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BACKGROUND: The recent publication of the MADIT-CRT and RAFT trials has more than doubled the number of patients in which a direct comparison of the combination of cardiac resynchronization therapy (CRT) and implantable cardioverter-defibrillator (ICD) versus ICD alone was carried out. The present meta-analysis aims to assess the impact of combined CRT and ICD therapy on survival of heart failure (HF) patients. METHODS AND RESULTS: Medline, Embase, and the Cochrane Library databases were searched, and all randomized controlled trials of CRT alone or combined with ICDs in HF resulting from left ventricular systolic dysfunction were included. Main outcome was all-cause mortality. Summary relative risk (RR) and 95% confidence interval (CI) were calculated employing random-effects models. Twelve studies were included, with a total of 8,284 randomized patients. For the comparison of CRT alone versus medical therapy, pooled analysis of 5 available trials demonstrated a significant reduction in all-cause mortality with CRT (RR 0.76, 95% CI: 0.64-0.9). Pooled analysis of 6 trials that compared the combination of CRT and ICD therapy to ICD alone also showed a statistically significant reduction in all-cause mortality (RR 0.83, 95% CI: 0.72-0.96). Stratified analysis showed significant mortality reductions in all New York Heart Association class subgroups, with greater effect in classes III-IV (RR 0.70; 95% CI: 0.57-0.88). Pooled estimates of implant-related risks were 0.6% for death and 8% for implant failure. CONCLUSION: Combined CRT and ICD therapy reduces overall mortality in HF patients when compared with ICD alone. [ABSTRACT FROM AUTHOR]

The purpose of this study is to compare clinical assessment of congestion performed by a nurse to that performed by cardiologist and correlate them with NT-ProBNP levels. The nurses' role in heart failure has been strongly focused in therapeutic, educational and self-care interventions. The diagnostic performance of nurses in heart failure outpatients is not well explored. N-terminal pro-B-type natriuretic peptide is a cardiac marker that reflects elevated filling pressures. Cross-sectional contemporaneous study. Heart failure outpatients underwent a systematic clinical assessment of clinical congestion score performed by cardiologist and nurse during the same visit. Assessments were performed independently and N-terminal pro-B-type natriuretic peptide levels obtained. The nurses' ability to classify patients in hemodynamic profile was compared to the cardiologist's. Eighty-nine assessments were performed in 63 patients with heart failure. The correlation of clinical congestion scores obtained by nurse with those obtained by cardiologist was r = 0·86; p < 0·001. The correlation of clinical congestion scores from nurse and cardiologist with levels of N-terminal pro-B-type natriuretic peptide were as follows: r = 0·45; p < 0·0001 and r = 0·51, respectively, p < 0·0001. Patients with clinical congestion score ≥3 had levels of NT-ProBNP significantly higher than those with clinical congestion score <3, in the assessment performed by the cardiologist (1866 SD 1151 vs. 757 SD 988 pg/ml; p < 0·0001) and by the nurse (1720 SD 1228 vs. 821 SD 914 pg/ml; p < 0·0001). The nurse and cardiologist had similar capacity in classifying patients in congested quadrants ( p = 0·027) or in dry quadrants ( p = 0·03), according to the levels of N-terminal pro-B-type natriuretic peptide. Area under the receiver-operating characteristic curve of the nurse and cardiologist to detect congestion was, respectively, 0·77 and 0·72. Our data suggests that nurses trained in heart failure may have a similar performance to that of the cardiologist for the clinical detection of congestion and assessment of the hemodynamic profile in patients with chronic heart failure. Considering that consistent clinical assessment can identify congested or hypovolemic patients with reasonable reliability, as well as patients with low or normal cardiac output, our results may help confirm nurses' capability in performing reliable clinical assessment in heart failure patients. While nurses' led heart failure programmes are usually focused on the management of patients, nurses' ability to perform accurate assessment would expand nurses' role in these programmes. As many institutions now focus on home visits by heart failure nurses, accurate assessment would benefit patients and improve their clinical outcomes. [ABSTRACT FROM AUTHOR]

Endomyocardial biopsy (EB) is the preferred procedure for post-heart transplant rejection diagnosis. The rigid bioptome technique has been used due to its greater simplicity and has been criticized for the potential risk of tricuspid regurgitation (TR). We aimed to review all the EBs performed by this technique in a tertiary center and estimate the rate of complications and/or aggravation of TR. Cross-sectional, retrospective, anterograde study. Data were collected from 729 EBs performed in 55 post-heart transplant patients with a rigid Scholten Novatome™ bioptome between September 2012 to March 2022. All EBs were performed via the right jugular vein under local anesthesia and through micro-puncture and ultrasound guidance. A total of 729 procedures had an echocardiography performed before and after the procedures. The estimate of TR was categorized as absent, minimal, mild, moderate, and severe. McNemar's chi-square test was used to analyze the degree of pre- and post-EB TR. There was a worsening enough to become moderate or severe post-biopsy TR in two (0.27%) procedures, and there was a slight change in TR from minimal to mild TR in 25 (3.42%) procedures. In 729 percutaneous EBs performed with a rigid bioptome, there was no myocardial perforation, cardiac tamponade or pneumothorax. One death occurred within 24 hours after the procedure for an unknown reason. EB using a rigid bioptome is safe and has not been associated with worsening TR in a follow-up of 729 EBs performed after cardiac transplantation. The overall complication rate, including moderate to severe TR, was 0.81%. The mortality rate was 0.14%.

Importance: Readmissions after an index heart failure (HF) hospitalization are a major contemporary health care problem., Objective: To evaluate the feasibility and efficacy of an intensive telemonitoring strategy in the vulnerable period after an HF hospitalization., Design, Setting, and Participants: This randomized clinical trial was conducted in 30 HF clinics in Brazil. Patients with left ventricular ejection fraction less than 40% and access to mobile phones were enrolled up to 30 days after an HF admission. Data were collected from July 2019 to July 2022., Intervention: Participants were randomly assigned to a telemonitoring strategy or standard care. The telemonitoring group received 4 daily short message service text messages to optimize self-care, active engagement, and early intervention. Red flags based on feedback messages triggered automatic diuretic adjustment and/or a telephone call from the health care team., Main Outcomes and Measures: The primary end point was change in N-terminal pro-brain natriuretic peptide (NT-proBNP) from baseline to 180 days. A hierarchical win-ratio analysis incorporating blindly adjudicated clinical events (cardiovascular deaths and HF hospitalization) and variation in NT-proBNP was also performed., Results: Of 699 included patients, 460 (65.8%) were male, and the mean (SD) age was 61.2 (14.5) years. A total of 352 patients were randomly assigned to the telemonitoring strategy and 347 to standard care. Satisfaction with the telemonitoring strategy was excellent (net promoting score at 180 days, 78.5). HF self-care increased significantly in the telemonitoring group compared with the standard care group (score difference at 30 days, -2.21; 95% CI, -3.67 to -0.74; P = .001; score difference at 180 days, -2.08; 95% CI, -3.59 to -0.57; P = .004). Variation of NT-proBNP was similar in the telemonitoring group compared with the standard care group (telemonitoring: baseline, 2593 pg/mL; 95% CI, 2314-2923; 180 days, 1313 pg/mL; 95% CI, 1117-1543; standard care: baseline, 2396 pg/mL; 95% CI, 2122-2721; 180 days, 1319 pg/mL; 95% CI, 1114-1564; ratio of change, 0.92; 95% CI, 0.77-1.11; P = .39). Hierarchical analysis of the composite outcome demonstrated a similar number of wins in both groups (telemonitoring, 49 883 of 122 144 comparisons [40.8%]; standard care, 48 034 of 122 144 comparisons [39.3%]; win ratio, 1.04; 95% CI, 0.86-1.26)., Conclusions and Relevance: An intensive telemonitoring strategy applied in the vulnerable period after an HF admission was feasible, well-accepted, and increased scores of HF self-care but did not translate to reductions in NT-proBNP levels nor improvement in a composite hierarchical clinical outcome., Trial Registration: ClinicalTrials.gov Identifier: NCT04062461.

Background: In advanced heart failure (HF), diagnostic performance of physical exam may be poor. Physical examination associated with lung ultrasound (LUS) may be an important tool to facilitate congestion screening., Objective: To evaluate performance of LUS for congestion screening in advanced HF referred for transplant, as compared to findings of right heart catheterization (RHC)., Methods: Prospective study of 23 subjects with advanced HF referred for RHC. LUS was performed in association with clinical congestion score (CCS), analogue-visual dyspnea scale (AVDS) and presence of trepopnea/bendopnea prior to catheterization. Congestion was assessed by the number of B-lines in the LUS, and by findings of physical examination as well as by NT-proBNP serum values., Results: Congestion was present in 43.4 % of patients by LUS (B-lines ≥ 15), as compared to 21.7 % by CCS (score greater than or equal to 5), 56.5 % by NT-proBNP (>1000 pg/ml), and 60.8 % by pulmonary capillary wedge pressure (PCWP) (>15 mm Hg). The number of B-lines was correlated to cardiac index (CI) (rho = -0.619; p 0.002), but not with PCWP (rho 0.190; p 0.386), RAP (rho -0.244; p 0.262), CCS (rho 0.198; p 0.36) and neither with NT-proBNP (rho 0.282; p 0.193). Otherwise, NT-proBNP was correlated with PCWP (rho = 0.636; p = 0.001) and with CI (rho -0.667 p 0.001)., Conclusions: In advanced HF patients referred for transplant, number of B-lines in LUS was not correlated with PCWP or RAP. Advanced HF patients seem to have increased filling pressures, but no interstitial pulmonary congestion that LUS could detect., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: Heart failure (HF) is a growing problem for healthcare systems worldwide. Sodium and fluid restriction are non-pharmacological treatments recommended for patients with HF by several guidelines over the years, even without consensus., Objective: To evaluate the effects of sodium and fluid restriction in patients with HF., Methods: We searched MEDLINE, Embase, and Cochrane CENTRAL databases up to June 2020 and screened the reference lists of relevant articles. We included randomized controlled trials evaluating sodium and/or fluid restriction in patients with HF. We assessed three independent comparisons: (a) sodium restriction versus control; (b) fluid restriction versus control; and (c) sodium and fluid restriction versus control. Main outcomes of interest were all-cause mortality and hospitalization. Two independent reviewers selected studies and extracted data. We pooled the results using random-effects meta-analysis. We used the RoB 2.0 and the GRADE framework to assess risk of bias and quality of evidence., Results: We included 16 studies totaling 3545 patients in our meta-analysis. Daily sodium intake was 1.5-2.4 g for the intervention group and >2.7 g for the control group, and daily fluid intake was 0.8-1.5 L for the intervention group and free oral fluid intake for the control group. Sodium restriction increased mortality (relative risk 1.92, 95% confidence interval 1.51 to 2.45, moderate quality of evidence) and hospitalization (relative risk 1.63, 1.11 to 2.40, low quality of evidence). Fluid restriction reduced mortality (relative risk 0.32, 0.13 to 0.82, low quality of evidence) and hospitalization (relative risk 0.46, 0.27 to 0.77, n = 331, low quality of evidence). The combination of sodium and fluid restriction did not significantly affect the risk of mortality (relative risk 0.92, 0.49 to 1.73, low quality of evidence) or the risk of hospitalization (relative risk 0.94, 0.75 to 1.19, low quality of evidence)., Conclusion: The combination of sodium and fluid restriction in clinical trials resulted in a null effect although results in the opposite direction were observed for each intervention independently. Combined sodium and fluid restriction are usually recommended for patients with HF. Our findings of sodium restriction harm, risk of mortality and hospitalization are consistent with publications from several clinical trial and physiologic explanations. A well-designed clinical trial nested by an implementation study is urgent for definitive sodium range recommendation, specially considering the change of currently guidelines, pushing up the cut-off of sodium restriction range., Competing Interests: Declaration of competing interest The methodological coordination for the development of these study was funded by the Institutional Development Program of the Brazilian Unified Health System (PROADI-SUS) together with Hospital Moinhos de Vento., (Copyright © 2022 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Competing Interests: We declare no competing interests.

Iron deficiency (ID) is an important comorbidity in heart failure with reduced ejection (HFrEF) and is highly prevalent in both anemic and non-anemic patients. In HFrEF, iron deficiency should be investigated by measurements of transferrin saturation and ferritin. There are two types of ID: absolute deficiency, with depletion of iron stores; and functional ID, where iron supply is not sufficient despite normal stores. ID is associated with worse functional class and higher risk of death in patients with HFrEF, and scientific evidence has indicated improvement of symptoms and quality of life of these patients with treatment with parenteral iron in the form of ferric carboxymaltose. Iron plays vital roles such as oxygen transportation (hemoglobin) and storage (myoblogin), and is crucial for adequate functioning of mitochondria, which are composed of iron-based proteins and the place of energy generation by oxidative metabolism at the electron transport chain. An insufficient generation and abnormal uptake of iron by skeletal and cardiac muscle cells contribute to the pathophysiology of HF. The present review aims to increase the knowledge of the pathophysiology of ID in HFrEF, and to address available tools for its diagnosis and current scientific evidence on iron replacement therapy.

Objective: New York Heart Association (NYHA) functional class plays a central role in heart failure (HF) assessment but might be unreliable in mild presentations. We compared objective measures of HF functional evaluation between patients classified as NYHA I and II in the Re de B rasileira de Estudos em I nsuficiência C ardíaca (ReBIC)-1 Trial., Methods: The ReBIC-1 Trial included outpatients with stable HF with reduced ejection fraction. All patients had simultaneous protocol-defined assessment of NYHA class, 6 min walk test (6MWT), N-terminal pro-brain natriuretic peptide (NT-proBNP) levels and patient's self-perception of dyspnoea using a Visual Analogue Scale (VAS, range 0-100)., Results: Of 188 included patients with HF, 122 (65%) were classified as NYHA I and 66 (35%) as NYHA II at baseline. Although NYHA class I patients had lower dyspnoea VAS Scores (median 16 (IQR, 4-30) for class I vs 27.5 (11-49) for class II, p=0.001), overlap between classes was substantial (density overlap=60%). A similar profile was observed for NT-proBNP levels (620 pg/mL (248-1333) vs 778 (421-1737), p=0.015; overlap=78%) and for 6MWT distance (400 m (330-466) vs 351 m (286-408), p=0.028; overlap=64%). Among NYHA class I patients, 19%-34% had one marker of HF severity (VAS Score >30 points, 6MWT <300 m or NT-proBNP levels >1000 pg/mL) and 6%-10% had two of them. Temporal change in functional class was not accompanied by variation on dyspnoea VAS (p=0.14)., Conclusions: Most patients classified as NYHA classes I and II had similar self-perception of their limitation, objective physical capabilities and levels of natriuretic peptides. These results suggest the NYHA classification poorly discriminates patients with mild HF., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Acute decompensated heart failure (ADHF) is the leading cause of hospitalization in patients aged 65 years or older, and most of them present with congestion. The use of hydrochlorothiazide (HCTZ) may increase the response to loop diuretics. To evaluate the effect of adding HCTZ to furosemide on congestion and symptoms in patients with ADHF. This randomized clinical trial compared HCTZ 50 mg versus placebo for 3 days in patients with ADHF and signs of congestion. The primary outcome of the study was daily weight reduction. Secondary outcomes were change in creatinine, need for vasoactive drugs, change in natriuretic peptides, congestion score, dyspnea, thirst, and length of stay. Fifty-one patients were randomized-26 to the HCTZ group and 25 to the placebo group. There was an increment of 0.73 kg/day towards additional weight reduction in the HCTZ group (HCTZ: - 1.78 ± 1.08 kg/day vs placebo: - 1.05 ± 1.51 kg/day; p = 0.062). In post hoc analysis, the HCTZ group demonstrated significant weight reduction for every 40 mg of intravenous furosemide (HCTZ: - 0.74 ± 0.47 kg/40 mg vs placebo: - 0.33 ± 0.80 kg/40 mg; p = 0.032). There was a trend to increase in creatinine in the HCTZ group (HCTZ: 0.50 ± 0.37 vs placebo: 0.27 ± 0.40; p = 0.05) but no significant difference in onset of acute renal failure (HCTZ: 58% vs placebo: 41%; p = 0.38). No differences were found in the remaining outcomes. Adding hydrochlorothiazide to usual treatment of patients with acute decompensated heart failure did not cause significant difference in daily body weight reduction compared to placebo. In analysis adjusted to the dose of intravenous furosemide, adding HCTZ 50 mg to furosemide resulted in a significant synergistic effect on weight loss.Trial registration: The Brazilian Clinical Trials Registry (ReBEC), a publically accessible primary register that participates in the World Health Organization International Clinical Trial Registry Platform; number RBR-5qkn8h. Registered in 23/07/2019 (retrospectively), http://www.ensaiosclinicos.gov.br/rg/RBR-5qkn8h/ ., (© 2021. The Author(s).)

Background: Epigastric or chest pain with an abnormal electrocardiogram (ECG) in a young, otherwise healthy patient should trigger an investigation to rule out myocarditis. The myocarditis covers a wide spectrum of severity. The search for the aetiologic factor could be definitive for the success of therapy., Case Summary: A previously healthy 29-year-old woman presented to the Emergency Room with epigastric pain, eosinophilia, and an abnormal ECG. A thorough evaluation including cardiac magnetic resonance and endomyocardial biopsy was undertaken. A diagnosis of acute necrotizing eosinophilic myocarditis was made., Discussion: The case is particularly unique for its suspected predisposing trigger: an antimigraine drug. A possible systemic hypersensitivity reaction, reflected by the occurrence of concomitant severe serum eosinophilia, acute myocarditis, and central nervous system vasculitis, was successfully treated with steroids, further supporting the diagnosis., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: The prognostic value of cardiopulmonary exercise testing (CPET) variables for major cardiovascular events in patients with heart failure (HF) is widely established. However, the prognostic value of these variables as predictors of appropriate implantable cardioverter-defibrillator (ICD) therapies has not been sufficiently well addressed. This study aimed to evaluate CPET variables such as peak oxygen uptake (VO 2 peak), relationship between change in minute ventilation (VE) and carbon dioxide output (VCO 2 ) during incremental exercise (VE/VCO 2 slope) and exercise-related periodic breathing (EPB) as appropriate ICD therapy predictors in HF patients. Methods: We retrospectively assessed 61 HF patients who underwent CPET and had ICD implanted for primary prevention. Patients were followed for 767 ± 601 days. Primary outcome was appropriate ICD-delivered therapy, either anti-tachycardia pacing (ATP) or shock. Results: The sample consisted mostly of male patients (65.6%), with severe ventricular dysfunction (mean left ventricular ejection fraction (LVEF) 27 ± 6%). The primary outcome occurred in 20 patients (32%). There were no significant differences in VO 2 peak (17.7 ± 4.1 and 16.9 ± 4.5 mL/kg/min), VE/VCO 2 slope (39.7 ± 8.4 and 39.6 ± 10.2) or EPB prevalence (20% and 19.5%) in patients with or without appropriate ICD therapy. According to Cox regression analysis, none of the CPET variables were significant predictors of appropriate ICD therapy. Conclusions: In this cohort study of HF patients, CPET variables did not predict appropriate ICD therapies. Further studies with large number of patients are warranted to address this issue.

Aims: Although loop diuretics are widely used to treat heart failure (HF), there is scarce contemporary data to guide diuretic adjustments in the outpatient setting., Methods and Results: In a prospective, randomized and double-blind protocol, we tested the safety and tolerability of withdrawing low-dose furosemide in stable HF outpatients at 11 HF clinics in Brazil. The trial had two blindly adjudicated co-primary outcomes: (i) symptoms assessment quantified as the area under the curve (AUC) of a dyspnoea score on a visual-analogue scale evaluated at 4 time-points (baseline, Day 15, Day 45, and Day 90) and (ii) the proportion of patients maintained without diuretic reuse during follow-up. We enrolled 188 patients (25% females; 59 ± 13 years old; left ventricular ejection fraction = 32 ± 8%) that were randomized to furosemide withdrawal (n = 95) or maintenance (n = 93). For the first co-primary endpoint, no significant difference in patients' assessment of dyspnoea was observed in the comparison of furosemide withdrawal with continuous administration [median AUC 1875 (interquartile range, IQR 383-3360) and 1541 (IQR 474-3124), respectively; P = 0.94]. For the second co-primary endpoint, 70 patients (75.3%) in the withdrawal group and 77 patients (83.7%) in the maintenance group were free of furosemide reuse during follow-up (odds ratio for additional furosemide use with withdrawal 1.69, 95% confidence interval 0.82-3.49; P = 0.16). Heart failure-related events (hospitalizations, emergency room visits, and deaths) were infrequent and similar between groups (P = 1.0)., Conclusions: Diuretic withdrawal did not result in neither increased self-perception of dyspnoea nor increased need of furosemide reuse. Diuretic discontinuation may deserve consideration in stable outpatients with no signs of fluid retention receiving optimal medical therapy., Clinicaltrials.gov Identifier: NCT02689180., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Objectives: Sodium and fluid restriction is commonly prescribed for heart failure patients. However, its role in the treatment of heart failure with preserved ejection fraction (HFpEF) remains unclear. The aim of this study was to compare the effect of a diet with sodium and fluid restriction with an unrestricted diet in patients admitted for decompensated HFpEF., Methods: Patients were randomized to a diet with sodium (0.8 g/d) and fluid (800 mL/d) restriction (intervention group [IG]) or an unrestricted diet (control group [CG]) and followed for 7 d or hospital discharge. The primary outcome was weight loss. Secondary outcomes included clinical stability, perception of thirst, neurohormonal activation, nutrient intake, readmission, and mortality rate after 30 d., Results: Fifty-three patients were included (30, IG; 23, CG). The mean ejection fraction was 62% ± 8% for IG and 60% ± 7% for CG (P = 0.44). Weight loss was similar in both groups, being 1.6 ± 2.2 kg in the IG and 1.8 ± 2.1 kg in CG (P = 0.49) as well as the reduction in the congestion score (IG = 3.4 ± 3.5; CG = 3.8 ± 3.4; P = 0.70). The daily perception of thirst was higher in the IG (P = 0.03). Lower energy consumption was seen in the IG (P <0.001). No significant between-group differences at 30 d were found., Conclusions: Aggressive sodium and fluid restriction does not provide symptomatic or prognosis benefits, but does produce greater perception of thirst, may impair the patient's food intake, and does not seem to have an important neurohormonal effect in patients admitted for decompensated HFpEF., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Physical examination and B-type natriuretic peptide (BNP) have been used to estimate hemodynamics and tailor therapy of acute decompensated heart failure (ADHF) patients. However, correlation between these parameters and left ventricular filling pressures is controversial., Objective: This study was designed to evaluate the diagnostic accuracy of physical examination, chest radiography (CR) and BNP in estimating left atrial pressure (LAP) as assessed by tissue Doppler echocardiogram., Methods: Patients admitted with ADHF were prospectively assessed. Diagnostic characteristics of physical signs of heart failure, CR and BNP in predicting elevation (> 15 mm Hg) of LAP, alone or combined, were calculated. Spearman test was used to analyze the correlation between non-normal distribution variables. The level of significance was 5%., Results: Forty-three patients were included, with mean age of 69.9 ± 11.1years, left ventricular ejection fraction of 25 ± 8.0%, and BNP of 1057 ± 1024.21 pg/mL. Individually, all clinical, CR or BNP parameters had a poor performance in predicting LAP ≥ 15 mm Hg. A clinical score of congestion had the poorest performance [area under the receiver operating characteristic curve (AUC) 0.53], followed by clinical score + CR (AUC 0.60), clinical score + CR + BNP > 400 pg/mL (AUC 0.62), and clinical score + CR + BNP > 1000 pg/mL (AUC 0.66)., Conclusion: Physical examination, CR and BNP had a poor performance in predicting a LAP ≥ 15 mm Hg. Using these parameters alone or in combination may lead to inaccurate estimation of hemodynamics.

Aims: Furosemide is commonly prescribed for symptom relief in heart failure (HF) patients. Although few data support the continuous use of loop diuretics in apparently euvolemic HF patients with mild symptoms, there is concern about safety of diuretic withdrawal in these patients. The ReBIC-1 trial was designed to evaluate the safety and tolerability of withdrawing furosemide in stable, euvolemic, chronic HF outpatients. This multicenter initiative is part of the Brazilian Research Network in Heart Failure (ReBIC) created to develop clinical studies in HF and composed predominantly by university tertiary care hospitals., Methods: The ReBIC-1 trial is currently enrolling HF patients in NYHA functional class I-II, left ventricular ejection fraction ≤45%, without a HF-related hospital admission within the last 6 months, receiving a stable dose of furosemide (40 or 80 mg per day) for at least 6 months. Eligible patients will be randomized to maintain or withdraw furosemide in a double-blinded protocol. The trial has two co-primary outcomes: (1) dyspnea assessment using a visual-analogue scale evaluated at 4 time points and (2) the proportion of patients maintained without diuretics during the follow-up period. Total sample size was calculated to be 220 patients. Enrolled patients will be followed up to 90 days after randomization, and diuretic will be restarted if clinical deterioration or signs of congestion are detected. Pre-defined sub-group analysis based on NT-proBNP levels at baseline is planned., Perspective: Evidence-based strategies aiming to simplify HF pharmacotherapy are needed in clinical practice. The ReBIC-1 trial will determine the safety of withdrawing furosemide in stable chronic HF patients., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Although half of all patients with heart failure (HF) have a normal or near-normal ejection fraction and their prognosis differs little from that of patients with a reduced ejection fraction, the pathophysiology of HF with preserved ejection fraction (HF-PEF) is still poorly understood, and its management poorly supported by clinical trials. Sodium and fluid restriction is the most common self-care measure prescribed to HF patients for management of congestive episodes. However, its role in the treatment of HF-PEF remains unclear. This trial seeks to compare the effects of a sodium- and fluid-restricted diet versus an unrestricted diet on weight loss, neurohormonal activation, and clinical stability in patients admitted for decompensated HF-PEF., Methods/design: This is a randomized, parallel trial with blinded outcome assessment. The sample will include adult patients (aged ≥18 years) with a diagnosis of HF-PEF admitted for HF decompensation. The patients will be randomized to receive a diet with sodium and fluid intake restricted to 0.8 g/day and 800 mL/day respectively (intervention group) or an unrestricted diet, with 4 g/day sodium and unlimited fluid intake (control group), and followed for 7 days or until hospital discharge. The primary outcome shall consist of weight loss at 7 days or discharge. The secondary outcome includes assessment of clinical stability, neurohormonal activation, daily perception of thirst and readmission rate at 30 days., Discussion: Assessment of the effects of sodium and fluid restriction on neurohormonal activation and clinical course of HF-PEF can promote a deeper understanding of the pathophysiology and progression of this complex syndrome., Trial Registration Number: ClinicalTrials.gov identifier: NCT01896908 (date of registration: 8 August 2013).

Aims: Home-based interventions for heart failure (HF) patients might be particularly effective in middle-income countries, where social, cultural, and economic constraints limit the effectiveness of HF treatment outside the hospital environment., Methods and Results: HELEN-II was a randomized clinical trial conducted in Brazil designed to evaluate the clinical efficacy of a nurse-based strategy, started after discharge following an acute decompensated HF (ADHF) admission. HELEN-II compares the efficacy of home visits and telephone reinforcement (n = 123) with that of the conventional strategy, which is based on medical follow-up (n = 129). The primary outcome was a composite endpoint of a first visit to the emergency department (≤ 24 h), a hospital readmission (> 24 h), or all-cause death, assessed during the first 6 months of follow-up. Most enrolled subjects were middle-aged (62 ± 13 years) males (63%) in NYHA functional class II-III (84%) with severe LV dysfunction (mean LVEF 29.6 ± 9%). The primary composite endpoint was decreased by 27% in the interventional group (relative risk 0.73; 95% confidence interval 0.54-0.99; P = 0.049). At the end of follow-up, the rate of use of the standard-of-care HF medications was similar in both groups, except for the higher use of furosemide in the interventional group. Also, HF knowledge and self-care were significantly increased in the interventional group., Conclusions: A post-discharge, nurse-led management strategy significantly decreases the morbidity of ADHF patients in the public health system of a developing middle-income country., (© 2014 The Authors. European Journal of Heart Failure © 2014 European Society of Cardiology.)

Background: QRS duration is considered to be an indicator of adverse outcome in patients with heart failure (HF), and genetic polymorphisms may be involved in this conductivity impairment. We studied the prognostic impact of the QRS widening rate (QRS-WR) on patients with HF and the influence of the matrix metalloproteinases gene polymorphisms on the QRS-WR., Methods: This prospective cohort study included 184 patients with left ventricular (LV) systolic dysfunction (LV ejection fraction [LVEF] < 45%). The QRS-WR was calculated as the difference between 2 electrocardiogram assessments (in ms) divided by the time elapsed between each evaluation (months). The MMP-1 -1607 1G/2G, MMP-2 -790G/T and -1575G/A, MMP-3 -1171 5A/6A, MMP-9 -1562 C/T and R279Q, and MMP-12 -82A/G polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism., Results: Patients were predominantly white (68%) men (67%) in New York Heart Association functional classes I and II (77%). Patients with HF with a QRS-WR ≥ 0.5 ms/month had more HF-related deaths and more combined clinical events than those with a QRS-WR < 0.5 ms/month (P = 0.03 and P = 0.01, respectively). After adjusting for other covariates, the QRS-WR remained an independent predictor of combined clinical events (hazard ratio, 1.6; 95% confidence interval, 1.1-2.5; P = 0.02). The MMP-1 2G2G genotype was associated with nearly a 2-fold increase in QRS-WR (P = 0.03). Conversely, patients with the MMP-3 5A5A genotype and a nonischemic cause of HF were protected against QRS enlargement (P = 0.03)., Conclusions: QRS-WR retains prognostic value in patients with chronic HF receiving guideline-based pharmacologic treatment. MMP gene polymorphisms can influence the rate of QRS enlargement over time., (Copyright © 2014 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Contemporaneous challenges in heart failure management include strategies to rationally use health economic resources and relative donor shortage to adequately offer electric devices (cardiac resynchronization therapy [CRT] and implantable cardioverter defibrillators [ICD]), ventricular assist devices (VADs) and heart transplant, respectively. These issues are particularly important in countries with middle-income rates and limited structured heart transplant centers, such as Brazil. Use of CRT and ICDs need to follow strict guidelines, further customized to public financial health conditions. Experience with VADs in is the early days in Brazil and will require extreme caution to allocate health public resources to develop VAD programs in highly selected centers. Chagas' disease is epidemiologically important in Brazil; outcomes of patients with Chagas' on electric devices are unclear while these patients fare better post-transplant than non-Chagas' patients. Thus, heart transplant remains an attractive option regarding both favorable outcomes and resource allocation for advanced heart failure patients in Brazil.

Background: Anemia in heart failure patients and has been associated with increased morbi-mortality. Previous studies have treated anemia in heart failure patients with either erythropoietin alone or combination of erythropoietin and intravenous (i.v.) iron. However, the effect of i.v. or oral (p.o.) iron supplementation alone in heart failure patients with anemia was virtually unknown., Aim: To compare, in a double-blind design, the effects of i.v. iron versus p.o. iron in anemic heart failure patients., Methods: IRON-HF study was a multicenter, investigator initiated, randomized, double-blind, placebo controlled trial that enrolled anemic heart failure patients with preserved renal function, low transferrin saturation (TSat) and low-to-moderately elevated ferritin levels. Interventions were Iron Sucrose i.v. 200 mg, once a week, for 5 weeks, ferrous sulfate 200 mg p.o. TID, for 8 weeks, or placebo. Primary endpoint was variation of peak oxygen consumption (peak VO2) assessed by ergospirometry over 3 month follow-up., Results: Eighteen patients had full follow-up data. There was an increment of 3.5 ml/kg/min in peak VO2 in the i.v. iron group. There was no increment in peak VO2 in the p.o. iron group. Patients' ferritin and TSat increased significantly in both treated groups. Hemoglobin increased similarly in all groups., Conclusion: I.v. iron seems to be superior in improving functional capacity of heart failure patients. However, correction of anemia seems to be at least similar between p.o. iron and i.v. iron supplementation., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Importance: The benefits of fluid and sodium restriction in patients hospitalized with acute decompensated heart failure (ADHF) are unclear., Objective: To compare the effects of a fluid-restricted (maximum fluid intake, 800 mL/d) and sodium-restricted (maximum dietary intake, 800 mg/d) diet (intervention group [IG]) vs a diet with no such restrictions (control group [CG]) on weight loss and clinical stability during a 3-day period in patients hospitalized with ADHF., Design: Randomized, parallel-group clinical trial with blinded outcome assessments., Setting: Emergency room, wards, and intensive care unit., Participants: Adult inpatients with ADHF, systolic dysfunction, and a length of stay of 36 hours or less., Intervention: Fluid restriction (maximum fluid intake, 800 mL/d) and additional sodium restriction (maximum dietary intake, 800 mg/d) were carried out until the seventh hospital day or, in patients whose length of stay was less than 7 days, until discharge. The CG received a standard hospital diet, with liberal fluid and sodium intake., Main Outcomes and Measures: Weight loss and clinical stability at 3-day assessment, daily perception of thirst, and readmissions within 30 days., Results: Seventy-five patients were enrolled (IG, 38; CG, 37). Most were male; ischemic heart disease was the predominant cause of heart failure (17 patients [23%]), and the mean (SD) left ventricular ejection fraction was 26% (8.7%). The groups were homogeneous in terms of baseline characteristics. Weight loss was similar in both groups (between-group difference in variation of 0.25 kg [95% CI, -1.95 to 2.45]; P = .82) as well as change in clinical congestion score (between-group difference in variation of 0.59 points [95% CI, -2.21 to 1.03]; P = .47) at 3 days. Thirst was significantly worse in the IG (5.1 [2.9]) than the CG (3.44 [2.0]) at the end of the study period (between-group difference, 1.66 points; time × group interaction; P = .01). There were no significant between-group differences in the readmission rate at 30 days (IG, 11 patients [29%]; CG, 7 patients [19%]; P = .41)., Conclusions and Relevance: Aggressive fluid and sodium restriction has no effect on weight loss or clinical stability at 3 days and is associated with a significant increase in perceived thirst. We conclude that sodium and water restriction in patients admitted for ADHF are unnecessary., Trial Registration: clinicaltrials.gov Identifier: NCT01133236.

Background: Anemia is a prevalent condition in heart failure with multiple potential causes. The complex interaction between iron stores, hepcidin, inflammation and anemia is poorly comprehended. We tested the hypothesis that, in stable heart failure patients with anemia, hepcidin is associated with iron deficiency status irrespective of inflammation., Methods and Results: Stable systolic heart failure outpatients with and without anemia underwent a complete iron panel, erythropoietin, hepcidin and tumor necrosis factor (TNF)-α assessment. Sixty outpatients were studied. Anemic patients (n = 38, mean hemoglobin 11.4 ± 1 g/dl) were older (69.6 ± 9.6 vs. 58 ± 10.8 years old, p < 0.01) compared with nonanemic patients (n = 22, mean hemoglobin 13.8 ± 1.1 g/dl). Iron deficiency was present in 42% of patients with anemia. TNF-α and hepcidin were 29 and 21% higher in patients with anemia, respectively, compared to nonanemic patients; however, no correlations were found between hepcidin and TNF-α levels. Hepcidin levels in the lower tertile (<31.7 ng/ml) were strongly associated with iron deficiency (OR 16.5, 95% CI 2.2-121.2; p < 0.01)., Conclusion: In stable heart failure patients with anemia, hepcidin levels may be more importantly regulated by patients' iron stores than by inflammation., (Copyright © 2012 S. Karger AG, Basel.)

Background: Physicians often overlook trepopnea as a symptom, and its prevalence and clinical repercussions are not usually described. We propose that trepopnea is a common symptom in heart failure (HF) and, because of patient avoidance of left lateral decubitus position, contributes to the greater prevalence of right-sided pleural effusion in patients with HF. Accordingly, this study aimed to determine trepopnea prevalence and to evaluate the association of trepopnea and the laterality of pleural effusion in decompensated HF., Methods: Consecutive patients (n = 37) with decompensated HF and evidence of pleural effusion by chest x-ray were included. Data were collected at the emergency department by a standard clinical examination in which patients were specifically asked about the presence of trepopnea and preferred decubitus position while recumbent. Chest x-ray and echocardiographic parameters were recorded., Results: Of the 37 patients, 19 (51%) reported trepopnea. Most patients presented with right-sided pleural effusion; only 2 patients (5.4%) presented with left-sided pleural effusion. Patients who reported trepopnea had predominant right-sided pleural effusion more frequently than patients without this symptom (73.7% vs 26.3%; P = .049). The participants that reported trepopnea or avoidance of left lateral decubitus position while recumbent or both had a greater probability of having predominant right-sided pleural effusion (likelihood ratio, 1.85; 95% confidence interval, 1.02-3.35)., Conclusions: Trepopnea is a common symptom in patients with decompensated HF and is associated with predominant right-sided pleural effusion in this population. Our results indicate that trepopnea may be a contributory factor for pleural effusion laterality in patients with decompensated HF., (Copyright © 2012 Elsevier Inc. All rights reserved.)