Management of Cardiovascular Disease in Patients With COVID-19 and Chronic Chagas Disease: Implications to Prevent a Scourge Still Larger.

Cardiovascular diseases (CVD) are the most important cause of morbidity and mortality in the general population. Because the high prevalence of COVID-19 and chronic Chagas disease (CCD) where the latter is endemic, all such diseases will likely be observed in the same patient. While COVID-19 can provoke generalized endotheliitis, which can lead to a cytokine storm and a hyper-coagulable state culminating into in-site and at a distance thrombosis. Therefore, small-vessel coronary artery disease (CAD), cerebrovascular disease, thromboembolism, and arrhythmias are prominent findings in COVID-19. In CCD, small-vessel CAD, cardioembolic stroke, pulmonary embolism, heart failure and arrhythmias are frequently observed as a result of a similar but less intense mechanism. Consequently, the association of CCD and COVID-19 will likely increase the incidence of CVD. Thus, doctors on the frontline should be on the alert for this diagnostic possibility so that the proper treatment can be given without any delay.

Undernutrition and Cachexia in Patients with Decompensated Heart Failure and Chagas Cardiomyopathy: Occurrence and Association with Hospital Outcomes. / Desnutrição e Caquexia na Insuficiência Cardíaca Descompensada e Cardiomiopatia Chagásica: Ocorrência e Associação com Desfechos Hospitalares.

BACKGROUND: Nutritional disorders are common among patients with heart failure (HF) and associated with poor prognosis. Importantly, some populations of patients, like the ones with Chagas disease, are frequently excluded from most analyses. OBJECTIVE: We sought to study the occurrence of undernutrition and cachexia in patients with Chagas disease during episodes of decompensated HF (DHF) as compared to other etiologies, and to investigate the influence of these findings on hospital outcomes. METHODS: We performed a consecutive case series study with patients hospitalized with DHF. Patients underwent the Subjective Global Assessment of nutritional status (SGA), besides anthropometric and laboratorial measures, and were evaluated for the occurrence of cachexia, low muscle mass and strength. We studied the occurrence of death or urgent heart transplantation during hospitalization. RESULTS: Altogether, 131 patients were analyzed and 42 (32.1%) had Chagas disease. Patients with Chagas disease had lower Body Mass Index (BMI) (22.4 kg/m2[19.9-25.3] vs. 23.6 kg/m2 [20.8-27.3], p=0.03), higher frequency of undernutrition (76.2% vs 55.1%, p=0.015) and higher occurrence of death or transplant (83.3% vs. 41.6%, p<0.001). We found that, in patients with Chagas etiology, the occurrence of death or cardiac transplantation were associated with undernutrition (3 [42.9%] patients with hospital discharge vs 29 [82.9%] patients with death or heart transplant, p=0.043). CONCLUSIONS: Taken together, our results indicate that patients with Chagas disease hospitalized with DHF often present with nutritional disorders, especially undernutrition; importantly, this finding was associated with the occurrence of death and heart transplant during hospitalization.

FUNDAMENTO: Problemas nutricionais são comuns em pacientes com insuficiência cardíaca (IC) e estão associados a um prognóstico ruim. É relevante mencionar que algumas populações de pacientes, como os com Doença de Chagas, são normalmente excluídas da maioria das análises. OBJETIVO: Buscamos analisar a ocorrência de desnutrição e caquexia em pacientes com Doença de Chagas durante episódios de IC descompensada (ICD) em comparação a outras etiologias, e investigar a influência desses achados em desfechos hospitalares. MÉTODO: Realizamos um estudo de série de casos consecutivos com pacientes hospitalizados com ICD. Os pacientes foram submetidos à Avaliação Nutricional Subjetiva Global (ASG), além de medidas antropométricas e laboratoriais, e foram avaliados para a ocorrência de caquexia, baixa massa muscular e força. Estudamos a ocorrência de morte e transplante cardíaco de urgência durante a internação. RESULTADOS: Ao todo, 131 pacientes foram analisados e 42 (32,1%) tinham Doença de Chagas. Pacientes com Doença de Chagas apresentavam índice de massa corporal (IMC) menor (22,4 kg/m2 [19,9-25,3] vs. 23,6 kg/m2 [20,8-27,3], p=0,03), maior frequência de desnutrição (76,2% vs 55,1%, p=0,015) e mais ocorrências de morte ou transplante (83,3% vs. 41,6%, p<0,001). Observamos que, dentre os pacientes com etiologia da Doença de Chagas, a ocorrência de morte ou transplante cardíaco esteve associada com desnutrição (3 [42,9%] pacientes com alta hospitalar vs. 29 [82,9%] pacientes que morreram ou receberam transplante cardíaco, P=0,043). CONCLUSÕES: Ao todo, nossos resultados indicam que pacientes com Doença de Chagas internados com ICD costumam apresentar problemas nutricionais, principalmente desnutrição. É importante mencionar que este achado esteve associado à ocorrência de morte e transplante cardíaco durante a internação.

Desnutrição e Caquexia na Insuficiência Cardíaca Descompensada e Cardiomiopatia Chagásica: Ocorrência e Associação com Desfechos Hospitalares / Undernutrition and Cachexia in Patients with Decompensated Heart Failure and Chagas Cardiomyopathy: Occurrence and Association with Hospital Outcomes

Resumo Fundamento Problemas nutricionais são comuns em pacientes com insuficiência cardíaca (IC) e estão associados a um prognóstico ruim. É relevante mencionar que algumas populações de pacientes, como os com Doença de Chagas, são normalmente excluídas da maioria das análises. Objetivo Buscamos analisar a ocorrência de desnutrição e caquexia em pacientes com Doença de Chagas durante episódios de IC descompensada (ICD) em comparação a outras etiologias, e investigar a influência desses achados em desfechos hospitalares. Método Realizamos um estudo de série de casos consecutivos com pacientes hospitalizados com ICD. Os pacientes foram submetidos à Avaliação Nutricional Subjetiva Global (ASG), além de medidas antropométricas e laboratoriais, e foram avaliados para a ocorrência de caquexia, baixa massa muscular e força. Estudamos a ocorrência de morte e transplante cardíaco de urgência durante a internação. Resultados Ao todo, 131 pacientes foram analisados e 42 (32,1%) tinham Doença de Chagas. Pacientes com Doença de Chagas apresentavam índice de massa corporal (IMC) menor (22,4 kg/m2 [19,9-25,3] vs. 23,6 kg/m2 [20,8-27,3], p=0,03), maior frequência de desnutrição (76,2% vs 55,1%, p=0,015) e mais ocorrências de morte ou transplante (83,3% vs. 41,6%, p<0,001). Observamos que, dentre os pacientes com etiologia da Doença de Chagas, a ocorrência de morte ou transplante cardíaco esteve associada com desnutrição (3 [42,9%] pacientes com alta hospitalar vs. 29 [82,9%] pacientes que morreram ou receberam transplante cardíaco, P=0,043). Conclusões Ao todo, nossos resultados indicam que pacientes com Doença de Chagas internados com ICD costumam apresentar problemas nutricionais, principalmente desnutrição. É importante mencionar que este achado esteve associado à ocorrência de morte e transplante cardíaco durante a internação.

Abstract Background Nutritional disorders are common among patients with heart failure (HF) and associated with poor prognosis. Importantly, some populations of patients, like the ones with Chagas disease, are frequently excluded from most analyses. Objective We sought to study the occurrence of undernutrition and cachexia in patients with Chagas disease during episodes of decompensated HF (DHF) as compared to other etiologies, and to investigate the influence of these findings on hospital outcomes. Methods We performed a consecutive case series study with patients hospitalized with DHF. Patients underwent the Subjective Global Assessment of nutritional status (SGA), besides anthropometric and laboratorial measures, and were evaluated for the occurrence of cachexia, low muscle mass and strength. We studied the occurrence of death or urgent heart transplantation during hospitalization. Results Altogether, 131 patients were analyzed and 42 (32.1%) had Chagas disease. Patients with Chagas disease had lower Body Mass Index (BMI) (22.4 kg/m2[19.9-25.3] vs. 23.6 kg/m2 [20.8-27.3], p=0.03), higher frequency of undernutrition (76.2% vs 55.1%, p=0.015) and higher occurrence of death or transplant (83.3% vs. 41.6%, p<0.001). We found that, in patients with Chagas etiology, the occurrence of death or cardiac transplantation were associated with undernutrition (3 [42.9%] patients with hospital discharge vs 29 [82.9%] patients with death or heart transplant, p=0.043). Conclusions Taken together, our results indicate that patients with Chagas disease hospitalized with DHF often present with nutritional disorders, especially undernutrition; importantly, this finding was associated with the occurrence of death and heart transplant during hospitalization.

Cardiovascular findings in Williams-Beuren Syndrome: Experience of a single center with 127 cases.

Williams-Beuren syndrome (WBS) is a rare, microdeletion syndrome characterized by facial dysmorphisms, intellectual disability, a friendly personality, cardiovascular and other abnormalities. Cardiovascular defects (CVD) are among the most prevalent characteristics in WBS, being supravalvular aortic stenosis (SVAS) the most frequent, followed by peripheral pulmonary stenosis (PPS). A comprehensive retrospective review of medical records of 127 patients with molecular diagnosis of WBS, in a period of 20 years, was done to evaluate the incidence, the natural history of cardiovascular disease, and the need for surgical intervention, including heart transplantation (HT). A total of 94/127 patients presented with CVD. Of these 94 patients, 50% presented with SVAS and 22.3% needed heart surgery and/or cardiac catheterization including one that required HT due to severe SVAS-related heart failure at 19 years of age. The patient died in the postoperative period due to infectious complications. Cardiovascular problems are the major cause of sudden death in patients with WBS, who have a significantly higher mortality risk associated with surgical interventions. There is a higher risk for anesthesia-related adverse events and for major adverse cardiac events following surgery. End-stage heart failure due to myocardial ischemia has been described in WBS patients and it is important to consider that HT can become their only viable option. To our knowledge, the case mentioned here is the first HT reported in an adolescent with WBS. HT can be a viable therapeutic option in WBS patients with adequate evaluation, planning, and a multidisciplinary team to provide the required perioperative care and follow-up.

The course of patients with Chagas heart disease during episodes of decompensated heart failure.

AIMS: This study aimed to analyse the clinical presentation and prognosis of patients with Chagas cardiomyopathy and decompensated heart failure (HF), as compared with other aetiologies. METHODS AND RESULTS: A prospective cohort of patients admitted with decompensated HF. We included 767 patients (63.9% male), with median age of 58 years [interquartile range 48.2-66.7 years]. Main aetiologies were non-Chagas/non-ischaemic cardiomyopathies in 389 (50.7%) patients, ischaemic disease in 209 (27.2%), and Chagas disease in 169 (22%). Median left ventricular ejection fraction was 26% (interquartile range 22-35%). Patients with Chagas differed from both patients with non-Chagas/non-ischaemic and ischaemic cardiomyopathies for a higher proportion of cardiogenic shock at admission (17.8%, 11.6%, and 11%, respectively, P < 0.001) and had lower blood pressure at admission (systolic blood pressure 90 [80-102.5], 100 [85-110], and 100 [88.2-120] mmHg, P < 0.001) and lower heart rate (heart rate 71 [60-80], 87 [70-102], and 79 [64-96.5] b.p.m., P < 0.001). Further, patients with Chagas had higher serum BNP level (1544 [734-3148], 1061 [465-239], and 927 [369-1455] pg/mL, P < 0.001), higher serum bilirubin (1.4 [0.922.44], 1.2 [0.77-2.19], and 0.84 [0.49-1.45] mg/dL, P < 0.001), larger left ventricular diameter (68 [63-73], 67 [58-74], and 62 [56.8-68.3] mm, respectively, P < 0.001), lower left ventricular ejection fraction (25 [21-30]%, 26 [22-35]%, and 30 [25-38]%, P < 0.001), and a higher proportion of patients with right ventricular function (48.8%, 40.7%, and 25.9%, P < 0.001). Patients with Chagas disease were more likely to receive inotropes than patients with non-Chagas/non-ischaemic and ischaemic cardiomyopathies (77.5%, 67.5%, and 62.5%, respectively, P = 0.007) and also to receive intra-aortic balloon pumping (30.8%, 16.2%, and 10.5%, P < 0.001). Overall, the rates of death or urgent transplant were higher among patients with Chagas than in other aetiologies, a difference that was driven mostly due to increased rate of heart transplant during hospital admission (20.2%, 10.3%, and 8.1%). The prognosis of patients at 180 days after hospital admission was worse for patients with Chagas disease as compared with other aetiologies. In patients with Chagas, age [odds ratio (OR) = 0.934, confidence interval (CI)95% 0.901-0.982, P = 0.005], right ventricular dysfunction by echocardiography (OR = 2.68, CI95% 1.055-6.81, P = 0.016), and urea (OR = 1.009, CI95% 1.001-1.018, P = 0.038) were significantly associated with prognosis. CONCLUSIONS: Patients with Chagas cardiomyopathy and decompensated HF have a distinct clinical presentation and worse prognosis compared with other aetiologies.

Exhaled breath acetone for predicting cardiac and overall mortality in chronic heart failure patients.

AIMS: Exhaled breath acetone (EBA) has been described as a new biomarker of heart failure (HF) diagnosis. EBA concentration increases according to severity of HF and is associated with poor prognosis, especially in acute decompensated HF. However, there are no data on chronic HF patients. The aim is to evaluate the role of EBA for predicting cardiac and overall mortality in chronic HF patients. METHODS AND RESULTS: In GENIUS-HF cohort, chronic patients were enrolled between August 2012 and December 2014. All patients had left ventricular ejection fraction ≤ 50%, and the diagnosis was established according to Framingham criteria. After consent, patients were submitted to clinical evaluation and exhaled breath collection. EBA identification and quantitative determination were done by spectrophotometry. The clinical characteristics associated with acetone were identified. All participants were followed for 18 months to assess cardiac and overall mortality. Around 700 participants were enrolled in the current analysis. Patients were 55.4 ± 12.2 years old, 67.6% male patients, and 81% New York Heart Association I/II with left ventricular ejection fraction of 32 ± 8.6%. EBA median concentration was 0.6 (0.3-1.2) ug/L. Acetone levels increased with the number of symptoms of HF and were associated with right HF signs/symptoms and liver biochemical changes. EBA at highest quartile (EBA > 1.2ug/L) was associated with a significantly worse prognosis (log rank test, P < 0.001). Cox proportional multivariable regression model revealed that EBA > 1.20ug/L was an independent predictor of cardiac (P = 0.011) and overall (P = 0.010) mortality in our population. CONCLUSIONS: This study shows that EBA levels reflect clinical HF features, especially right HF signs/symptoms. EBA is an independent predictor of cardiac and overall mortality in chronic HF patients.

Diretriz Brasileira de Insuficiência Cardíaca Crônica e Aguda

INTRODUÇÃO: A organização de uma diretriz clínica é tarefa complexa, que necessariamente deve envolver planejamento prévio, coordenação apropriada, revisão aprofundada da literatura científica, com envolvimento de múltiplos profissionais da área da saúde com notório reconhecimento. A elaboração de uma diretriz clínica de insuficiência cardíaca é ainda mais difícil, por conta da complexidade da síndrome, da amplitude das evidências científicas que permeiam o tópico e do grande impacto que as recomendações propostas têm sobre os pacientes, a comunidade médica e a sociedade como um todo. No presente documento, o Departamento de Insuficiência Cardíaca (DEIC) da Sociedade Brasileira de Cardiologia (SBC) apresenta uma revisão e uma atualização detalhadas de sua Diretriz de Insuficiência Cardíaca Crônica. Os trabalhos se iniciaram em setembro de 2017, com a definição da Comissão Coordenadora, que estabeleceu prioridades, dividiu grupos de trabalho e definiu o cronograma das atividades. Os grupos de trabalho, compostos por três a cinco participantes, deram início a intensas discussões virtuais, que culminaram com a redação de tabelas preliminares, sendo posteriormente amplamente divulgadas e revisadas pelos 34 participantes da diretriz. As discussões finais foram realizadas em reunião presencial em março de 2018, com a participação de todos os colaboradores, nas quais as principais recomendações foram votadas individualmente. As decisões quanto à classe das recomendações foram definidas por maioria plena (concordância de mais de 75% dos participantes). As recomendações terapêuticas propostas no presente documento se embasam nas evidências científicas mais atuais, considerando não apenas aspectos de eficácia clínica demonstrados em grandes ensaios clínicos, mas também contextualizando seus achados para o cenário de saúde brasileiro e incorporando aspectos econômicos definidos em estudos de custo-efetividade. Buscamos sumarizar as principais recomendações em fluxogramas e algoritmos de fácil entendimento e grande aplicabilidade clínica, propondo abordagens para o diagnóstico e o tratamento da síndrome em formato moderno, atualizado e didático. Na última seção da diretriz, o que não podemos deixar de fazer e o que não devemos fazer no diagnóstico, prevenção e tratamento da síndrome foram sumarizados em apenas três tabelas. Em especial, destacamos seis intervenções que foram consideradas de alta prioridade, por apresentarem relações de custo-efetividade altamente favoráveis. Sobretudo, esperamos que a publicação deste documento possa auxiliar na redução das elevadas taxas de mortalidade que ainda estão associadas com a insuficiência cardíaca no Brasil, além de minimizar o cruel impacto que a síndrome causa na qualidade de vida de nossos pacientes. Acreditamos que esta diretriz apresenta, de forma hierarquizada, a linha mestra que deve nortear a prática clínica em diferentes níveis de atenção à saúde, permitindo reconhecimento precoce de pacientes em risco, diagnóstico apropriado e implementação de tratamento de forma escalonada, eficaz e coerente com nossa realidade.

Cost-Effectiveness Benefits of a Disease Management Program:The REMADHE Trial Results.

BACKGROUND: Published studies have generated mixed, controversial results regarding the cost-effectiveness of heart failure disease management programs (HF-DMPs). This study assessed the cost-effectiveness of an HF-DMP in ambulatory patients compared with usual care (UC). METHODS: In the prospective randomized REMADHE trial, we evaluated incremental costs per quality-adjusted life-year (QALY) and life-year (LY) gained as effectiveness ratios (ICERs) over a study period of 2.47 ± 1.75 years. RESULTS: The REMADHE HF-DMP was more effective and less costly than UC in terms of both QALYs and LYs (95% and 55% chance of dominance, respectively). Average saving was US$7345 (2.5%-97.5% bootstrapped confidence interval -16,573 to +921). The chance of DMP being cost-effective at a willingness to pay US$10,000 per QALY or LY was 99% and 96%, respectively. Cost-effectiveness of HF-DMP was highest in subgroups with left ventricular ejection fraction <35%, age >50 years, male sex, New York Heart Association (NYHA) functional class ≥III, and ischemic etiology. The chance of DMP being cost-effective at a willingness to pay US$10,000 per QALY was ≥90% in all subgroups apart from NYHA functional class I-II, where it was 70%. Even when the intervention costs increased by 500% or when excluding outliers in costs, DMP had a high chance of being cost-effective (87%-99%). CONCLUSIONS: The HF-DMP of the REMADHE trial, which encompasses long-term repeated education alongside telephone monitoring, has a high probability of being cost-effective in ambulatory patients with HF.

Thromboembolic findings in patients with heart failure at autopsy.

BACKGROUND: The risk of thromboembolic events is increased in patients with heart failure (HF); however, few studies have reported thromboembolic findings in HF patients who have undergone autopsy. METHODS AND RESULTS: We reviewed 1457 autopsies (January 2000/July 2006) and selected 595 patients with HF. We studied the occurrence of thromboembolic events in patients' autopsy reports. Mean age was 61.8±15.9 years; 376 (63.2%) were men and 219 (36.8%) women; left ventricular ejection fraction was 42.1±18.7%. HF etiologies were coronary artery disease in 235 (39.5%) patients, valvular disease in 121 (20.3%), and Chagas' disease in 81 (13.6%). The main cause of death was progressive HF in 253 (42.5%) patients, infections in 112 (18.8%), myocardial infarction in 86 (14.5%), and pulmonary embolism in 81 (13.6%). Altogether, 233 patients (39.2%) suffered 374 thromboembolic events. A thromboembolic event was considered the direct cause of death in 93 (24.9%) patients and related to death in 158 (42.2%). The most frequent thromboembolism was pulmonary embolism in 135 (36.1%) patients; in 81 events (60%), it was considered the cause of death. When we compared clinical characteristics of patients, sex (OR=1.511, CI 95% 1.066-2.143, P=.021) and Chagas disease (OR=2.362, CI 95% 1.424-3.918, P=.001) were independently associated with the occurrence of thromboembolisms. CONCLUSIONS: Thromboembolic events are frequent in patients with heart failure revealed at autopsy, and are frequently associated with the death process. Our findings warrant a high degree of suspicion for these occurrences, especially during the care of more susceptible populations, such as women and Chagas patients.

Carvedilol for Prevention of Chemotherapy-Related Cardiotoxicity: The CECCY Trial.

BACKGROUND: Anthracycline (ANT) chemotherapy is associated with cardiotoxicity. Prevention with ß-blockers remains controversial. OBJECTIVES: This prospective, randomized, double-blind, placebo-controlled study sought to evaluate the role of carvedilol in preventing ANT cardiotoxicity. METHODS: The authors randomized 200 patients with HER2-negative breast cancer tumor status and normal left ventricular ejection fraction (LVEF) referred for ANT (240 mg/m2) to receive carvedilol or placebo until chemotherapy completion. The primary endpoint was prevention of a ≥10% reduction in LVEF at 6 months. Secondary outcomes were effects of carvedilol on troponin I, B-type natriuretic peptide, and diastolic dysfunction. RESULTS: Primary endpoint occurred in 14 patients (14.5%) in the carvedilol group and 13 patients (13.5%) in the placebo group (p = 1.0). No differences in changes of LVEF or B-type natriuretic peptide were noted between groups. A significant difference existed between groups in troponin I levels over time, with lower levels in the carvedilol group (p = 0.003). Additionally, a lower incidence of diastolic dysfunction was noted in the carvedilol group (p = 0.039). A nonsignificant trend toward a less-pronounced increase in LV end-diastolic diameter during the follow-up was noted in the carvedilol group (44.1 ± 3.64 mm to 45.2 ± 3.2 mm vs. 44.9 ± 3.6 mm to 46.4 ± 4.0 mm; p = 0.057). CONCLUSIONS: In this largest clinical trial of ß-blockers for prevention of cardiotoxicity under contemporary ANT dosage, the authors noted a 13.5% to 14.5% incidence of cardiotoxicity. In this scenario, carvedilol had no impact on the incidence of early onset of LVEF reduction. However, the use of carvedilol resulted in a significant reduction in troponin levels and diastolic dysfunction. (Carvedilol Effect in Preventing Chemotherapy-Induced Cardiotoxicity [CECCY]; NCT01724450).

Clinical findings and prognosis of patients hospitalized for acute decompensated heart failure: Analysis of the influence of Chagas etiology and ventricular function.

AIMS: Explore the association between clinical findings and prognosis in patients with acute decompensated heart failure (ADHF) and analyze the influence of etiology on clinical presentation and prognosis. METHODS AND RESULTS: Prospective cohort of 500 patients admitted with ADHF from Aug/2013-Feb/2016; patients were predominantly male (61.8%), median age was 58 (IQ25-75% 47-66 years); etiology was dilated cardiomyopathy in 141 (28.2%), ischemic heart disease in 137 (27.4%), and Chagas heart disease in 113 (22.6%). Patients who died (154 [30.8%]) or underwent heart transplantation (53[10.6%]) were younger (56 years [IQ25-75% 45-64 vs 60 years, IQ25-75% 49-67], P = 0.032), more frequently admitted for cardiogenic shock (20.3% vs 6.8%, P<0.001), had longer duration of symptoms (14 days [IQ25-75% 4-32.8 vs 7.5 days, IQ25-75% 2-31], P = 0.004), had signs of congestion (90.8% vs 76.5%, P<0.001) and inadequate perfusion more frequently (45.9% vs 28%, P<0.001), and had lower blood pressure (90 [IQ25-75% 80-100 vs 100, IQ25-75% 90-120], P<0.001). In a logistic regression model analysis, systolic blood pressure (P<0.001, OR 0.97 [95%CI 0.96-0.98] per mmHg) and jugular distention (P = 0.004, OR 1.923 [95%CI 1.232-3.001]) were significant. Chagas patients were more frequently admitted for cardiogenic shock (15%) and syncope/arrhythmia (20.4%). Pulmonary congestion was rare among Chagas patients and blood pressure was lower. The rate of in-hospital death or heart transplant was higher among patients with Chagas (50.5%). CONCLUSIONS: A physical exam may identify patients at higher risk in a contemporaneous population. Our findings support specific therapies targeted at Chagas patients in the setting of ADHF.