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Aims: Combination of hypertonic saline solution (HSS) with intravenous loop diuretics has been suggested to improve diuretic response in patients hospitalized for heart failure (HF). The efficacy and safety of this approach in the ambulatory setting remain unexplored., Methods and Results: In this multicentre, double-blind, randomized study, we allocated ambulatory patients with worsening heart failure (WHF) to a 1-h infusion of intravenous furosemide ( iv Furosemide)-HSS versus iv Furosemide. The primary endpoint was the volume of diuresis at 3 h. Secondary endpoints included 3-h natriuresis and weight variation, 7-day congestion data, kidney function and electrolytes, and 30-day clinical events. Overall, 167 participants (median age: 81 years, 30.5% female) were randomized across 13 sites between December 2020 and March 2023. There were no differences in 3-h diuresis between treatments ( iv Furosemide-HSS: 1099 ml vs. iv Furosemide: 1103 ml, p = 0.963), 3-h natriuresis (∆ +2.642 mEq/L, p = 0.559), or 3-h weight (∆ +0.012 kg, p = 0.920). Patients in the iv Furosemide-HSS arm experienced significant weight decrease at 7 days (Δ -0.586 kg, p = 0.048). There were no between-treatment differences in clinical congestion score, biomarkers, inferior vena cava diameter, or the presence of lung ultrasound B-lines. At 30 days, 26.5% of the patients in the iv Furosemide-HSS group versus 33.3% in the iv Furosemide group experienced WHF (hazard ratio 0.76, p = 0.330). The incidence of death from any cause or HF hospitalization was 6% of patients in the iv Furosemide-HSS group and 8.3% of patients in the iv Furosemide group (hazard ratio 0.69, p = 0.521). The incidence of worsening kidney function or metabolic derangements was not significantly different in the two arms., Conclusions: A single infusion of iv Furosemide-HSS did not improve 3-h diuresis or congestion parameters in patients with ambulatory WHF. This therapy showed an appropriate safety profile., (© 2024 European Society of Cardiology.)

Background: The addition of hydrochlorothiazide (HCTZ) to furosemide in the CLOROTIC (Combining Loop with Thiazide Diuretics for Decompensated Heart Failure) trial improved the diuretic response in patients with acute heart failure (AHF)., Objectives: This work aimed to evaluate if these results differ across the spectrum of left ventricular ejection fraction (LVEF)., Methods: This post hoc analysis of the randomized, double-blind, placebo-controlled CLOROTIC trial enrolled 230 patients with AHF to receive either HCTZ or a placebo in addition to an intravenous furosemide regimen. The influence of LVEF on primary and secondary outcomes was evaluated., Results: The median LVEF was 55%: 166 (72%) patients had LVEF >40%, and 64 (28%) had LVEF ≤40%. Patients with a lower LVEF were younger, more likely to be male, had a higher prevalence of ischemic heart disease, and had higher natriuretic peptide levels. The addition of HCTZ to furosemide was associated with the greatest weight loss at 72 of 96 hours, better metrics of diuretic response, and greater 24-hour diuresis compared with placebo, with no significant differences according to the LVEF category (using 2 LVEF cutoff points: 40% and 50%) or LVEF as a continuous variable (all P values were insignificant). There were no significant differences observed with the addition of HCTZ in terms of mortality, rehospitalizations, or safety endpoints (impaired renal function, hyponatremia, and hypokalemia) among the 2 LVEF groups (all P values were insignificant)., Conclusions: Adding HCTZ to intravenous furosemide seems to be effective strategy for improving diuretic response in AHF without treatment effect modification according to baseline LVEF. (Combining Loop with Thiazide Diuretics for Decompensated Heart Failure [CLOROTIC], NCT01647932; Randomized, double blinded, multicenter study, to asses Safety and Efficacy of the Combination of Loop With Thiazide-type Diuretics vs Loop diuretics with placebo in Patients With Decompensated, EudraCT Number 2013-001852-36)., Competing Interests: Funding Support and Author Disclosures This work was supported by the Heart Failure Working Group of the Spanish Society of Internal Medicine. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Cardiac amyloidosis (CA) is a common pathology in elderly patients that usually presents as heart failure (HF). However, it is not clear whether CA associated with HF has a worse prognosis compared with HF due to other etiologies., Material and Methods: Prospective, observational cohort study that recruited patients ≥65 years of age with HF in 30 Spanish centers. The cohort was divided according to whether the patients had AC or not. Patients were followed for 1 year., Results: A total of 484 patients were included in the analysis. The population was elderly (median 86 years) and 49% were women CA was present in 23.8 % of the included patients. In the CA group, there was a lower prevalence of diabetes mellitus and valvular disease. At one year of follow-up, mortality was significantly more frequent in patients with CA compared to those without (33.0 vs.14.9%, p < 0.001). However, there were no differences between both groups in visits to the emergency room or readmissions. In the multivariate analysis, the variables that were shown to predict all-cause mortality at one year of follow-up were chronic kidney disease (HR 1.75 (1.01-3.05) p 0.045), NT-proBNP levels (HR 2.51 (1.46-4.30) p < 0.001), confusion (HR 2.05 (1.01-4.17), p 0.048), and the presence of CA (HR 1.77 (1.11-2.84), p 0.017)., Conclusion: The presence of CA in elderly patients with HF is related to a worse prognosis at one year of follow-up. Early diagnosis of the pathology and multidisciplinary management can help improve patient outcomes., (Copyright © 2024 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.)

Purpose of Review: Diuretics are the cornerstone therapy for acute heart failure (HF) and congestion. Patients chronically exposed to loop diuretics may develop diuretic resistance as a consequence of nephron remodelling, and the combination of diuretics will be necessary to improve diuretic response and achieve decongestion. This review integrates data from recent research and offers a practical approach to current pharmacologic therapies to manage congestion in HF with a focus on combinational therapy., Recent Findings: Until recently, combined diuretic treatment was based on observational studies and expert opinion. Recent evidence from clinical trials has shown that combined diuretic treatment can be started earlier without escalating the doses of loop diuretics with an adequate safety profile. Diuretic combination is a promising strategy for overcoming diuretic resistance in HF. Further studies aiming to get more insights into the pathophysiology of diuretic resistance and large clinical trials confirming the safety and efficacy over standard diuretics regimens are warranted., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aims: To determine the prevalence and the impact on prognosis of metabolic alkalosis (MA) in patients admitted for acute heart failure (AHF)., Methods and Results: The ALCALOTIC is a multicenter, observational cohort study that prospectively included patients admitted for AHF. Patients were classified into four groups according to their acid-base status on admission: acidosis, MA, respiratory alkalosis, and normal pH (reference group for comparison). Primary endpoint was all-cause in-hospital mortality, and secondary endpoints included 30/90-day all-cause mortality, all-cause readmission, and readmission for HF. Associations between endpoints and acid-base alterations were estimated in a multivariate Cox regression model including sex, age, comorbidities, and Barthel index and expressed as hazard ratio (HR) with 95% confidence interval (95% CI). Six hundred sixty-five patients were included (84 years and 57% women), and 40% had acid-base alterations on admission: 188 (28%) acidosis and 78 (12%) alkalosis. The prevalence (95% CI) of MA was 9% (6.8-11.2%). Patients with MA were more women; had fewer comorbidities, better renal function, and higher left ventricle ejection fraction values; and received more treatment with oral acetazolamide during hospitalization and at discharge. MA was not associated with a higher risk of in-hospital mortality and 30/90-day all-cause mortality or readmissions but was associated with a significant increase in readmissions for HF at 30 and 90 days (adjusted HR [95% CI] 3.294 [1.397-7.767], p = 0.006 and 2.314 [1.075-4.978], p = 0.032)., Conclusion: The prevalence of MA in patients admitted for AHF was 9%, and its presence was associated with more readmissions for HF but not with all-cause mortality., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Most of the signs and symptoms of heart failure can be explained by fluid overload, which is also related to disease progression. Fluid overload is a complex phenomenon that extends beyond increased intravascular pressures and poses challenges for accurate diagnosis and effective treatment. Current recommendations advise a multiparametric approach, including clinical data (symptoms/signs), imaging tests, and biomarkers. This article proposes a practical therapeutic approach to managing hydrosaline overload in heart failure in both inpatient and outpatient settings. This document is an initiative of the Spanish Society of Internal Medicine (SEMI) in collaboration with the Spanish Society of Cardiology (SEC) and the Spanish Society of Nephrology (S.E.N.)., (Copyright © 2024 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Aims: Hypertonic saline solution (HSS) plus intravenous (IV) loop diuretic appears to enhance the diuretic response in patients hospitalized for heart failure (HF). The efficacy and safety of this therapy in the ambulatory setting have not been evaluated. We aimed to describe the design and baseline characteristics of the SALT-HF trial participants., Methods and Results: 'Efficacy of Saline Hypertonic Therapy in Ambulatory Patients with HF' (SALT-HF) trial was a multicenter, double-blinded, and randomized study involving ambulatory patients who experienced worsening heart failure (WHF) without criteria for hospitalization. Enrolled patients had to present at least two signs of volume overload, use ≥ 80 mg of oral furosemide daily, and have elevated natriuretic peptides. Patients were randomized 1:1 to treatment with a 1-h infusion of IV furosemide plus HSS (2.6-3.4% NaCl depending on plasmatic sodium levels) versus a 1-h infusion of IV furosemide at the same dose (125-250 mg, depending on basal loop diuretic dose). Clinical, laboratory, and imaging parameters were collected at baseline and after 7 days, and a telephone visit was planned after 30 days. The primary endpoint was 3-h diuresis after treatment started. Secondary endpoints included (a) 7-day changes in congestion data, (b) 7-day changes in kidney function and electrolytes, (c) 30-day clinical events (need of IV diuretic, HF hospitalization, cardiovascular mortality, all-cause mortality or HF-hospitalization)., Results: A total of 167 participants [median age, 81 years; interquartile range (IQR), 73-87, 30.5% females] were randomized across 13 sites between December 2020 and March 2023. Half of the participants (n = 82) had an ejection fraction >50%. Most patients showed a high burden of comorbidities, with a median Charlson index of 3 (IQR: 2-4). Common co-morbidities included diabetes mellitus (41%, n = 69), atrial fibrillation (80%, n = 134), and chronic kidney disease (64%, n = 107). Patients exhibited a poor functional NYHA class (69% presenting NYHA III) and several signs of congestion. The mean composite congestion score was 4.3 (standard deviation: 1.7). Ninety per cent of the patients (n = 151) presented oedema and jugular engorgement, and 71% (n = 118) showed lung B lines assessed by ultrasound. Median inferior vena cava diameter was 23 mm, (IQR: 21-25), and plasmatic levels of N-terminal-pro-B-type natriuretic peptide (NTproBNP) and antigen carbohydrate 125 (CA125) were increased (median NT-proBNP 4969 pg/mL, IQR: 2508-9328; median CA125 46 U/L, IQR: 20-114)., Conclusions: SALT-HF trial randomized 167 ambulatory patients with WHF and will determine whether an infusion of hypertonic saline therapy plus furosemide increases diuresis and improves decongestion compared to equivalent furosemide administration alone., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: The addition of hydrochlorothiazide (HCTZ) to furosemide improved the diuretic response in patients with acute heart failure (AHF) in the CLOROTIC trial. Our aim was to evaluate if there were differences in clinical characteristics and outcomes according to sex., Methods: This is a post-hoc analysis of the CLOROTIC trial, including 230 patients with AHF randomized to receive HCTZ or placebo in addition to an intravenous furosemide regimen. The primary and secondary outcomes included changes in weight and patient-reported dyspnoea 72 and 96 h after randomization, metrics of diuretic response and mortality/rehospitalizations at 30 and 90 days. The influence of sex on primary, secondary and safety outcomes was evaluated., Results: One hundred and eleven (48%) women were included in the study. Women were older and had higher values of left ventricular ejection fraction. Men had more ischemic cardiomyopathy and chronic obstructive pulmonary disease and higher values of natriuretic peptides. The addition of HCTZ to furosemide was associated to a greatest weight loss at 72/96 h, better metrics of diuretic response and higher 24-h diuresis compared to placebo without significant differences according to sex (all p-values for interaction were not significant). Worsening renal function occurred more frequently in women (OR [95%CI]: 8.68 [3.41-24.63]) than men (OR [95%CI]: 2.5 [0.99-4.87]), p = 0.027. There were no differences in mortality or rehospitalizations at 30/90 days., Conclusion: Adding HCTZ to intravenous furosemide is an effective strategy to improve diuretic response in AHF with no difference according to sex, but worsening renal function was more frequent in women., Clinical Trial Registration: Clinicaltrials.gov: NCT01647932; EudraCT Number: 2013-001852-36., (Copyright © 2024 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.)

Acute heart failure (AHF) is associated with significant morbidity and mortality and it stands as the primary cause of hospitalization for individuals over the age of 65 in Spain. This document outlines the main recommendations as follows: (1) Upon admission, it is crucial to conduct a comprehensive assessment, taking into account the patient's standard treatment and comorbidities, as these factors determine the prognosis of the disease. (2) During the initial hours of hospital care, prioritizing decongestive treatment is essential. It is recommended to adopt an early staged diuretic therapeutic approach based on the patient's response. (3) In order to manage patients in the stable phase, it is advisable to consider initiating and/or adjusting evidence-based drug treatments such as sacubitril/valsartan or angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, beta blockers, aldosterone antagonists, and SGLT2 inhibitors. (4) Upon hospital discharge, utilizing a checklist is recommended to optimize the patient's management and identify the most efficient options for ensuring continuity of care post-discharge., (Copyright © 2023 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.)

Aims: In patients with acute heart failure (AHF), the addition of hydrochlorothiazide (HCTZ) to furosemide improved diuretic response in the CLOROTIC trial. This work aimed to evaluate if these effects differ across the estimated glomerular filtration rate (eGFR) spectrum., Methods and Results: This post-hoc analysis of the CLOROTIC trial analysed 230 patients with AHF and explored the influence of eGFR on primary and secondary endpoints. The median eGFR was 43 ml/min/1.73 m 2 (range 14-109) and 23% had eGFR ≥60 ml/min/1.73 m 2 (group 1), 24% from 45 to 59 ml/min/1.73 m 2 (group 2), and 53% <45 ml/min/1.73 m 2 (group 3). Patients treated with HCTZ had greatest weight loss at 72 h in all three groups, but patients in group 1 had a significantly greater response (-2.1 kg [-3.0 to 0.5]), compared to patients in groups 2 (-1.3 kg [-2.3 to 0.2]) and 3 (-0.1 kg [-1.3 to 0.4]) (p-value for interaction = 0.246). At 96 h, the differences in weight were -1.8 kg (-3.0 to -0.3), -1.4 kg (-2.6 to 0.3), and -0.5 kg (-1.3 to -0.1) in groups 1, 2, and 3, respectively (p-value for interaction = 0.256). There were no significant differences observed with the addition of HCTZ in terms of diuretic response, mortality or rehospitalizations, or safety endpoints (impaired renal function, hyponatraemia, and hypokalaemia) among the three eGFR groups (all p-values for interaction were no significant)., Conclusion: The addition of eGFR-adjusted doses of oral HCTZ to loop diuretics in patients with AHF improved diuretic response across the eGFR spectrum., Clinical Trial Registration: ClinicalTrials.gov: NCT01647932; EudraCT number: 2013-001852-36., (© 2023 European Society of Cardiology.)

Background: Cardiac amyloidosis (CA) could be a common cause of heart failure (HF). The objective of the study was to estimate the prevalence of CA in patients with HF., Methods: Observational, prospective, and multicenter study involving 30 Spanish hospitals. A total of 453 patients ≥ 65 years with HF and an interventricular septum or posterior wall thickness > 12 mm were included. All patients underwent a 99m Tc-DPD/PYP/HMDP scintigraphy and monoclonal bands were studied, following the current criteria for non-invasive diagnosis. In inconclusive cases, biopsies were performed., Results: The vast majority of CA were diagnosed non-invasively. The prevalence was 20.1%. Most of the CA were transthyretin (ATTR-CM, 84.6%), with a minority of cardiac light-chain amyloidosis (AL-CM, 2.2%). The remaining (13.2%) was untyped. The prevalence was significantly higher in men (60.1% vs 39.9%, p = 0.019). Of the patients with CA, 26.5% had a left ventricular ejection fraction less than 50%., Conclusions: CA was the cause of HF in one out of five patients and should be screened in the elderly with HF and myocardial thickening, regardless of sex and LVEF. Few transthyretin-gene-sequencing studies were performed in older patients. In many patients, it was not possible to determine the amyloid subtype.

Aims: To evaluate whether the addition of hydrochlorothiazide (HCTZ) to intravenous furosemide is a safe and effective strategy for improving diuretic response in acute heart failure (AHF)., Methods and Results: A prospective, double-blind, placebo-controlled trial, including patients with AHF randomized to receive HCTZ or placebo in addition to an intravenous furosemide regimen. The coprimary endpoints were changes in body weight and patient-reported dyspnoea 72 h after randomization. Secondary outcomes included metrics of diuretic response and mortality/rehospitalizations at 30 and 90 days. Safety outcomes (changes in renal function and/or electrolytes) were also assessed. Two hundred and thirty patients (48 women, 83 years) were randomized. Patients assigned to HCTZ were more likely to lose weight at 72 h than those assigned to placebo [2.3 vs. 1.5 kg; adjusted estimated difference (notionally 95 confidence interval) 1.14 (1.84 to 0.42); P 0.002], but there were no significant differences in patient-reported dyspnoea (area under the curve for visual analogue scale: 960 vs. 720; P 0.497). These results were similar 96 h after randomization. Patients allocated to HCTZ showed greater 24 h diuresis (1775 vs. 1400 mL; P 0.05) and weight loss for each 40 mg of furosemide (at 72 and at 96 h) (P 0.001). Patients assigned to HCTZ more frequently presented impaired renal function (increase in creatinine 26.5 moL/L or decrease in eGFR 50; 46.5 vs. 17.2; P 0.001), but hypokalaemia and hypokalaemia were similar between groups. There were no differences in mortality or rehospitalizations., Conclusion: The addition of HCTZ to loop diuretic therapy improved diuretic response in patients with AHF., Competing Interests: Conflict of interest: All authors declare no conflict of interest for this contribution., (The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The changes in shield strategies, treatments, emergence variants, and healthcare pathways might shift the profile and outcome of patients hospitalized with COVID-19 in successive waves of the outbreak., Methods: We retrospectively analysed the characteristics and in-hospital outcomes of all patients admitted with COVID-19 in eight university hospitals of Catalonia (North-East Spain) between Feb 28, 2020 and Feb 28, 2021. Using a 7-joinpoint regression analysis, we split admissions into four waves. The main hospital outcomes included 30-day mortality and admission to intensive care unit (ICU)., Findings: The analysis included 17,027 subjects admitted during the first wave (6800; 39.9%), summer wave (1807; 10.6%), second wave (3804; 22.3%), and third wave (4616; 27.1%). The highest 30-day mortality rate was reported during the first wave (17%) and decreased afterwards, remaining stable at 13% in the second and third waves (overall 30% reduction); the lowest mortality was reported during the summer wave (8%, 50% reduction). ICU admission became progressively more frequent during successive waves. In Cox regression analysis, the main factors contributing to differences in 30-day mortality were the epidemic wave, followed by gender, age, diabetes, chronic kidney disease, and neoplasms., Interpretation: Although in-hospital COVID-19 mortality remains high, it decreased substantially after the first wave and is highly dependent of patient's characteristics and ICU availability. Highest mortality reductions occurred during a wave characterized by younger individuals, an increasingly frequent scenario as vaccination campaigns progress., Funding: This work did not receive specific funding., Competing Interests: KK is a member of the UK Scientific Advisory Group for Emergencies. The rest of the authors have no conflicts of interest to declare., (© 2022 Published by Elsevier Inc.)

Background: Heart failure (HF) is a syndrome with high prevalence, mainly affecting elderly patients, where the presence of associated comorbidities is of great importance. Methods: An observational study from a prospective registry was conducted. Patients identified from the National Registry of Heart Failure (RICA), which belongs to the Working Group on Heart Failure and Atrial Fibrillation of the Spanish Society of Internal Medicine (SEMI), were included. The latter is a prospective, multicenter registry that has been active since 2008. It includes individual consecutive patients over 50 years of age with a diagnosis of HF at hospital discharge (acute decompensated or new-onset HF). Results: In total, 5424 patients were identified from the registry. Forty-seven percent were men and mean left ventricular ejection fraction (LVEF) was 51.4%; 1132 had a score of 0 to 2 according to the PROFUND index, 3087 had a score of 3 to 6, and 952 patients had a score of 7 to 10 points. In the sample, 252 patients had a score above 11 points. At the end of the year of follow-up, 61% of the patients died. This mortality increased proportionally as the PROFUND index increased, specifically 75% for patients with PROFUND greater than 11. The Kaplan-Meier survival curve shows that survival at one year progressively decreases as the PROFUND index value increases. Thus, subjects with scores greater than seven (intermediate-high and high-risk) presented the worst survival with a log rank of 0.96 and a p < 0.05. In the regression analysis, we found a higher risk of death from any cause at one year in the group with the highest risk according to the PROFUND index (score greater than 11 points (HR 1.838 (1.410−2.396)). Conclusions: The PROFUND index is a good index for predicting mortality in patients admitted for acute HF, especially in those subjects at intermediate to high risk with scores above seven. Future studies should seek to determine whether the PROFUND index score is simply a prognostic marker or whether it can also be used to make therapeutic decisions for those subjects with very high short-term mortality.

Aims: The aim of the LAICA study was to evaluate the long-term effectiveness and safety of intermittent levosimendan infusion in patients with advanced heart failure (AdHF)., Methods and Results: This was a multicentre, randomized, double-blind, placebo-controlled clinical trial of intermittent levosimendan 0.1 μg/kg/min as a continuous 24-h intravenous infusion administered once monthly for 1 year in patients with AdHF. The primary endpoint [incidence of rehospitalization (admission to the emergency department or hospital ward for >12 h) for acute decompensated HF or clinical deterioration of the underlying HF] occurred in 23/70 (33%) of the levosimendan group (Group I) and 12/27 (44%) of the placebo group (Group II) (P = 0.286). The incidence of hospital readmissions for acute decompensated HF (Group I vs. Group II) at 1, 3, 6, and 12 months was 4.2% vs. 18.2% (P = 0.036); 12.8% vs. 33.3% (P = 0.02); 25.7% vs. 40.7% (P = 0.147); 32.8% vs. 44.4% (P = 0.28), respectively. In a secondary pre-specified time-to-event analysis no differences were observed in admission for acute decompensated HF between patients treated with levosimendan compared with placebo (hazard ratio 0.66; 95% CI, 0.32-1.32; P = 0.24). Cumulative incidence for the aggregated endpoint of acute decompensation of HF and/or death at 1 and 3 months were significatively lower in the levosimendan group than in placebo group [5.7% vs. 25.9% (P = 0.004) and 17.1% vs. 48.1% (P = 0.001), respectively], but not at 6 and 12 months [34.2% vs. 59.2% (P = 0.025); 41.4% vs. 66.6% (P = 0.022), respectively]. Survival probability was significantly higher in patients who received levosimendan compared with those who received placebo (log rank: 4.06; P = 0.044). There were no clinically relevant differences in tolerability between levosimendan and placebo and no new safety signals were observed., Conclusions: In our study, intermittent levosimendan in patients with AdHF produced a statistically non-significant reduction in the incidence of hospital readmissions for acute decompensated HF, a significantly lower cumulative incidence of acute decompensation of HF and/or death at 1 and 3 month of treatment and a significant improvement in survival during 12 months of treatment., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: The use of low dose radiotherapy (LD-RT) for the treatment of COVID-19 pneumonia is supported by biological rationale for its immunomodulatory effect. Some institutions have started to treat these patients showing encouraging results. To shorten procedure times is crucial for the comfort of symptomatic patients receiving respiratory support and to optimize institutional facilities., Patients and Methods: At our institution, LD-RT is offered to hospitalized patients with COVID-19 pneumonia and signs of early cytokine-released syndrome on behalf of a multicenter study. We designed a coordinated process flow starting from the patient transfer to the simulation CT-scan (first-step), to the end of the LD-RT treatment (last step). The times spent on each step of the process flow were evaluated., Results: Mean age of treated patients was 83 (72-91) years-old. The timing parameters of the first 10 consecutive patients were analyzed. Except for the first (dummy run), patients were managed from the first to the last step in a median of 38 min (25-58, SD 10.67). The most time-consuming sub-process was the contouring of the treatment volumes and dosimetry., Conclusions: LD-RT is not only an encouraging option for COVID-19 pneumonia patients, but a convenient and feasible procedure if performed in a coordinated way by reducing procedure times., (© 2021. Federación de Sociedades Españolas de Oncología (FESEO).)

Background: Malnutrition is frequent in patients with heart failure (HF) and contributes to increased systemic congestion, but also hinders its correct assessment, especially during decompensations. Estimating the degree of malnutrition and its relationship with systemic congestion is important to optimize treatment during decompensations., Material and Methods: Retrospective cohort study in patients with acute HF. The population was stratified according to CONUT (Controlling Nutritional Status) and PNI (Prognostic Nutritional Index) nutrition indices in order to analyse their relationship with objective parameters of congestion and the prognostic value of malnutrition., Results: 309 patients were included. More than half presented some degree of malnutrition upon admission. The degree of congestion was significantly higher in malnourished patients, with a higher proportion of «comet tail artifacts» and a higher relative plasma volume. NT-proBNP concentrations, both on admission and at discharge, were also significantly higher in malnourished patients, regardless of the scale used. The univariate analysis identified the CONUT and PNI index as factors associated with one-year mortality from any cause (HR 1.62 [1.22-2.14]; p = 0.001) and PNI (HR 65 [0.53-0.80]; p = < 0.001), respectively., Conclusions: A higher degree of malnutrition (determined by means of the CONUT and PNI indices) in patients with acute HF was associated with a higher presence of objective parameters of congestion and a higher one-year all-cause mortality., (Copyright © 2020 Elsevier España, S.L.U. All rights reserved.)

Acute heart failure (AHF) is a highly prevalent clinical entity in individuals older than 45 years in Spain. AHF is associated with significant morbidity and mortality and is the leading cause of hospitalisation for individuals older than 65 years in Spain, a quarter of whom die within 1 year of the hospitalisation. In recent years, there has been an upwards trend in hospitalisations for AHF, which increased 76.7% from 2003 to 2013. Readmissions at 30 days for AHF have also increased (from 17.6% to 22.1%), at a relative mean rate of 1.36% per year, with the consequent increase in the use of resources and the economic burden for the healthcare system. The aim of this document (developed by the Heart Failure and Atrial Fibrillation Group of the Spanish Society of Internal Medicine) is to guide specialists on the most important aspects of treatment and follow-up for patients with AHF during hospitalisation and the subsequent follow-up. The main recommendations listed in this document are as follows: 1) At admission, perform a comprehensive assessment, considering the patient's standard treatment and comorbidities, given that these determine the disease prognosis to a considerable measure. 2) During the first few hours of hospital care, decongestive treatment is a priority, and a staged diuretic therapeutic approach based on the patient's response is recommended. 3) To manage patients in the stable phase, consider starting and/or adjusting evidence-based drug treatment (e.g., sacubitril/valsartan or angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, beta blockers and aldosterone antagonists). 4) At hospital discharge, use a checklist to optimise the patient's management and identify the most efficient options for maintaining continuity of care after discharge., (Copyright © 2020 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.)

Acute heart failure (AHF) is a highly prevalent clinical entity in individuals older than 45years in Spain. AHF is associated with significant morbidity and mortality and is the leading cause of hospitalisation for individuals older than 65years in Spain, a quarter of whom die within 1year of the hospitalisation. In recent years, there has been an upwards trend in hospitalisations for AHF, which increased 76.7% from 2003 to 2013. Readmissions at 30days for AHF have also increased (from 17.6% to 22.1%), at a relative mean rate of 1.36% per year, with the consequent increase in the use of resources and the economic burden for the healthcare system. The aim of this document (developed by the Heart Failure and Atrial Fibrillation Group of the Spanish Society of Internal Medicine) is to guide specialists on the most important aspects of treatment and follow-up for patients with AHF during hospitalisation and the subsequent follow-up. The main recommendations listed in this document are as follows: (1)At admission, perform a comprehensive assessment, considering the patient's standard treatment and comorbidities, given that these determine the disease prognosis to a considerable measure. (2)During the first few hours of hospital care, decongestive treatment is a priority, and a staged diuretic therapeutic approach based on the patient's response is recommended. (3)To manage patients in the stable phase, consider starting and/or adjusting evidence-based drug treatment (e.g., sacubitril/valsartan or angiotensin-converting enzyme inhibitors/angiotensinII receptor blockers, beta blockers and aldosterone antagonists). (4)At hospital discharge, use a checklist to optimise the patient's management and identify the most efficient options for maintaining continuity of care after discharge., (Copyright © 2020 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.)

Aims: The role of non-invasive telemedicine (TM) combining telemonitoring and teleintervention by videoconference (VC) in patients recently admitted due to heart failure (HF) ('vulnerable phase' HF patients) is not well established. The aim of the Heart failure Events reduction with Remote Monitoring and eHealth Support (HERMeS) trial is to assess the impact on clinical outcomes of implementing a TM service based on mobile health (mHealth), which includes remote daily monitoring of biometric data and symptom reporting (telemonitoring) combined with VC structured, nurse-based follow-up (teleintervention). The results will be compared with those of the comprehensive HF usual care (UC) strategy based on face-to-face on-site visits at the vulnerable post-discharge phase., Methods and Results: We designed a 24 week nationwide, multicentre, randomized, controlled, open-label, blinded endpoint adjudication trial to assess the effect on cardiovascular (CV) mortality and non-fatal HF events of a TM-based comprehensive management programme, based on mHealth, for patients with chronic HF. Approximately 508 patients with a recent hospital admission due to HF decompensation will be randomized (1:1) to either structured follow-up based on face-to-face appointments (UC group) or the delivery of health care using TM. The primary outcome will be a composite of death from CV causes or non-fatal HF events (first and recurrent) at the end of a 6 month follow-up period. Key secondary endpoints will include components of the primary event analysis, recurrent event analysis, and patient-reported outcomes., Conclusions: The HERMeS trial will assess the efficacy of a TM-based follow-up strategy for real-world 'vulnerable phase' HF patients combining telemonitoring and teleintervention., (© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Congestive symptoms are the key to recognising decompensated heart failure, whose treatment is based on reducing the congestion until a clinical situation has been reached that allows the patient to be discharged to continue outpatient treatment. The important aspect is not the degree of congestion at admission but rather the congestion that persists after energetic diuretic therapy. The persistence of congestive signs following an apparently correct and effective therapy has been called residual congestion and is associated with a poor prognosis. The tools for determining this condition are still rudimentary. Methods therefore need to be developed that enable a more accurate assessment., (Copyright © 2019 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.)

Diuretic resistance (DR) is common in patients with decompensated heart failure (HF), and is associated with adverse outcomes. To determine the prevalence of DR and its impact on survival among patients with decompensated HF, we prospectively evaluated the prevalence and influence on prognosis of DR (defined as persistent congestion despite ≥ 80 mg of furosemide per day) in a cohort of elderly patients from the Spanish HF registry (RICA) admitted for an acute decompensation of HF. Patients with new-onset HF were excluded. From the global cohort of 2067 patients, 435 (21%; 95% CI 19.3%-22.7%) patients met criteria for DR. Patients with DR had more comorbidities (hypercholesterolemia, diabetes mellitus, valvular disease, chronic kidney disease, and cancer) and a worse functional status compared to patients without DR. In addition, patients with DR had a higher proportion of ischemic etiology, more advanced functional class and lower left ventricular ejection fraction values. After 1 year of follow-up, all-cause mortality was higher in patients with DR with an adjusted hazard ratio of 1.37 (95% CI 1.06-1.79; p = 0.018). The prevalence of DR in a cohort of elderly patients admitted for acute HF decompensation is 21%. DR is an independent predictor of 1-year mortality.

Background: The incidence of pleural effusions (PEs) in acute decompensated heart failure (ADHF) is not well established. We aimed to determine their prevalence, clinical characteristics and prognostic implications., Methods: Retrospective review of 3245 consecutive patients with ADHF from the Spanish RICA Registry. The clinical characteristics of those with or without PEs on chest radiographs were compared and a predictive PE model was generated., Results: Patient's median age was 80 years and 60% had a left ventricular ejection fraction (LVEF) >50%. PEs were seen in 46% of the cases, and their distribution was as follows: 58% bilateral, 27% right-sided and 14% left-sided. Male gender (OR 2.18; 95%CI 1.23-3.87), serum amino-terminal fraction of the pro-brain natriuretic peptide (NT-pro-BNP) levels >3500 pg/ml (OR 2.2; 95%CI 1.25-3.77), estimated systolic pulmonary artery pressure (sPAP) >55 mm Hg by echocardiography (OR 2.05; 95%CI 1.12-3.75), and serum prealbumin <15 mg/l (OR 1.96; 95%CI 1.08-3.52) were associated with PE development in a multivariate analysis. Serum NT-proBNP >8000 pg/ml, and systolic arterial pressure <110 mm Hg, but not PEs, independently predicted overall 1-year mortality., Conclusions: PEs are present on chest radiographs in nearly half of ADHF patients. They are mainly bilateral or right-sided and predominate in males with elevated sPAP on echocardiography and high serum levels of NT-proBNP. PEs do not independently predict 1-year mortality., (Copyright © 2018 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Hepatocyte growth factor (HGF) plays a role in the improvement of cardiac function and remodeling. Their serum levels are strongly related with mortality in chronic systolic heart failure (HF). The aim of this study was to study prognostic value of HGF in acute HF, interaction with ejection fraction, renal function, and natriuretic peptides. We included 373 patients (age 76 ± 10 years, left ventricular ejection fraction [LVEF] 46 ± 14%, 48% men) consecutively admitted for acute HF. Blood samples were obtained at admission. All patients were followed up until death or close of study (>1 year, median 371 days). HGF concentrations were determined using a commercial enzyme-linked immunosorbent assay (human HGF immunoassay). The predictive power of HGF was estimated by Cox regression with calculation of Harrell C-statistic. HGF had a median of 1,942 pg/ml (interquartile rank 1,354). According to HGF quartiles, mortality rates (per 1,000 patients/year) were 98, 183, 375, and 393, respectively (p <0.001). In Cox regression analysis, HGF (hazard ratio1SD = 1.5, 95% confidence interval 1.1 to 2.1, p = 0.002) and N-terminal pro b-type natriuretic peptide (NT-proBNP; hazard ratio1SD = 1.8, 95% confidence interval 1.2 to 2.6, p = 0.002) were independent predictors of mortality. Interaction between HGF and LVEF, origin, and renal function was nonsignificant. The addition of HGF improved the predictive ability of the models (C-statistic 0.768 vs 0.741, p = 0.016). HGF showed a complementary value over NT-proBNP (p = 0.001): mortality rate was 490 with both above the median versus 72 with both below. In conclusion, in patients with acute HF, serum HGF concentrations are elevated and identify patients at higher risk of mortality, regardless of LVEF, ischemic origin, or renal function. HGF had independent and additive information over NT-proBNP., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Fluid overload refractory to loop diuretic therapy can complicate acute or chronic heart failure (HF) management. The Safety and Efficacy of the Combination of Loop with Thiazide-type Diuretics in Patients with Decompensated Heart Failure (CLOROTIC) trial (Clinicaltrials.gov identifier NCT01647932) will test the hypothesis that blocking distal tubule sodium reabsorption with hydrochlorothiazide can antagonize the renal adaptation to chronic loop diuretic therapy and improve diuretic resistance., Methods: CLOROTIC is a randomized, placebo-controlled, double-blind, multicenter study. Three hundred and four patients with decompensated HF will be randomly assigned to receive hydrochlorothiazide or placebo in addition to a furosemide regimen. The main inclusion criteria are: age ≥18 years, history of chronic HF (irrespective of etiology and/or ejection fraction), admission for acute decompensation, and previous treatment with an oral loop diuretic for at least 1 month before randomization. The 2 coprimary endpoints are changes in body weight and changes in patient-reported dyspnea during hospital admission. Morbidity, mortality, and safety aspects will also be addressed., Conclusions: CLOROTIC is the first large-scale trial to evaluate whether the addition of a thiazide diuretic (hydrochlorothiazide) to a loop diuretic (furosemide) is a safe and effective strategy for improving congestive symptoms resulting from HF. This trial will provide important information and will therefore have a major impact on treatment strategies and future trials in these patients., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Heart failure (HF) patients present frequently comorbidities and the diagnosis of HF in this setting is a challenge. The symptoms and signs of HF may be atypical and can be simulated or disguised by co-morbidities such as respiratory disease and/or obesity. For this reasons, confirmation of the diagnosis always requires further tests. Natriuretic peptides accurately exclude cardiac dysfunction as a cause of symptoms, but the optimal cut-off levels for ruling out and ruling in HF diagnosis are influenced by different co-morbidities. Echocardiography should be performed in all patients to confirm the diagnosis of HF, except in those cases with low clinical probability and a concentration of brain natriuretic peptides below the exclusion cut-off. This review aims to provide a practical clinical approach for the diagnosis of HF in patients with comorbidity, focusing in older patients and patients with chronic obstructive pulmonary disease and/or obesity., (Copyright © 2016. Published by Elsevier España, S.L.U.)

Unlike chronic heart failure (HF), the treatment for acute HF has not changed over the last decade. The drugs employed have shown their ability to control symptoms but have not achieved organ protection or managed to reduce medium to long-term morbidity and mortality. Advances in our understanding of the pathophysiology of acute HF suggest that treatment should be directed not only towards correcting the haemodynamic disorders and achieving symptomatic relief but also towards preventing organ damage, thereby counteracting myocardial remodelling and cardiac and extracardiac disorders. Compounds that exert vasodilatory and anti-inflammatory action in the acute phase of HF and can stop cell death, thereby boosting repair mechanisms, could have an essential role in organ protection., (Copyright © 2016 Elsevier España, S.L.U. y Sociedad Española de Medicina Interna (SEMI). All rights reserved.)

Background: In patients with acute decompensated heart failure (ADHF), both natriuretic peptides and renal impairment predict adverse outcomes. Our aim was to evaluate the complementary prognosis role of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and the newly developed Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations based on cystatin C (CysC) for glomerular filtration rate (GFR) estimation in ADHF patients., Hypothesis: Renal impairment assessed by CysC-based CKD-EPI equations and natriuretic peptides have complementary prognostic value in ADHF patients., Methods: The study included 613 consecutive patients presenting with ADHF. At admission, plasma levels of NT-proBNP and CysC were determined. The GFR was estimated using CysC-based CKD-EPI equations. The primary endpoint was death from any cause and heart failure readmission., Results: During the median follow-up of 365 days (interquartile range, 227-441 days), 323 patients (0.65 %patient-year) died or were readmitted for heart failure. After multivariate adjustment, estimated GFR <60 mL/min/1.73 m(2) and NT-proBNP >3251 pg/mL were independent predictors of adverse outcomes (P < 0.01). The combination of GFR <60 mL/min/1.73 m(2) and NT-proBNP >3251 pg/mL was associated with the highest risk of adverse outcomes. Furthermore, reclassification analyses demonstrated that use of both NT-proBNP and CysC-based CKD-EPI equations resulted in improving the accuracy for adverse outcomes prediction., Conclusions: In patients with ADHF, the combination of NT-proBNP with estimated GFR using CysC-based CKD-EPI equations better predicts outcomes than either parameter alone and adds valuable complementary prognosis information to other established risk factors., (© 2015 Wiley Periodicals, Inc.)

Diuretics are widely recommended in patients with acute heart failure (AHF). Unfortunately, despite their widespread use, limited data are available from randomized clinical trials to guide clinicians on the appropriate management of diuretic therapy. Loop diuretics are considered the first-line diuretic therapy, especially intravenous furosemide, but the best mode of administration (high-dose versus low-dose and continuous infusion versus bolus) is unclear. When diuretic resistance develops, different therapeutic strategies can be adopted, including combined diuretic therapy with thiazide diuretics and/or aldosterone antagonists. Low or "non-diuretic" doses (25-50mg QD) of aldosterone antagonists have been demonstrated to confer a survival benefit in patients with heart failure and reduced ejection fraction and consequently should be prescribed in all such patients, unless contraindicated by potassium and/or renal function values. There is less evidence on the use of aldosterone antagonists at higher or "diuretic" doses (≥ 100mg QD) but these drugs could be useful in relieving congestive symptoms in combination with furosemide. Thiazide diuretics can also be helpful as they have synergic effects with loop diuretics by inhibiting sodium reabsorption in distal parts of the nephron. The effect of diuretic therapy in AHF should be monitored with careful observation of clinical signs and symptoms of congestion. Serum electrolytes and kidney function should also be monitored during the use of intravenous diuretics., (Copyright © 2014 Elsevier España, S.L. All rights reserved.)

Although treatment of acute heart failure is based primarily on the administration of intravenous loop diuretics, evidence supporting this practice is still scarce and there is uncertainty about the optimal dose. The existence of a considerable percentage of patients refractory to diuretic therapy and worsening of renal failure associated with the use of these drugs, with possible implications for medium-term mortality, have prompted the search for more effective and safer alternatives. Extracorporeal purification techniques, such as ultrafiltration, have demonstrated efficacy, although their superiority is unclear, due to the possible adverse effects associated with the procedure. The use of low-dose dopamine is not superior to conventional diuretic therapy after the first few hours of treatment. Moreover, combination with furosemide and hypertonic saline could be a valid alternative for patients with refractory congestion and depressed ejection fraction and serum creatinine ≤ 2.5mg/dL, but further studies are needed before its widespread use. The use of tolvaptan may be an effective alternative in the short-term but its use may be limited by its price. There is still controversy about whether treatment with loop diuretics is associated with higher mortality in all groups of patients with HF exacerbations. These controversies should be clarified by future clinical trials., (Copyright © 2014 Elsevier España, S.L. All rights reserved.)

Many of the primary clinical manifestations of heart failure (HF) are due to fluid retention, and treatments targeting congestion play a central role in HF management. Diuretic therapy remains the cornerstone of congestion treatment, and diuretics are prescribed to the majority of HF patients. Despite this ubiquitous use, there is limited evidence from prospective randomized studies to guide the use of diuretics. With the chronic use of diuretic and usually in advanced stages of HF, diuretics may fail to control salt and water retention. This review describes the mechanism of action of available diuretic classes, reviews their clinical use based on scientific evidence and discusses strategies to overcome diuretic resistance., (Copyright © 2013 Elsevier España, S.L. All rights reserved.)

Aim: Changes in N-terminal pro B-type natriuretic peptide (NT-proBNP) levels and cystatin C (CysC) are predictors of adverse outcomes in acute heart failure. This study assess whether NT-proBNP variations might provide independent information in addition to that obtained from CysC levels., Methods: NT-proBNP levels were assessed in patients admitted due to acute heart failure using an observational study. Patients were classified as follows: group 1, those with a decrease in NT-proBNP levels of at least 30% from admission to 4 weeks after discharge; group 2, those with no significant changes in levels; and group 3, those who showed an increase in NT-proBNP of 30%. A multivariable Cox regression model and c-statistics were used. The primary end-point was all-cause mortality at 1-year follow-up., Results: A total of 195 patients completed the follow-up. The mortality rate reached 20.5% (40 patients); 14 out of the 32 in group 3. The cumulative incidence of death, according to the change in NT-proBNP and Kaplan-Meier analysis, showed a significant increase in group 3 (log-rank P = 0.004). In the multivariable analysis, NT-proBNP variation for group 3 (hazard ratio 4.27; P <0.001) and for group 2 (hazard ratio 2.19; P = 0.043) in comparison with group 1 were independently associated with all-cause mortality, as well as anemia, hyponatremia, and admission CysC levels. Patients in group 3, and those with levels of serum CysC above the median, were also associated with slight increase in mortality., Conclusion: An increase of at least 30% in NT-proBNP levels after hospitalization is related to all-cause mortality in patients with acute heart failure and provides supplementary prognostic information in patients with high levels of CysC. A decrease in NT-proBNP of at least 30% is a desirable target to achieve.

Aims: This study was conducted to determine whether galectin-3 (Gal3), a β-galactoside-binding lectin, has usefulness to predict outcomes in patients with heart failure (HF) and preserved left ventricular ejection fraction (LVEF)., Methods and Results: We measured Gal3, urea, creatinine and natriuretic peptides on admission in 419 selected patients with HF and LVEF over 45%. The primary endpoint was all-cause mortality and/or readmission at one-year follow-up. Multivariable Cox proportional hazards models were generated for Gal3 and classical risk factors. We also evaluated the reclassification of patients on the basis of the different score category after adding Gal3 levels. A total of 219 patients had combined adverse events, and 129 patients died during the follow-up. Kaplan-Meir survival curve showed significantly increased primary endpoint and all-cause mortality according to quartiles of Gal3 (log rank, P<0.001). Serum Gal3 levels above median (13.8 ng/ml) was a significant predictor of primary endpoint risk after adjustment for age, estimated glomerular filtration rate, anemia, diabetes, serum sodium, brain natriuretic peptide levels, NYHA class and urea, respectively (hazard ratio 1.43, 95% CI 1.07-1.91 P=0.015). The reclassification index increased significantly after addition of Gal3 (9.5%, P<0.001) and the integrated discrimination index was 0.022, (P=0.001). The clinical prediction model with Gal3 increased the c-statistic from 0.711 to 0.731 (difference of 0.020, P=0.001)., Conclusions: Serum Gal3 is a strong and independent predictor of unfavorable outcomes in patients with HF and preserved LVEF. We also demonstrated the improvement of adding the new biomarker to the model., (© 2013.)

Background: Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations estimate glomerular filtration rate (eGFR) more accurately than the Modification of Diet in Renal Disease (MDRD) equation. The aim of this study was to evaluate whether CKD-EPI equations based on serum creatinine and/or cystatin C (CysC) predict risk for adverse outcomes more accurately than the MDRD equation in a hospitalized cohort of patients with acute decompensated heart failure (ADHF)., Methods and Results: A total of 526 subjects with ADHF were studied. Blood was collected within 48 hours from admission. eGFR was calculated with the use of MDRD and CKD-EPI equations. The occurrences of mortality and heart failure (HF) hospitalization were recorded. Over the study period (median 365 days [interquartile range 238-370]), 305 patients (58%) died or were rehospitalized for HF. Areas under the receiver operator characteristic curves for CKD-EPI CysC and CKD-EPI creatinine-CysC equations were significantly higher than that for the MDRD equation, especially in patients with >60 mL min(-1) 1.73 m(-2). After multivariate adjustment, all eGFR equations were independent predictors of adverse outcomes (P < .001). However, only CKD-EPI CysC and CKD-EPI creatinine-CysC equations were associated with significant improvement in reclassification analyses (net reclassification improvements 10.8% and 12.5%, respectively)., Conclusions: In patients with ADHF, CysC-based CKD-EPI equations were superior to the MDRD equation for predicting mortality and/or HF hospitalization especially in patients with >60 mL min(-1) 1.73 m(-2), and both CKD-EPI equations improved clinical risk stratification., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background and Objective: The purpose of this study was to compare the diagnostic utility of pleural fluid N-terminal pro-B-type natriuretic peptide (NT-proBNP), midregion pro-atrial natriuretic peptide (MR-proANP) and midregion pro-adrenomedullin (MR-proADM) for discriminating heart failure (HF)-associated effusions., Methods: NT-proBNP, MR-proANP and MR-proADM were measured by commercially available methodologies in the pleural fluid of a retrospective cohort of 185 consecutive patients with pleural effusions, of whom 95 had acute decompensated HF. Receiver-operating characteristic and area under the curve (AUC) analyses allowed comparisons of the discriminative properties of these biomarkers to be made at their optimal cut-off points., Results: The diagnostic accuracy of NT-proBNP and MR-proANP for HF as quantified by the AUC was 0.935 and 0.918, respectively, whereas MR-proADM was of limited value (AUC = 0.62). A pleural fluid MR-proANP >260 pmol/L or NT-proBNP >1700 pg/mL argues for HF (likelihood ratio (LR) positive >5), while levels below these cut-off values significantly decrease the probability of having the disease (respective LR negative 0.19 and 0.10). The optimal cut-off points for natriuretic peptides were influenced by age, renal function and body mass index. Finally, both NT-proBNP and the albumin gradient correctly identified more than 80% of those cardiac effusions misclassified as exudates by standard criteria., Conclusions: MR-proANP is as valuable a diagnostic tool as NT-proBNP for diagnosing or excluding HF as the cause of pleural effusion., (© 2012 The Authors. Respirology © 2012 Asian Pacific Society of Respirology.)

Background: Cystatin C (CysC) is a good prognostic marker in heart failure. However, there is not much information of CysC combined with other biomarkers in acute heart failure (AHF)., Aim: To assess prognostic value of CysC and N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients hospitalized for AHF with no apparent deterioration of renal function., Design: Prospective, multicenter, observational study., Methods: CysC and NTpro-BNP were measured in patients consecutively admitted with a diagnosis of AHF. Patients with, NTpro-BNP concentration above 900 pg/mL and serum creatinine below 1.3mg/dL, were included for statistical analysis. End-point of the study was all-cause mortality during a 12-month follow-up., Results: 526 patients with AHF and NTpro-BNP concentration above 900 pg/mL were included in the study. From this group, 367 patients (69.8%) had serum creatinine below 1.3mg/dL. Receiver operating characteristic (ROC) curves were used to determine the best cut-off value for CysC. Patients with a concentration of CsyC above 1.25mg/dL had a 37.8% mortality rate, vs. 13.6% for those below cut-off (p<0.001). After Cox proportional hazard model, age, CysC, low total cholesterol and HF with preserved ejection fraction remained significantly associated with all-cause mortality during one-year follow-up., Conclusions: In AHF and normal or slightly impaired renal function, performance of CysC may be superior to NT-proBNP. Hence, CysC may be the preferred biomarker in the assessment of patients with AHF and slightly impaired renal function., (Copyright © 2012 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Cystatin C (CysC) is an antiprotease useful for measuring kidney function. Beyond such property, it carries significant prognostic information in several fields of cardiovascular diseases. We review data that support CysC as a prognostic factor in cardiovascular diseases among healthy elderly, hypertensive and heart failure patients. In addition, it has been speculated that CysC may be an early marker of ventricular remodelling, primarily involved in its pathogenesis, as a local antiprotease. Its role in physiopathology and clinical issues of cardiovascular pathology is yet to be elucidated., (Copyright © 2009 Elsevier España, S.L. All rights reserved.)

Objectives: To determine whether serum Cystatin C (CysC) and NTproBNP have prognostic value among patients with long-standing chronic lung disease., Design: Prospective, observational, non-interventional study., Setting: CysC and NTproBNP are prognostic markers in several cardiac conditions. In addition, CysC acts as an antiprotease following Cathepsin activation, which has been involved in the pathogenesis of chronic obstructive pulmonary disease., Participants: Patients with a basal functional status of II-IV (NYHA), admitted for an acute exacerbation of chronic pulmonary diseases and no previous history of symptoms related to pulmonary hypertension or heart failure., Main Outcome Measures: NTproBNP and CysC were determined at admission in 107 patients with acute exacerbation of chronic lung disease. During 12-month follow-up, mortality, new hospital admissions and prescription of diuretics were recorded., Results: During follow-up there were eight patient deaths (7.5%). Mean NTproBNP among the deceased was 1510.20 pg/mL (95% CI 498.44-4628.55) vs 502.70 pg/mL (95% CI 395.44-645.48) among survivors (p = 0.01). Twenty-seven patients (25%) were prescribed loop diuretics. Mean concentration of CysC was 1.45 mg/dL (95% CI 1.21-1.69 mg/dL) vs 1.17 mg/dL (95% IC 1.09-1.25 mg/dL) in those not prescribed (p = 0.004). NTproBNP concentration was 837.14 pg/mL (95% CI 555.57-1274.10 pg/mL) in patients prescribed diuretics vs 473.42 pg/mL (95% CI 357.80-632.70 pg/mL) in those not prescribed (p = 0.03). Kaplan-Meier analysis revealed a significant difference between death and diuretic prescription during follow-up when cut-off value for NTproBNP was 550 pg/mL (p = 0.03 and p = 0.02, respectively). For 1.16mg/dL of CsysC, a significant difference was only observed in diuretic prescription (p = 0.007)., Conclusions: In patients with chronic respiratory diseases NTproBNP has predictive value in terms of mortality whereas CysC does not. However, it is still possible that both can contribute to the early identification of patients at risk of developing clinical ventricular dysfunction.

Introduction: Interleukin-6 (IL-6) has been identified as a predictor of death, new heart failure (HF) episodes and need for heart transplantation in patients with advanced HF. The aim of this study was to examine the relationship between plasma IL-6 levels in patients with decompensated HF and either survival or new admissions due to HF., Methods: We studied 111 patients admitted due to decompensated HF. Long-term survival was assessed from the day of admission to the hospital to the day of death or new admissions due to HF., Results: The mean IL-6 concentration was 90 +/- 115 pg/ml (range 1.5-743 pg/ml). There were no differences in IL-6 concentration with regard to age, gender and cause of HF. At the end of follow-up period, 22 patients (20 percent) had died due to causes related to HF and 54 patients (48 percent) had been readmitted to the hospital due to new HF episodes. Using regression analyses, serum IL-6 levels were not identified as a prognostic factor. Systolic dysfunction, previous diagnosis of HF and diabetes mellitus were independent predictors of death., Conclusion: These findings suggest that a single measurement of serum IL-6 in patients with decompensated HF lacks clinical usefulness in long-term follow-up.

Background: Changes in extracellular matrix are recognized as a contributing factor in the cardiac remodeling process. Several studies have addressed the value of turnover markers of collagen as predictors of death or new heart failure episodes. The aim of the present study was to evaluate the relationship between peripheral serum concentration of propeptide of procollagen type I (PIP) and outcomes in patients with decompensated heart failure., Methods: A total of 111 patients admitted to our Unit between September 2000 and May 2003 for decompensated heart failure were analyzed. Death from any cause or due to heart failure and readmission were considered primary endpoints., Results: The mean PIP concentration was 80.84+/-36.40 ng/mL. The PIP serum level was significantly higher among those patients who suffered some endpoint during follow-up (88.12+/-37.31 ng/mL vs 73.13+/-34.06 ng/mL; p=0.029). Twenty-five (22.52%) of the 111 patients died during the 21 months of follow-up, and 54 (48.6%) were readmitted with new bouts of heart failure. Using Cox proportional hazards regression analyses, serum PIP levels, systolic dysfunction, and diabetes mellitus were identified as independent predictors of death. Serum PIP levels, age, and sex were independent predictors of new heart failure episodes and readmission., Conclusion: A single serum measurement of PIP seems to have prognostic value in patients with decompensated heart failure. Accordingly, patients with higher values of PIP at decompensation are at a higher risk of death or readmission during follow-up.

Objective: Heart failure (HF) is one of the most frequent diagnosis in Internal Medicine Units. High age of patients is an important characteristic in these admissions. Our objective was to evaluate how age interact with mortality, to medium-term, in HF after a decompensated episode., Method: Through the patient medical record we obtained data about patients hospitalised in a Internal Medicine Unit, with HF diagnosis, for a year (from September 2000 to August 2001) and their survival at 1st January 2003. 215 patients were reviewed., Results: During follow-up, 60 patients died (27.9% of overall). In elderly patients, we observed a higher number of women and less use of echocardiography and treatment with beta-blockers and warfarin (in patients with atrial fibrillation). In Cox proportional-hazards model, age (OR 1.043 IC 95% 1.002-1.085), days of hospitalization (OR 1.04 IC 95% 1.003-1.078), diabetes mellitus (OR 2.51 IC 95% 1.37-4.60) and do not prescribe warfarin in patients with atrial fibrillation (OR 2.71 IC 95% 1.10-6.60) were independent prognostic factors., Conclusions: Age was an important prognostic factor in patients with HF. Clinical trials should be done in patients with these characteristics. So, we can know better clinical evolution of HF in this population.

Metastatic cancer of unknown primary site represents approximately three percent of all new cancer diagnoses. Expensive and invasive diagnostic procedures are often performed although the primary tumour is detected in less than 25 percent of cases. We present a 63-year-old woman presenting with low back pain and was found on positron emission tomography (PET) to have lung cancer. The pros and cons of PET in the diagnostic process of patients with metastatic cancer of unknown primary site are reviewed. PET should be considered in the diagnostic process of patients with unknown primaries, and unnecessary invasive procedures may be avoided.

Introduction: Stroke is very seldom seen as the first manifestation of a neoplasia. The mechanisms that are most frequently involved in its pathogenesis are Trousseau's syndrome, haematological disorders such as disseminated intravascular coagulation or thrombocytosis, and the release of mucin by the tumour. Secondarily, non bacterial thrombotic endocarditis, septic or neoplastic cell embolism, venous sinus thrombosis and atherosclerosis secondary to radiotherapy have been reported., Case Reports: Case 1: a 27-year-old male who presented a stroke in the right thalamus with a torpid progression and digestive complications; neuroimaging studies revealed unknown neoplasia of the head of the pancreas. Case 2: a 53-year-old male with repeated stroke (left sylvian and right occipitotemporal) and progressive neurological deterioration secondary to disseminated neoplastic disease, which had its origins in the body and tail of the pancreas. In both cases all the diagnostic explorations carried out in an attempt to determine the aetiopathogenesis of the stroke were negative. The post mortem study in the second patient revealed the existence of a non bacterial thrombotic endocarditis, which was taken as being one of the mechanisms involved., Conclusions: The pathogenic mechanisms of cerebral ischemia associated to neoplasia are discussed and the primary and secondary forms are differentiated. We highlight the idea that when dealing with a stroke with an unknown aetiology and a torpid progression, the neurologist must consider the existence of a concealed neoplasia with stroke as its first manifestation.

Introduction: Syncope is a frequent disorder shows diagnostic difficulties, so that an important percentage of patients remain without diagnosis after the implementation of diagnostic tests that sometimes are unnecessary., Method: A retrospective analysis of the patients admitted during a period of two years because of syncope in an Internal Medicine Service was carried out., Results: Of a total of 2,878 patients hospitalized during the years 1999 and 2000, 79 were admitted because of syncope (2.74%). Forty-five (57%) were men and 34 (43%) were women, with a median age of 68.8 years. Twenty-seven patients (34%) had history of syncope. After a median hospitalization of 9.5 days, the etiological diagnosis was established in 53 (67%) patients: in 25 patients (31.6%) the syncope was mediated by neurological mechanisms, in 16 (20.25%) it was of cardiology origin, in 4 (5.06%) it was of neurological origin and in 8 (10.1%) the syncope was secondary to other causes. In 54 patient (68.8%) at least one cardiology test was carried out (41 Holter, 32 echocardiograms, 6 tilt board tests, 3 maneuvers of massage of the carotid sinus, 3 ergometry studies, 3 electrophysiological studies, 2 coronary angiographies and 3 ventilation perfusion lung gammagraphies). In 51 patient (64%) at least one neurological test was carried out (31 EEG, 42 CT, 2 MNR, 1 Doppler cranial ultrasound and 3 electroneuromyogram). Only 4 of the Holter carried out were diagnostic, as well as 3 of the echocardiograms and only 2 of the CT carried out. No EEG was useful for the etiological diagnosis of the syncope., Conclusions: There is an excessive utilization of some diagnostic tests (EEG, Holter, cerebral CT), in spite of which in an important percentage of patients with syncope the etiological diagnosis is no done (33%). The use of diagnostic algorithms based on detailed clinical history, physical exploration and assessment of the ECG is proposed, that they would make it possible to issue a diagnostic hypothesis from which there could be begun the diagnostic study with a use as rational as possible of the complementary examinations.

Mucosa associated lymphoid tissue (MALT) lymphomas are a group of non- Hodgkin"s lymphomas of low malignancy degree. The most frequent location is the gastrointestinal tract. Its primary pulmonary presentation is unusual and heterogeneous from point of view radiological. Woman 61 years old with antecedents of vitiligo, gastric ulcus, cirrhosis by VHC, that go into the hospital by sudden disnea, thoracic paint with pleural characterises and fever of 38.5 degrees C, Her thorax radiography and thoracic TAC showed nodes that affect to different pulmonary lobes. The cytology by PAAF confirms their malignant nature. In subsequent radiological controls it was notice the nodels took away completely and returns in different pulmonary place in each recurrence. The presentation like fluctuant pulmonary nodes is exceptional in a MALT lymphoma. It was described a higher incidence of VHC infection and tumour. The evidence of chronic hepatitis by virus C disease, and local chronic inflammatory process as well as autoimmune disorders may be considerate like a factor that contribute to MALT lymphoma.