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BACKGROUND: Equations to predict maximum heart rate (HR(max)) in heart failure (HF) patients receiving [beta]-adrenergic blocking (BB) agents do not consider the cause of HF. We determined equations to predict HR(max) in patients with ischemic and nonischemic HF receiving BB therapy. METHODS AND RESULTS: Using treadmill cardiopulmonary exercise testing, we studied HF patients receiving BB therapy being considered for transplantation from 1999 to 2010. Exclusions were pacemaker and/or implantable defibrillator, left ventricle ejection fraction (LVEF) >50%, peak respiratory exchange ratio (RER) <1.00, and Chagas disease. We used linear regression equations to predict HR(max) based on age in ischemic and nonischemic patients. We analyzed 278 patients, aged 47 ± 10 years, with ischemic (n = 75) and nonischemic (n = 203) HF. LVEF was 30.8 ± 9.4% and 28.6 ± 8.2% (P = .04), peak VO(2) 16.9 ± 4.7 and 16.9 ± 5.2 mL kg(-1) min(-1) (P = NS), and the HR(max) 130.8 ± 23.3 and 125.3 ± 25.3 beats/min (P = .051) in ischemic and nonischemic patients, respectively. We devised the equation HR(max) = 168 - 0.76 x age (R(2) = 0.095; P = .007) for ischemic HF patients, but there was no significant relationship between age and HR(max) in nonischemic HF patients (R(2) = 0.006; P = NS). CONCLUSIONS: Our study suggests that equations to estimate HR(max) should consider the cause of HF. [ABSTRACT FROM AUTHOR]

Background: Heart failure (HF) is associated with poor prognosis, and the identification of biomarkers of its severity could help in its treatment. In a pilot study, we observed high levels of acetone in the exhaled breath of patients with HF. The present study was designed to evaluate exhaled acetone as a biomarker of HF diagnosis and HF severity.Methods: Of 235 patients with systolic dysfunction evaluated between May 2009 and September 2010, 89 patients (HF group) fulfilled inclusion criteria and were compared with sex- and age-matched healthy subjects (control group, n = 20). Patients with HF were grouped according to clinical stability (acute decompensated HF [ADHF], n = 59; chronic HF, n = 30) and submitted to exhaled breath collection. Identification of chemical species was done by gas chromatography-mass spectrometry and quantification by spectrophotometry. Patients with diabetes were excluded.Results: The concentration of exhaled breath acetone (EBA) was higher in the HF group (median, 3.7 μg/L; interquartile range [IQR], 1.69-10.45 μg/L) than in the control group (median, 0.39 μg/L; IQR, 0.30-0.79 μg/L; P < .001) and higher in the ADHF group (median, 7.8 μg/L; IQR, 3.6-15.2 μg/L) than in the chronic HF group (median, 1.22 μg/L; IQR, 0.68-2.19 μg/L; P < .001). The accuracy and sensitivity of this method in the diagnosis of HF and ADHF were about 85%, a value similar to that obtained with B-type natriuretic peptide (BNP). EBA levels differed significantly as a function of severity of HF (New York Heart Association classification, P < .001). There was a positive correlation between EBA and BNP (r = 0.772, P < .001).Conclusions: EBA not only is a promising noninvasive diagnostic method of HF with an accuracy equivalent to BNP but also a new biomarker of HF severity. [ABSTRACT FROM AUTHOR]

Continued assessment of temporal trends in mortality and epidemiology of specific cardiovascular diseases in South America is needed to provide a scientific basis for rational allocation of the limited healthcare resources and introduction of strategies to reduce risk and predict the future burden of cardiovascular disease. The epidemiology of cardiomyopathies, adult valve disease and heart failure (HF) in South America is reviewed here. Diseases of the circulatory system are the main cause of death based on data from about 50% of the South American population. Among the cardiovascular causes of death, cerebrovascular disease is predominant followed by ischaemic heart disease, other heart diseases and hypertensive disease. Of note, cerebrovascular disease is the main cause of death in women, and race also influenced cardiovascular mortality rates. HF is the most important cardiovascular reason for admission to hospital due to cardiovascular disease of ischaemic, idiopathic dilated cardiomyopathic, valvular, hypertensive and chagasic aetiologies. Also, mortality due to HF is high, especially owing to Chagas' disease. HF and aetiologies associated with HF are responsible for 6.3% of deaths. Rheumatic fever is the leading cause of valvular heart disease. The findings have important public health implications because the allocation of healthcare resources, and strategies to reduce the risk of HF should also consider controlling Chagas' disease and rheumatic fever in South American countries. [ABSTRACT FROM AUTHOR]

Study Objective: To determine and compare the cardiopulmonary responses of healthy children and children with heart failure due to idiopathic dilated cardiomyopathy (IC) to progressive treadmill exercise testing.Setting: University teaching hospital specializing in cardiology.Patients or Participants: Twenty-six children with stable, chronic heart failure (left ventricular ejection fraction < 45%) caused by IC (IC group) and 12 healthy children (control group).Interventions: After 12-lead resting ECG, all children underwent progressive treadmill exercise testing using a modified Naughton protocol. Tests were performed in a controlled-temperature exercise facility, at least 2 h after a light meal.Measurements and Results: Cardiopulmonary parameters were assessed at rest, at anaerobic threshold (AT), and at peak exercise. At rest, the tidal volume (VT) and O(2) consumption (VO(2)) for heart rate (O(2) pulse) were lower, while the heart rate, respiratory rate, and ventilatory equivalent for O(2) (minute ventilation [VE]/VO(2)) were higher in the IC group compared with the control group. At AT, the systolic BP, O(2) pulse, VT, exercise duration, VO(2), CO(2) production (VCO(2)), and VE were lower, while the VE/VO(2) and ventilatory equivalent for CO(2) (E/CO(2)) were higher in the IC group (p < 0.05). At peak exercise, the IC group had a significantly lower systolic BP, O(2) pulse, VE, VT, exercise duration, VO(2), and VCO(2), but higher VE/VO(2) and VE/VCO(2) than the control group (p < 0.05). The VE/VCO(2) slope was significantly higher for the IC group. No correlation existed between variables evaluated at rest vs during exercise.Conclusions: Gas exchange analysis performed during exercise successfully differentiated children with heart failure from healthy children. [ABSTRACT FROM AUTHOR]

Objectives: We hypothesized that exercise-related periodic breathing (EPB) would be associated with poor prognosis in advanced chronic heart failure (CHF).Background: Patients with CHF might present instability of the ventilatory control system characterized by cyclic waxing and waning of tidal volume (periodic breathing [PB]). This condition is associated with several deleterious circulatory and neuro-endocrine responses; in fact, PB in awake and asleep patients has been identified as an independent risk factor for cardiac death. During exercise, however, the prognostic value of PB is still unknown in CHF patients awaiting heart transplantation.Methods: Eighty-four patients with established CHF (65 male, 19 female) were submitted to clinical evaluation, echocardiogram, ventricular scintigraphy, determination of resting serum norepinephrine levels, and an incremental cardiopulmonary exercise test on cycle ergometer. Patients were followed for up to 49.7 months (median = 15.3), and 26 patients (30.9%) died during this period.Results: Twenty-five of 84 patients presented EPB (29.7%). The following variables were related to mortality according to Kaplan-Meier and univariate Cox regression analysis: EPB (p = 0.004), New York Heart Association class (p = 0.04), serum norepinephrine (p = 0.06), peak oxygen uptake (ml.min(-1).kg(-1) and % predicted; p = 0.085 and p = 0.10, respectively), slope of the ratio of change in minute ventilation to change in carbon dioxide output during exercise (p = 0.10), and scintigraphic left ventricular ejection fraction (p = 0.10). Cox multivariate analysis identified EPB as the only independent variable for cardiac death prediction (p = 0.007). Therefore, EPB alone was associated with a 2.97-fold increase in risk of death in this population (95% confidence interval = 1.34 to 6.54).Conclusions: Exercise-related periodic breathing independently predicts cardiac mortality in CHF patients considered for heart transplantation. [ABSTRACT FROM AUTHOR]

Objectives: We performed a prospective, randomized, double-blind, placebo-controlled study of carvedilol effects in children with severe, chronic heart failure (HF), despite the use of conventional therapy.Background: Little is known about the effects of carvedilol in youngsters with chronic HF and severe left ventricular (LV) dysfunction.Methods: We conducted a double-blind, placebo-controlled study of 22 consecutive children with severe LV dysfunction. The children had chronic HF and left ventricular ejection fraction (LVEF) <30%. Patients were randomly assigned to receive either placebo (8 patients) or the beta-blocker carvedilol (14 patients) at 0.01 mg/kg/day titrated up to 0.2 mg/kg/day, followed-up for six months.Results: During the follow-up and the up-titration period in the carvedilol group, four patients died and one underwent heart transplantation. In patients receiving carvedilol evaluated after six months, a significant increase occurred in LVEF, from 17.8% (95% confidence interval [CI], 14.1 to 21.4%) to 34.6% (95% CI, 25.2 to 44.0%); p = 0.001. Modified New York Heart Association (NYHA) functional class improved in nine patients taken off the transplant waiting list. All nine patients were alive at follow-up. In the placebo group, during the six-month follow-up, two patients died, and two underwent heart transplantation. Four patients persisted with HF symptoms (NYHA functional class IV). No significant change occurred in LVEF or fractional shortening.Conclusions: Carvedilol added to standard therapy may reduce HF progression and improve cardiac function, allowing some youngsters to be removed from the heart transplantation waiting list. [ABSTRACT FROM AUTHOR]

Background: Patients with heart failure with reduced ejection fraction (HFrEF) who achieve reverse remodelling (RR) can experience a new decrease in ejection fraction (EF), and the predictors of sustained RR (SRR) are not completely understood., Objectives: The study aims to identify predictors of SRR in patients with HFrEF after an increase in EF and evaluate SRR prognosis., Methods: In this retrospective, observational study, we evaluated a real-life cohort of patients with HFrEF and ≥2 consecutive echocardiograms, divided according to left ventricular EF (LVEF) trajectory: no RR (NRR: 3/3 LVEF measurements < 40%), non-SRR (NSRR: second LVEF ≥ 40%, third LVEF < 40%), and SRR (SRR: second and third LVEF ≥ 40%)., Results: We included 3628 of 8072 assessed HF patients in the analysis, with mean age 56.2 (±13.4) years, 64.4% male and 77.7% New York Heart Association (NYHA) I-II. Improved EF was observed for 1342 (37%) patients. Among those who achieved RR, 310 (23%) were NSRR, and 1032 (77%) were SRR. The mean (±SE) survival after the second echocardiogram was 10.6 (±0.2) years. The SRR group had the longest survival (12.2 ± 0.3 years), followed by the NSRR (10.6 ± 0.5) and NRR (9.8 ± 0.2 years) groups (P < 0.001). According to logistic multivariable regression, second LVEF [odds ratio (OR) = 1.06, confidence interval (CI) = 1.03-1.90, P < 0.001], second left ventricular end-systolic diameter (LVESD) (OR = 0.93, CI = 0.90-0.96, P < 0.001), second IV septum thickness (OR = 1.12, CI = 1.03-1.23, P = 0.012), systolic blood pressure (OR = 1.01, CI = 1.00-1.02, P = 0.014), NYHA I-II (OR = 1.86, CI = 1.27-2.74, P = 0.001) and furosemide non-use (OR = 1.87, CI = 1.27-2.74, P < 0.001) independently predicted SRR., Conclusions: Patients with greater EF increases and LVESD reductions at EF recovery, greater septum thickness, higher blood pressure, no need for diuretics and NYHA I/II maintenance had the best chance of maintaining recovered ventricular function., (© 2025 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Worsening heart failure (WHF) challenges health care with frequent rehospitalizations and reduced quality of life for patients. Despite therapeutic advances, high rehospitalization risks highlight the urgent need for new treatments., Objectives: This study evaluated the effectiveness of initiating novel therapies during hospitalization or vulnerable phase for WHF patients to reduce rehospitalization risks and determine the optimal treatment sequence., Methods: A systematic review and network meta-analysis were performed in accordance with Cochrane Collaboration and Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. We included randomized clinical trials from January 2013, to December 2022, sourced from PUBMED and EMBASE, comparing novel heart failure therapies against control. The primary outcome was heart failure rehospitalization., Results: Analysis of 9 randomized clinical trials involving 18,540 patients showed significant rehospitalization reductions with novel treatments, especially sodium-glucose co-transporter 2 inhibitors, angiotensin-neprilysin receptor inhibitor (ARNI), and ferric carboxymaltose. Sotagliflozin led to more pronounced reductions in heart failure hospitalization (OR: 0.50; 95% CI: 0.39-0.63; P  < 0.0001), followed by ARNI (OR: 0.54; 95% CI: 0.35-0.83; P  = 0.005), ferric carboxymaltose (OR: 0.55; 95% CI: 0.44-0.70; P  < 0.0001), empagliflozin (OR: 0.56; 95% CI: 0.39-0.78; P  = 0.0007), vericiguat 10 mg (OR: 0.83; 95% CI: 0.74-0.92; P  = 0.0008), and finerenone 15 mg (OR: 0.59; 95% CI: 0.38-0.91; P  = 0.016). These therapies, when initiated during hospitalization, markedly influenced rehospitalization outcomes., Conclusions: Early administration of sodium-glucose co-transporter 2 inhibitors, ARNI, and ferric carboxymaltose for WHF patients significantly reduces rehospitalization risk. Our findings support a strategic shift in WHF management, advocating for the rapid introduction of these novel therapies to enhance patient prognosis., Competing Interests: Dr Bocchi has received consulting fees from Servier, AstraZeneca, and Boehringer Ingelheim; has received subsidized travel/hotel/registration fees from Servier; has a membership in steering committee for Servier, Novartis, and Boehringer Ingelheim; has received research grant support through the Heart Institute (Incor) from Jansen, Bayer/Merck, AstraZeneca, Boehringer Ingelheim, Pfizer, and Novartis; and has received honoraria from Servier, Novartis, AstraZeneca, and Boehringer Ingelheim. Dr McDonald has served on the advisory board for Abbott. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Observational studies suggest a U-shaped association between serum potassium (K⁺) levels and mortality in patients with chronic heart failure (CHF). However, the mode of death in patients with HF and K⁺ disorders remains speculative. To investigate the association between potassium disorders and the mode of death in patients with CHF. A retrospective cohort of 10,378 CHF outpatients was analyzed over an average of 3.28 ± 2.5 years. Kaplan-Meier method, Cox proportional hazards regression models, Poisson regression models adjusting for confounders, and e-value determination (e' > 1.6) were used to observe associations between potassium disorders and outcomes. Chagas etiology (p < 0.01) and triple HF therapy (p < 0.01) were associated with hyperkalemia. Atrial fibrillation was associated with hypokalemia (p < 0.01). Chronic kidney disease (CKD) (p < 0.01) and diabetes (p = 0.03) were associated with both. Hypertension was inversely related to hyperkalemia (p < 0.01); age was inversely related to hypokalemia. Associations with mortality were significant for Chagas (p < 0.01, e-value 2.16), stroke (p < 0.01, e-value 1.85), hypokalemia (p = 0.02, e-value 1.94), severe hyperkalemia (p = 0.08, e-value 1.93), and CKD (p < 0.01, e-value > 1.63). Decompensated HF or cardiogenic shock was the cause of death in 54% of patients with normokalemia, 67.8% with hypokalemia, 44.9% with mild hyperkalemia, 57.8% with moderate hyperkalemia, and 69% with severe hyperkalemia. Most patients with hypokalemia and severe hyperkalemia died from decompensated HF (p = 0.007). Data suggest hypokalemia and severe hyperkalemia, along with Chagas and CKD, are associated with death. Unexpectedly, progressive HF was the most frequent mode of death rather than arrhythmias. Further studies are needed to confirm these findings and explore the underlying mechanisms., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Chronic Chagas cardiomyopathy (CCC) has unique pathogenic and clinical features with worse prognosis than other causes of heart failure (HF), despite the fact that patients with CCC are often younger and have fewer comorbidities. Patients with CCC were not adequately represented in any of the landmark HF studies that support current treatment guidelines. PARACHUTE-HF (Prevention And Reduction of Adverse outcomes in Chagasic Heart failUre Trial Evaluation) is an active-controlled, randomized, phase IV trial designed to evaluate the effect of sacubitril/valsartan 200 mg twice daily vs enalapril 10 mg twice daily added to standard of care treatment for HF. The study aims to enroll approximately 900 patients with CCC and reduced ejection fraction at around 100 sites in Latin America. The primary outcome is a hierarchical composite of time from randomization to cardiovascular death, first HF hospitalization, or relative change from baseline to week 12 in NT-proBNP levels. PARACHUTE-HF will provide new data on the treatment of this high-risk population. (Efficacy and Safety of Sacubitril/Valsartan Compared With Enalapril on Morbidity, Mortality, and NT-proBNP Change in Patients With CCC [PARACHUTE-HF]; NCT04023227)., Competing Interests: Funding Support and Author Disclosures PARACHUTE-HF is funded by Novartis Pharma AG. Dr Bocchi has received consulting fees from Servier, AstraZeneca, and Boehringer Ingelheim; has received travel/hotel/registration fees from Servier; has served as a member of the steering committee for Servier, Novartis, Boehringer Ingelheim; has received research grant support through the Heart Institute (Incor) from Janssen, Bayer/Merck, AstraZeneca, Boehringer Ingelheim, Pfizer, and Novartis; and has received honoraria from Servier, Novartis, AstraZeneca, and Boehringer Ingelheim. Dr Echeverria has received research support from Pfizer, Novartis, and Boehringer Ingelheim; has received consulting fees from Novartis and Boehringer Ingelheim, AstraZeneca, and Bayer. Drs Demacq, Chiang, Ferrari, and Gimpelewicz are Novartis employees. Dr de Barros e Silva has received research support from Pfizer, Bayer, and Roche Diagnostics; and has received consulting fees from Pfizer, Bayer, and Roche Diagnostics. Dr Morillo has received research support from Abbott, Medtronic, and Novartis; and has received consulting fees from Abbott, Medtronic, Novartis, and Pfizer. Dr Ramires has received speaker fees from AstraZeneca, Amgen, Pfizer, Novartis, and Bristol; and has received consulting fees from Novartis and Bristol. Dr Bahit has received honoraria (modest) from Merck Sharp & Dohme, Pfizer, Bristol Myers Squibb, CSL Behring, Janssen, and Boehringer Ingelheim. Dr Chavez-Mendoza has received a speaker fee from Novartis. Dr McMurray has received payments through Glasgow University from work on clinical trials, consulting, and other activities from Amgen, AstraZeneca, Bayer, Cardurion, Cytokinetics, GlaxoSmithKline, KBP Biosciences, and Novartis; has received personal consultancy fees from Alnylam Pharma, Bayer, Bristol Myers Squibb, George Clinical PTY Ltd, Ionis Pharma, Novartis, Regeneron Pharma, and River 2 Renal Corporation; has received personal lecture fees from Abbott, Alkem Metabolics, AstraZeneca, Blue Ocean Scientific Solutions Ltd, Boehringer Ingelheim, Canadian Medical and Surgical Knowledge, Emcure Pharma. Ltd, Eris Lifesciences, European Academy of CME, Hikma Pharmaceuticals, Imagica health, Intas Pharma, J.B. Chemicals and Pharma Ltd, Lupin Pharma, Medscape/Heart.Org, ProAdWise Communications, Radcliffe Cardiology, Sun Pharma, The Corpus, Translation Research Group, and Translational Medicine Academy; and is a director of Global Clinical Trial Partners Ltd. Dr Lopes has received research support from Bristol Myers Squibb, GlaxoSmithKline, Medtronic, and Pfizer; and has received consulting fees from Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, GlaxoSmithKline, Medtronic, Merck, Pfizer, and Portola. All other 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.)

Competing Interests: We declare no competing interests.

Background: Chagas disease, endemic in Latin America and spreading globally due to emigration, has a significant health burden, particularly in relation to chagasic heart failure (HF). Chagasic cardiomyopathy (CCM) is characterized by chronic inflammatory myocardial disease. This study aimed to identify inflammatory parameters and biomarkers that could aid in the management of patients with chagasic HF., Methods and Findings: A cohort study was conducted at a tertiary cardiology single-center over a mean follow-up period of 2.4 years. The study included patients with HF secondary to CCM enrolled between October 2013 and July 2017. Various clinical parameters, echocardiography findings, parasitemia status, brain natriuretic peptide (BNP) and troponin T (TnT) levels, and inflammatory biomarkers (IL-6, IL-10, IL-12p70, IL-17A, adiponectin, and IFN-γ) were assessed. The study encompassed a cohort of 103 patients, with a median age of 53 years and 70% being male. The left ventricular ejection fraction (LVEF) was 28%, with 40% of patients classified as NYHA II functional class. The median BNP level was 291 pg/ml. The observed mortality rate during the study period was 38.8%. Predictors of lower survival were identified as elevated levels of BNP, TnT, reduced LVEF, and increased adiponectin (thresholds: BNP > 309 pg/ml, TnT > 27.5 ng/ml, LVEF < 25.5%, adiponectin > 38 μg/mL). Notably, there was no evidence indicating a relationship between parasitemia and the inflammatory parameters with lower survival in these patients, including INF-γ, IL-6, IL-10, IL12-(p70), and IL17a., Conclusion: Despite the presence of a chronic inflammatory process, the evaluated inflammatory biomarkers in this cohort were not predictive of survival in patients with chagasic HF with reduced ejection fraction (HFrEF). However, reduced LVEF, elevated BNP, adiponectin levels, and troponin T were identified as predictors of lower survival in these patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Bocchi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: The use of ventricular assist devices (VAD) is increasing; however, diagnosis and management of device complications, such as the driveline exit site (DES) being the portal of entry for fungal infection, is not well known., Method: A systematic review involving searching PubMed (2005 to July 2020) was conducted. The case of a 43-year-old female patient who had a left VAD (LVAD) (HeartMate 3, Abbott, US) is also reported., Results: The patient was successfully treated with ketoconazole cream and oral fluconazole for likely superficial DES fungal infections. We included 36 studies that met our inclusion criteria; however, only one was included in our review. In the literature, five cases of DES fungal infection were reported, with Candida being the only fungal pathogen., Conclusion: LVAD fungal infections are uncommon but can be responsible for high mortality rates, require a prolonged period of treatment, and can present a huge problem when surgical alternatives are not available. However, Candida species are most common. Fungal infections can only produce clear discharge, and so the classic definition of driveline infection based on purulent secretion can vary. Negative skin culture does not exclude the diagnosis of infection of the DES, and so empirical diagnosis may only be clinically based., Competing Interests: Declaration of interest: The authors have no conflicts of interest.

Background: Limited research has explored sex-specific differences in death predictors of HF patients with ischemic (iCMP) and nonischemic (niCMP) cardiomyopathy. This study assessed sex differences in niCMP and iCMP prognosis., Methods: We studied 7487 patients with HF between February 2017 and September 2020. Clinical features and echocardiographic findings were collected. We used Kaplan-Meier, Cox proportional hazard models, and chi-square scores of Cox regression to determine death predictors in women and men., Results: The mean age was 64.3 ± 14.2 years, with 4417 (59%) males. Women with iCMP and niCMP exhibited a significantly higher mean age, higher mean left ventricular ejection fraction, and smaller left ventricular diastolic diameter than men. Over 2.26 years of follow-up, 325 (14.7%) women and 420 (15.7%) men, and 211 women (24.5%) and 519 men (29.8%) with niCMP ( p = NS) and iCMP ( p = 0.004), respectively, died. The cumulative incidence of death was higher in men with iCMP (log-rank p < 0.0001) but similar with niCMP. Cox regression showed chronic kidney disease, diabetes, stroke, atrial fibrillation, age, and myocardial infarction as the main predictors of death for iCMP in women and men., Conclusions: Women exhibited a better prognosis than men with iCMP, but similar for niCMP. Nevertheless, sex was not an independent predictor of death for both CMP.

Background: The evidence supporting the use of renin-angiotensin-aldosterone system (RAAS) inhibitors and beta-blockers for the prevention of anthracycline-induced cardiomyopathy is controversial., Objective: We performed a meta-analysis to assess the effectiveness of these drugs in preventing cardiotoxicity., Methods: The meta-analysis included prospective, randomized studies in adults receiving anthracycline chemotherapy and compared the use of RAAS inhibitors or beta-blockers versus placebo with a follow-up of 6 to 18 months. The primary outcome was change in left ventricular ejection fraction (LVEF) during chemotherapy. Secondary outcomes were the incidence of heart failure, all-cause mortality, and changes in end-diastolic measurement. Heterogeneity was assessed by stratification and meta-regression. A significance level of p < 0.05 was adopted., Results: The search resulted in 17 studies, totaling 1,530 patients. The variation (delta) in LVEF was evaluated in 14 studies. Neurohormonal therapy was associated with a lower delta in pre- versus post-therapy LVEF (weighted mean difference 4.42 [95% confidence interval 2.3 to 6.6]) and higher final LVEF (p < 0.001). Treatment resulted in a lower incidence of heart failure (risk ratio 0.45 [95% confidence interval 0.3 to 0.7]). There was no effect on mortality (p = 0.3). For analysis of LVEF, substantial heterogeneity was documented, which was not explained by the variables explored in the study., Conclusion: The use of RAAS inhibitors and beta-blockers to prevent anthracycline-induced cardiotoxicity was associated with less pronounced reduction in LVEF, higher final LVEF, and lower incidence of heart failure. No changes in mortality were observed. (CRD PROSPERO 42019133615).

The Kansas City Cardiomyopathy Questionnaire-12 (KCCQ-12) is a simple, feasible, and sensitive questionnaire developed in English for assessing the health status (symptoms, function, and quality of life) of patients with heart failure (HF). We aimed to assess the internal consistency and construct validity of the Portuguese version of KCCQ-12. We administered the KCCQ-12, the Minnesota Living Heart Failure (MLHFQ), and the New York Heart Association (NYHA) classification by telephone. Internal consistency was assessed with Cronbach's Alpha (α-Cronbach) and construct validity with correlations to the MLHFQ and NYHA. Internal consistency was high (α-Cronbach = 0.92 for the Overall Summary score and 0.77-0.85 for the subdomains). Construct validity was supported by finding high correlations between the KCCQ-12 Physical Limitation and the Symptom Frequency domains with the physical domain of the MLHFQ (r = -0.70 and r = -0.76, p < 0.001 for both) and the Overall Summary scale with NYHA classifications (r = -0.72, p < 0.001). The Portuguese version of KCCQ-12 has high internal consistency and shows a convergent construct validity with other measures quantifying the health status of patients with chronic HF and can be used confidently in Brazil for research and clinical care.

Background: Heart failure (HF) is one of the leading causes of death worldwide. Studies show that women have better survival rates than men despite higher hospitalizations. However, little is known about differences in mortality and predictors of death in women and men with HF with preserved (HFpEF), mildly reduced (HFmrEF), and reduced ejection fraction (HFrEF)., Methods: From February 2017 to September 2020, mortality and predictors of death were analyzed in women and men with HF. Baseline data included clinical characteristics and echocardiographic findings., Results: A total of 11,282 patients, 63.9 ± 14.4 years, including 6256 (55.4%) males, were studied. Females were older, had a higher baseline mean left ventricular ejection fraction (LVEF) and lower left ventricular diastolic diameter. During follow-ups, 1375 (22%) men and 925 (18.4%) women died. Cumulative incidence of death was higher in men with HFrEF but similar for HFmrEF and HFpEF. Cox regression for death showed renal dysfunction, stroke, diabetes, atrial fibrillation, age, LVEF, valve disease, MI, and hypertensive CMP as independent death predictors for all HF patients., Conclusions: Women had a better prognosis than men in HFrEF and similar mortality for HFmrEF and HFpEF, but sex was not an independent predictor of death for all HF subtypes.

Background: Trypanosoma cruzi shows an exuberant genetic diversity. Currently, seven phylogenetic lineages, called discrete typing units (DTUs), are recognised: TcI-TcVI and Tcbat. Despite advances in studies on T. cruzi and its populations, there is no consensus regarding its heterogeneity., Objectives: This study aimed to perform molecular characterisation of T. cruzi strains, isolated in the state of São Paulo, to identify the DTUs involved and evaluate their genetic diversity., Methods: T. cruzi strains were isolated from biological samples of chronic chagasic patients, marsupials and triatomines through culture techniques and subjected to molecular characterisation using the fluorescent fragment length barcoding (FFLB) technique. Subsequently, the results were correlated with complementary information to enable better discrimination between the identified DTUs., Findings: It was possible to identify TcI in two humans and two triatomines; TcII/VI in 19 humans, two marsupials and one triatomine; and TcIII in one human host, an individual that also presented a result for TcI, which indicated the possibility of a mixed infection. Regarding the strains characterised by the TcII/VI profile, the correlation with complementary information allowed to suggest that, in general, these parasite populations indeed correspond to the TcII genotype., Main Conclusions: The TcII/VI profile, associated with domestic cycles and patients with chronic Chagas disease, was the most prevalent among the identified DTUs. Furthermore, the correlation of the study results with complementary information made it possible to suggest that TcII is the predominant lineage of this work.

Background: cardiovascular diseases (CVD) are Brazil's leading causes of death in women and men. This study analyzed age-adjusted death rate (DRaj) trends from all causes of death (ACD), CVD, ischemic heart disease (IHD), and stroke in women and men aged 35 to 74 years from 1996 to 2019., Methods: We analyzed DRaj trends for all causes of death (ACD), CVD, IHD, and stroke. Data were from the Ministry of Health mortality database. Joinpoint Regression Program™ performed trend analysis and adjustments in death rates. Average annual percentage change (AAPC) determined the intensity of changes., Results: In women, DRaj reduced for ACD (AAPC = -1.6%); CVD (AAPC = -2.6%); IHD (AAPC = -1.9%); and stroke (AAPC = -4.6%) ( p < 0.001 for all). In men, ACD reduced from 1996 to 2004 (AAPC = -0.9%; p < 0.001), from 2012 to 2019 (AAPC = -1.9%; p < 0.001), and unchanged from 2004 to 2012; CVD (AAPC = -2.1%); IHD (AAPC = -1.5%); stroke (AAPC = -4.9%) ( p < 0.001 for all) reduced from 1996 to 2019. From 1996 to 2019, the male/female ratio for ACD remained unchanged. CVD increased from 1.58 to 1.83, IHD from 1.99 to 2.30, and stroke from 1.52 to 1.83., Conclusion: ACD, CVD, IHD, and stroke were reduced more significantly in women, and the ratio of CVD, IHD, and CVD in men and women increased more in men. Future studies will be needed to determine the main factors responsible for a better outcome in women.

Competing Interests: 1. Consulting Fee: Servier, AstraZeneca, Boehringer Ingelheim 2. Subsidized Travel/Hotel/Registration Fees: Servier, Novartis 3. Membership in Steering Committee: Servier, Novartis, Boehringer Ingelheim, AstraZeneca, Bayer 4. Research grant support through the Heart Institute (InCor) from: Jansen, Bayer/Merck, AstraZeneca, Boehringer Ingelheim, Pfizer 5. Honoraria: Servier, Novartis, AstraZeneca, Boehringer Ingelheim

Chagas disease, caused by the protozoan Trypanosoma cruzi , is an endemic parasitic disease of Latin America, affecting 7 million people. Although most patients are asymptomatic, 30% develop complications, including the often-fatal Chronic Chagasic Cardiomyopathy (CCC). Although previous studies have demonstrated some genetic deregulations associated with CCCs, the causes of their deregulations remain poorly described. Based on bulk RNA-seq and whole genome DNA methylation data, we investigated the genetic and epigenetic deregulations present in the moderate and severe stages of CCC. Analysis of heart tissue gene expression profile allowed us to identify 1407 differentially expressed transcripts (DEGs) specific from CCC patients. A tissue DNA methylation analysis done on the same tissue has permitted the identification of 92 regulatory Differentially Methylated Regions (DMR) localized in the promoter of DEGs. An in-depth study of the transcription factors binding sites (TFBS) in the DMRs corroborated the importance of TFBS's DNA methylation for gene expression in CCC myocardium. TBX21, RUNX3 and EBF1 are the transcription factors whose binding motif appears to be affected by DNA methylation in the largest number of genes. By combining both transcriptomic and methylomic analysis on heart tissue, and methylomic analysis on blood, 4 biological processes affected by severe CCC have been identified, including immune response, ion transport, cardiac muscle processes and nervous system. An additional study on blood methylation of moderate CCC samples put forward the importance of ion transport and nervous system in the development of the disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Brochet, Ianni, Laugier, Frade, Silva Nunes, Teixeira, Mady, Ferreira, Ferré, Santos, Kuramoto, Cabantous, Steffen, Stolf, Pomerantzeff, Fiorelli, Bocchi, Pissetti, Saba, Cândido, Dias, Sampaio, Gaiotto, Marin-Neto, Fragata, Zaniratto, Siqueira, Peixoto, Rigaud, Bacal, Buck, Almeida, Lin-Wang, Schmidt, Martinelli, Hirata, Donadi, Costa Pereira, Rodrigues Junior, Puthier, Kalil, Spinelli, Cunha-Neto and Chevillard.)

Background: Exercise oscillatory ventilation (EOV) is an abnormal breathing pattern that occurs in ~20% of patients with heart failure (HF) and is associated with poor prognosis and exercise intolerance. β-blockers (βb) are prescribed for most HF patients; however, their effect on EOV remains unclear. We evaluated the effect of βb on EOV in HF patients with reduced ejection fraction (HFrEF)., Methods: Fifteen patients diagnosed with HF, ejection fraction < 45%, aged from 18 to 65 years, were included before starting βb therapy. Patients underwent clinical evaluation, cardiopulmonary exercise testing, echocardiography, laboratory exams (norepinephrine levels, B type natriuretic peptide) at baseline and after βb therapy optimized for six months. Presence of exercise oscillatory breathing was determined by two experienced observers who were blinded to the moment of the test (pre or post)., Results: Fifteen patients (1 female), aged 49.5 ± 2.5 years, with HFrEF, NYHA I-III enrolled in the study. The etiologies of the HFrEF were idiopathic (n = 8) and hypertensive (n = 7). LVEF increased after βb therapy from 25.9 ± 2.5% to 33 ± 2.6%, P = 0.02; peak VO 2 did not significantly change (21.8 ± 1.7 vs 24.7 ± 1.9, P = 0.4); VE/VCO 2 slope changed from 32.1 ± 10.6-27.5 ± 9.1, P = 0.03. Before βb initiation, nine patients (60%) had EOV, but only two (13%) did after optimized therapy. McNemar test was used to evaluate the significance of the association between the two moments (P = 0.02)., Conclusion: In patients with HF, medical therapy with βb can reverse EOV. This may explain why these patients experience symptom improvement after βb therapy., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Endomyocardial fibrosis (EMF) is a rare and underdiagnosed cause of restrictive cardiomyopathy. Its aetiology is not yet defined and could be caused by the influence of different clinical factors that seem to combine with genetic aspects of individuals susceptible to an inflammatory process that leads to formation of fibrosis., Case Summary: We describe a case of a 50-year-old man from the northeastern region of Brazil, where there is high prevalence of schistosomiasis. He presented to our centre with symptoms of right heart failure. The echocardiogram showed normal left ventricular ejection fraction. Right ventricular had normal systolic function but in the apical region was filled with a homogeneous and hypoechoic image causing obliteration and restriction of the apex. The late gadolinium enhancement with cardiac magnetic resonance showed diffuse and heterogeneous subendocardial fibrosis in the right ventricle apex consistent with EMF, but declined endocardiectomy., Discussion: This report presents an interesting case of EMF and schistosomiasis simultaneously. The hypothesis of parasitosis as a probable cause of EMF was raised by helminth-induced hypereosinophilia. Complementary imaging tests such as magnetic resonance imaging and echocardiography, in addition to clinical and epidemiological suspicion, are essential for its diagnosis. Early surgical resolution becomes crucial for long-term survival., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Chagas disease (CD) is a neglected infectious disease associated with early mortality and substantial disability. Three-dimensional speckle tracking (3D STE) may play a role in the evaluation of CD. We aim to characterize new echocardiographic variables in patients with CD and to assess the hypothesis that 3D STE may predict outcomes. Seventy-two patients with CD were included. Clinical and conventional 2D and 3D STE analysis were performed. Patients were followed up for 60 months. Clinical events were defined as hospitalization for heart failure, complex ventricular arrhythmias, heart transplant and all-cause death. Seventy-two patients were recruited and enrolled in three groups: left ventricular ejection fraction (LVEF) < 0.40 (N = 22; reduced LVEF or rLVEF); 0.40 ≤ LVEF ≤ 0.50 (N = 10; mildly reduced LVEF or mrLVEF) and LVEF > 0.50 (N = 30; preserved LVEF or pLVEF). After a Cox model analysis, the top predictors of composite endpoints were 2D LV global longitudinal strain (GLS) ≤ - 11.3% (AUC = 0.87), 2D LV global circumferential strain (GCS) ≤  - 10.1% (AUC = 0.79), 3D LV GLS ≤ - 13% (AUC = 0.82), 3D LV area strain ≤ - 16% (AUC = 0.81) and right ventricle (RV) GLS ≤ - 17.2% (AUC = 0.78). Patients with CD and mrLVEF were morphologically similar to the rLVEF patients despite the benign evolution as the pLVEF group. RV GLS, 2D LV GLS, 2D LV GCS, 3D LV GLS, and 3D LV area strain are strong predictors of 60 months outcomes in patients with CD., (© 2022. The Author(s).)

Background: Heart failure (HF) associated with atrial fibrillation increases patients' physical inactivity, worsening their clinical condition and mortality. Exercise training is safe and has clear benefits in HF. However, little is known about the effects of exercise training on patients with HF with reduced ejection fraction and permanent atrial fibrillation (HFAF)., Objective: The purpose of this study was to test the hypothesis that exercise training improves functional capacity, cardiac function, and quality of life in patients with HFAF., Methods: This randomized clinical trial was conducted at the Heart Institute. Patients with HFAF, left ventricular ejection fraction ≤40%, and resting heart rate (HR) ≤80 beats/min were included in the study. Cardiopulmonary testing, echocardiography, nervous system, and quality of life assessment were performed before and after the 12-week protocol period., Results: Twenty-six patients (mean age 58 ± 1 years) were randomized to exercise training (HFAF-trained group; n = 13) or no training (HFAF-untrained group; n = 13). At baseline, no differences between the groups were found. Exercise improved peak oxygen consumption, slope of ventilation per minute/carbon dioxide production, and quality of life. The HFAF-trained group had significantly decreased resting HR (from 73 ± 2 to 69 ± 2 beats/min; P = .02) and recovery HR (from 148 ± 11 to 128 ± 9 beats/min; P = .001). Concomitantly, left ventricular ejection fraction increased (from 31% ± 1% to 36% ± 0.9%; P = .01), left atrial dimension decreased (from 52 ± 1.2 to 47 ± 1 mm; P = .03), and left ventricular end-systolic volume and left ventricular end-diastolic volume deceased (from 69 ± 2 to 64 ± 1.8 mL/m 2 and from 99 ± 2.1 to 91 ± 2 mL/m 2 , respectively; P < .05). No changes were observed in the HFAF-untrained group., Conclusion: Exercise training can improve exercise capacity, quality of life, and cardiac function in patients with HF with reduced ejection fraction and permanent atrial fibrillation., (Copyright © 2022 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)