Guidelines on the Diagnosis and Treatment of Hypertrophic Cardiomyopathy ­ 2024 / Diretriz sobre Diagnóstico e Tratamento da Cardiomiopatia Hipertrófica ­ 2024

Hypertrophic cardiomyopathy (HCM) is a form of genetically caused heart muscle disease, characterized by the thickening of the ventricular walls. Diagnosis requires detection through imaging methods (Echocardiogram or Cardiac Magnetic Resonance) showing any segment of the left ventricular wall with a thickness > 15 mm, without any other probable cause. Genetic analysis allows the identification of mutations in genes encoding different structures of the sarcomere responsible for the development of HCM in about 60% of cases, enabling screening of family members and genetic counseling, as an important part of patient and family management. Several concepts about HCM have recently been reviewed, including its prevalence of 1 in 250 individuals, hence not a rare but rather underdiagnosed disease. The vast majority of patients are asymptomatic. In symptomatic cases, obstruction of the left ventricular outflow tract (LVOT) is the primary disorder responsible for symptoms, and its presence should be investigated in all cases. In those where resting echocardiogram or Valsalva maneuver does not detect significant intraventricular gradient (> 30 mmHg), they should undergo stress echocardiography to detect LVOT obstruction. Patients with limiting symptoms and severe LVOT obstruction, refractory to beta-blockers and verapamil, should receive septal reduction therapies or use new drugs inhibiting cardiac myosin. Finally, appropriately identified patients at increased risk of sudden death may receive prophylactic measure with implantable cardioverter-defibrillator (ICD) implantation.

La miocardiopatía hipertrófica (MCH) es una forma de enfermedad cardíaca de origen genético, caracterizada por el engrosamiento de las paredes ventriculares. El diagnóstico requiere la detección mediante métodos de imagen (Ecocardiograma o Resonancia Magnética Cardíaca) que muestren algún segmento de la pared ventricular izquierda con un grosor > 15 mm, sin otra causa probable. El análisis genético permite identificar mutaciones en genes que codifican diferentes estructuras del sarcómero responsables del desarrollo de la MCH en aproximadamente el 60% de los casos, lo que permite el tamizaje de familiares y el asesoramiento genético, como parte importante del manejo de pacientes y familiares. Varios conceptos sobre la MCH han sido revisados recientemente, incluida su prevalencia de 1 entre 250 individuos, por lo tanto, no es una enfermedad rara, sino subdiagnosticada. La gran mayoría de los pacientes son asintomáticos. En los casos sintomáticos, la obstrucción del tracto de salida ventricular izquierdo (TSVI) es el trastorno principal responsable de los síntomas, y su presencia debe investigarse en todos los casos. En aquellos en los que el ecocardiograma en reposo o la maniobra de Valsalva no detecta un gradiente intraventricular significativo (> 30 mmHg), deben someterse a ecocardiografía de esfuerzo para detectar la obstrucción del TSVI. Los pacientes con síntomas limitantes y obstrucción grave del TSVI, refractarios al uso de betabloqueantes y verapamilo, deben recibir terapias de reducción septal o usar nuevos medicamentos inhibidores de la miosina cardíaca. Finalmente, los pacientes adecuadamente identificados con un riesgo aumentado de muerte súbita pueden recibir medidas profilácticas con el implante de un cardioversor-desfibrilador implantable (CDI).

A cardiomiopatia hipertrófica (CMH) é uma forma de doença do músculo cardíaco de causa genética, caracterizada pela hipertrofia das paredes ventriculares. O diagnóstico requer detecção por métodos de imagem (Ecocardiograma ou Ressonância Magnética Cardíaca) de qualquer segmento da parede do ventrículo esquerdo com espessura > 15 mm, sem outra causa provável. A análise genética permite identificar mutações de genes codificantes de diferentes estruturas do sarcômero responsáveis pelo desenvolvimento da CMH em cerca de 60% dos casos, permitindo o rastreio de familiares e aconselhamento genético, como parte importante do manejo dos pacientes e familiares. Vários conceitos sobre a CMH foram recentemente revistos, incluindo sua prevalência de 1 em 250 indivíduos, não sendo, portanto, uma doença rara, mas subdiagnosticada. A vasta maioria dos pacientes é assintomática. Naqueles sintomáticos, a obstrução do trato de saída do ventrículo esquerdo (OTSVE) é o principal distúrbio responsável pelos sintomas, devendo-se investigar a sua presença em todos os casos. Naqueles em que o ecocardiograma em repouso ou com Manobra de Valsalva não detecta gradiente intraventricular significativo (> 30 mmHg), devem ser submetidos à ecocardiografia com esforço físico para detecção da OTSVE.   Pacientes com sintomas limitantes e grave OTSVE, refratários ao uso de betabloqueadores e verapamil, devem receber terapias de redução septal ou uso de novas drogas inibidoras da miosina cardíaca. Por fim, os pacientes adequadamente identificados com risco aumentado de morta súbita podem receber medida profilática com implante de cardiodesfibrilador implantável (CDI).

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.

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

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.

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.

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.

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

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).

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).

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)

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.

Impact of Aortic Valve Function and the Need for Aortic Valve Repair on Long-Term Outcomes of Valve-Sparing Aortic Root Replacement: 13-Year Experience of David Operation.

BACKGROUND: The best approach for aortic root disease remains controversial. Composite valve-graft conduit (CVG) replacement offers good results at short-term and long-term follow-up; on the other hand, valve-sparing aortic root replacement (VSARR) has proven to be an excellent treatment alternative. This study aimed to analyse the outcomes after VSARR and compare whether preoperative moderate or severe aortic regurgitation (AR) and or the need for aortic valve repair (AVR) during this procedure influenced survival and freedom from reoperation rates. METHODS: From September 2005 to June 2018, 104 patients underwent VSARR using the reimplantation technique: 64% presented with preoperative moderate or severe AR, concomitant AVR was performed in 43.3%, Marfan syndrome was present in 16.3%, and 12.5% had a bicuspid aortic valve. Complete follow-up was obtained in 91% of the sample, echocardiographic results were available for 86% and the mean follow-up time was 1,893 days. RESULTS: In-hospital mortality was 2.9% and one death occurred 42 days after hospital discharge. In the latest echocardiographic assessment, 88.3% presented with mild AR or better. Freedom from reoperation at 8 years was 95.4%. There was no case of endocarditis and one patient had a stroke 2 years after the operation. There were no between-group differences in morbidity, mortality and complications during the follow-up. CONCLUSION: VSARR can be performed with low mortality rates and reasonable durability of the aortic valve. Neither moderate or severe AR nor the need for aortic valve repair during the procedure altered survival and freedom from reoperation.

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.

Influence of Angiotensin-converting Enzyme Insertion/Deletion Gene Polymorphism in Progression of Chagas Heart Disease.

INTRODUCTION: Chagas disease (CD) is a neglected disease caused by the parasite Trypanosoma cruzi. One-third of infected patients will develop the cardiac form, which may progress to heart failure (HF). However, the factors that determine disease progression remain unclear. Increased angiotensin II activity is a key player in the pathophysiology of HF. A functional polymorphism of the angiotensin-converting enzyme (ACE) gene is associated with plasma enzyme activity. In CD, ACE inhibitors have beneficial effects supporting the use of this treatment in chagasic cardiomyopathy. METHODS: We evaluated the association of ACE I/D polymorphism with HF, performing a case-control study encompassing 343 patients with positive serology for CD staged as non-cardiomyopathy (stage A; 100), mild (stage B1; 144), and severe (stage C; 99) forms of Chagas heart disease. For ACE I/D genotyping by PCR, groups were compared using unconditional logistic regression analysis and adjusted for nongenetic covariates: age, sex, and trypanocidal treatment. RESULTS: A marginal, but not significant (p=0.06) higher prevalence of ACE I/D polymorphism was observed in patients in stage C compared with patients in stage A. Patients in stage C (CD with HF), were compared with patients in stages A and B1 combined into one group (CD without HF); DD genotype/D carriers were prevalent in the HF patients (OR = 2; CI = 1.013.96; p = 0.04). CONCLUSIONS: Our results of this cohort study, comprising a population from the Northeast region of Brazil, suggest that ACE I/D polymorphism is more prevalent in the cardiac form of Chagas disease with HF.

Galectin-3 Levels in Patients with Chronic Constrictive Pericarditis. / Galectina-3 em Pacientes com Pericardite Constritiva Crônica.

Background Galectin-3 (Gal-3) is a proinflammatory, profibrotic molecule implicated in the pathogenesis of heart failure. The role of Gal-3 in patients with chronic constrictive pericarditis (CCP) is not clear. Objective The aim of this study was to assess plasma Gal-3 in patients with CCP and correlate it with clinical, functional and histologic parameters. Methods We prospectively evaluated 25 symptomatic patients with CCP referred for pericardiectomy and 21 healthy controls. Patients underwent clinical assessment, Gal-3 and B-type natriuretic peptide (BNP) measurements, echocardiography, cardiac magnetic resonance imaging and cardiopulmonary exercise test (CPET) at baseline. Six months after pericardiectomy CPET was repeated. An alpha error < 5% was considered statistically significant, with a confidence interval of 95%. Results Twenty-five patients with a median age of 45 years were included. Etiology was mainly idiopathic (n = 19, 76%); and 14 (56%) patients had NYHA functional class III/IV. Median BNP and Gal-3 were 143 (89-209) pg/dL and 14.8 (9.7-17.2) ng/mL, respectively. Gal-3 levels were not significantly higher in CCP patients than in control (p = 0.22). There were no significant correlations of Gal-3 with BNP, echocardiographic and cardiac magnetic resonance measures and histological findings. After pericardiectomy, it was found a statistically significant correlation between Gal-3 and the CPTE measures test duration (r = -0.79; p < 0.001) and exercise time (r = -0.79; p < 0.001). Conclusions Patients with CCP had normal levels of Gal-3 as compared to the controls. Gal-3 did not correlate with morphological and functional measures before pericardiectomy. However, the associations between Gal-3 and exercise intolerance after pericardiectomy may suggest a role of Gal-3 in prognosis prediction after pericardiectomy. (Arq Bras Cardiol. 2020; 114(4):683-689).