Avaliação Prognóstica da Microalternância da onda T na Cardiomiopatia Hipertrófica em um Seguimento Clínico de 9 anos / Prognostic Evaluation of Microvolt T-Wave Alternans in Hypertrophic Cardiomyopathy: 9-year Clinical Follow-up

Resumo Fundamento: A morte súbita cardíaca (MSC), decorrente de arritmias ventriculares, é a principal complicação da cardiomiopatia hipertrófica (CMH). A microalternância da onda T (MAOT) está associada à ocorrência de arritmias ventriculares em diversas cardiopatias, mas seu papel na CMH permanece incerto. Objetivo: Avaliar associação da MAOT com a ocorrência de MSC ou arritmias ventriculares malignas em pacientes com CMH. Método: Pacientes com diagnóstico de CMH e classe funcional I-II (NYHA) foram selecionados de forma consecutiva. No início do seguimento os participantes realizaram a avaliação da MAOT pela metodologia da média móvel modificada no teste de esforço. Os resultados foram classificados em alterado ou normal. O desfecho foi composto por MSC, fibrilação ventricular, taquicardia ventricular sustentada (TVS) e terapia apropriada do cardioversor desfibrilador implantável (CDI). O nível de significância estatística foi de 5%. Resultados: Um total de 132 pacientes (idade média de 39,5±12,6 anos) foram incluídos, com tempo de seguimento médio de 9,5 anos. A MAOT foi alterada em 74 (56%) participantes e normal em 58 (44%). Durante o seguimento, nove (6,8%) desfechos ocorreram, com prevalência de 1,0%/ano, sendo seis casos de MSC, dois choques apropriados do CDI e um episódio de TVS. MAOT alterada foi associada à taquicardia ventricular não sustentada no Holter (p=0,016), espessura septal≥30 mm (p<0,001) e resposta inadequada da pressão arterial ao esforço (p=0,046). Cinco pacientes (7%) e quatro pacientes (7%) com MAOT alterada e normal, respectivamente, apresentaram desfecho primário [OR=0,85(IC95%: 0,21-3,35, p=0,83)]. Curvas de eventos de Kaplan-Meir não apresentaram diferenças entre MAOT normal e alterada. Conclusão: A MAOT alterada não foi associada à ocorrência de MSC ou arritmias ventriculares potencialmente fatais em pacientes com CMH, e a baixa taxa desses eventos em um seguimento em longo prazo sugere o bom prognóstico dessa cardiopatia.

Abstract Background: Sudden cardiac death (SCD) resulting from ventricular arrhythmia is the main complication of hypertrophic cardiomyopathy (HCM). Microvolt T-wave alternans (MTWA) is associated with the occurrence of ventricular arrhythmias in several heart diseases, but its role in HCM remains uncertain. Objective: To evaluate the association of MTWA with the occurrence of SCD or potentially fatal ventricular arrhythmias in HCM patients in a long-term follow-up. Methods: Patients diagnosed with HCM and NYHA functional class I-II were consecutively selected. At the beginning of the follow-up, the participants performed the MTWA evaluation using the modified moving average during the stress test. The results were classified as altered or normal. The composite endpoint of SCD, ventricular fibrillation, sustained ventricular tachycardia (SVT) or appropriate implantable cardiac defibrillation (ICD) therapy was assessed. The level of significance was set at 5%. Results: A total of 132 patients (mean age of 39.5 ± 12.6 years) were recruited and followed for a mean of 9.5 years. The MTWA test was altered in 74 (56%) participants and normal in 58 (44%). Nine events (6.8%) occurred during the follow-up, with a prevalence of 1.0%/year - six SCDs, two appropriate ICD shocks and one episode of (SVT). Altered MTWA was associated with non-sustained ventricular tachycardia on Holter (p = 0.016), septal thickness ≥30 mm (p < 0.001) and inadequate blood pressure response to effort (p = 0.046). Five patients with altered MTWA (7%) and four patients with normal MTWA (7%) had the primary outcome [OR = 0.85 (95% CI: 0.21 - 3.35, p=0.83)]. Kaplan-Meir event curves showed no differences between normal and altered MTWA. Conclusion: Altered MTWA was not associated with the occurrence of SCD or potentially fatal ventricular arrhythmias in HCM patients, and the low rate of these events during long-term follow-up suggests the good prognosis of this heart disease.

Blood DNA methylation marks discriminate Chagas cardiomyopathy disease clinical forms.

Chagas disease is a parasitic disease from South America, affecting around 7 million people worldwide. Decades after the infection, 30% of people develop chronic forms, including Chronic Chagas Cardiomyopathy (CCC), for which no treatment exists. Two stages characterized this form: the moderate form, characterized by a heart ejection fraction (EF) ≥ 0.4, and the severe form, associated to an EF < 0.4. We propose two sets of DNA methylation biomarkers which can predict in blood CCC occurrence, and CCC stage. This analysis, based on machine learning algorithms, makes predictions with more than 95% accuracy in a test cohort. Beyond their predictive capacity, these CpGs are located near genes involved in the immune response, the nervous system, ion transport or ATP synthesis, pathways known to be deregulated in CCCs. Among these genes, some are also differentially expressed in heart tissues. Interestingly, the CpGs of interest are tagged to genes mainly involved in nervous and ionic processes. Given the close link between methylation and gene expression, these lists of CpGs promise to be not only good biomarkers, but also good indicators of key elements in the development of this pathology.

Análise Crítica e Limitações do Diagnóstico de Insuficiência Cardíaca com Fração de Ejeção Preservada (ICFEp) / Critical Analysis and Limitations of the Diagnosis of Heart Failure with Preserved Ejection Fraction (HFpEF)

Resumo Com o aumento da expectativa de vida da população e a maior frequência de fatores de risco como obesidade, hipertensão arterial e diabetes, espera-se um aumento na prevalência de insuficiência cardíaca com fração de ejeção preservada (ICFEp). Entretanto, no momento, o diagnóstico e o tratamento de pacientes com ICFEp permanecem desafiadores. O diagnóstico sindrômico de ICFEp inclui diversas etiologias e doenças com tratamentos específicos, mas que apresentam pontos em comum em relação à apresentação clínica e à avaliação laboratorial no que diz respeito aos biomarcadores como BNP e NT-ProBNP, à avaliação ecocardiográfica do remodelamento cardíaco e às pressões de enchimento diastólico ventricular esquerdo. Extensos ensaios clínicos randomizados envolvendo a terapia nesta síndrome falharam na demonstração de benefícios para o paciente, fazendo-se necessária uma reflexão acerca do diagnóstico, dos mecanismos de morbidade, da taxa de mortalidade e da reversibilidade. Na revisão, serão abordados os conceitos atuais, as controvérsias e, especialmente, os desafios no diagnóstico da ICFEp através de uma análise crítica do escore da European Heart Failure Association.

Abstract With the increase in the population's life expectancy and the higher frequency of risk factors such as obesity, hypertension and diabetes, an increase in the prevalence of heart failure with preserved ejection fraction (HFpEF) is expected. However, to date, the diagnosis and treatment of patients with HFpEF remain challenging. The syndromic diagnosis of HFpEF includes several etiologies and diseases with specific treatments but has points in common regarding the clinical presentation, laboratory evaluation related to biomarkers, such as BNP and NT-ProBNP, and echocardiographic evaluation of cardiac remodeling and left ventricular diastolic filling pressures. Extensive randomized clinical trials involving the treatment of this condition have failed to demonstrate benefits to the patient, making it necessary to reflect on the diagnosis, mechanisms of morbidity, mortality and reversibility in this syndrome. In this review, the current concepts, controversies and challenges, especially regarding diagnosis, will be addressed, critically analyzing the European Heart Failure Association score for the diagnosis of HFpEF.

Air Pollution's Impact on Cardiac Remodeling in an Experimental Model of Chagas Cardiomyopathy.

Background: Chagas disease is characterized by intense myocardial fibrosis stimulated by the exacerbated production of inflammatory cytokines, oxidative stress, and apoptosis. Air pollution is a serious public health problem and also follows this same path. Therefore, air pollution might amplify the inflammatory response of Chagas disease and increase myocardial fibrosis. Methods: We studied groups of Trypanosoma cruzi infected Sirius hamsters (Chagas=CH and Chagas exposed to pollution=CH+P) and 2 control groups (control healthy animals=CT and control exposed to pollution=CT+P). We evaluated acute phase (60 days post infection) and chronic phase (10 months). Echocardiograms were performed to assess left ventricular systolic and diastolic diameter, in addition to ejection fraction. Interstitial collagen was measured by morphometry in picrosirius red staining tissue. The evaluation of inflammation was performed by gene and protein expression of cytokines IL10, IFN-γ, and TNF; oxidative stress was quantified by gene expression of NOX1, MnSOD, and iNOS and by analysis of reactive oxygen species; and apoptosis was performed by gene expression of BCL2 and Capsase3, in addition to TUNEL analysis. Results: Chagas groups had increased collagen deposition mainly in the acute phase, but air pollution did not increase this deposition. Also, Chagas groups had lower ejection fraction in the acute phase (p = 0.002) and again air pollution did not worsen ventricular function or dilation. The analysis of the inflammation and oxidative stress pathways were also not amplified by air pollution. Apoptosis analysis showed increased expression of BCL2 and Caspase3 genes in chagasic groups in the acute phase, with a marginal p of 0.054 in BCL2 expression among infected groups, and TUNEL technique showed amplified of apoptotic cells by pollution among infected groups. Conclusions: A possible modulation of the apoptotic pathway was observed, inferring interference from air pollution in this pathway. However, it was not enough to promote a greater collagen deposition, or worsening ventricular function or dilation caused by air pollution in this model of Chagas cardiomyopathy.

Nonatherosclerotic Giant Right Coronary Artery Aneurysm.

We present an unusual case of a 67-year-old woman with an incidental finding of a cardiac mass on a chest computed tomography. Coronary angiotomography confirmed the diagnosis of right coronary artery aneurysm, with 5.7×5.7 cm. The patient underwent aneurysm resection and coronary bypass surgery, with subsequent histologic study suggestive of arteritis sequelae. Giant coronary artery aneurysms have a high risk of complications and aneurysm exclusion must be beneficial. This is a rare condition that can also be part of a systemic inflammatory disease.

Nonatherosclerotic Giant Right Coronary Artery Aneurysm

Abstract We present an unusual case of a 67-year-old woman with an incidental finding of a cardiac mass on a chest computed tomography. Coronary angiotomography confirmed the diagnosis of right coronary artery aneurysm, with 5.7×5.7 cm. The patient underwent aneurysm resection and coronary bypass surgery, with subsequent histologic study suggestive of arteritis sequelae. Giant coronary artery aneurysms have a high risk of complications and aneurysm exclusion must be beneficial. This is a rare condition that can also be part of a systemic inflammatory disease.

Clinical, Laboratory, and Imaging Profile in Patients with Systemic Amyloidosis in a Brazilian Cardiology Referral Center. / Perfil Clínico, Laboratorial e de Métodos de Imagem na Amiloidose Sistêmica em um Centro de Referência Cardiológico Brasileiro.

BACKGROUND: Systemic amyloidosis is a disease with heterogeneous clinical manifestations. Diagnosis depends on clinical suspicion combined with specific complementary methods. OBJECTIVE: To describe the clinical, laboratory, electrocardiographic, and imaging profile in patients with systemic amyloidosis with cardiac involvement. METHODS: This study was conducted with a convenience sample, analyzing clinical, laboratory, electrocardiographic, echocardiographic, nuclear medicine, and magnetic resonance data. Statistical significance was set at p < 0.05. RESULTS: A total of 105 patients were evaluated (median age of 66 years), 62 of whom were male. Of all patients, 83 had transthyretin (ATTR) amyloidosis, and 22 had light chain (AL) amyloidosis. With respect to ATTR cases, 68.7% were the hereditary form (ATTRh), and 31.3% were wild type (ATTRw). The most prevalent mutations were Val142Ile (45.6%) and Val50Met (40.3%). Time from onset of symptoms to diagnosis was 0.54 and 2.15 years, in the AL and ATTR forms, respectively (p < 0.001). Cardiac involvement was observed in 77.9% of patients with ATTR and in 90.9% of those with AL. Alterations were observed in atrioventricular and intraventricular conduction in 20% and 27.6% of patients, respectively, with 33.7% in ATTR and 4.5% in AL (p = 0.006). In the ATTRw form, there were more atrial arrhythmias than in ATTRh (61.5% versus 22.8%; p = 0.001). On echocardiogram, median septum thickness in ATTRw, ATTRh, and AL was 15 mm, 12 mm, and 11 mm, respectively (p = 0.193). Elevated BNP was observed in 89.5% of patients (median 249, ICR 597.7), and elevated troponin was observed in 43.2%. CONCLUSION: In this setting, it was possible to characterize cardiac involvement in systemic amyloidosis in its different subtypes by means of clinical history and the diagnostic methods described.

FUNDAMENTO: Amiloidose sistêmica é uma doença com manifestações clínicas diversas. O diagnóstico envolve suspeita clínica, aliada a métodos complementares. OBJETIVO: Descrever o perfil clínico, laboratorial, eletrocardiográfico e de imagem no acometimento cardíaco da amiloidose sistêmica. MÉTODOS: Estudo de uma amostra de conveniência, analisando dados clínicos, laboratoriais, eletrocardiográficos, ecocardiográficos, medicina nuclear e ressonância magnética. Considerou-se significância estatística quando p < 0,05. RESULTADOS: Avaliaram-se 105 pacientes (com mediana de idade de 66 anos), sendo 62 homens, dos quais 83 indivíduos apresentavam amiloidose por transtirretina (ATTR) e 22 amiloidose por cadeia leve (AL). Na ATTR, 68,7% eram de caráter hereditário (ATTRh) e 31,3% do tipo selvagem (ATTRw). As mutações mais prevalentes foram Val142Ile (45,6%) e Val50Met (40,3%). O tempo de início dos sintomas ao diagnóstico foi 0,54 e 2,15 anos nas formas AL e ATTR (p < 0,001), respectivamente. O acometimento cardíaco foi observado em 77,9% dos ATTR e 90,9% dos AL. Observaram-se alterações de condução atrioventricular em 20% e intraventricular em 27,6% dos pacientes, sendo 33,7 % na ATTR e 4,5% das AL (p = 0,006). A forma ATTRw apresentou mais arritmias atriais que os ATTRh (61,5% x 22,8%; p = 0,001). Ao ecocardiograma a mediana da espessura do septo na ATTRw x ATTRh x AL foi de 15 mm x 12 mm x 11 mm (p = 0,193). Observou-se BNP elevado em 89,5% dos indivíduos (mediana 249 ng/mL, IQR 597,7) e elevação da troponina em 43,2%. CONCLUSÃO: Foi possível caracterizar, em nosso meio, o acometimento cardíaco na amiloidose sistêmica, em seus diferentes subtipos, através da história clínica e dos métodos diagnósticos descritos.

Perfil Clínico, Laboratorial e de Métodos de Imagem na Amiloidose Sistêmica em um Centro de Referência Cardiológico Brasileiro / Clinical, Laboratory, and Imaging Profile in Patients with Systemic Amyloidosis in a Brazilian Cardiology Referral Center

Resumo Fundamento Amiloidose sistêmica é uma doença com manifestações clínicas diversas. O diagnóstico envolve suspeita clínica, aliada a métodos complementares. Objetivo Descrever o perfil clínico, laboratorial, eletrocardiográfico e de imagem no acometimento cardíaco da amiloidose sistêmica. Métodos Estudo de uma amostra de conveniência, analisando dados clínicos, laboratoriais, eletrocardiográficos, ecocardiográficos, medicina nuclear e ressonância magnética. Considerou-se significância estatística quando p < 0,05. Resultados Avaliaram-se 105 pacientes (com mediana de idade de 66 anos), sendo 62 homens, dos quais 83 indivíduos apresentavam amiloidose por transtirretina (ATTR) e 22 amiloidose por cadeia leve (AL). Na ATTR, 68,7% eram de caráter hereditário (ATTRh) e 31,3% do tipo selvagem (ATTRw). As mutações mais prevalentes foram Val142Ile (45,6%) e Val50Met (40,3%). O tempo de início dos sintomas ao diagnóstico foi 0,54 e 2,15 anos nas formas AL e ATTR (p < 0,001), respectivamente. O acometimento cardíaco foi observado em 77,9% dos ATTR e 90,9% dos AL. Observaram-se alterações de condução atrioventricular em 20% e intraventricular em 27,6% dos pacientes, sendo 33,7 % na ATTR e 4,5% das AL (p = 0,006). A forma ATTRw apresentou mais arritmias atriais que os ATTRh (61,5% x 22,8%; p = 0,001). Ao ecocardiograma a mediana da espessura do septo na ATTRw x ATTRh x AL foi de 15 mm x 12 mm x 11 mm (p = 0,193). Observou-se BNP elevado em 89,5% dos indivíduos (mediana 249 ng/mL, IQR 597,7) e elevação da troponina em 43,2%. Conclusão Foi possível caracterizar, em nosso meio, o acometimento cardíaco na amiloidose sistêmica, em seus diferentes subtipos, através da história clínica e dos métodos diagnósticos descritos.

Abstract Background Systemic amyloidosis is a disease with heterogeneous clinical manifestations. Diagnosis depends on clinical suspicion combined with specific complementary methods. Objective To describe the clinical, laboratory, electrocardiographic, and imaging profile in patients with systemic amyloidosis with cardiac involvement. Methods This study was conducted with a convenience sample, analyzing clinical, laboratory, electrocardiographic, echocardiographic, nuclear medicine, and magnetic resonance data. Statistical significance was set at p < 0.05. Results A total of 105 patients were evaluated (median age of 66 years), 62 of whom were male. Of all patients, 83 had transthyretin (ATTR) amyloidosis, and 22 had light chain (AL) amyloidosis. With respect to ATTR cases, 68.7% were the hereditary form (ATTRh), and 31.3% were wild type (ATTRw). The most prevalent mutations were Val142Ile (45.6%) and Val50Met (40.3%). Time from onset of symptoms to diagnosis was 0.54 and 2.15 years, in the AL and ATTR forms, respectively (p < 0.001). Cardiac involvement was observed in 77.9% of patients with ATTR and in 90.9% of those with AL. Alterations were observed in atrioventricular and intraventricular conduction in 20% and 27.6% of patients, respectively, with 33.7% in ATTR and 4.5% in AL (p = 0.006). In the ATTRw form, there were more atrial arrhythmias than in ATTRh (61.5% versus 22.8%; p = 0.001). On echocardiogram, median septum thickness in ATTRw, ATTRh, and AL was 15 mm, 12 mm, and 11 mm, respectively (p = 0.193). Elevated BNP was observed in 89.5% of patients (median 249, ICR 597.7), and elevated troponin was observed in 43.2%. Conclusion In this setting, it was possible to characterize cardiac involvement in systemic amyloidosis in its different subtypes by means of clinical history and the diagnostic methods described.

Pericardial Effusion and Cardiac Tamponade: Etiology and Evolution in the Contemporary Era

Abstract Background: Pericardial effusion is a relatively common finding and can progress to cardiac tamponade; etiological diagnosis is important for guiding treatment decisions. With advances in medicine and improvement in the social context, the most frequent etiological causes have changed. Objectives: To evaluate the clinical and laboratory characteristics, etiology, and clinical course of patients with pericardial effusion and cardiac tamponade. Materials and methods: Patients with pericardial effusion classified as small (< 10 mm), moderate (between 10-20 mm), or severe (> 20 mm) were included. Data from the clinical history, physical examination, laboratory tests, and complementary tests were evaluated in patients with pericardial effusion and cardiac tamponade. The significance level was set at 5%. Results: A total of 254 patients with a mean age of 53.09 ± 17.9 years were evaluated, 51.2% of whom were female. A total of 40.4% had significant pericardial effusion (> 20 mm). Pericardial tamponade occurred in 44.1% of patients. Among pericardial effusion patients without tamponade, the most frequent etiologies were: idiopathic (44.4%) and postsurgical (17.6%), while among those with tamponade, the most frequent etiologies were postsurgical (21.4%) and postprocedural (19.6%). The mean follow-up time was 2.2 years. Mortality was 42% and 23.2 in those with and without tamponade, respectively (p=0.001). Conclusions: There is an etiological difference between pericardial effusion patients with and without cardiac tamponade. An idiopathic etiology is more common among those without tamponade, while postinterventional/postsurgical is more common among those with tamponade. The tamponade group had a higher mortality rate.

Impact of COVID-19 Pandemic in a Brazilian High-Volume Aortic Center.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic brought an unprecedented lack of control of what was to come. The intent of this document is to provide a balance of how much was ceased to be done for patients with aortic disease, to assess the mortality of these patients, and to show what happened to those who became COVID-19 positive during their hospitalization. METHODS: From April 1st to July 31st 2020, the worst period of the pandemic in São Paulo, Brazil, the Institute's aortic surgical patients operated on were evaluated and those were compared with patients operated during the same period in 2019. RESULTS: In 2019, 88 surgeries were performed; most of them were elective (66 [75%]), 10 were urgent, and 12 were emergency surgeries. In 2020, during the COVID-19 pandemic, we operated on only 31 patients, being 74.2% non-elective surgeries (P<0,001). There was a higher mortality for patients operated on during the pandemic surge of COVID-19 (P<0,001), but it was not specifically related to infected patients. CONCLUSION: The COVID-19 pandemic had an impact on surgical volume and outcome of patients with aortic disease, although it did not directly increase mortality.

Impact of COVID-19 Pandemic in a Brazilian High-Volume Aortic Center

Abstract Introduction: The coronavirus disease 2019 (COVID-19) pandemic brought an unprecedented lack of control of what was to come. The intent of this document is to provide a balance of how much was ceased to be done for patients with aortic disease, to assess the mortality of these patients, and to show what happened to those who became COVID-19 positive during their hospitalization. Methods: From April 1st to July 31st 2020, the worst period of the pandemic in São Paulo, Brazil, the Institute's aortic surgical patients operated on were evaluated and those were compared with patients operated during the same period in 2019. Results: In 2019, 88 surgeries were performed; most of them were elective (66 [75%]), 10 were urgent, and 12 were emergency surgeries. In 2020, during the COVID-19 pandemic, we operated on only 31 patients, being 74.2% non-elective surgeries (P<0,001). There was a higher mortality for patients operated on during the pandemic surge of COVID-19 (P<0,001), but it was not specifically related to infected patients. Conclusion: The COVID-19 pandemic had an impact on surgical volume and outcome of patients with aortic disease, although it did not directly increase mortality.

Galectina-3 Associada a Formas Graves e Mortalidade em Longo Prazo em Pacientes com Doença de Chagas / Galectin-3 Associated with Severe Forms and Long-term Mortality in Patients with Chagas Disease

Resumo Fundamento As características histopatológicas da doença de Chagas (DCC) são: presença de miocardite, destruição das fibras cardíacas e fibrose miocárdica. A Galectina-3 (Gal-3) é um biomarcador envolvido no mecanismo de fibrose e inflamação que pode ser útil para a estratificação de indivíduos com DCC por risco. Objetivos Nosso objetivo foi avaliar se níveis elevados de Gal-3 estão associados a formas graves de cardiomiopatia chagásica (CC) e são preditivos de mortalidade. Métodos Estudamos doadores de sangue (DS) positivos para anti-T. cruzi: não-CC-DS (187 DS sem CC com eletrocardiograma [ECG] e fração de ejeção do ventrículo esquerdo [FEVE] normais); CC-Não-Dis-DS (46 DS com CC e apresentando ECG anormal, mas FEVE normal); e 153 controles negativos correspondentes. Esta amostra foi composta por 97 pacientes com CC grave (CC-Dis). Usamos as correlações de Kruskall-Wallis e Spearman para testar a hipótese de associações, assumindo um p bicaudal <0,05 como significativo. Resultados O nível de Gal-3 foi de 12,3 ng/mL para não-CC-DS, 12,0 ng/mL para CC-Não-Dis-DS, 13,8 ng/mL para controles e 15,4 ng/mL para CC-Dis. FEVE <50 foi associada a níveis mais elevados de Gal-3 (p=0,0001). Em nosso modelo de regressão linear ajustado, encontramos associação entre os níveis de Gal-3 e os parâmetros do ecocardiograma em indivíduos positivos para T. cruzi. Nos pacientes CC-Dis, encontramos uma associação significativa de níveis mais elevados de Gal-3 (≥15,3 ng/mL) e morte ou transplante cardíaco em acompanhamento de cinco anos (Hazard ratio - HR 3,11; IC95% 1,21- 8,04; p=0,019). Conclusões Em pacientes com CC, níveis mais elevados de Gal-3 estiveram significativamente associados a formas graves da doença e maior taxa de mortalidade em longo prazo, o que significa que pode ser um meio efetivo para identificar pacientes de alto risco. (Arq Bras Cardiol. 2021; 116(2):248-256)

Abstract Background The histopathological characteristics of Chagas disease (ChD) are: presence of myocarditis, destruction of heart fibers, and myocardial fibrosis. Galectin-3 (Gal-3) is a biomarker involved in the mechanism of fibrosis and inflammation that may be useful for risk stratification of individuals with ChD. Objectives We sought to evaluate whether high Gal-3 levels are associated with severe forms of Chagas cardiomyopathy (CC) and whether they are predictive of mortality. Methods We studied anti-T. cruzi positive blood donors (BD): Non-CC-BD (187 BD without CC with normal electrocardiogram [ECG] and left ventricular ejection fraction [LVEF]); CC-Non-Dys-BD (46 BD with CC with abnormal ECG but normal LVEF); and 153 matched serum-negative controls. This cohort was composed of 97 patients with severe CC (CC-Dys). We used Kruskall-Wallis and Spearman's correlation to test hypothesis of associations, assuming a two-tailed p<0.05 as significant. Results The Gal-3 level was 12.3 ng/mL for Non-CC-BD, 12.0 ng/mL for CC-Non-Dys-BD, 13.8 ng/mL for controls, and 15.4 ng/mL for CC-Dys. LVEF<50 was associated with higher Gal-3 levels (p=0.0001). In our linear regression adjusted model, we found association between Gal-3 levels and echocardiogram parameters in T. cruzi-seropositive subjects. In CC-Dys patients, we found a significant association of higher Gal-3 levels (≥15.3 ng/mL) and subsequent death or heart transplantation in a 5-year follow-up (Hazard ratio - HR 3.11; 95%CI 1.21-8.04; p=0.019). Conclusions In ChD patients, higher Gal-3 levels were significantly associated with severe forms of the disease and more long-term mortality, which means it may be a useful means to identify high-risk patients. (Arq Bras Cardiol. 2021; 116(2):248-256)

Effect of exercise training on cardiovascular autonomic and muscular function in subclinical Chagas cardiomyopathy: a randomized controlled trial.

PURPOSE: Patients with chronic chagasic cardiomyopathy with preserved ventricular function present with autonomic imbalance. This study evaluated the effects of exercise training (ET) in restoring peripheral and cardiac autonomic control and skeletal muscle phenotype in patients with subclinical chronic chagasic cardiomyopathy. METHODS: This controlled trial (NCT02295215) included 24 chronic chagasic cardiomyopathy patients who were randomized www.random.org/lists/ into two groups: those who underwent exercise training (n = 12) and those who continued their usual activities (n = 12). Eight patients completed the exercise training protocol, and 10 patients were clinically followed up for 4 months. Muscular sympathetic nerve activity was measured by microneurography and muscle blood flow (MBF) using venous occlusion plethysmography. The low-frequency component of heart rate variability in normalized units (LFnuHR) reflects sympathetic activity in the heart, and the low-frequency component of systolic blood pressure variability in normalized units reflects sympathetic activity in the vessels. The infusion of vasoactive drugs (phenylephrine and sodium nitroprusside) was used to evaluate cardiac baroreflex sensitivity, and a vastus lateralis muscle biopsy was performed to evaluate atrogin-1 and MuRF-1 gene expression. RESULTS: The baroreflex sensitivity for increases (p = 0.002) and decreases (p = 0.02) in systolic blood pressure increased in the ET group. Muscle blood flow also increased only in the ET group (p = 0.004). Only the ET group had reduced resting muscular sympathetic nerve activity levels (p = 0.008) and sympathetic activity in the heart (LFnu; p = 0.004) and vessels (p = 0.04) after 4 months. Regarding skeletal muscle, after 4 months, participants in the exercise training group presented with lower atrogin-1 gene expression than participants who continued their activities as usual (p = 0.001). The reduction in muscular sympathetic nerve activity was positively associated with reduced atrogin-1 (r = 0.86; p = 0.02) and MuRF-1 gene expression (r = 0.64; p = 0.06); it was negatively associated with improved baroreflex sensitivity both for increases (r = -0.72; p = 0.020) and decreases (r = -0.82; p = 0.001) in blood pressure. CONCLUSIONS: ET improved cardiac and peripheral autonomic function in patients with subclinical chagasic cardiomyopathy. ET reduced MSNA and sympathetic activity in the heart and vessels and increased cardiac parasympathetic tone and baroreflex sensitivity. Regarding peripheral muscle, after 4 months, patients who underwent exercise training had an increased cross-sectional area of type I fibers and oxidative metabolism of muscle fibers, and decreased atrogin-1 gene expression, compared to participants who continued their activities as usual. In addition, the reduction in MSNA was associated with improved cardiac baroreflex sensitivity, reduced sympathetic cardiovascular tone, and reduced atrogin-1 and MuRF-1 gene expression. TRIAL REGISTRATION: ID: NCT02295215. Registered in June 2013.

Effects of sympathectomy on myocardium remodeling and function

OBJECTIVES: To evaluate the effects of sympathectomy on the myocardium in an experimental model. METHODS: The study evaluated three groups of male Wistar rats: control (CT; n=15), left unilateral sympathectomy (UNI; n=15), and bilateral sympathectomy (BIL; n=31). Sympathectomy was performed by injection of absolute alcohol into the space of the spinous process of the C7 vertebra. After 6 weeks, we assessed the chronotropic properties at rest and stress, cardiovascular autonomic modulation, myocardial and peripheral catecholamines, and beta-adrenergic receptors in the myocardium. The treadmill test consisted of an escalated protocol with a velocity increment until the maximal velocity tolerated by the animal was reached. RESULTS: The bilateral group had higher levels of peripheral catecholamines, and consequently, a higher heart rate (HR) and blood pressure levels. This suggests that the activation of a compensatory pathway in this group may have deleterious effects. The BIL group had basal tachycardia immediately before the exercise test and increased tachycardia at peak exercise (p<0.01); the blood pressure had the same pattern (p=0.0365). The variables related to autonomic modulation were not significantly different between groups, with the exception of the high frequency (HF) variable, which showed significant differences in CT vs UNI. There was no significant difference in beta receptor expression between groups. There was a higher concentration of peripheral norepinephrine in the BIL group (p=0.0001), and no significant difference in myocardial norepinephrine (p=0.09). CONCLUSION: These findings suggest that an extra cardiac compensatory pathway increases the sympathetic tonus and maintains a higher HR and higher levels of peripheral catecholamines in the procedure groups. The increase in HF activity can be interpreted as an attempt to increase the parasympathetic tonus to balance the greater sympathetic activity.