Chagas Cardiomyopathy and Myocardial Sympathetic Denervation.

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.

Coronary microvascular dysfunction due to Chagas disease: where are we now?

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.

Perfil clínico e hemodinâmico de pacientes consecutivos com estenose aórtica valvar estudados na era pré-implante transcateter valvar aórtico em instituição acadêmica. Análise comparativa da avaliação invasiva com a ecocardiográfica / Clinical and hemodynamic profile of consecutive patients with aortic valve stenosis studied in the pre-transcatheter aortic valve implantation era at an academic institution. Comparative analysis of invasive evaluation with echocardiography

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.

Correlation of TcII discrete typing units with severe chronic Chagas cardiomyopathy in patients from various Brazilian geographic regions.

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.

Association of left ventricular abnormalities with incident cerebrovascular events and sources of thromboembolism in patients with chronic Chagas cardiomyopathy.

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.

Guideline of the Brazilian Society of Cardiology on Diagnosis and Treatment of Patients with Chagas Disease Cardiomyopathy / Diretriz da Sociedade Brasileira de Cardiologia sobre Diagnóstico e Tratamento de Pacientes com Cardiomiopatia da Doença de Chagas

This guideline aimed to update the concepts and formulate the standards of conduct and scientific evidence that support them, regarding the diagnosis and treatment of the Cardiomyopathy of Chagas disease, with special emphasis on the rationality base that supported it.  Chagas disease in the 21st century maintains an epidemiological pattern of endemicity in 21 Latin American countries. Researchers and managers from endemic and non-endemic countries point to the need to adopt comprehensive public health policies to effectively control the interhuman transmission of T. cruzi infection, and to obtain an optimized level of care for already infected individuals, focusing on diagnostic and therapeutic opportunistic opportunities.   Pathogenic and pathophysiological mechanisms of the Cardiomyopathy of Chagas disease were revisited after in-depth updating and the notion that necrosis and fibrosis are stimulated by tissue parasitic persistence and adverse immune reaction, as fundamental mechanisms, assisted by autonomic and microvascular disorders, was well established. Some of them have recently formed potential targets of therapies.  The natural history of the acute and chronic phases was reviewed, with enhancement for oral transmission, indeterminate form and chronic syndromes. Recent meta-analyses of observational studies have estimated the risk of evolution from acute and indeterminate forms and mortality after chronic cardiomyopathy. Therapeutic approaches applicable to individuals with Indeterminate form of Chagas disease were specifically addressed. All methods to detect structural and/or functional alterations with various cardiac imaging techniques were also reviewed, with recommendations for use in various clinical scenarios. Mortality risk stratification based on the Rassi score, with recent studies of its application, was complemented by methods that detect myocardial fibrosis.  The current methodology for etiological diagnosis and the consequent implications of trypanonomic treatment deserved a comprehensive and in-depth approach. Also the treatment of patients at risk or with heart failure, arrhythmias and thromboembolic events, based on pharmacological and complementary resources, received special attention. Additional chapters supported the conducts applicable to several special contexts, including t. cruzi/HIV co-infection, risk during surgeries, in pregnant women, in the reactivation of infection after heart transplantation, and others.     Finally, two chapters of great social significance, addressing the structuring of specialized services to care for individuals with the Cardiomyopathy of Chagas disease, and reviewing the concepts of severe heart disease and its medical-labor implications completed this guideline.

Esta diretriz teve como objetivo principal atualizar os conceitos e formular as normas de conduta e evidências científicas que as suportam, quanto ao diagnóstico e tratamento da CDC, com especial ênfase na base de racionalidade que a embasou. A DC no século XXI mantém padrão epidemiológico de endemicidade em 21 países da América Latina. Investigadores e gestores de países endêmicos e não endêmicos indigitam a necessidade de se adotarem políticas abrangentes, de saúde pública, para controle eficaz da transmissão inter-humanos da infecção pelo T. cruzi, e obter-se nível otimizado de atendimento aos indivíduos já infectados, com foco em oportunização diagnóstica e terapêutica. Mecanismos patogênicos e fisiopatológicos da CDC foram revisitados após atualização aprofundada e ficou bem consolidada a noção de que necrose e fibrose sejam estimuladas pela persistência parasitária tissular e reação imune adversa, como mecanismos fundamentais, coadjuvados por distúrbios autonômicos e microvasculares. Alguns deles recentemente constituíram alvos potenciais de terapêuticas. A história natural das fases aguda e crônica foi revista, com realce para a transmissão oral, a forma indeterminada e as síndromes crônicas. Metanálises recentes de estudos observacionais estimaram o risco de evolução a partir das formas aguda e indeterminada e de mortalidade após instalação da cardiomiopatia crônica. Condutas terapêuticas aplicáveis aos indivíduos com a FIDC foram abordadas especificamente. Todos os métodos para detectar alterações estruturais e/ou funcionais com variadas técnicas de imageamento cardíaco também foram revisados, com recomendações de uso nos vários cenários clínicos. Estratificação de risco de mortalidade fundamentada no escore de Rassi, com estudos recentes de sua aplicação, foi complementada por métodos que detectam fibrose miocárdica. A metodologia atual para diagnóstico etiológico e as consequentes implicações do tratamento tripanossomicida mereceram enfoque abrangente e aprofundado. Também o tratamento de pacientes em risco ou com insuficiência cardíaca, arritmias e eventos tromboembólicos, baseado em recursos farmacológicos e complementares, recebeu especial atenção. Capítulos suplementares subsidiaram as condutas aplicáveis a diversos contextos especiais, entre eles o da co-infecção por T. cruzi/HIV, risco durante cirurgias, em grávidas, na reativação da infecção após transplante cardíacos, e outros.    Por fim, dois capítulos de grande significado social, abordando a estruturação de serviços especializados para atendimento aos indivíduos com a CDC, e revisando os conceitos de cardiopatia grave e suas implicações médico-trabalhistas completaram esta diretriz. 

Epigenetic regulation of transcription factor binding motifs promotes Th1 response in Chagas disease cardiomyopathy.

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.

Epigenetic regulation of transcription factor binding motifs promotes Th1 response in Chagas disease cardiomyopathy

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.

Electrocardiogram abnormalities in chronic Chagas cardiomyopathy correlate with scar mass and left ventricular dysfunction as assessed by cardiac magnetic resonance imaging.

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.

Otimização da Terapia de Reperfusão no Infarto Agudo do Miocárdio com Supradesnível do Segmento ST por Meio de Telemedicina Baseada no WhatsApp® / Reperfusion Therapy Optimization in Acute Myocardial Infarction with ST-Segment Elevation using WhatsApp®-Based Telemedicine

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.

Reperfusion Therapy Optimization in Acute Myocardial Infarction with ST-Segment Elevation using WhatsApp®-Based Telemedicine. / Otimização da Terapia de Reperfusão no Infarto Agudo do Miocárdio com Supradesnível do Segmento ST por Meio de Telemedicina Baseada no WhatsApp®.

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.

Regional myocardial sympathetic denervation precedes the development of left ventricular systolic dysfunction in chronic Chagas' cardiomyopathy.

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.

Time-driven activity-based costing as a strategy to increase efficiency: An analyses of interventional coronary procedures.

Monitoring the costs is one of the key components underlying value-based health care. This study aimed to evaluate the cost-saving opportunities of interventional coronary procedures (ICPs). Data from 90 patients submitted to elective ICP were evaluated in five Brazilian hospitals. Time-driven activity-based costing, that guides the cost estimates using the time consumed and the capacity cost rates per resource as the data input, was used to assess costs and the time spent over the care pathway. Descriptive cost analyses were followed by a labour cost-saving estimate potentially achieved by the redesign of the ICP pathway. The mean cost per patient varied from $807 to $2639. The length of the procedure phase per patient was similar among the hospitals, while the post-procedure phase presented the highest variation in length. The highest direct cost saving opportunities are concentrated in the procedure phase. By comparing the benchmark service with the most expensive one, it was estimated that redesigning physician practices could decrease 51% of the procedure cost. This application is pioneered in Brazil and demonstrates how detailed cost information can contribute to driving health care management to value by identifying cost-saving opportunities.

Parasitic Load Correlates With Left Ventricular Dysfunction in Patients With Chronic Chagas Cardiomyopathy.

Background: Chronic Chagas disease (CChD), one of the infectious parasitic diseases with the greatest social and economic impact upon a large part of the American continent, has distinct clinical manifestations in humans (cardiac, digestive, or mixed clinical forms). The mechanisms underlying the development of the most common and ominous clinical form, the chronic Chagas cardiomyopathy (CCC) have not been completely elucidated, despite the fact that a high intensity of parasite persistence in the myocardium is deemed responsible for an untoward evolution of the disease. The present study aimed to assess the parasite load CCC and its relation to left ventricular ejection fraction (LVEF), a definite prognostic marker in patients with CCC. Methods: Patients with CCC were clinically evaluated using 12-lead-electrocardiogram, echocardiogram, chest X-ray. Peripheral blood sampling (5 ml of venous blood in guanidine/EDTA) was collected from each patient for subsequent DNA extraction and the quantification of the parasite load using real-time PCR. Results: One-hundred and eighty-one patients with CCC were evaluated. A total of 140 (77.3%) had preserved left ventricular ejection fraction (of ≥40%), and 41 individuals had LV dysfunction (LVEF of <40%). A wide variation in parasite load was observed with a, mean of 1.3460 ± 2.0593 (0.01 to 12.3830) par. Eq./mL. The mean ± SD of the parasite load was 0.6768 ± 0.9874 par. Eq./mL and 3.6312 ± 2.9414 par. Eq./mL in the patients with LVEF ≥ 40% and <40%, respectively. Conclusion: The blood parasite load is highly variable and seems to be directly related to the reduction of LVEF, an important prognostic factor in CCC patients.

Prospective study of ventricular function and myocardial deformation related to survival in acute Chagas disease: an experimental animal model.

Chagas disease (CD) has been changing from an endemic Latino-American disease to a condition found outside endemic regions, due to migratory movements. Although often subclinical, its acute phase can be lethal. This study aimed to assess survival during the acute phase of CD and its relationship with ventricular function in an experimental model. To this end, 30 Syrian hamsters were inoculated with Trypanosoma cruzi (IG) and other 15 animals received saline solution (CG). Groups were monitored daily and submitted to echocardiography in two moments: before the challenge and 15 days post-infection. Left ventricular ejection fraction (LVEF) and global longitudinal myocardial strain (GLS) of the LV were measured. The IG was divided into groups of animals with and without clinical signs of disease. ANOVA for mixed models was used to compare ventricular function parameters. Survival analysis was studied using Kaplan-Meier curves and the log-rank test. The follow-up lasted 60 days. LVEF in IG was reduced through time (53.80 to 43.55%) compared to CG (57.86 to 59.73%) (p=0.002). There was also a reduction of GLS (-18.97% to -12.44%) in the IG compared to CG (p=0.012). Twelve animals from IG died compared to one animal from CG. Eleven out of the 12 animals from the IG group died before presenting with clinical signs of infection. Survival was reduced in the IG compared to CG over time (p=0.02). The reduced survival during the acute phase of this experimental model of Chagas disease was related to the significant reduction of LV function. The mortality rate in the IG was higher in the group presenting with clinical signs of infection.

Statins Prescriptions and Lipid Levels in a Tertiary Public Hospital. / Perfil de Prescrição de Estatinas e de Níveis Lipêmicos em Ambulatórios de Hospital Terciário Público.

BACKGROUND: The development of a new class of medications that are highly capable of reducing LDL-cholesterol renewed the interest in the characterization of familial hypercholesterolemia patients. Nevertheless, little is known about the lipid profile of patients in tertiary healthcare centers in Brazil in order to better estimate the real occurrence of familial hypercholesterolemia, with initial suspect of LDL-cholesterol levels above 190 mg/d/L. OBJECTIVES: This study evaluated the lipid profile (total cholesterol and LDL-cholesterol) in ambulatory patients from a general tertiary public hospital. METHODS: Retrospective study comparing prescriptions of statins and lipid profile results. The significance level was established in 5%. RESULTS: In one year, 9,594 individuals received statin prescriptions, of whom 51.5% were females and the mean age was 63.7±12.9 years-old (18 to 100 years-old). Thirty-two medical specialties prescribed statins. Cardiology was responsible for 43% of the total. Nearly 15% of those patients with a prescription did not have a recent total cholesterol result and 1,746 (18%) did not have a recent LDL-cholesterol measurement. The occurrence of the latter between 130 and 190 mg/dL was present in 1,643 (17.1%) individuals, and 228 (2.4%) patients had an LDL-cholesterol ≥190mg/dL among those using statins at distinct doses. Only two statins were used: simvastatin and atorvastatin. The first was prescribed in 77.6% of the prescriptions. CONCLUSION: In this cross-sectional cohort at a tertiary general hospital, statins have been widely prescribed but with little success in achieving recognized levels of control. There is probably a significant number of FH individuals in this cohort that need to be properly diagnosed in order to receive adequate treatment due to its prognostic implications.

FUNDAMENTO: O surgimento de nova classe de medicamentos com elevada capacidade de reduzir o LDL-colesterol (LDL-c) renovou o interesse na caracterização da hipercolesterolemia familiar (HF). Pouco se conhece do perfil lipídico de pacientes em atendimento terciário em nosso meio para caracterizar a real ocorrência de HF, que começa a ser suspeitada com níveis de LDL-c acima de 190mg/dL. OBJETIVOS: O estudo avaliou o perfil lipídico (colesterol total [CT] e LDL-c) de pacientes de hospital público terciário. MÉTODOS: Estudo retrospectivo de avaliação de prescrições de estatinas e resultados dos lipídios. O nível de significância foi estabelecido em 5%. RESULTADOS: Em 1 ano, 9.594 indivíduos receberam prescrição ambulatorial de estatinas, 51,5% do gênero feminino, idade média de 63,7±12,9 anos (18 a 100 anos). Trinta e duas especialidades prescreveram estatinas, sendo a cardiologia responsável por 43%. Cerca de 15% das prescrições não tinham dosagem recente de CT, e 1.746 (18,0%) não apresentavam resultado recente de LDL-c. A ocorrência de LDL-c > 130mg/dL e < 190mg/dL ocorreu em 1.643 (17,1%) casos, e 228 (2,4%) apresentaram LDL-c ≥ 190mg/dL dentre os que utilizavam estatinas nas diversas doses. Apenas duas estatinas foram utilizadas: sinvastatina e atorvastatina, e a primeira foi prescrita em 77,6% das receitas. CONCLUSÃO: Nesta coorte transversal de hospital terciário, foi possível verificar que a prescrição de estatinas é disseminada, mas que a obtenção de metas adequadas de CT e LDL-c não é atingida em grande percentual, e que há, possivelmente, significativo contingente de portadores de HF que necessitariam ser investigados por suas implicações prognósticas.