In-Hospital Management and Long-term Clinical Outcomes and Adherence in Patients With Acute Decompensated Heart Failure: Primary Results of the First Brazilian Registry of Heart Failure (BREATHE).

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 SUGGESTION FOR REPHRASING: 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.

Reply to the letter "Understanding lactate and its clearance during extracorporeal membrane oxygenation for supporting refractory cardiogenic shock patients".

This is a reply to the letter titled "Understanding lactate and its clearance during extracorporeal membrane oxygenation for supporting refractory cardiogenic shock patients" by Eva Rully Kurniawati et al. In response to the concerns raised about our paper published in BMC Cardiovascular Disorders, titled "Association between serum lactate levels and mortality in patients with cardiogenic shock receiving mechanical circulatory support: a multicenter retrospective cohort study," we have addressed the confounding bias on the population included and the use of VA-ECMO and Impella CP. Furthermore, we have provided new data on the correlation of oxygen supply and lactate levels at admission of cardiogenic shock.

Association between serum lactate levels and mortality in patients with cardiogenic shock receiving mechanical circulatory support: a multicenter retrospective cohort study.

BACKGROUND: To evaluate the prognostic value of peak serum lactate and lactate clearance at several time points in cardiogenic shock treated with temporary mechanical circulatory support (MCS) using veno-arterial extracorporeal membrane oxygenation (VA-ECMO) or Impella CP®. METHODS: Serum lactate and clearance were measured before MCS and at 1 h, 6 h, 12 h, and 24 h post-MCS in 43 patients at four tertiary-care centers in Southern Brazil. Prognostic value was assessed by univariable and multivariable analysis and receiver operating characteristic (ROC) curves for 30-day mortality. RESULTS: VA-ECMO was the most common MCS modality (58%). Serum lactate levels at all time points and lactate clearance after 6 h were associated with mortality on unadjusted and adjusted analyses. Lactate levels were higher in non-survivors at 6 h, 12 h, and 24 h after MCS. Serum lactate > 1.55 mmol/L at 24 h was the best single prognostic marker of 30-day mortality [area under the ROC curve = 0.81 (0.67-0.94); positive predictive value = 86%). Failure to improve serum lactate after 24 h was associated with 100% mortality. CONCLUSIONS: Serum lactate was an important prognostic biomarker in cardiogenic shock treated with temporary MCS. Serum lactate and lactate clearance at 24 h were the strongest independent predictors of short-term survival.

Sudden cardiac death markers in non-ischemic cardiomyopathy.

Heart failure is an increasingly prevalent disease associated with high morbidity and mortality. In 30-40% of patients, the etiology is non-ischemic. In this group of patients, the implantable cardioverter-defibrillator (ICD) prevents sudden death and decreases total mortality. However, due to burden of cost, the fact that many ICD patients will never need any therapy, and possible complications involved in implant and follow-up, the device should not be implanted in every patient with non-ischemic heart failure. There is an urgent need to adequately identify patients with highest sudden death risk, in whom the implant is most cost-effective. In the present paper, the authors discuss current available tests for risk stratification of sudden cardiac death in patients with non-ischemic heart failure.

Serum levels and polymorphisms of matrix metalloproteinases (MMPs) in carotid artery atherosclerosis: higher MMP-9 levels are associated with plaque vulnerability.

CONTEXT: Matrix metalloproteinases are involved in atherosclerosis and plaque vulnerability. OBJECTIVE: To investigate serum levels and genetic polymorphisms of matrix metalloproteinases (MMPs) -1, -3 and -9 in patients submitted to carotid endarterectomy. METHODS: Genetic polymorphisms were evaluated using polymerase chain reaction (PCR-RFLP); serum levels were measured using ELISA; histological sections were stained with Picrosirius Red to analyze the fibrous cap thickness, lipid core and collagen content and with hematoxylin--eosin to detect the presence of intraplaque hemorrhage. RESULTS: MMP-9 serum levels were significantly higher in patients with a thinner fibrous cap (p = 0.033) or acute or recent intraplaque hemorrhage (p = 0.008) on histology, as well as in patients with previous stroke (p = 0.009) or peripheral vascular disease (p = 0.049). No consistent associations were observed between different MMP genotypes and fibrous cap thickness, lipid core, collagen content or intraplaque hemorrhage. CONCLUSIONS: MMP-9 serum levels were consistently associated with markers of carotid atherosclerosis and lesion vulnerability, whereas specific MMP genotypes were not.

Non­synonymous polymorphisms in the HRC and ADRB1 genes may be associated with all­cause death in patients with non­ischemic heart failure.

Sudden cardiac death (SCD) is an unpredictable and common mode of death in patients with heart failure (HF). Alterations in calcium handling may lead to malignant arrhythmias, resulting in SCD, and variants in calcium signaling-related genes have a significant association with SCD. Therefore, the aim of the present retrospective cohort study was to investigate the association of Ser96Ala [histidine-rich calcium-binding protein (HRC)], Ser49Gly [ß1-adrenergic receptor (ADRB1)], Arg389Gly (ADRB1) and Gly1886Ser [ryanodine receptor 2 (RYR2)] polymorphisms with serious arrhythmic events and overall mortality in patients with HF with reduced left ventricular ejection fraction of non-ischemic etiology. In total, 136 patients with HF underwent physical examination, routine laboratory tests, non-invasive assessment of cardiac function and an invasive electrophysiological study. The primary outcome was the occurrence of serious arrhythmic events, set as either SCD or appropriate implantable cardioverter-defibrillator (ICD) therapy, and the secondary outcome was all-cause death. During a median follow-up of 37 months, arrhythmic events occurred in 26 patients (19%) and 41 patients (30%) died. Patients carrying the Ser allele of the Ser96Ala polymorphism in HRC had worse survival than those with the Ala/Ala genotype (log-rank P=0.043). Despite the difference in survival time, the Ala/Ala genotype was not associated with all-cause death in the regression analysis [unadjusted hazard ratio (HR)=0.17; 95% CI, 0.02-1.21]. Regarding the Ser49Gly and Arg389Gly polymorphisms in ADRB1, homozygosity for the major alleles at both sites (Ser49Ser and Arg389Arg) was associated with a two-fold increased risk of all-cause death compared with the other genotype combinations (unadjusted HR=1.98; 95% CI, 1.02-3.82). However, this association was lost after controlling for clinical covariates. No association was observed for the Gly1886Ser polymorphism in RYR2. Overall, the present findings are concurrent with the hypothesis that the Ser96Ala (HRC), Ser49Gly (ADRB1) and Arg389Gly (ADRB1) polymorphisms may be associated with HF prognosis. In particular, the Ser96Ala polymorphism might aid in risk stratification and patient selection for ICD implantation.

Left ventricular structural abnormalities in the assessment of diastolic function in the elderly: source of discrepancies between the 2009 and 2016 criteria.

Diastolic dysfunction (DD) is routinely evaluated in echocardiography to support diagnosis, prognostication, and management of heart failure, a condition highly prevalent in elderly patients. Clinical guidelines were published in 2009, and updated in 2016, pursuing to standardize and improve DD categorization. We aimed to assess the concordance of DD between these two documents in an elderly population and to investigate how left ventricular structural abnormalities (LVSA) impact the reclassification. To evaluate this we analyzed the 308 consecutive transthoracic echocardiograms in patients older than 60 years (70.4 ± 7.7 years-old, 59% women) that fulfilled the inclusion criteria out of the 1438 echocardiograms performed in a tertiary hospital. We found that the prevalence of DD was lower according to the 2016 criteria (64% vs. 91%; p < 0.001), with 207 (67.2%) patients changing category, indicating poor agreement between the guidelines (kappa = 0.21). There were 188 (61%) patients with LVSA, which drove most of the reclassifications in 2016 Grade I DD cases. The prevalence of elevated filling pressures by Doppler halved in this elderly population using the updated recommendations (20.9% vs. 39.2%; p < 0.001). In conclusion the prevalence of DD was lower applying the 2016 guidelines, with a poor agreement with 2009 guidelines in all DD grades. The role of LVSA in reclassifications was particularly evident in Grade I DD, while Doppler parameters drove reclassifications among the more severe grades. If not properly addressed, these discrepancies may undermine the reliance on DD as a diagnostic and prognostic tool, particularly in an elderly population at a higher risk of heart failure.

Incremental Role of New York Heart Association Class and Cardiopulmonary Exercise Test Indices for Prognostication in Heart Failure: A Cohort Study. / Papel Incremental da Classificação da New York Heart Association e dos Índices do Teste de Exercício Cardiopulmonar para Prognóstico na Insuficiência Cardíaca: um Estudo de Coorte.

BACKGROUND: Central Illustration : Incremental Role of New York Heart Association Class and Cardiopulmonary Exercise Test Indices for Prognostication in Heart Failure: A Cohort Study LVEF: left ventricular ejection fraction; HR: hazard ratio; CI: confidence interval; NYHA: New York Heart Association; VO 2: oxygen consumption. BACKGROUND: The accuracy of the New York Heart Association (NYHA) classification to assess prognosis may be limited compared with objective cardiopulmonary exercise test (CPET) parameters in heart failure (HF). OBJECTIVE: To investigate the prognostic value of the NYHA classification in addition to Weber class. METHODS: Adult outpatients with HF undergoing CPET in a Brazilian tertiary care center were included. The physician-assigned NYHA class and the CPET-derived Weber class were stratified into "favorable" (NYHA I or II; Weber A or B) or "adverse" (NYHA III or IV; Weber C or D). Patients with one favorable class and one adverse class were defined as "discordant." The primary endpoint was time to all-cause mortality. A 2-sided p value < 0.05 was considered statistically significant. RESULTS: A total of 834 patients were included. Median age was 57 years; 42% (351) were female, and median left ventricular ejection fraction was 32%. Among patients with concordant NYHA and Weber classes, those with adverse NYHA and Weber classes had significantly higher all-cause mortality compared to those with favorable classes (hazard ratio [HR]: 5.65; 95% confidence interval [CI]: 3.38 to 9.42). Among patients with discordant classes, there was no significant difference in all-cause mortality (HR: 1.38; 95% CI: 0.82 to 2.34). In the multivariable model, increments in NYHA class (HR: 1.55 per class increase; 95% CI: 1.26 to 1.92) and reductions in peak VO 2 (HR: 1.47 per 3 ml/kg/min decrease; 95% CI: 1.28 to 1.70) significantly predicted mortality. CONCLUSIONS: Physician-assigned NYHA class and objective CPET measures provide complementary prognostic information for patients with HF.

Functional assessment based on cardiopulmonary exercise testing in mild heart failure: A multicentre study.

AIMS: In this multicentre study, we compared cardio-pulmonary exercise test (CPET) parameters between heart failure (HF) patients classified as New York Heart Association (NYHA) class I and II to assess NYHA performance and prognostic role in mild HF. METHODS AND RESULTS: We included consecutive HF patients in NYHA class I or II who underwent CPET in three Brazilian centres. We analysed the overlap between kernel density estimations for the per cent-predicted peak oxygen consumption (VO2 ), minute ventilation/carbon dioxide production (VE/VCO2 ) slope, and oxygen uptake efficiency slope (OUES) by NYHA class. Area under the receiver-operating characteristic curve (AUC) was used to assess the capacity of per cent-predicted peak VO2 to discriminate between NYHA class I and II. For prognostication, time to all-cause death was used to produce Kaplan-Meier estimates. Of 688 patients included in this study, 42% were classified as NYHA I and 58% as NYHA II, 55% were men, and mean age was 56 years. Median global per cent-predicted peak VO2 was 66.8% (IQR 56-80), VE/VCO2 slope was 36.9 (31.6-43.3), and mean OUES was 1.51 (±0.59). Kernel density overlap between NYHA class I and II was 86% for per cent-predicted peak VO2 , 89% for VE/VCO2 slope, and 84% for OUES. Receiving-operating curve analysis showed a significant, albeit limited performance of per cent-predicted peak VO2 alone to discriminate between NYHA class I vs. II (AUC 0.55, 95% CI 0.51-0.59, P = 0.005). Model accuracy for probability of being classified as NYHA class I (vs. NYHA class II) across the spectrum of the per cent-predicted peak VO2 was limited, with an absolute probability increment of 13% when per cent-predicted peak VO2 increased from 50% to 100%. Overall mortality in NYHA class I and II was not significantly different (P = 0.41), whereas NYHA class III patients displayed a distinctively higher death rate (P < 0.001). CONCLUSIONS: Patients with chronic HF classified as NYHA I overlapped substantially with those classified as NYHA II in objective physiological measures and prognosis. NYHA classification may represent a poor discriminator of cardiopulmonary capacity in patients with mild HF.

Early loss of cardiac function in acute myocardial infarction is associated with redox imbalance.

BACKGROUND: The loss of viable myocardium subsequent to myocardial infarction (MI) impairs cardiac function, and oxidative stress is considered to be critical in this process. OBJECTIVES: To assess cardiac function and correlate it with oxidative stress and antioxidant levels in cardiac tissue at 48 h post-MI. METHODS: Adult male Wistar rats (n=6 per group) with a mean (± SD) weight of 229±24 g were randomly assigned to either an infarcted group or a control group. MI was induced by occlusion of the left coronary artery. Cardiac function was evaluated by measuring left ventricular (LV) ejection fraction, LV fractional shortening, cardiac output, myocardial performance index and the peak early diastolic velocity/peak atrial velocity ratio using echocardiography. The myocardial oxidative stress profile was assessed by measuring the reduced glutathione/oxidized glutathione ratio, H2O2 levels, peroxiredoxin-6 protein levels and activity levels of superoxide dismutase, catalase and glutathione peroxidase. Lipid peroxidation was quantified using chemiluminescence, and protein oxidation was determined by measuring protein carbonyl levels. RESULTS: LV ejection fraction and LV fractional shortening were lower in the infarcted group compared with the sham group, whereas the peak early diastolic velocity/peak atrial velocity ratio and myocardial performance index were significantly increased, indicating systolic dysfunction. Lipid peroxidation, protein carbonyls and superoxide dismutase and catalase activity levels did not differ between the groups. Peroxyredoxin-6 levels were increased in the infarcted group, while H2O2 levels were reduced. The reduced glutathione/oxidized glutathione ratio and the glutathione peroxidase activity were reduced in the infarcted group compared with control. DISCUSSION AND CONCLUSION: These data suggest that MI-induced cardiac dysfunction and impaired redox balance may be associated with the activation of counter-regulatory responses to maintain reduced H2O2 concentrations and, thereby, prevent further oxidative damage at this early time point.

Cardiogenic shock treated with temporary mechanical circulatory support in Brazil: The effect of learning curve.

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.

Mortality reduction of cardiac resynchronization and implantable cardioverter-defibrillator therapy in heart failure: an updated meta-analysis. Does recent evidence change the standard of care?

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.

Influence of genetic, biological and pharmacological factors on warfarin dose in a Southern Brazilian population of European ancestry.

AIMS: To investigate the influence of polymorphisms in CYP2C9, VKORC1, CYP4F2 and F2 genes on warfarin dose-response and develop a model including genetic and non-genetic factors for warfarin dose prediction needed for each patient. METHODS: A total of 279 patients of European ancestry on warfarin medication were investigated. Genotypes for -1639G>A, 1173C>T, and 3730G>A SNPs in the VKORC1 gene, CYP2C9*2 and CYP2C9*3, 1347C>T in the CYP4F2 gene and 494C>T in the F2 gene were determined by allelic discrimination with Taqman 5'-nuclease assays. RESULTS: The CYP2C9*2 and CYP2C9*3 polymorphisms in the CYP2C9 gene, -1639G>A and 1173C>T in the VKORC1 gene and 494C>T in the F2 gene are responsible for lower anticoagulant doses. In contrast, 1347C>T in the CYP4F2 gene and 3730G>A in the VKORC1 gene are responsible for higher doses of warfarin. An algorithm including genetic, biological and pharmacological factors that explains 63.3% of warfarin dose variation was developed. CONCLUSION: The model suggested has one of the highest coefficients of determination among those described in the literature.

Cost-effectiveness of supervised exercise therapy in heart failure patients.

OBJECTIVE: Exercise therapy in heart failure (HF) patients is considered safe and has demonstrated modest reduction in hospitalization rates and death in recent trials. Previous cost-effectiveness analysis described favorable results considering long-term supervised exercise intervention and significant effectiveness of exercise therapy; however, these evidences are now no longer supported. To evaluate the cost-effectiveness of supervised exercise therapy in HF patients under the perspective of the Brazilian Public Healthcare System. METHODS: We developed a Markov model to evaluate the incremental cost-effectiveness ratio of supervised exercise therapy compared to standard treatment in patients with New York Heart Association HF class II and III. Effectiveness was evaluated in quality-adjusted life years in a 10-year time horizon. We searched PUBMED for published clinical trials to estimate effectiveness, mortality, hospitalization, and utilities data. Treatment costs were obtained from published cohort updated to 2008 values. Exercise therapy intervention costs were obtained from a rehabilitation center. Model robustness was assessed through Monte Carlo simulation and sensitivity analysis. Cost were expressed as international dollars, applying the purchasing-power-parity conversion rate. RESULTS: Exercise therapy showed small reduction in hospitalization and mortality at a low cost, an incremental cost-effectiveness ratio of Int$26,462/quality-adjusted life year. Results were more sensitive to exercise therapy costs, standard treatment total costs, exercise therapy effectiveness, and medications costs. Considering a willingness-to-pay of Int$27,500, 55% of the trials fell below this value in the Monte Carlo simulation. CONCLUSIONS: In a Brazilian scenario, exercise therapy shows reasonable cost-effectiveness ratio, despite current evidence of limited benefit of this intervention.

GDF-15 as a Biomarker in Cardiovascular Disease. / GDF-15 como Biomarcador em Doenças Cardiovasculares.

In the last years, several diagnostic and prognostic biomarkers have been studied in cardiovascular disease. Growth differentiation factor-15 (GDF-15), a cytokine belonging to the transforming growth factor- (TGF-) family, is highly up-regulated in stress and inflammatory conditions and has been correlated to myocardial injury and pressure cardiac overload in animal models. This new biomarker has been positively correlated with increased risk of cardiovascular events in population studies and shown an independent predictor of mortality in patients with coronary artery disease and heart failure. This review aimed to summarize the current evidence on the diagnostic and prognostic value of GDF-15 in different settings in cardiology.

Nos últimos anos, vários biomarcadores estão ganhando importância clínica na avaliação diagnóstica e prognóstica de pacientes com doenças cardiovasculares. O fator de crescimento e diferenciação celular-15 (GDF-15) é uma citocina induzida por estresse e inflamação, membro da família do TGF-, cuja produção no miocárdio foi demonstrada experimentalmente em resposta à injúria isquêmica ou sobrecarga cardíaca. Este novo marcador foi positivamente correlacionado com aumento do risco de eventos cardiovasculares em estudos populacionais e configurou-se preditor independente de mortalidade e prognóstico adverso em pacientes com doença arterial coronariana e insuficiência cardíaca. Este trabalho tem como objetivo revisar o valor diagnóstico e prognóstico do GDF-15 em diferentes cenários na cardiologia.

Predictors of Total Mortality and Serious Arrhythmic Events in Non-Ischemic Heart Failure Patients: The Role of Galectin-3. / Preditores de Mortalidade Total e Eventos Arrítmicos Graves em Pacientes com Insuficiência Cardíaca Não Isquêmica: O Papel da Galectina-3.

BACKGROUND: Risk stratification remains clinically challenging in patients with heart failure (HF) of non-ischemic etiology. Galectin-3 is a serum marker of fibrosis that might help in prognostication. OBJECTIVE: To determine the role of galectin-3 as a predictor of major arrhythmic events and overall mortality. METHODS: We conducted a prospective cohort study that enrolled 148 non-ischemic HF patients. All patients underwent a comprehensive baseline clinical and laboratory assessment, including levels of serum galectin-3. The primary outcome was the occurrence of arrhythmic syncope, appropriate implantable cardioverter defibrillator therapy, sustained ventricular tachycardia, or sudden cardiac death. The secondary outcome was all-cause death. For all statistical tests, a two-tailed p-value<0.05 was considered significant. RESULTS: In a median follow-up of 941 days, the primary and secondary outcomes occurred in 26 (17.5%) and 30 (20%) patients, respectively. Serum galectin-3>22.5 ng/mL (highest quartile) did not predict serious arrhythmic events (HR: 1.98, p=0.152). Independent predictors of the primary outcome were left ventricular end-diastolic diameter (LVEDD)>73mm (HR: 3.70, p=0.001), exercise periodic breathing (EPB) on cardiopulmonary exercise testing (HR: 2.67, p=0.01), and non-sustained ventricular tachycardia (NSVT)>8 beats on Holter monitoring (HR: 3.47, p=0.027). Predictors of all-cause death were galectin-3>22.5 ng/mL (HR: 3.69, p=0.001), LVEDD>73mm (HR: 3.35, p=0.003), EPB (HR: 3.06, p=0.006), and NSVT>8 beats (HR: 3.95, p=0.007). The absence of all risk predictors was associated with a 91.1% negative predictive value for the primary outcome and 96.6% for total mortality. CONCLUSIONS: In non-ischemic HF patients, elevated galectin-3 levels did not predict major arrhythmic events but were associated with total mortality. Absence of risk predictors revealed a prevalent subgroup of HF patients with an excellent prognosis.

FUNDAMENTO: A estratificação de risco continua sendo clinicamente desafiadora em pacientes com insuficiência cardíaca (IC) de etiologia não isquêmica. A galectina-3 é um marcador sérico de fibrose que pode ajudar no prognóstico. OBJETIVO: Determinar o papel da galectina-3 como preditora de eventos arrítmicos graves e mortalidade total. MÉTODOS: Este é um estudo de coorte prospectivo que incluiu 148 pacientes com IC não isquêmica. Todos os pacientes foram submetidos a uma avaliação clínica e laboratorial abrangente para coleta de dados de referência, incluindo níveis de galectina-3 sérica. O desfecho primário foi a ocorrência de síncope arrítmica, intervenções apropriadas do cardioversor desfibrilador implantável, taquicardia ventricular sustentada ou morte súbita cardíaca. O desfecho secundário foi a morte por todas as causas. Para todos os testes estatísticos, considerou-se significativo o valor p<0,05 (bicaudal). RESULTADOS: Em seguimento mediano de 941 dias, os desfechos primário e secundário ocorreram em 26 (17,5%) e 30 (20%) pacientes, respectivamente. A galectina-3 sérica>22,5 ng/mL (quartil mais alto) não foi preditora de eventos arrítmicos graves (HR: 1,98; p=0,152). Os preditores independentes do desfecho primário foram diâmetro diastólico final do ventrículo esquerdo (DDFVE)>73 mm (HR: 3,70; p=0,001), ventilação periódica durante o exercício (VPE) no teste de esforço cardiopulmonar (HR: 2,67; p=0,01) e taquicardia ventricular não sustentada (TVNS)>8 batimentos na monitorização por Holter (HR: 3,47; p=0,027). Os preditores de morte por todas as causas foram: galectina-3>22,5 ng/mL (HR: 3,69; p=0,001), DDFVE>73 mm (HR: 3,35; p=0,003), VPE (HR: 3,06; p=0,006) e TVNS>8 batimentos (HR: 3,95; p=0,007). A ausência de todos os preditores de risco foi associada a um valor preditivo negativo de 91,1% para o desfecho primário e 96,6% para a mortalidade total. CONCLUSÕES: Em pacientes com IC não isquêmica, níveis elevados de galectina-3 não foram preditores de eventos arrítmicos graves, mas foram associados à mortalidade total. A ausência de preditores de risco revelou um subgrupo prevalente de pacientes com IC com excelente prognóstico.

Acute Hemodynamic Index Predicts In-Hospital Mortality in Acute Decompensated Heart Failure. / Índice Hemodinâmico Agudo Prediz Mortalidade Intra-Hospitalar de Pacientes com Insuficiência Cardíaca Aguda Descompensada.

BACKGROUND: The physical examination enables prognostic evaluation of patients with decompensated heart failure (HF), but lacks reliability and relies on the professional's clinical experience. Considering hemodynamic responses to "fight or flight" situations, such as the moment of admission to the emergency room, we proposed the calculation of the acute hemodynamic index (AHI) from values of heart rate and pulse pressure. OBJECTIVE: To evaluate the in-hospital prognostic ability of AHI in decompensated HF. METHODS: A prospective, multicenter, registry-based observational study including data from the BREATHE registry, with information from public and private hospitals in Brazil. The prognostic ability of the AHI was tested by receiver-operating characteristic (ROC) analyses, C-statistics, Akaike's information criteria, and multivariate regression analyses. p-values < 0.05 were considered statistically significant. RESULTS: We analyzed data from 463 patients with heart failure with low ejection fraction. In-hospital mortality was 9%. The median AHI value was used as cut-off (4 mmHg⋅bpm). A low AHI (≤ 4 mmHg⋅bpm) was found in 80% of deceased patients. The risk of in-hospital mortality in patients with low AHI was 2.5 times that in patients with AHI > 4 mmHg⋅bpm. AHI independently predicted in-hospital mortality in acute decompensated HF (sensitivity: 0.786; specificity: 0.429; AUC: 0.607 [0.540-0.674]; p = 0.010) even after adjusting for comorbidities and medication use [OR: 0.061 (0.007-0.114); p = 0.025). CONCLUSIONS: The AHI independently predicts in-hospital mortality in acute decompensated HF. This simple bed-side index could be useful in an emergency setting. (Arq Bras Cardiol. 2021; 116(1):77-86).

FUNDAMENTO: O exame físico permite a avaliação prognóstica de pacientes com insuficiência cardíaca (IC) descompensada, porém não é suficientemente confiável e depende da experiência clínica do profissional. Considerando as respostas hemodinâmicas a situações do tipo "luta ou fuga" tais como a admissão no serviço de emergência, foi proposto o índice hemodinâmico agudo (IHA), calculado a partir da frequência cardíaca e pressão de pulso. OBJETIVO: avaliar a capacidade prognóstica intra-hospitalar do IHA na IC descompensada. MÉTODOS: estudo prospectivo, multicêntrico e observacional baseado no registro BREATHE, incluindo dados de hospitais públicos e privados no Brasil. Foram utilizadas análises ROC (Receiver Operating Characteristic), de estatística c e de regressão multivariada, assim como o critério de informação de Akaike, para testar a capacidade prognóstica do IHA. O valor-p < 0,05 foi considerado estatisticamente significativo. RESULTADOS: Foram analisados dados de 463 pacientes com IC com fração de ejeção reduzida a partir do registro BREATHE. A mortalidade intra-hospitalar foi de 9%. A mediana do IHA foi considerada o valor de corte (4 mmHg⋅bpm). Um baixo IHA (≤ 4 mmHg⋅bpm) foi encontrado em 80% dos pacientes falecidos. O risco de mortalidade intra-hospitalar em pacientes com baixo IHA foi 2,5 vezes maior que aquele para pacientes com IHA > 4 mmHg⋅bpm. O IHA foi capaz de predizer independentemente a mortalidade intra-hospitalar na IC aguda descompensada [sensibilidade: 0,786; especificidade: 0,429; AUC (área sob a curva): 0,607 (0,540-0,674), p = 0,010] mesmo depois dos ajustes para comorbidades e uso de medicamentos [razão de chances (RC): 0,061 (0,007-0,114), p = 0,025]. CONCLUSÕES: O IHA é capaz de predizer independentemente a mortalidade intra-hospitalar na IC aguda descompensada. Esse índice simples e realizado à beira do leito pode se mostrar útil em serviços de emergência. (Arq Bras Cardiol. 2021; 116(1):77-86).

Heart failure secondary to myocarditis after SARS-CoV-2 reinfection: a case report.

INTRODUCTION: Cardiac involvement in COVID-19 can range from mild damage to severe myocarditis. The precise mechanism by which COVID-19 causes myocardial injury is still unknown. Myocarditis following administration of COVID-19 vaccines, especially those based on mRNA, has also been described. However, no reports of heart failure following reinfection with SARS-CoV-2 in patients immunized with an inactivated vaccine have been identified. CASE DESCRIPTION: The patient was a 47-year-old male construction worker of African descent, with type II diabetes and a history of infection by SARS-CoV-2 in December 2020 and May 2021, confirmed by RT-PCR. He received two doses of an inactivated vaccine against COVID-19. Between the two COVID-19 episodes with positive RT-PCR, he had two episodes of bacterial lung infection. After the second episode of SARS-CoV-2 infection, he was diagnosed with severe heart failure as a sequela of myocarditis. CONCLUSION: It is essential to perform a thorough follow-up after infection with SARS-CoV-2 since, even with proper immunization, it is possible that the patient was reinfected and suffered severe cardiac sequelae as a consequence. The hypothesis of an etiology associated with the use of an inactivated vaccine against COVID-19, with a potential immune enhancement mechanism following reinfection with SARS-CoV-2, cannot be rejected.

Cost-effectiveness of implantable cardioverter-defibrillators in Brazil: primary prevention analysis in the public sector.

BACKGROUND: Several studies have demonstrated the effectiveness and cost-effectiveness of implantable cardioverter-defibrillators (ICDs) in chronic heart failure (CHF) patients. Despite its widespread use in developing countries, limited data exist on its cost-effectiveness in these settings. OBJECTIVE: To evaluate the cost-effectiveness of ICD in CHF patients under the perspective of the Brazilian Public Healthcare System (PHS). METHODS: We developed a Markov model to evaluate the incremental cost-effectiveness ratio (ICER) of ICD compared with conventional therapy in patients with CHF and New York Heart Association class II and III. Effectiveness was evaluated in quality-adjusted life years (QALYs) and time horizon was 20 years. We searched MEDLINE for clinical trials and cohort studies to estimate data from effectiveness, complications, mortality, and utilities. Costs from the PHS were retrieved from national administrative databases. The model's robustness was assessed through Monte Carlo simulation and one-way sensitivity analysis. Costs were expressed as international dollars, applying the purchasing power parity conversion rate (PPP US$). RESULTS: ICD therapy was more costly and more effective, with incremental cost-effectiveness estimates of PPP US$ 50,345/QALY. Results were more sensitive to costs related to the device, generator replacement frequency and ICD effectiveness. In a simulation resembling the MADIT-I population survival and ICD benefit, the ICER was PPP US$ 17,494/QALY and PPP US$ 15,394/life years. CONCLUSIONS: In a Brazilian scenario, where ICD cost is proportionally more elevated than in developed countries, ICD therapy was associated with a high cost-effectiveness ratio. The results were more favorable for a patient subgroup at increased risk of sudden death.

Impaired Right Ventricular Function in Heart Transplant Rejection.

BACKGROUND: The practice of screening for complications has provided high survival rates among heart transplantation (HTx) recipients. OBJECTIVES: Our aim was to assess whether changes in left ventricular (LV) and right ventricular (RV) global longitudinal strain (GLS) are associated with cellular rejection. METHODS: Patients who underwent HTx in a single center (2015 - 2016; n = 19) were included in this retrospective analysis. A total of 170 biopsies and corresponding echocardiograms were evaluated. Comparisons were made among biopsy/echocardiogram pairs with no or mild (0R/1R) evidence of cellular rejection (n = 130 and n = 25, respectively) and those with moderate (2R) rejection episodes (n=15). P-values < 0.05 were considered statistically significant Results: Most patients were women (58%) with 48 ± 12.4 years of age. Compared with echocardiograms from patients with 0R/1R rejection, those of patients with 2R biopsies showed greater LV posterior wall thickness, E/e' ratio, and E/A ratio compared to the other group. LV systolic function did not differ between groups. On the other hand, RV systolic function was more reduced in the 2R group than in the other group, when evaluated by TAPSE, S wave, and RV fractional area change (all p < 0.05). Furthermore, RV GLS (-23.0 ± 4.4% in the 0R/1R group vs. -20.6 ± 4.9% in the 2R group, p = 0.038) was more reduced in the 2R group than in the 0R/1R group. CONCLUSION: In HTx recipients, moderate acute cellular rejection is associated with RV systolic dysfunction as evaluated by RV strain, as well as by conventional echocardiographic parameters. Several echocardiographic parameters may be used to screen for cellular rejection.