteroids to modulate the hyperinflammatory response (cytokine storm) in hospitalized patients with severe COVID-19 to prevent mortality. There is, however, a wide uncertainty about its pros and cons in patients with COVID-19, particularly, its possible immunosuppressive effect is of serious concern for the clinicians. The present study aimed to report response of a cohort of severely-ill hospitalized COVID-19 pneumonia patients who were treated with tocilizumab after the initial corticosteroids therapy failed to improve the patients' clinical condition. This was a single-arm retrospective study of 100 severely-ill COVID-19 pneumonia patients who were admitted to the specialized COVID-19 units of Mayo Hospital, Lahore, Pakistan from March 12, 2020, to May 25, 2021. These COVID-19 patients had progressed to cytokine storm with persistent hypoxia, associated with pneumonia, and markedly elevated serum levels of inflammatory biomarkers including C-reactive protein (CRP), D-dimer, and ferritin. All the patients had received two separate doses of intravenous 400 mg (4 mg/kg) tocilizumab with an 8-hour interval alongside standard COVID-19 care which includes corticosteroid, antibiotics, and anticoagulants. Following tocilizumab intervention, 75 (75.0%) patients showed clinical improvement, continued to recover, and were safely discharged from the hospital, while in 25 (25.0%) patients, TCZ failed to prevent clinical deterioration, and patients eventually died in the hospital. Amongst the 25 (25.0%) deaths, 8 (32.0%) patients had a single comorbidity, while 9 (36.0%) had two or more comorbidities. The median IQR age for survivors was 57.0 (50.0, 60.0) years, and non-survivors was 60.0 (55.0, 70.0) years; and the period of hospitalization was 25 (20, 40) days and 20 (14, 34) days, respectively. Tocilizumab treatment improved serum inflammatory biomarker levels including CRP, D-dimer, and ferritin, by almost a similar magnitude in both survivors and non-survivors. Development of secondary infections were reported in 25 (25.0%) patients, including 21% patients with bacterial (Pseudomonas, Klebsiella, Acinetobacter) and 4% with fungal (Aspergillus) infection. The emergence of secondary infection was higher in patients who died (72.0%) as compared to those who survived (28.0%). In conclusion: in low- and middle-income countries in the presence of limited therapeutic options, a timely intervention of TCZ alongside corticosteroids may be a suitable anti-inflammatory therapy for severely-ill hospitalized COVID-19 pneumonia patients to prevent mortality. However, patients must be closely monitored for secondary bacterial/fungal infections. Early diagnosis and management of secondary infection can reduce morbidity and mortality.

Management of patients with heart failure treated in cardiology consultations: IC-BERG Study. / Manejo de los pacientes con insuficiencia cardiaca atendidos en la consulta de cardiología: Estudio IC-BERG.

OBJECTIVE: To determine the perception and management of heart failure with reduced ejection fraction (HFrEF) by clinical cardiologists and to establish a consensus with recommendations. METHODS: We employed the modified Delphi method among a panel of 150 experts who answered a questionnaire that included three blocks: definition and perception of patients with «stable¼ HFrEF (15 statements), management of patients with «stable¼ HFrEF (51 statements) and recommendations for optimising the management and follow-up (9 statements). The level of agreement was assessed with a Likert 9-point scale. RESULTS: A consensus of agreement was reached on 49 statements, a consensus of disagreement was reached on 16, and 10 statements remained undetermined. There was consensus regarding the definition of «stable¼ HF (82%), that HFrEF had a silent nature that could increase the mortality risk for mildly symptomatic patients (96%) and that the drug treatment should be optimised, regardless of whether a patient with HFrEF remains stable in the same functional class (98.7%). In contrast, there was a consensus of disagreement regarding the notion that treatment with an angiotensin receptor-neprilysin inhibitor is justified only when the functional class worsens (90.7%). CONCLUSIONS: Our current understanding of «stable¼ HF is insufficient, and the treatment needs to be optimised, even for apparently stable patients, to decrease the risk of disease progression.

Differences in the Interleukin-1ß/Soluble ST2 Interplay Between Acute and Chronic Heart Failure.

Recently, novel findings about the interleukin 1ß (IL-1 ß) axis in acute decompensated heart failure (ADHF) have been published. There is a positive correlation between IL-1 ß and interleukin-1 receptor like 1 (sST2) in ADHF patients. Is there also a correlation between the values of IL-1 ß and sST2 in chronic heart failure patients?

Yin-Yang 1 transcription factor modulates ST2 expression during adverse cardiac remodeling post-myocardial infarction.

BACKGROUND: The cardioprotective effects of metformin remain poorly defined. Interleukin (IL)-33/ST2L signaling is a novel cardioprotective pathway, which is antagonized by the soluble isoform sST2. No data exist about the regulation of ST2 expression. This study aimed to evaluate the pathophysiological implication of Yin-Yang 1 (Yy1) transcription factor in cardiac remodeling and the expression of the soluble ST2 isoform. METHODS AND RESULTS: Myocardial infarction (MI) was induced in Wistar rats randomly receiving metformin or saline solution by permanent ligation of the left anterior coronary artery. In addition, a model of cardiomyocyte "biochemical strain" was used. Metformin administration improved post-MI cardiac remodeling, an effect that was associated with increased IL-33 and reduced sST2 levels in the myocardium. The anti-remodeling effects of metformin were also associated with a decrease in the transcription factor Yy1 intranuclear level and lower levels of phosphorylated HDAC4 within the cytoplasmic space. These effects were also observed in a cardiomyocyte biochemical strain model, where Yy1 silencing or HDAC4 inhibition blocked sST2 production in cardiomyocytes. Metformin blocked the HDAC4 phosphorylation induced by MI, preventing its export from the nucleus to the cytosol. The presence of dephosphorylated HDAC4 in the nucleus acted as a co-repressor of Yy1, repressing sST2 expression. CONCLUSION: The transcription factor Yy1 regulates sST2 expression, and repression of Yy1 by metformin results in lower levels of sST2 that are associated with favorable myocardial remodeling. The manipulation of YY1 or its co-repressor HDAC4 emerge as new targets to modulate ST2/IL33 signaling and prevent adverse cardiac remodeling.

Galectina-3 as a biomarker of acute kidney injury risk in patients with decompensated heart failure. / Galectina-3 como biomarcador de riesgo de daño renal agudo en pacientes con insuficiencia cardiaca descompensada.

INTRODUCTION: In decompensated heart failure (HF), both acute kidney injury (AKI) and high Galectina-3 (Gal-3) levels have been associated with poorer outcomes. Plasma Gal-3 levels are affected by renal function; however, the potential role of Gal-3 as a predictor of AKI has not been established. METHODS: We measured Gal-3 concentrations at admission for 175 patients hospitalised for HF and recorded the onset of AKI according to the Risk, Injury, Failure, Loss and End-stage kidney disease (RIFLE) analytical criteria. RESULTS: During hospitalisation, 44 patients (25.1%) developed AKI, although only 14 (8%) corresponded to more advanced stages. These 14 patients had significantly higher Gal-3 levels at admission, which remained a predictor of AKI after the multivariate adjustment by other predictors and by baseline renal function. CONCLUSIONS: High Gal-3 levels at admission are associated with a higher risk of AKI during hospitalisation for decompensated HF.

Consensus document and recommendations on the use of natriuretic peptides in clinical practice. / Documento de consenso y recomendaciones sobre el uso de los péptidos natriuréticos en la práctica clínica.

Natriuretic peptides are a useful laboratory tool for the diagnosis, prognosis and treatment of patients with heart failure. Natriuretic peptides are used in various healthcare settings (consultations, emergency department, hospitalization, laboratory) and by various primary care and specialised professionals. However, their use in clinical practice is still scare and uneven. Properly using and interpreting natriuretic peptides in clinical practice requires a minimum of prelaboratory (pathophysiology), laboratory (methods) and postlaboratory (interpretation and integration of clinical data) expertise. The objective of this consensus document, developed by several scientific societies, is to update the necessary concepts and expertise on natriuretic peptides that enable its application in the diagnosis, prognosis and treatment of heart failure, in various healthcare environments.

Reformulated meat products protect against ischemia-induced cardiac damage.

The protective effects of the antioxidants present in food are of great relevance for cardiovascular health. This study evaluates whether the extracts from reformulated meat products with a reduction in fat and/or sodium content exert a cardioprotective effect against ischemia-induced oxidative stress in cardiomyocytes, compared with non-meat foods. Ischemic damage caused loss of cell viability, increased reactive oxygen species and lipid peroxidation and decreased the antioxidant activity. Pretreatment for 24 h with digested or non-digested extracts from reformulated meat products led to protection against ischemia-induced oxidative damage: increased cell viability, reduced oxidative stress and restored the antioxidant activity. Similar results were obtained using extracts from tuna fish, but not with the extracts of green peas, salad or white beans. These results suggest that reformulated meat products have a beneficial impact in protecting cardiac cells against ischemia, and they may represent a source of natural antioxidants with benefits for cardiovascular health.

Absence of cystatin C involvement in ventricular remodelling and heart failure.

UNLABELLED: Cystatin C (CysC) is a protease encoded by housekeeping genes. Although its prognostic value in heart failure (HF) is well known, it is debatable whether this value is due to the greater accuracy of CysC in calculating the glomerular filtration rate or to its involvement in pathological ventricular remodelling. The aim of this study was to determine whether CysC expression changes in the myocardium of foetuses of different ages and in the myocardium of adults with various cardiovascular diseases, as well as to analyse the correlation between its serum concentrations and cardiac structure and morphology in a patient group with HF. PATIENTS AND METHODS: We analysed the correlations (Pearson's r and Spearman's test) between the serum CysC levels and echocardiographic parameters of 351 patients with HF. We also performed immunohistochemical staining for CysC, metalloproteinase-9 (MMP-9) and desmin in 9 cardiac tissue samples from autopsies of 4 foetuses of different gestational ages and 5 healthy adults or adults with cardiovascular disease. RESULTS: For the patients with HF, there was no correlation between the CysC concentrations and the cardiac parameters measured by 2D echocardiography. The immunohistochemistry showed a weak background staining for CysC in all samples, regardless of age and the presence or absence of cardiovascular diseases. CONCLUSIONS: Our results suggest that CysC does not have a significant role in the pathological remodelling of the left ventricle in HF.

The falling incidence of hematologic cancer after heart transplantation.

BACKGROUND: A number of changes in the management of heart transplantation (HT) patients have each tended to reduce the risk of post-HT hematologic cancer, but little information is available concerning the overall effect on incidence in the HT population. METHODS: Comparison of data from the Spanish Post-Heart-Transplantation Tumour Registry for the periods 1991-2000 and 2001-2010. RESULTS: The incidence among patients who underwent HT in the latter period was about half that observed in the former, with a particularly marked improvement in regard to incidence more than five yr post-HT. CONCLUSIONS: Changes in HT patient management have jointly reduced the risk of hematologic cancer in the Spanish HT population. Long-term risk appears to have benefited more than short-term risk.

Post-transplant increase in soluble human leukocyte antigen-G associated with non-severe cardiac allograft vasculopathy.

Cardiac allograft vasculopathy (CAV) is the single most important long-term limitation to heart transplantation. This study aimed to assess the value of monitoring soluble human leukocyte antigen-G (sHLA-G) during the first year post-transplantation to predict the severity of CAV, in 21 out of 77 heart recipients assessed by intravascular ultrasound (IVUS). Serum sHLA-G concentration increased after transplant in recipients free of severe CAV, but decreased in recipients suffering from severe CAV, significant differences between these two groups were found 6 to 12 months post-transplantation. The optimal value of the change in post-transplant sHLA-G for identifying severe CAV was ≥0.062%, which maximized sensitivity (80%) and specificity (100%). Importantly, increases in post-transplant sHLA-G were inversely associated with severe CAV, but directly associated with human cytomegalovirus reactivation. In addition, recipients presenting non-severe CAV or an increased sHLA-G post-transplantation, showed higher numbers of CD8(+)CD28(-) T cells and a down-modulation of CD28 on CD4(+) lymphocytes, which typically identifies CD8(+) regulatory T cells and anergic/tolerogenic T helper cells, respectively. In conclusion, quantification of sHLA-G might offer a complementary non-invasive method for identifying recipients at risk of more severe CAV and who might benefit from earlier preventive therapies, although these results need to be confirmed in larger series.

Serial monitoring of soluble interleukin family member ST2 in patients with acutely decompensated heart failure.

OBJECTIVES: To determine whether serial measures of the interleukin receptor family member soluble ST2 (sST2) provide additional prognostic information to baseline measures for long-term risk stratification of acutely decompensated heart failure (ADHF) patients. METHODS: We prospectively enrolled 72 ADHF patients. Blood samples were collected to measure sST2 concentrations at presentation and on day 4 of hospitalization. All patients were clinically followed, and vital status was registered. RESULTS: Between presentation and day 4, sST2 concentrations decreased from 62 ng/ml (interquartile range 38-105) to 44 ng/ml (interquartile range 26-72; p < 0.001). Both sST2 concentrations at presentation [hazard ratio (HR) 1.011, 95% confidence interval (CI) 1.005-1.016; p < 0.001] and on day 4 (HR 1.015, 95% CI 1.005-1.024; p = 0.003) were independent predictors of mortality. Patients with sST2 ≤ 76 ng/ml at presentation and ≤ 46 ng/ml on day 4 had the lowest mortality rates (3%), whereas those with both sST2 values above these cutoff points had the highest mortality (50%). C index and reclassification analyses demonstrated that the use of serial sST2 measures resulted in an improvement in the accuracy of mortality prediction. CONCLUSIONS: Among ADHF patients, sST2 concentrations tend to decrease following initiation of treatment and are prognostic both at presentation and during hospitalization. Serial sampling of sST2 adds prognostic information and may provide a basis for enhanced clinical decision making.