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Background: Heart failure (HF), a common cause of hospitalization, is associated with poor short-term clinical outcomes. Little is known about the long-term prognoses of patients with HF in Latin America., Methods: BREATHE was the first nationwide prospective observational study in Brazil that included patients hospitalized due to acute heart failure (HF). Patients were included during 2 time periods: February 2011-December 2012 and June 2016-July 2018 In-hospital management, 12-month clinical outcomes and adherence to evidence-based therapies were evaluated., Results: A total of 3013 patients were enrolled at 71 centers in Brazil. At hospital admission, 83.8% had clear signs of pulmonary congestion. The main cause of decompensation was poor adherence to HF medications (27.8%). Among patients with reduced ejection fraction, concomitant use of beta-blockers, renin-angiotensin-aldosterone inhibitors and spironolactone decreased from 44.5% at hospital discharge to 35.2% at 3 months. The cumulative incidence of mortality at 12 months was 27.7%, with 24.3% readmission at 90 days and 44.4% at 12 months., Conclusions: In this large national prospective registry of patients hospitalized with acute HF, rates of mortality and readmission were higher than those reported globally. Poor adherence to evidence-based therapies was common at hospital discharge and at 12 months of follow-up., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is known to present with pulmonary and extra-pulmonary organ complications. In comparison with the 2009 pandemic (pH1N1), SARS-CoV-2 infection is likely to lead to more severe disease, with multi-organ effects, including cardiovascular disease. SARS-CoV-2 has been associated with acute and long-term cardiovascular disease, but the molecular changes that govern this remain unknown. In this study, we investigated the host transcriptome landscape of cardiac tissues collected at rapid autopsy from seven SARS-CoV-2, two pH1N1, and six control patients using targeted spatial transcriptomics approaches. Although SARS-CoV-2 was not detected in cardiac tissue, host transcriptomics showed upregulation of genes associated with DNA damage and repair, heat shock, and M1-like macrophage infiltration in the cardiac tissues of COVID-19 patients. The DNA damage present in the SARS-CoV-2 patient samples, were further confirmed by γ-H2Ax immunohistochemistry. In comparison, pH1N1 showed upregulation of interferon-stimulated genes, in particular interferon and complement pathways, when compared with COVID-19 patients. These data demonstrate the emergence of distinct transcriptomic profiles in cardiac tissues of SARS-CoV-2 and pH1N1 influenza infection supporting the need for a greater understanding of the effects on extra-pulmonary organs, including the cardiovascular system of COVID-19 patients, to delineate the immunopathobiology of SARS-CoV-2 infection, and long term impact on health., (© 2022 The Authors. Immunology published by John Wiley & Sons Ltd.)

Aims: Treatment with mechanical circulatory support (MCS) has been proposed to mitigate mortality in cardiogenic shock (CS). However, there is a lack of data on MCS programs implementation and the effect of the learning curve on its outcomes in limited resources countries such as Brazil., Methods: Prospective cohort of patients with CS admitted in four tertiary-care centers treated with Impella CP or veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Clinical outcomes were peri-procedural complications, short-term mortality rate, and the centers' learning curve. The cohort was divided into two periods: from April 2017 to July 2018 ( n  = 24), and from August 2018 to December 2020 ( n  = 25)., Results: The study enrolled 49 patients [age 59 (43-63) years; 34 (70%) males]. The most common causes for CS were acute myocardial infarction in 22 (45%) and acute decompensation of chronic heart failure in 10 (20%). VA-ECMO was employed in 35 (71%) and Impella CP in 14 (29%) of patients. Overall complications occurred in 37 (76%) of patients, where major bleeding in 19 (38%) was the most common. The overall mortality rate was 61%, but it was lower in the second period (40%) in comparison to the first period (83%), p  = 0.002. The learning curve analysis showed a decrease in the mortality rate after 40 consecutive cases., Conclusions: Implementation of a temporary MCS program for refractory CS in a limited resource country is feasible. The learning curve effect might have played a role on survival rate since high morbimortality has decreased within time reaching optimal results by the end of the study.

Objectives: This observational, cross-sectional study based aimed to test whether heart failure (HF)-disease management program (DMP) components are influencing care and clinical decision-making in Brazil., Methods: The survey respondents were cardiologists recommended by experts in the field and invited to participate in the survey via printed form or email. The survey consisted of 29 questions addressing site demographics, public versus private infrastructure, HF baseline data of patients, clinical management of HF, performance indicators, and perceptions about HF treatment., Results: Data were obtained from 98 centers (58% public and 42% private practice) distributed across Brazil. Public HF-DMPs compared to private HF-DMP were associated with a higher percentage of HF-DMP-dedicated services (79% vs 24%; OR: 12, 95% CI: 94-34), multidisciplinary HF (MHF)-DMP [84% vs 65%; OR: 3; 95% CI: 1-8), HF educational programs (49% vs 18%; OR: 4; 95% CI: 1-2), written instructions before hospital discharge (83% vs 76%; OR: 1; 95% CI: 0-5), rehabilitation (69% vs 39%; OR: 3; 95% CI: 1-9), monitoring (44% vs 29%; OR: 2; 95% CI: 1-5), guideline-directed medical therapy-HF use (94% vs 85%; OR: 3; 95% CI: 0-15), and less B-type natriuretic peptide (BNP) dosage (73% vs 88%; OR: 3; 95% CI: 1-9), and key performance indicators (37% vs 60%; OR: 3; 95% CI: 1-7). In comparison to non- MHF-DMP, MHF-DMP was associated with more educational initiatives (42% vs 6%; OR: 12; 95% CI: 1-97), written instructions (83% vs 68%; OR: 2: 95% CI: 1-7), rehabilitation (69% vs 17%; OR: 11; 95% CI: 3-44), monitoring (47% vs 6%; OR: 14; 95% CI: 2-115), GDMT-HF (92% vs 83%; OR: 3; 95% CI: 0-15). In addition, there were less use of BNP as a biomarker (70% vs 84%; OR: 2; 95% CI: 1-8) and key performance indicators (35% vs 51%; OR: 2; 95% CI: 91,6) in the non-MHF group. Physicians considered changing or introducing new medications mostly when patients were hospitalized or when observing worsening disease and/or symptoms. Adherence to drug treatment and non-drug treatment factors were the greatest medical problems associated with HF treatment., Conclusion: HF-DMPs are highly heterogeneous. New strategies for HF care should consider the present study highlights and clinical decision-making processes to improve HF patient care.

Infection with the coronavirus known as COVID-19 has promoted growing interest on the part of cardiologists, emergency care specialists, intensive care specialists, and researchers, due to the study of myocardial involvement based on different clinical forms resulting from immunoinflammatory and neurohumoral demodulation.Myocardial involvement may be minimal and identifiable only by electrocardiographic changes, mainly increased cardiac troponins, or, on the other side of the spectrum, by forms of fulminant myocarditis and takotsubo syndrome.The description of probable acute myocarditis has been widely supported by the observation of increased troponin in association with dysfunction. Classical definition of myocarditis, supported by endomyocardial biopsy of inflammatory infiltrate, is rare; it has been observed in only one case report to date, and the virus has not been identified inside cardiomyocytes.Thus, the phenomenon that has been documented is acute myocardial injury, making it necessary to rule our obstructive coronary disease based on increased markers of myocardial necrosis, whether or not they are associated with ventricular dysfunction, likely associated with cytokine storms and other factors that may synergistically promote myocardial injury, such as sympathetic hyperactivation, hypoxemia, arterial hypotension, and microvascular thrombotic phenomena.Systemic inflammatory and myocardial phenomena following viral infection have been well documented, and they may progress to cardiac remodeling and myocardial dysfunction. Cardiac monitoring of these patients is, therefore, important in order to monitor the development of the phenotype of dilated myocardiopathy.This review presents the main etiological and physiopathological findings, a description of the taxonomy of these types of cardiac involvement, and their correlation with the main clinical forms of the myocardial component present in patients in the acute phase of COVID-19.

The use of sacubitril/valsartan significantly reduces death or hospitalization in patients with ejection fraction < 40%. There is no study evaluating this drug effects in non-compaction cardiomyopathy (NCCM) individuals. The aim of this article is to report a case of a patient with NCCM initially refractory to gold standard treatment and afterwards treated with sacubitril/valsartan and its improvements. This is a case report of a 48-year-old woman, presenting with NCCM heart failure, who had received standard guideline-directed medical therapy for 18 months without any improvement in clinical and echocardiographic parameters. After that period, sacubitril/valsartan was initiated. After 18 months of refractory usage of guideline-directed medical therapy, sacubitril/valsartan was started, and significant change in functional class (III to I) and important ventricular remodelling were achieved with an improvement of 29% in the ejection fraction, reduction of 7 mm in ventricular diastolic diameter, and mild to none mitral valve functional regurgitation. In this case report, sacubitril/valsartan use was associated with improvement of echocardiographic and clinical parameters in a patient with NCCM., (© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

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.)

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: 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.)

Background: The origin of dyspnea in chronic heart failure (HF) is multifactorial, and excessive ventilation is thought to play a role in inducing this symptom. Chemosensivity is augmented in HF, correlates with increased pulmonary ventilation (VE), and is an adverse prognostic marker. Despite increased blood levels of natriuretic peptides in clinical conditions associated with dyspnea, their effect on pulmonary VE and chemoreceptor activity remains unexplored., Methods: We tested in a prospective, placebo-controlled, three-way cross-over, double-blind randomized study the effects of the recombinant form of the natural human B-type natriuretic peptide (R-BNP) in comparison with placebo and levosimendan on chemoreflex sensitivity at rest, as well as their effects on pulmonary VE, systemic blood pressure, heart rate and sympathetic serum activity both at rest and during exercise., Results: Eleven stable chronic HF patients were randomized to sessions of 6-min treadmill-walking tests during placebo, or levosimendan or R-BNP intravenous infusion in the following conditions: room air, hypoxia, and hypercapnia. R-BNP administration determined higher pulmonary ventilatory response at rest and during exercise (P < 0.001) consequent to a boost of respiratory rate (P < 0.001) under room air and hypoxia conditions. Norepinephrine blood levels increased from rest to exercise in all conditions without differences among placebo, levosimendan, and R-BNP effects. BNP blood levels remained unchanged., Conclusions: The novelty of the present findings is that R-BNP infusion in HF patients can boost pulmonary ventilatory response at rest and during exercise., (© 2011 Blackwell Publishing Ltd.)

Background: Heart failure (HF) is associated with resting increased peripheral and central chemosensitivity which may correlate with an increased ventilatory response to exercise. However, its sensitivity in HF during exercise was never really reported., Objective: We tested if stimulation of central and peripheral chemoreceptors in HF patients could modulate ventilatory, chronotropic, and neurohormonal response during submaximal exercise., Methods: We investigated central and peripheral chemosensitivity in 15 HF and 7 control (C) comparing response through three 6 minute walking tests conducted in a treadmill with : room air, hypoxia, and hypercapnia (in a randomic order)., Results: RR at room air C and HF was 17±2 and 22±2 (p<.0001); at hypoxia 17±1 and 23±2 (p<.02); at CO25% was 20±2 and 22±5 (p<.02). Tidal volume (TV) at room air was 1.25±0.17 and 1.08±0.19 (p<.01); at hypoxia 1.65±0.34 and 1.2±0.2 (p<.0001); at CO25% 1.55±0.46 and 1.29±0.39 (p<.0001). At rest the increment in HF was higher for VE (C 33±40%, HF 62±94%, p<.01), HR(C 7±10%, HF 10±10%, p<0.05) at rest. During hypoxia exercise increment in HF was higher for RR (C 1±4, HF 11±6,p<.05), HR (C 12±2, HF 14±3, p<.05), VE/VO₂ (C -4±18%, HF 24±21%, p<.01), HR/VO₂ (C -26±11%, HF 11±5%, p<.01), VE/WD (C 36±10%, 46±14, p<.05%) and HR/WD (C 18±8%, HF 29±11, p<.01). During HF hypoxia exercise NO reduced, and IL-6, aldosterone levels increased. Neurohormonal levels unchanged in C., Conclusion: Exercise peripheral and central chemosensitivity are increased in HF and may modulate respiratory pattern, cardiac chronotropic, and neurohormonal activity during exercise.

A 27-year-old patient with tertiary syphilis, manifested as myocardial ischemia, presenting unstable angina, secondary to left coronary trunk occlusion. The diagnosis was confirmed by the serological findings and the pathological assessment of the aorta fragment.

Background: Anemia is a common finding in heart failure (HF) patients and has been associated with increased morbidity and mortality. It is generally denominated as anemia of chronic disease (ACD), but the association with true ferropenic anemia is common. Many studies have investigated the effects of treating anemia in HF patients with either erythropoietin alone or combination of erythropoietin and intravenous iron. However, the effect of iron supplementation alone in HF patients with ACD, ferropenic anemia, or both is unknown., Methods and Results: IRON-HF study is a multicenter, investigator initiated, randomized, double-blind, placebo controlled trial that will enroll anemic HF patients with relatively preserved renal function, low transferrin saturation, low iron levels, and low to moderately elevated ferritin levels. Interventions are iron sucrose intravenously 200 mg once per week for 5 weeks, ferrous sulfate 200 mg by mouth 3 times per day for 8 weeks, or placebo. The primary objective is to assess the impact of iron supplementation (intravenously or by mouth) compared with placebo in HF patients with anemia from deficient iron availability. The primary end point is variation of peak oxygen consumption assessed by ergospirometry over 3-month follow-up. Secondary end points include functional class, brain natriuretic peptide levels, quality of life scores, left ventricular ejection fraction, adverse events, HF hospitalization, and death., Conclusions: The results of IRON-HF should help to clarify the potential clinical impact of mild to moderate anemia correction in HF patients.