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Importance: Over 10â¯000 people with Chagas disease experience sudden cardiac death (SCD) annually, mostly caused by ventricular fibrillation. Amiodarone hydrochloride and the implantable cardioverter-defibrillator (ICD) have been empirically used to prevent SCD in patients with chronic Chagas cardiomyopathy. Objective: To test the hypothesis that ICD is more effective than amiodarone therapy for primary prevention of all-cause mortality in patients with chronic Chagas cardiomyopathy and moderate to high mortality risk, assessed by the Rassi score. Design, Setting, and Participants: CHAGASICS is an open-label, randomized clinical trial. The study enrolled patients from 13 centers in Brazil from May 30, 2014, to August 13, 2021, with the last follow-up November 8, 2021. Patients with serological findings positive for Chagas disease, a Rassi risk score of at least 10 points (intermediate to high risk), and at least 1 episode of nonsustained ventricular tachycardia were eligible to participate. Data were analyzed from May 3, 2022, to June 16, 2023. Interventions: Patients were randomized 1:1 to receive ICD or amiodarone (with a loading dose of 600 mg after randomization). Main Outcomes and Measures: The primary outcome was all-cause mortality, and secondary outcomes included SCD, hospitalization for heart failure, and necessity of a pacemaker during the entire follow-up. Results: The study was stopped prematurely for administrative reasons, with 323 patients randomized (166 in the amiodarone group and 157 in the ICD group), rather than the intended 1100 patients. Analysis was by intention to treat at a median follow-up of 3.6 (IQR, 1.8-4.4) years. Mean (SD) age was 57.4 (9.8) years, 185 patients (57.3%) were male, and the mean (SD) left ventricular ejection fraction was 37.0% (11.6%). There were 60 deaths (38.2%) in the ICD arm and 64 (38.6%) in the amiodarone group (hazard ratio [HR], 0.86 [95% CI, 0.60-1.22]; P = .40). The rates of SCD (6 [3.8%] vs 23 [13.9%]; HR, 0.25 [95% CI, 0.10-0.61]; P = .001), bradycardia requiring pacing (3 [1.9%] vs 27 [16.3%]; HR, 0.10 [95% CI, 0.03-0.34]; P < .001), and heart failure hospitalization (14 [8.9%] vs 28 [16.9%]; HR, 0.46 [95% CI, 0.24-0.87]; P = .01) were lower in the ICD group compared with the amiodarone arm. Conclusions and Relevance: In patients with chronic Chagas cardiomyopathy at moderate to high risk of mortality, ICD did not reduce the risk of all-cause mortality. However, ICD significantly reduced the risk of SCD, pacing need, and heart failure hospitalization compared with amiodarone therapy. Further studies are warranted to confirm the evidence generated by this trial. Trial Registration: ClinicalTrials.gov Identifier: NCT01722942.
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IMPORTANCE: Over 10 000 people with Chagas disease experience sudden cardiac death (SCD) annually, mostly caused by ventricular fibrillation. Amiodarone hydrochloride and the implantable cardioverter-defibrillator (ICD) have been empirically used to prevent SCD in patients with chronic Chagas cardiomyopathy. OBJECTIVE: To test the hypothesis that ICD is more effective than amiodarone therapy for primary prevention of all-cause mortality in patients with chronic Chagas cardiomyopathy and moderate to high mortality risk, assessed by the Rassi score. DESIGN, SETTING, AND PARTICIPANTS: CHAGASICS is an open-label, randomized clinical trial. The study enrolled patients from 13 centers in Brazil from May 30, 2014, to August 13, 2021, with the last follow-up November 8, 2021. Patients with serological findings positive for Chagas disease, a Rassi risk score of at least 10 points (intermediate to high risk), and at least 1 episode of nonsustained ventricular tachycardia were eligible to participate. Data were analyzed from May 3, 2022, to June 16, 2023. INTERVENTIONS: Patients were randomized 1:1 to receive ICD or amiodarone (with a loading dose of 600 mg after randomization). MAIN OUTCOMES AND MEASURES: The primary outcome was all-cause mortality, and secondary outcomes included SCD, hospitalization for heart failure, and necessity of a pacemaker during the entire follow-up. RESULTS: The study was stopped prematurely for administrative reasons, with 323 patients randomized (166 in the amiodarone group and 157 in the ICD group), rather than the intended 1100 patients. Analysis was by intention to treat at a median follow-up of 3.6 (IQR, 1.8-4.4) years. Mean (SD) age was 57.4 (9.8) years, 185 patients (57.3%) were male, and the mean (SD) left ventricular ejection fraction was 37.0% (11.6%). There were 60 deaths (38.2%) in the ICD arm and 64 (38.6%) in the amiodarone group (hazard ratio [HR], 0.86 [95% CI, 0.60-1.22]; P = .40). The rates of SCD (6 [3.8%] vs 23 [13.9%]; HR, 0.25 [95% CI, 0.10-0.61]; P = .001), bradycardia requiring pacing (3 [1.9%] vs 27 [16.3%]; HR, 0.10 [95% CI, 0.03-0.34]; P < .001), and heart failure hospitalization (14 [8.9%] vs 28 [16.9%]; HR, 0.46 [95% CI, 0.24-0.87]; P = .01) were lower in the ICD group compared with the amiodarone arm. CONCLUSIONS AND RELEVANCE: In patients with chronic Chagas cardiomyopathy at moderate to high risk of mortality, ICD did not reduce the risk of all-cause mortality. However, ICD significantly reduced the risk of SCD, pacing need, and heart failure hospitalization compared with amiodarone therapy. Further studies are warranted to confirm the evidence generated by this trial.
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Humanos , Prevenção Primária , Cardiomiopatia Chagásica , Morte Súbita Cardíaca , Doença de Chagas , Desfibriladores Implantáveis , Amiodarona , Fibrilação Ventricular , Fatores de Risco , Taquicardia Ventricular , Insuficiência CardíacaRESUMO
PURPOSE OF REVIEW: More than a century since its discovery, the pathogenesis of Chagas heart disease (CHD) remains incompletely understood. The role of derangements in the autonomic control of the heart in triggering malignant arrhythmia before the appearance of contractile ventricular impairment was reviewed. RECENT FINDINGS: Although previous investigations had demonstrated the anatomical and functional consequences of parasympathetic dysautonomia upon the heart rate control, only recently, coronary microvascular disturbances and sympathetic denervation at the ventricular level have been reported in patients and experimental models of CHD, exploring with nuclear medicine methods their impact on the progression of myocardial dysfunction and cardiac arrhythmias. More important than parasympathetic impaired sinus node regulation, recent evidence indicates that myocardial sympathetic denervation associated with coronary microvascular derangements is causally related to myocardial injury and arrhythmia in CHD. Additionally, 123I-MIBG imaging is a promising tool for risk stratification of progression of ventricular dysfunction and sudden death.
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Cardiomiopatia Chagásica , Simpatectomia , Humanos , Simpatectomia/métodos , Cardiomiopatia Chagásica/fisiopatologia , Cardiomiopatia Chagásica/cirurgia , Cardiomiopatia Chagásica/complicações , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/fisiopatologia , Coração/inervação , Coração/diagnóstico por imagem , 3-Iodobenzilguanidina , Sistema Nervoso Simpático/fisiopatologiaAssuntos
Cardiomiopatias , Cardiomiopatia Chagásica , Doença de Chagas , Humanos , Doença de Chagas/complicações , Doença de Chagas/diagnóstico , Doença de Chagas/terapia , Cardiomiopatias/diagnóstico , Cardiomiopatias/terapia , Cardiomiopatia Chagásica/diagnóstico , Cardiomiopatia Chagásica/terapiaRESUMO
INTRODUCTION: Myocardial ischemia is common in patients with chronic Chagas cardiomyopathy (CCC), but only recently clinical and experimental studies highlighted the involvement of this abnormality as contributing to the progression of myocardial damage. AREAS COVERED: Despite the absence of obstructive epicardial coronary artery disease at angiography, and limited evidence of abnormal flow regulation at the macrovascular level, remarkable functional and structural microvascular abnormalities are consistently reported by independent investigations of CCC. These derangements occur early and contribute to myocardial dysfunction. Recent research focused on reversing microvascular dysfunction as a target to positively impact the course of CCC. We conducted an extensive review of the scientific literature, aiming to summarize the role of coronary dysfunction causing myocardial ischemia in CCC, with a focus on implications for clinical management of individuals affected by this disease. EXPERT OPINION: Preclinical studies showed a clear correlation between perfusion defects and inflammation in viable but impaired dysfunctional myocardium. These findings provided further insight into the CCC complex pathophysiology and support the role of very few recent therapeutic interventions aiming to relieve myocardial ischemia. Further research is warranted to assess the efficacy of new interventions addressing reversal of microvascular ischemia and inflammation modulation and halting ventricular dysfunction progression in CCC.
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Cardiomiopatias , Cardiomiopatia Chagásica , Doença de Chagas , Doença da Artéria Coronariana , Isquemia Miocárdica , Humanos , Isquemia Miocárdica/etiologia , Doença de Chagas/complicações , Inflamação , Vasos CoronáriosRESUMO
BACKGROUND: Myocardial perfusion defect (MPD) is common in chronic Chagas cardiomyopathy (CCC) and is associated with inflammation and development of left ventricular systolic dysfunction. We tested the hypothesis that pentoxifylline (PTX) could reduce inflammation and prevent the development of MPD in a model of CCC in hamsters. METHODS AND RESULTS: We investigated with echocardiogram and rest myocardial perfusion scintigraphy at baseline (6-months after T. cruzi infection/saline) and post-treatment (after additional 2-months of PTX/saline administration), female Syrian hamsters assigned to 3 groups: T. cruzi-infected animals treated with PTX (CH + PTX) or saline (CH + SLN); and uninfected control animals (CO). At the baseline, all groups showed similar left ventricular ejection fraction (LVEF) and MPD areas. At post-treatment evaluation, there was a significant increase of MPD in CH + SLN group (0.8 ± 1.6 to 9.4 ± 9.7%), but not in CH + PTX (1.9 ± 3.0% to 2.7 ± 2.7%) that exhibited MPD area similar to CO (0.0 ± 0.0% to 0.0 ± 0.0%). The LVEF decreased in both infected groups. Histological analysis showed a reduced inflammatory infiltrate in CH + PTX group (395.7 ± 88.3 cell/mm2), as compared to CH + SLN (515.1 ± 133.0 cell/mm2), but larger than CO (193.0 ± 25.7 cell/mm2). The fibrosis and TNF-α expression was higher in both infected groups. CONCLUSIONS: The prolonged use of PTX is associated with positive effects, including prevention of MPD development and reduction of inflammation in the chronic hamster model of CCC.
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Cardiomiopatia Chagásica , Doença de Chagas , Pentoxifilina , Cricetinae , Animais , Feminino , Cardiomiopatia Chagásica/diagnóstico por imagem , Pentoxifilina/farmacologia , Pentoxifilina/uso terapêutico , Volume Sistólico , Função Ventricular Esquerda , Tomografia Computadorizada por Raios X , Inflamação , PerfusãoRESUMO
Introdução: Face à melhor compreensão da fisiopatologia da estenose valvar aórtica, cresceu paralelamente a complexidade da avaliação de sua gravidade, persistindo relevante incerteza quanto à aplicabilidade dos métodos invasivos pelo cateterismo cardíaco e os não invasivos, com base em ecocardiografia. O objetivo deste estudo foi analisar os padrões hemodinâmicos da avaliação com ecocardiografia comparativamente à estimativa da gravidade da estenose aórtica com o cateterismo em pacientes consecutivos referidos para avaliação diagnóstica por laboratório de hospital acadêmico terciário no triênio 2016-2018. Métodos: Estudo observacional, descritivo e retrospectivo das características clínicas e dos resultados das avaliações da gravidade da estenose valvar aórtica obtidas em 96 pacientes consecutivos, por meio de cateterismo e ecocardiografia. Resultados: Amostra populacional de 49 homens e 47 mulheres, com mediana de idade de 66,5 (56,5 a 72,8) anos, estenose valvar aórtica degenerativa em 49% e reumática em 40%, além de diversas comorbidades, inclusive doença coronária (37%). Pelo cateterismo, com base no gradiente pico de 48 (20 a 68), a estenose valvar aórtica foi avaliada como grave em 56%, sendo a pressão telediastólica ventricular de 20mmHg (16 a 30mmHg). Pela ecocardiografia, a área valvar foi 0,9cm2 (0,7 a 1,2cm2), sendo indexado 0,5cm2/m2 (0,43 a 0,5cm2/m2), com gradiente pico de 62±26 mmHg. A estenose valvar aórtica foi considerada severa em 69,2%. Houve discordância entre os métodos sobre a severidade da estenose valvar aórtica em 30% dos exames, com coeficiente de Spearman entre área valvar pelo ecocardiograma e gradiente pico pelo cateterismo de -0,7 (p<0,001). Conclusão: Em amostra representativa dos vários padrões hemodinâmicos, a avaliação da gravidade da estenose valvar aórtica, como praticada rotineiramente em laboratório acadêmico, limitou-se à medida de pico de gradiente transvalvar. A estimativa da área valvar pelo método ecocardiográfico, sendo indireta e também passível de crítica, contribui para as discrepâncias encontradas, tornando-se justificável buscar o aperfeiçoamento de ambos os métodos, em vista da complexidade clínica e hemodinâmica detectada.
Background: In view of the better understanding of the pathophysiology of aortic valve stenosis, the complexity of assessing its severity has simultaneously grown, with relevant uncertainty persisting as to the applicability of invasive methods by cardiac catheterization and non-invasive methods based on echocardiography. The objective of this study was to analyze the hemodynamic patterns of evaluation with echocardiography compared to the estimation of severity of aortic stenosis with catheterization in consecutive patients referred for diagnostic evaluation by the laboratory of a tertiary academic hospital in the 2016 to 2018 triennium. Methods: An observational, descriptive and retrospective study of clinical characteristics and results of assessments of severity of aortic valve stenosis obtained in 96 consecutive patients, through catheterization and echocardiography. Results: A population sample of 49 men and 47 women, with a median age of 66.5 (56.5 to 72.8) years, degenerative aortic valve stenosis in 49%, and rheumatic aortic stenosis in 40%, in addition to several comorbidities, including coronary disease (37%). Using catheterization, based on the peak gradient of 48 (20 to 68), aortic valve stenosis was assessed as severe in 56%, with ventricular end-diastolic pressure of 20mmHg (16 to 30mmHg). Using echocardiography, the valve area was 0.9cm2 (0.7 to 1.2cm2), indexed valve area was 0.5cm2/m2 (0.43 to 0.5cm2/m2), with peak gradient of 62±26mmHg. Aortic valve stenosis was considered severe in 69.2%. There was disagreement between the methods regarding severity of aortic valve stenosis in 30% of exams, with a Spearman coefficient between the valve area on the echocardiogram and the peak gradient on catheterization of -0.7 (p<0.001). Conclusion: In a representative sample of various hemodynamic patterns, the assessment of severity of aortic valve stenosis, as routinely practiced in an academic laboratory, was limited to measuring the peak transvalvular gradient. The estimation of the valve area using the echocardiographic method was indirect and also subject to criticism, and contributed to the discrepancies found, rendering it justifiable to seek the improvement of both methods, in view of the clinical and hemodynamic complexity detected.
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BACKGROUND: Chagas disease (ChD) is caused by Trypanosoma cruzi. The genetic structure of the species is divided into seven distinct genetic groups, TcI to TcVI, and Tcbat, which have shown differences in terms of geographic distribution, biological properties, and susceptibility to drugs. However, the association between genetic variability and clinical forms of ChD has not yet been fully elucidated. The predominance of TcII and TcVI discrete typing units (DTUs) (genetic groups) is known to occur in several Brazilian regions and is associated with both the domestic and the wild cycles of ChD. Thus, this study aimed to verify the genotypes of the parasites present in 330 patients with chronic Chagas cardiomyopathy (CCC) from different Brazilian states attended at the Clinical Hospital of the Ribeirão Preto Medical School and to assess the existence of a correlation between the clinical forms with the main cardiovascular risk factors and the genetics of the parasite. METHODOLOGY PRINCIPAL FINDINGS: All patients with CCC were clinically evaluated through anamnesis, physical examination, biochemical tests, 12-lead electrocardiogram, echocardiogram and chest X-ray. Peripheral blood (5 mL) was collected in guanidine/ethylenediaminetetraacetic acid from each patient for DNA extraction and real-time polymerase chain reaction (PCR) for Chagas disease and genotyping of the parasite in the 7 DTUs. Parasite genotyping was performed using conventional multilocus PCR. Samples of only 175 patients were positive after amplification of the specific genes contained in the T. cruzi genotyping criteria. TcII (64/175), TcVI (9/175), and TcI (3/175) DTUs were predominant, followed by TcII/TcV/TcVI (74/175), and TcII/TcVI (23/175). The TcIII and TcIV DTU´s was detected in only one sample of CCC patients. CONCLUSIONS/SIGNIFICANCE: Our data corroborate previous findings, indicating the predominance of the TcII genotype in patients with CCC of Brazilian origin. Moreover, this study pioneered disclosing a direct correlation between the TcII DTU and severe CCC.
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Cardiomiopatia Chagásica , Doença de Chagas , Trypanosoma cruzi , Humanos , Cardiomiopatia Chagásica/epidemiologia , Cardiomiopatia Chagásica/parasitologia , Brasil/epidemiologia , Doença de Chagas/parasitologia , Trypanosoma cruzi/genética , Genótipo , Reação em Cadeia da Polimerase em Tempo Real , Variação GenéticaRESUMO
Resumo Fundamento A morte súbita cardíaca (MSC) é a causa mais comum de óbito na cardiomiopatia crônica da doença de Chagas (CCDC). Visto que muitos pacientes com CCDC que são candidatos a receber um cardioversor desfibrilador implantável (CDI) atendem a critérios que sugerem alto risco de apresentarem limiares de desfibrilação elevados, sugere-se realizar um teste de limite de desfibrilação (LDF). Objetivos Investigamos o uso do teste de LDF em pacientes com CCDC, com enfoque nos óbitos relacionados ao implante do CDI e na ocorrência de eventos arrítmicos e o tratamento oferecido durante o seguimento de longo prazo. Métodos Avaliações retrospectivas de 133 pacientes com CCDC que receberam CDI, principalmente para prevenção secundária. Foram coletados dados demográficos, clínicos e laboratoriais, escore de Rassi e dados do teste de LDF. Adotou-se p<0,05 como estatisticamente significativo. Resultados A média de idade foi 61±13 anos, e 72% da amostra era do sexo masculino. A fração de ejeção basal do ventrículo esquerdo foi 40±15%, e o escore de Rassi médio foi 10±4 pontos. Não ocorreram óbitos durante o teste de LDF, e não foram documentadas falhas do CDI. Foi identificada relação entre escore de Rassi basal mais elevado e LDFs mais elevados (ANOVA =0,007). O tempo médio até o primeiro choque foi de 474±628 dias, mas a aplicação de choque foi necessária em apenas 28 (35%) pacientes com TV, visto que a maioria dos casos se resolveu espontaneamente ou através da programação de ATP. Após seguimento clínico de 1728±1189 dias, em média, ocorreram 43 óbitos, relacionados principalmente a insuficiência cardíaca progressiva e sepse. Conclusões Um teste de LDF de rotina pode não ser necessário para pacientes com CCDCs que receberam CDI para prevenção secundária. LDFs elevados parecem ser incomuns e podem estar relacionados a escore de Rassi elevado.
Abstract Background Sudden cardiac death is the most common cause of death in chronic Chagas cardiomyopathy (CCC). Because most CCC patients who are candidates for implantable cardioverter-defibrillators (ICD) meet criteria for high defibrillation threshold values, a defibrillator threshold test (DTT) is suggested. Objectives We investigated the use of DTT in CCC patients, focusing on deaths related to ICD and arrhythmic events, as well as treatment during long-term follow-up. Methods We retrospectively evaluated 133 CCC patients who received an ICD mainly for secondary prevention. Demographic, clinical, laboratory data, Rassi score, and DTT data were collected, with p < 0.05 considered significant. Results The mean patient age was 61 (SD, 13) years and 72% were men. The baseline left ventricular ejection fraction was 40 (SD, 15%) and the mean Rassi score was 10 (SD, 4). No deaths occurred during DTT and no ICD failures were documented. There was a relationship between higher baseline Rassi scores and higher DTT scores (ANOVA = 0.007). The mean time to first shock was 474 (SD, 628) days, although shock was only necessary for 28 (35%) patients with ventricular tachycardia, since most cases resolved spontaneously or through antitachycardia pacing. After a mean clinical follow-up of 1728 (SD, 1189) days, 43 deaths occurred, mainly related to progressive heart failure and sepsis. Conclusions A routine DTT may not be necessary for CCC patients who receive an ICD for secondary prevention. High DTT values seem to be unusual and may be related to high Rassi scores.
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BACKGROUND: Although Chagas cardiomyopathy is related to thromboembolic stroke, data on risk factors for cerebrovascular events in Chagas disease is limited. Thus, we assessed the relationship between left ventricular (LV) impairment and cerebrovascular events and sources of thromboembolism in patients with Chagas cardiomyopathy. METHODS: This retrospective cohort included patients with chronic Chagas cardiomyopathy who underwent cardiovascular magnetic resonance (CMR). CMR was performed with a 1.5 T scanner to provide LV volumes, mass, ejection fraction (LVEF), and myocardial fibrosis. The primary outcome was a composite of incident ischemic cerebrovascular events (stroke or transient ischemic attack-TIA) and potential thromboembolic sources (atrial fibrillation (AF), atrial flutter, or intracavitary thrombus) during the follow-up. RESULTS: A total of 113 patients were included. Median age was 56 years (IQR: 45-67), and 58 (51%) were women. The median LVEF was 53% (IQR: 41-62). LV aneurysms and LV fibrosis were present in 38 (34%) and 76 (67%) individuals, respectively. The median follow-up time was 6.9 years, with 29 events: 11 cerebrovascular events, 16 had AF or atrial flutter, and two had LV apical thrombosis. In the multivariable model, only lower LVEF remained significantly associated with the outcomes (HR: 0.96, 95% CI: 0.93-0.99). Patients with reduced LVEF lower than 40% had a much higher risk of cerebrovascular events and thromboembolic sources (HR: 3.16 95% CI: 1.38-7.25) than those with normal LVEF. The combined incidence rate of the combined events in chronic Chagas cardiomyopathy patients with reduced LVEF was 13.9 new cases per 100 persons-year. CONCLUSIONS: LV systolic dysfunction is an independent predictor of adverse cerebrovascular events and potential sources of thromboembolism in patients with chronic Chagas cardiomyopathy.
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Fibrilação Atrial , Flutter Atrial , Cardiomiopatias , Cardiomiopatia Chagásica , Cardiopatias , Acidente Vascular Cerebral , Tromboembolia , Disfunção Ventricular Esquerda , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Cardiomiopatia Chagásica/complicações , Cardiomiopatia Chagásica/diagnóstico por imagem , Cardiomiopatia Chagásica/epidemiologia , Estudos Retrospectivos , Valor Preditivo dos Testes , Função Ventricular Esquerda , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/epidemiologia , Disfunção Ventricular Esquerda/etiologia , Volume Sistólico , Tromboembolia/diagnóstico por imagem , Tromboembolia/epidemiologia , Tromboembolia/etiologiaRESUMO
BACKGROUND: Sudden cardiac death is the most common cause of death in chronic Chagas cardiomyopathy (CCC). Because most CCC patients who are candidates for implantable cardioverter-defibrillators (ICD) meet criteria for high defibrillation threshold values, a defibrillator threshold test (DTT) is suggested. OBJECTIVES: We investigated the use of DTT in CCC patients, focusing on deaths related to ICD and arrhythmic events, as well as treatment during long-term follow-up. METHODS: We retrospectively evaluated 133 CCC patients who received an ICD mainly for secondary prevention. Demographic, clinical, laboratory data, Rassi score, and DTT data were collected, with p < 0.05 considered significant. RESULTS: The mean patient age was 61 (SD, 13) years and 72% were men. The baseline left ventricular ejection fraction was 40 (SD, 15%) and the mean Rassi score was 10 (SD, 4). No deaths occurred during DTT and no ICD failures were documented. There was a relationship between higher baseline Rassi scores and higher DTT scores (ANOVA = 0.007). The mean time to first shock was 474 (SD, 628) days, although shock was only necessary for 28 (35%) patients with ventricular tachycardia, since most cases resolved spontaneously or through antitachycardia pacing. After a mean clinical follow-up of 1728 (SD, 1189) days, 43 deaths occurred, mainly related to progressive heart failure and sepsis. CONCLUSIONS: A routine DTT may not be necessary for CCC patients who receive an ICD for secondary prevention. High DTT values seem to be unusual and may be related to high Rassi scores.
FUNDAMENTO: A morte súbita cardíaca (MSC) é a causa mais comum de óbito na cardiomiopatia crônica da doença de Chagas (CCDC). Visto que muitos pacientes com CCDC que são candidatos a receber um cardioversor desfibrilador implantável (CDI) atendem a critérios que sugerem alto risco de apresentarem limiares de desfibrilação elevados, sugere-se realizar um teste de limite de desfibrilação (LDF). OBJETIVOS: Investigamos o uso do teste de LDF em pacientes com CCDC, com enfoque nos óbitos relacionados ao implante do CDI e na ocorrência de eventos arrítmicos e o tratamento oferecido durante o seguimento de longo prazo. MÉTODOS: Avaliações retrospectivas de 133 pacientes com CCDC que receberam CDI, principalmente para prevenção secundária. Foram coletados dados demográficos, clínicos e laboratoriais, escore de Rassi e dados do teste de LDF. Adotou-se p<0,05 como estatisticamente significativo. RESULTADOS: A média de idade foi 61±13 anos, e 72% da amostra era do sexo masculino. A fração de ejeção basal do ventrículo esquerdo foi 40±15%, e o escore de Rassi médio foi 10±4 pontos. Não ocorreram óbitos durante o teste de LDF, e não foram documentadas falhas do CDI. Foi identificada relação entre escore de Rassi basal mais elevado e LDFs mais elevados (ANOVA =0,007). O tempo médio até o primeiro choque foi de 474±628 dias, mas a aplicação de choque foi necessária em apenas 28 (35%) pacientes com TV, visto que a maioria dos casos se resolveu espontaneamente ou através da programação de ATP. Após seguimento clínico de 1728±1189 dias, em média, ocorreram 43 óbitos, relacionados principalmente a insuficiência cardíaca progressiva e sepse. CONCLUSÕES: Um teste de LDF de rotina pode não ser necessário para pacientes com CCDCs que receberam CDI para prevenção secundária. LDFs elevados parecem ser incomuns e podem estar relacionados a escore de Rassi elevado.
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Doença de Chagas , Desfibriladores Implantáveis , Taquicardia Ventricular , Masculino , Humanos , Pessoa de Meia-Idade , Feminino , Seguimentos , Volume Sistólico , Estudos Retrospectivos , Fatores de Risco , Função Ventricular Esquerda , Taquicardia Ventricular/terapia , Taquicardia Ventricular/complicações , Morte Súbita Cardíaca/prevenção & controle , Morte Súbita Cardíaca/etiologia , Doença de Chagas/complicações , Desfibriladores Implantáveis/efeitos adversosRESUMO
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.
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Cardiomiopatia Chagásica , Doença de Chagas , Metilação , Doenças Parasitárias , Terapêutica , BiomarcadoresRESUMO
Abstract: Chagas disease, caused by the protozoan Trypanosoma cruzi, is an endemic parasitic disease of Latin America, affecting 7 million people. Although most patients are asymptomatic, 30% develop complications, including the often-fatal Chronic Chagasic Cardiomyopathy (CCC). Although previous studies have demonstrated some genetic deregulations associated with CCCs, the causes of their deregulations remain poorly described. Based on bulk RNA-seq and whole genome DNA methylation data, we investigated the genetic and epigenetic deregulations present in the moderate and severe stages of CCC. Analysis of heart tissue gene expression profile allowed us to identify 1407 differentially expressed transcripts (DEGs) specific from CCC patients. A tissue DNA methylation analysis done on the same tissue has permitted the identification of 92 regulatory Differentially Methylated Regions (DMR) localized in the promoter of DEGs. An in-depth study of the transcription factors binding sites (TFBS) in the DMRs corroborated the importance of TFBS's DNA methylation for gene expression in CCC myocardium. TBX21, RUNX3 and EBF1 are the transcription factors whose binding motif appears to be affected by DNA methylation in the largest number of genes. By combining both transcriptomic and methylomic analysis on heart tissue, and methylomic analysis on blood, 4 biological processes affected by severe CCC have been identified, including immune response, ion transport, cardiac muscle processes and nervous system. An additional study on blood methylation of moderate CCC samples put forward the importance of ion transport and nervous system in the development of the disease.
Assuntos
Humanos , Cardiomiopatia Chagásica , Doença de Chagas/genética , Fatores de Transcrição/genética , Trypanosoma cruzi , Epigênese Genética , MetilaçãoRESUMO
Electrocardiographic (ECG) abnormalities are frequently identified in Chronic Chagas cardiomyopathy (CCC) patients and advanced abnormalities are related to a worse prognosis. Cardiac Magnetic Resonance (CMR) can precisely assess ventricular systolic dysfunction and quantify myocardial fibrosis (MF), both identified as prognostic factors. We sought to investigate if ECG abnormalities in CCC patients were associated with more severe myocardial involvement as evaluated by CMR. METHODS: CCC patients with 12lead ECG and CMR closely obtained were included. ECG analysis evaluated rhythm, presence, and type of intraventricular conduction disturbances (IVCD) and, ventricular premature beats (VPB). CMR short-axis cine and late gadolinium enhancement images were evaluated to obtain left and right ventricular ejection fractions and MF mass, respectively. Statistical significance was set in 5%. RESULTS: 194 CCC patients (98 women, 56 ± 14 years) were evaluated, and no IVCD was detected in 71. The most common IVCD was the association of right bundle branch block and left anterior fascicular block (RBBB+LAFB) in 58 patients, followed by isolated RBBB in 34, isolated LAFB in 17, and left bundle branch block (LBBB) in 14 patients. Of patients with no IVCD, 63% had MF and the burden of fibrosis (no IVCD - 7.4 ± 8.6%; RBBB - 6.6 ± 6.5%; p = 1.00), as well as left ventricular ejection fraction (LVEF) (no IVCD - 52 ± 14%; RBBB - 55 ± 10%; p = 1.00) were similar to patients with isolated RBBB. Left conduction system impairment was associated with lower LVEF (LAFB - 39 ± 15%; RBBB+LAFB- 41 ± 15%; and LBBB - 35 ± 15%; p < 0.001) and more MF (RBBB+LAFB - 12.2 ± 10.4%; LBBB - 10.6 ± 7.5%; and LAFB - 12.0 ± 7.0%; p < 0.001). The univariable model showed that the presence of MF was related to RBBB+LAFB (OR 5.0; p = 0.001) and VPB (OR 6.3; p = 0.014). After adjustment for age, gender, and different risk factors in a multivariable model, the same findings were still significantly related to CMR myocardial fibrosis (RBBB+LAFB OR 5.0; p = 0.002 / VPB OR 6.9; p = 0.015). CONCLUSIONS: ECG without IVCD does not exclude serious cardiac abnormalities in CCC, and isolated RBBB seems to have a benign course. The presence of VPB and left branch conduction impairment, especially LAFB associated with RBBB, indicate a more severe cardiac involvement.
Assuntos
Cardiomiopatias , Cardiomiopatia Chagásica , Doença de Chagas , Disfunção Ventricular Esquerda , Arritmias Cardíacas/complicações , Bloqueio de Ramo , Cardiomiopatias/complicações , Cardiomiopatia Chagásica/complicações , Cardiomiopatia Chagásica/diagnóstico por imagem , Doença de Chagas/complicações , Cicatriz/complicações , Meios de Contraste , Eletrocardiografia , Feminino , Gadolínio , Humanos , Imageamento por Ressonância Magnética , Volume Sistólico , Disfunção Ventricular Esquerda/complicações , Disfunção Ventricular Esquerda/etiologia , Função Ventricular EsquerdaRESUMO
Resumo Fundamento Cerca de 40% dos pacientes com infarto agudo do miocárdio com supradesnível do segmento ST (IAMCSST) no Brasil não recebem terapia de reperfusão. Objetivo A utilização de uma rede de telemedicina baseada no WhatsApp® poderia aumentar a porcentagem de pacientes que recebem terapia de reperfusão. Métodos Estudo transversal do tipo antes e depois da organização de uma rede de telemedicina para envio e análise do eletrocardiograma através do WhatsApp® dos pacientes suspeitos de IAMCSST oriundos dos 25 municípios integrantes do Departamento Regional de Saúde de Ribeirão Preto (DRS−XIII), para hospital terciário que poderia autorizar a transferência imediata do paciente utilizando o mesmo sistema. O desfechos analisados foram a porcentagem de pacientes que receberam terapia de reperfusão e a taxa de mortalidade intra-hospitalar. Considerou-se valor de p <0,05 como estatisticamente significativo. Resultados Foram comparados 82 pacientes antes desta rede (1º de fevereiro de 2016 a 31 de janeiro de 2018) com 196 pacientes depois da implantação da mesma (1º de fevereiro de 2018 a 31 de janeiro de 2020). Após a implantação da rede, houve aumento significativo da proporção de pacientes que receberam terapia de reperfusão (60% vs. 92%), risco relativo (RR): 1,594 [intervalo de confiança (IC) 95% 1,331 - 1,909], p <0,0001 e redução da mortalidade intra-hospitalar (13,4% vs. 5,6%), RR: 0,418 [IC 95% 0,189 - 0,927], p = 0,028. Conclusão Rede de telemedicina baseada no WhatsApp® associou-se a aumento da porcentagem de pacientes com IAMCSST que receberam terapia de reperfusão e a redução na mortalidade intra-hospitalar.
Abstract Background About 40% of patients with ST-segment elevation myocardial infarction (STEMI) in Brazil do not receive reperfusion therapy. Objective The use of a telemedicine network based on WhatsApp® could increase the percentage of patients receiving reperfusion therapy. Methods A cross-sectional study analyzed outcomes before and after the organization of a telemedicine network to send the electrocardiogram via WhatsApp® of patients suspected of STEMI from 25 municipalities that are members of the Regional Health Department of Ribeirão Preto (DRS−XIII) to a tertiary hospital, which could authorize immediate patient transfer using the same system. The analyzed outcomes included the percentage of patients who received reperfusion therapy and the in-hospital mortality rate. A p value < 0.05 was considered statistically significant. Results The study compared 82 patients before (February 1, 2016 to January 31, 2018) with 196 patients after this network implementation (February 1, 2018 to January 31, 2020). After implementing this network, there was a significant increase in the proportion of patients who received reperfusion therapy (60% vs. 92%), relative risk (RR): 1.594 [95% confidence interval (CI) 1.331 - 1.909], p < 0.0001 and decrease in the in-hospital mortality rate (13.4% vs. 5.6%), RR: 0.418 [95%CI 0.189 - 0.927], p = 0.028. Conclusion The use of WhatsApp®-based telemedicine has led to an increase in the percentage of patients with STEMI who received reperfusion therapy and a decrease in the in-hospital mortality rate.
Assuntos
Humanos , Telemedicina , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Infarto do Miocárdio/terapia , Reperfusão Miocárdica , Estudos Transversais , Mortalidade Hospitalar , EletrocardiografiaRESUMO
BACKGROUND: About 40% of patients with ST-segment elevation myocardial infarction (STEMI) in Brazil do not receive reperfusion therapy. OBJECTIVE: The use of a telemedicine network based on WhatsApp® could increase the percentage of patients receiving reperfusion therapy. METHODS: A cross-sectional study analyzed outcomes before and after the organization of a telemedicine network to send the electrocardiogram via WhatsApp® of patients suspected of STEMI from 25 municipalities that are members of the Regional Health Department of Ribeirão Preto (DRS-XIII) to a tertiary hospital, which could authorize immediate patient transfer using the same system. The analyzed outcomes included the percentage of patients who received reperfusion therapy and the in-hospital mortality rate. A p value < 0.05 was considered statistically significant. RESULTS: The study compared 82 patients before (February 1, 2016 to January 31, 2018) with 196 patients after this network implementation (February 1, 2018 to January 31, 2020). After implementing this network, there was a significant increase in the proportion of patients who received reperfusion therapy (60% vs. 92%), relative risk (RR): 1.594 [95% confidence interval (CI) 1.331 - 1.909], p < 0.0001 and decrease in the in-hospital mortality rate (13.4% vs. 5.6%), RR: 0.418 [95%CI 0.189 - 0.927], p = 0.028. CONCLUSION: The use of WhatsApp®-based telemedicine has led to an increase in the percentage of patients with STEMI who received reperfusion therapy and a decrease in the in-hospital mortality rate.
FUNDAMENTO: Cerca de 40% dos pacientes com infarto agudo do miocárdio com supradesnível do segmento ST (IAMCSST) no Brasil não recebem terapia de reperfusão. OBJETIVO: A utilização de uma rede de telemedicina baseada no WhatsApp® poderia aumentar a porcentagem de pacientes que recebem terapia de reperfusão. MÉTODOS: Estudo transversal do tipo antes e depois da organização de uma rede de telemedicina para envio e análise do eletrocardiograma através do WhatsApp® dos pacientes suspeitos de IAMCSST oriundos dos 25 municípios integrantes do Departamento Regional de Saúde de Ribeirão Preto (DRS−XIII), para hospital terciário que poderia autorizar a transferência imediata do paciente utilizando o mesmo sistema. O desfechos analisados foram a porcentagem de pacientes que receberam terapia de reperfusão e a taxa de mortalidade intra-hospitalar. Considerou-se valor de p <0,05 como estatisticamente significativo. RESULTADOS: Foram comparados 82 pacientes antes desta rede (1º de fevereiro de 2016 a 31 de janeiro de 2018) com 196 pacientes depois da implantação da mesma (1º de fevereiro de 2018 a 31 de janeiro de 2020). Após a implantação da rede, houve aumento significativo da proporção de pacientes que receberam terapia de reperfusão (60% vs. 92%), risco relativo (RR): 1,594 [intervalo de confiança (IC) 95% 1,331 1,909], p <0,0001 e redução da mortalidade intra-hospitalar (13,4% vs. 5,6%), RR: 0,418 [IC 95% 0,189 0,927], p = 0,028. CONCLUSÃO: Rede de telemedicina baseada no WhatsApp® associou-se a aumento da porcentagem de pacientes com IAMCSST que receberam terapia de reperfusão e a redução na mortalidade intra-hospitalar.
Assuntos
Infarto do Miocárdio , Infarto do Miocárdio com Supradesnível do Segmento ST , Telemedicina , Estudos Transversais , Eletrocardiografia , Mortalidade Hospitalar , Humanos , Infarto do Miocárdio/terapia , Reperfusão Miocárdica , Infarto do Miocárdio com Supradesnível do Segmento ST/terapiaRESUMO
BACKGROUND: Regional myocardial sympathetic denervation is a conspicuous and early disorder in patients with chronic Chagas' cardiomyopathy (CCC), potentially associated to the progression of myocardial dysfunction OBJECTIVE: To evaluate in a longitudinal study the association between the presence and the progression of regional myocardial sympathetic denervation with the deterioration of global and segmental left ventricular dysfunction in CCC. METHODS: 18 patients with CCC were submitted at initial evaluation and after 5.5 years to rest myocardial scintigraphy with 123Iodo-metaiodobenzylguanidine and 99mTc-sestamibi and to two-dimensional echocardiography to assess myocardial sympathetic denervation, extent of fibrosis, and the left ventricular ejection fraction (LVEF) and wall motion abnormalities. RESULTS: In the follow-up evaluation, compared to the initial one, we observed a significant decrease in LVEF (56 ± 11 to 49% ± 12; P = .01) and increased summed defects scores in the myocardial innervation scintigraphy (15 ± 10 to 20 ± 9; P < .01). The presence of regional myocardial sympathetic denervation in ventricular regions of viable non-fibrotic myocardium presented an odds ratio of 4.25 for the development of new wall motion abnormalities (P = .001). CONCLUSION: Regional and global myocardial sympathetic denervation is a progressive derangement in CCC. In addition, the regional denervation is topographically associated with areas of future development of regional systolic dysfunction in patients with CCC.
Assuntos
Cardiomiopatia Chagásica , Doença de Chagas , Disfunção Ventricular Esquerda , Humanos , Cardiomiopatia Chagásica/diagnóstico por imagem , Cardiomiopatia Chagásica/complicações , Volume Sistólico , Estudos Longitudinais , Função Ventricular Esquerda , Miocárdio , Simpatectomia , Doença de Chagas/complicaçõesRESUMO
Speckle tracking echocardiography (STE) enables early diagnosis of myocardial damage by evaluating myocardial strain. We aimed to study sequential changes in structural and ventricular functional parameters during Chagas disease (CD) natural history in an animal model. 37 Syrian hamsters were inoculated intraperitoneally with Trypanosoma cruzi (Chagas) and 20 with saline (Control). Echocardiography was performed before the infection (baseline), at 1 month (acute phase), 4, 6, and 8 months (chronic phase) using Vevo 2100 (Fujifilm Inc.) ultrasound system. Left ventricular end-diastolic diameter, Left ventricular end-systolic diameter (LVESD), Left ventricular ejection fraction (LVEF), Global longitudinal (GLS), circumferential (GCS) and radial (GRS) strain were evaluated. Tricuspid annular plane systolic excursion (TAPSE) was used to assess right ventricular function. At 8 months, animals were euthanized and LV myocardial samples were analyzed for quantitation of inflammation and fibrosis. LVEF decreased over time in Chagas group and a difference from Control was detected at 6 months (p-value of groups#time interaction = 0.005). There was a pronounced decrease in GLS, GCS and TAPSE in Chagas group (p-value of groups#time interaction = 0.003 for GLS, < 0.001 for GCS and < 0.009 for TAPSE vs Control) since the first month. LVESD, LVEF and GLS were significantly correlated to the number of inflammatory cells (r = 0.41, p = 0.046; r = - 0.42, p = 0.042; r = 0.41, p = 0.047) but not to fibrosis. In the Syrian hamster model of CD STE parameters (GLS and GCS) showed an early decrease. Changes in LVEF, LVESD, and GLS were correlated to myocardial inflammation but not to fibrosis.