Enhancing risk assessment in Chagas cardiomyopathy: Electrophysiology study stratified by Rassi score.

BACKGROUND: Chagas cardiomyopathy (CCM) is increasingly prevalent in developed countries due to migration from endemic areas. Accurate risk stratification is crucial due to the variable clinical course of CCM. OBJECTIVE: To analyze the association between Rassi score progression and electrophysiology study (EPS) changes in CCM patients. METHODS: This prospective, observational cohort study involved CCM patients from two tertiary hospitals. Patients were classified as low, intermediate, or high risk based on the Rassi score. Data collected included demographics, clinical history, and diagnostic tests. EPS assessed AH, HH, and HV intervals, and inducibility of ventricular arrhythmias. Follow-ups were at 30 days and six-month intervals, with individualized discussions for cardiac implantable electric devices (CIED) based on EPS results. RESULTS: Of 67 screened CCM patients, 59 underwent EPS. The mean Rassi score was 8.7 ± 4.5 points, with 33.8 % low, 38.9 % intermediate, and 27.1 % high risk. EPS abnormalities were found in 57.6 % of patients, mainly VT/VF (52.5 %). Most induced ventricular arrhythmias were monomorphic VT (80.7 %). A significant association was found between Rassi score risk classification and EPS changes (OR = 1.88 95 %CI: 1.15-3.06 p = 0.02). Higher Rassi scores correlated with VT presence on EPS (p = 0.0036). Syncope/pre-syncope had an OR 2.45 95 %CI:1.21-4.94; p = 0.012, independent of Rassi risk. Decreased ejection fraction was linked to EPS changes (p = 0.04). CONCLUSION: EPS changes among CCM was associated with progression of the Rassi score, indicating its utility as a stratification tool. Factors such as the presence of syncope/pre-syncope, decreased LVEF and wall motion abnormalities emerged as independent predictors within Rassi scores for changes in EPS.

Causality and Severity of Adverse Reactions and Biochemical Changes to Benznidazole Treatment in Patients with Chronic Chagas Disease. / Causalidade e Gravidade das Reações Adversas e Alterações Laboratoriais ao Tratamento com Benznidazol em Pacientes com Doença de Chagas Crônica.

BACKGROUND: Chagas disease (CD) is a serious public health problem in Latin America. Benznidazole (BNZ) is used for the treatment of CD and, despite its wide use, little information is available about its toxicity and mechanisms of adverse drug reactions (ADR). OBJECTIVES: To identify and classify clinical and laboratory adverse reactions caused by BNZ in terms of causality and severity. METHODS: Prospective cohort study from January 2018 to December 2021. Treatment follow-up included visits and biochemical tests (complete blood count, liver and kidney function tests) before, during and after treatment. ADR were classified according to causality and severity. In the statistical analysis, the significance level was set at p<0.05. RESULTS: Forty patients with chronic CD were included. A high prevalence of ADR was observed 161 ADR in 30 patients [90%]; of these, 104 (64.6%) were classified as possible and 57 (35.4%) as probable. The ADR were classified as moderate and mild. Of the 40 patients, nine (22.5%) discontinued treatment. ADR associated with treatment discontinuation and interventions were those that affected the dermatological system, central and peripheral nervous system and sense organs such as ageusia. Mild hematological and biochemical changes such as lymphopenia were observed after 30 days of treatment. CONCLUSION: Many patients were able to complete the treatment even with ADR, which can be attributed to the successful follow-up strategy with symptomatic treatment and counseling, leading to patient's awareness of symptoms and treatment adherence.

FUNDAMENTO: A Doença de Chagas (DC) representa um grave problema de saúde pública na América Latina. O Benznidazol (BNZ) é utilizado para o tratamento DC e, apesar do seu amplo uso, poucas informações estão disponíveis sobre sua toxicidade e mecanismos das Reações Adversas ao Medicamento (RAM). OBJETIVOS: Identificar e classificar as reações adversas clínicas e laboratoriais ocasionadas pelo uso do BNZ quanto à sua causalidade e gravidade. MÉTODOS: Estudo de coorte prospectivo realizado no período de janeiro de 2018 a dezembro de 2021. O acompanhamento do tratamento incluiu consultas e análises laboratoriais antes, 30 e 60 dias após o início do tratamento. As RAM foram classificadas quanto à causalidade e gravidade. Na análise estatística o nível de significância adotado foi p<0,05. RESULTADOS: Participaram do estudo 40 pacientes com DC crônica, observou-se alta prevalência de RAM com um total de 161 em 30 (90%) pacientes. Destas, 104 (64,6%) foram classificadas como possíveis e 57 (35,4%) como prováveis. As reações foram classificadas em moderadas e leves. Dos 40 pacientes, nove (22,5%) suspenderam o tratamento. As RAM associadas à interrupção e intervenções foram as que afetaram o sistema dermatológico, sistema nervoso central e periférico ou que culminaram em ageusia. Após 30 dias de tratamento, alterações hematológicas e bioquímicas leves foram observadas como linfopenia. CONCLUSÃO: Apesar do elevado percentual de RAM, muitos pacientes foram capazes de completar o tratamento, o que se atribui ao êxito da estratégia de acompanhamento com intervenções de tratamento sintomático juntamente ao aconselhamento, levando à compreensão da sintomatologia e manutenção do tratamento.

Predictors of Appropriate Therapies and Death in Patients with Implantable Cardioverter-Defibrillator and Chronic Chagas Heart Disease. / Preditores de Terapias Apropriadas e Óbito em Pacientes com Cardiodesfibrilador Implantável e Cardiopatia Chagásica Crônica.

BACKGROUND: There are few retrospective and prospective studies on implantable cardioverter-defibrillators (ICD) in primary and secondary prevention of sudden death in chronic Chagas heart disease (CCHD). OBJECTIVES: To describe the long-term evolution of patients with CCHD and ICD and to identify and analyze predictors of mortality and appropriate device therapy in this population. METHODS: This was a historical prospective study with 117 patients with ICD and CCHD. Devices were implanted from January 2003 to December 2021. Predictors of appropriate therapies and long-term mortality were identified and analyzed. The level of statistical significance was p < 0.05. RESULTS: Patients (n = 117) had a median follow-up of 61 months (25 to 121 months); they were predominantly male (74%), with a median age of 55 years (48 to 64 years). There were 43.6% appropriate shocks, 26.5% antitachycardia pacing (ATP), and 51% appropriate therapies. During follow-up, 46 patients (39.7%) died. Mortality was 6.2% person-years (95% confidence interval [CI]: 4.6 to 8.3), with 2 sudden deaths during follow-up. Secondary prevention (hazard ratio [HR] 2.1; 95% CI: 1.1 to 4.3; p = 0.029) and ejection fraction less than 30% (HR 1.8; 95% CI: 1.1 to 3.1; p < 0.05) were predictors of appropriate therapies. Intermediate Rassi score showed a strong association with the occurrence of ATP alone (p = 0.015). Functional class IV (p = 0.007), left ventricular ejection fraction < 30 (p = 0.010), and age above 75 years (p = 0.042) were predictors of total mortality. CONCLUSION: ICDs in CCHD showed a high incidence of appropriate activation, especially in patients with secondary prevention, low left ventricular ejection fraction, and intermediate Rassi score. Patients with congestive heart failure, elevated functional class, and age over 75 years showed elevated mortality. Survival function of patients with implantable cardioverter-defibrillators and chronic Chagas heart disease. A - According to New York Heart Association functional class; B - According to left ventricular ejection fraction; C - According to Rassi score. D - According to age. CCHD: chronic Chagas heart disease; HR: hazard ratio; ICD: implantable cardioverter-defibrillator.

Preditores de Terapias Apropriadas e Óbito em Pacientes com Cardiodesfibrilador Implantável e Cardiopatia Chagásica Crônica / Predictors of Appropriate Therapies and Death in Patients with Implantable Cardioverter-Defibrillator and Chronic Chagas Heart Disease

Resumo Fundamento: Existem poucos estudos retrospectivos e prospectivos sobre cardiodesfibrilador implantável (CDI) na prevenção primária e secundária de morte súbita na cardiopatia chagásica crônica (CCC). Objetivos: Descrever a evolução a longo prazo dos portadores de CCC com CDI e identificar e analisar os preditores de mortalidade e de terapia apropriada do dispositivo nessa população. Métodos: Trata-se de um estudo prospectivo histórico com 117 pacientes portadores de CDI e CCC. Dispositivos foram implantados de janeiro de 2003 a dezembro de 2021. Fatores preditores de terapias apropriadas e mortalidade a longo prazo foram identificados e analisados. O nível de significância estatística é de p < 0,05. Resultados: Pacientes (n = 117) tiveram mediana de seguimento de 61 meses (25 a 121 meses), sendo o gênero masculino (74%) predominante e a mediana de idade de 55 anos (48 a 64 anos). Houve 43,6% de choques apropriados, 26,5% de estimulação cardíaca antitaquicardia (ATP) e 51% de terapias apropriadas. Durante o seguimento, 46 pacientes (39,7%) foram a óbito. A mortalidade foi de 6,2% pessoas-ano (intervalo de confiança [IC] 95%: 4,6 a 8,3), com 2 mortes súbitas durante o seguimento. A prevenção secundária (hazard ratio [HR] 2.1; IC 95%: 1,1 a 4,3; p = 0,029) e a fração de ejeção menor que 30% (HR 1.8; IC 95%: 1,1 a 3,1; p < 0,05) foram preditores de terapias apropriadas. Escore de Rassi intermediário apresentou uma forte associação com ocorrência de ATP isoladamente (p = 0,015). A classe funcional IV (p = 0,007), fração de ejeção do ventrículo esquerdo < 30 (p = 0,010) e a idade maior que 75 anos (p = 0,042) foram preditores de mortalidade total. Conclusão: Os desfibriladores na CCC apresentaram elevada incidência de acionamento apropriado especialmente naqueles pacientes de prevenção secundária, fração de ejeção do ventrículo esquerdo baixa e escore de Rassi intermediário. Os pacientes com insuficiência cardíaca congestiva, classe funcional avançada e idade maior que 75 anos apresentaram elevada mortalidade.

Abstract Background: There are few retrospective and prospective studies on implantable cardioverter-defibrillators (ICD) in primary and secondary prevention of sudden death in chronic Chagas heart disease (CCHD). Objectives: To describe the long-term evolution of patients with CCHD and ICD and to identify and analyze predictors of mortality and appropriate device therapy in this population. Methods: This was a historical prospective study with 117 patients with ICD and CCHD. Devices were implanted from January 2003 to December 2021. Predictors of appropriate therapies and long-term mortality were identified and analyzed. The level of statistical significance was p < 0.05. Results: Patients (n = 117) had a median follow-up of 61 months (25 to 121 months); they were predominantly male (74%), with a median age of 55 years (48 to 64 years). There were 43.6% appropriate shocks, 26.5% antitachycardia pacing (ATP), and 51% appropriate therapies. During follow-up, 46 patients (39.7%) died. Mortality was 6.2% person-years (95% confidence interval [CI]: 4.6 to 8.3), with 2 sudden deaths during follow-up. Secondary prevention (hazard ratio [HR] 2.1; 95% CI: 1.1 to 4.3; p = 0.029) and ejection fraction less than 30% (HR 1.8; 95% CI: 1.1 to 3.1; p < 0.05) were predictors of appropriate therapies. Intermediate Rassi score showed a strong association with the occurrence of ATP alone (p = 0.015). Functional class IV (p = 0.007), left ventricular ejection fraction < 30 (p = 0.010), and age above 75 years (p = 0.042) were predictors of total mortality. Conclusion: ICDs in CCHD showed a high incidence of appropriate activation, especially in patients with secondary prevention, low left ventricular ejection fraction, and intermediate Rassi score. Patients with congestive heart failure, elevated functional class, and age over 75 years showed elevated mortality.

Pacemaker Reuse in Portuguese Speaking Countries: A Clinical Reflection. / Reprocessamento de Marca-Passos em Países de Língua Portuguesa: Uma Reflexão Clínica.

There is a gap between high-income countries and others in terms of access to medical cardiac devices, such as pacemakers and implantable cardioverter defibrillators. Costs are one of the main barriers to the use of cardiac devices in these countries. There are international initiatives that aim to reduce the gap. The reuse of pacemakers has been discussed as a possible alternative to this problem. The concept of reusing pacemakers is not new; however, recent studies have proven to be safe, ethical, and effective for those who need cardiac implantable electronic devices and cannot afford them. Part of the Portuguese-speaking countries, especially in Africa, need an immediate response that benefits their countless patients who suffer from treatable arrhythmias.

Há uma enorme disparidade entre os países de alta renda e outros em termos de acesso a dispositivos médicos cardíacos, como marca-passos e desfibriladores implantáveis. Os custos são uma das principais barreiras ao uso de dispositivos cardíacos nesses países. Existem iniciativas internacionais que visam reduzir essa disparidade, e o reuso de marca-passos tem sido discutido como uma possível alternativa. O conceito de reutilização de marca-passos não é novo; entretanto, estudos recentes têm se mostrado seguros, éticos e eficazes para aqueles que precisam de dispositivos eletrônicos cardíacos implantáveis e não tem como adquiri-los. Parte dos países de língua portuguesa, especialmente na África, precisam de uma resposta imediata que beneficie seus inúmeros pacientes que sofrem de arritmias tratáveis.

Association between endothelial biomarkers and lipid and glycemic levels: a cross-sectional study with diabetic patients.

Background: Biomarkers can help understand the impact of achieving therapeutic goals in developing vascular diseases in diabetics. Aim: To assess the association between lipid and glycemic profiles and endothelial biomarkers in diabetics. Methods: Cross-sectional study that evaluated lipid and glycemic levels and biomarkers (VCAM-1, Sdc-1, FGF-23 and KIM-1 in diabetics. Results: Higher VCAM-1 levels were associated with higher low-density lipoprotein cholesterol and non-high-density lipoprotein (HDL) cholesterol levels (in the group with inadequate glycohemoglobin A1c [HbA1c] levels), with higher glycemic levels (in the group with inadequate HDL cholesterol levels) and with lower HDL cholesterol levels (both groups). VCAM-1 was independently associated with not achieving adequate HbA1c levels. Conclusion: In uncontrolled diabetics, VCAM-1 was independently associated with having inadequate HbA1c levels, suggesting they may already have endothelial damage.

Exercise Stress Test in The Assessment of Brugada Syndrome Patients

Abstract Brugada syndrome (BS) is a genetic channelopathy, clinically characterized by an increased risk of sudden cardiac death. The diagnosis requires a typical electrocardiographic pattern, and data on risk stratification are limited in the literature. The aim of this study was to conduct a review on the importance of exercise stress test (EST) in risk stratification in BS. Articles were searched in the PubMed, Scielo and Google Scholar databases. From the 200 articles retrieved, eight were included, with a total of 712 patients (95% men) aged between 35 and 60 years. Severe symptoms and ventricular arrhythmias were reported by 256 patients before the EST, with syncope being reported in 70% of cases. The reviewed articles suggest that the EST is a safe method that can help in the diagnosis and risk stratification for malignant arrhythmias in patients with BS. Potential predictors of poor prognosis were: augmentation in ST-segment elevation > 0.5 mV in V1, V2 or V3 in early recovery; J-point elevation in lead > 2mm in aVR in late recovery; heart rate reduction < 40% from maximum heart rate in late recovery and occurrence of ventricular extrasystoles in early recovery.

Reprocessamento de Marca-Passos em Países de Língua Portuguesa: Uma Reflexão Clínica / Pacemaker Reuse in Portuguese Speaking Countries: A Clinical Reflection

Resumo Há uma enorme disparidade entre os países de alta renda e outros em termos de acesso a dispositivos médicos cardíacos, como marca-passos e desfibriladores implantáveis. Os custos são uma das principais barreiras ao uso de dispositivos cardíacos nesses países. Existem iniciativas internacionais que visam reduzir essa disparidade, e o reuso de marca-passos tem sido discutido como uma possível alternativa. O conceito de reutilização de marca-passos não é novo; entretanto, estudos recentes têm se mostrado seguros, éticos e eficazes para aqueles que precisam de dispositivos eletrônicos cardíacos implantáveis e não tem como adquiri-los. Parte dos países de língua portuguesa, especialmente na África, precisam de uma resposta imediata que beneficie seus inúmeros pacientes que sofrem de arritmias tratáveis.

Abstract There is a gap between high-income countries and others in terms of access to medical cardiac devices, such as pacemakers and implantable cardioverter defibrillators. Costs are one of the main barriers to the use of cardiac devices in these countries. There are international initiatives that aim to reduce the gap. The reuse of pacemakers has been discussed as a possible alternative to this problem. The concept of reusing pacemakers is not new; however, recent studies have proven to be safe, ethical, and effective for those who need cardiac implantable electronic devices and cannot afford them. Part of the Portuguese-speaking countries, especially in Africa, need an immediate response that benefits their countless patients who suffer from treatable arrhythmias.

Remote monitoring of pacemakers and defibrillators: Effective and safe in Brazil?

Background: The remote monitoring (RM) of cardiac implantable electronic devices (CIEDs) has become a common method of in-home monitoring and follow-up in high-income countries given its effectiveness, safety, convenience, and the possibility of early intervention. However, in Brazil, RM is still underutilized. Objectives: This observational study aims to demonstrate our experience of using RM in Brazil and the predictive factors of RM of CIED follow-up in Brazil. Methods: This was a prospective cohort study of patients with a CIED. Event rates are reported and clinical responses to those findings and outcomes based on the detection of RM. A logistic regression model was performed to identify predictors of more events, with P < .05 for statistical significance. Results: This study evaluated consecutive 119 patients: 30.2% with pacemakers, 42.8% with implantable cardioverter-defibrillator, 22.7% with cardiac resynchronization therapy (CRT) with defibrillator, and 3.3% with CRT with pacemaker. Events were detected in 63.9% of the cases in 29.5 ± 23 months of follow-up. The outcomes found were that 44.5% needed elective evaluation in medical treatment and 23.5% needed immediate evaluation in therapy. Logistic regression analysis showed that the groups with CRT or CRT with defibrillator (75.0%), reduced ejection fraction (76.5%), and New York Heart Association functional class ≥II (75.0%) had the highest RM event rates. Conclusions: RM proved to be effective and safe in the follow-up of patients with CIEDs in Brazil, allowing early interventions and facilitating therapeutic management.

Dysautonomia: A Forgotten Condition - Part 1. / Disautonomia: Uma Condição Esquecida ­ Parte 1.

Dysautonomia covers a range of clinical conditions with different characteristics and prognoses. They are classified as Reflex Syndromes, Postural Orthostatic Tachycardia Syndrome (POTS), Chronic Fatigue Syndrome, Neurogenic Orthostatic Hypotension (nOH) and Carotid Sinus Hypersensitivity Syndrome. Reflex (vasovagal) syndromes will not be discussed in this article. Reflex (vasovagal) syndromes are mostly benign and usually occur in patients without an intrinsic autonomic nervous system (ANS) or heart disease. Therefore, they are usually studied separately. Cardiovascular Autonomic Neuropathy (CAN) is the term most currently used to define dysautonomia with impairment of the sympathetic and/or parasympathetic cardiovascular autonomic nervous system. It can be idiopathic, such as multisystemic atrophy or pure autonomic failure, or secondary to systemic pathologies such as diabetes mellitus, neurodegenerative diseases, Parkinson's disease, dementia syndromes, chronic renal failure, amyloidosis and it may also occur in the elderly. The presence of Cardiovascular Autonomic Neuropathy (CAN) implies greater severity and worse prognosis in various clinical situations. Detection of Orthostatic Hypotension (OH) is a late sign and means greater severity in the context of dysautonomia, defined as Neurogenic Orthostatic Hypotension (nOH). It must be differentiated from hypotension due to hypovolemia or medications, called non-neurogenic orthostatic hypotension (nnOH). OH can result from benign causes, such as acute, chronic hypovolemia or use of various drugs. However, these drugs may only reveal subclinical pictures of Dysautonomia. All drugs of patients with dysautonomic conditions should be reevaluated. Precise diagnosis of CAN and the investigation of the involvement of other organs or systems is extremely important in the clinical suspicion of pandysautonomia. In diabetics, in addition to age and time of disease, other factors are associated with a higher incidence of CAN, such poor glycemic control, hypertension, dyslipidemia and obesity. Among diabetic patients, 38-44% can develop Dysautonomia, with prognostic implications and higher cardiovascular mortality. In the initial stages of DM, autonomic dysfunction involves the parasympathetic system, then the sympathetic system and, later on, it presents as orthostatic hypotension. Valsalva, Respiratory and Orthostatic tests (30:15) are the gold standard methods for the diagnosis of CAN. They can be associated with RR Variability tests in the time domain, and mainly in the frequency domain, to increase the sensitivity (protocol of the 7 tests). These tests can detect initial or subclinical abnormalities and assess severity and prognosis. The Tilt Test should not be the test of choice for investigating CAN at an early stage, as it detects cases at more advanced stages. Tilt response with a dysautonomic pattern (gradual drop in blood pressure without increasing heart rate) may suggest CAN. Treatment of patients at moderate to advanced stages of dysautonomia is quite complex and often refractory, requiring specialized and multidisciplinary evaluation. There is no cure for most types of Dysautonomia at a late stage. NOH patients can progress with supine hypertension in more than 50% of the cases, representing a major therapeutic challenge. The immediate risk and consequences of OH should take precedence over the later risks of supine hypertension and values greater than 160/90 mmHg are tolerable. Sleeping with the head elevated (20-30 cm), not getting up at night, taking short-acting antihypertensive drugs for more severe cases, such as losartan, captopril, clonidine or nitrate patches, may be necessary and effective in some cases. Preventive measures such as postural care; good hydration; higher salt intake; use of compression stockings and abdominal straps; portioned meals; supervised physical activity, mainly sitting, lying down or exercising in the water are important treatment steps. Various drugs can be used for symptomatic nOH, especially fludrocortisone, midodrine and droxidopa, the latter not available in Brazil. The risk of exacerbation or triggering supine hypertension should be considered. Chronic Fatigue Syndrome represents a form of Dysautonomia and has been renamed as a systemic disease of exercise intolerance, with new diagnostic criteria: 1 - Unexplained fatigue, leading to occupational disability for more than 6 months; 2 - Feeling ill after exercising; 3 - Non-restorative sleep; 4 - One of the following findings: cognitive impairment or orthostatic intolerance. Several pathologies today have evolved with chronic fatigue, being called chronic diseases associated with chronic fatigue. Postural orthostatic tachycardia syndrome (POTS), another form of presentation of dysautonomic syndromes, is characterized by sustained elevation of heart rate (HR) ≥30 bpm (≥40 bpm if <20 years) or HR ≥120 bpm, in the first 10 minutes in an orthostatic position or during the tilt test, without classical orthostatic hypotension associated. A slight decrease in blood pressure may occur. Symptoms appear or get worse in an orthostatic position, with dizziness, weakness, pre-syncope, palpitations, and other systemic symptoms being common.

O termo disautonomia abrange um conjunto de condições clínicas com características e prognósticos distintos. Classificam-se em síndromes reflexas, síndrome postural ortostática taquicardizante (SPOT), síndrome da fadiga crônica, Hipotensão Ortostática Neurogênica (HON) e a Síndrome da hipersensibilidade do seio carotídeo. As síndromes reflexas (vasovagal) não serão discutidas neste artigo. As síndromes reflexas (vasovagal) são, na maioria das vezes, benignas, e ocorrem usualmente em pacientes sem doença intrínseca do sistema nervoso autônomo (SNA) ou do coração. Por isso, geralmente são estudadas separadamente. O termo neuropatia autonômica cardiovascular (NAC) é o mais utilizado na atualidade para definir as disautonomias com comprometimento do sistema nervoso autônomo cardiovascular simpático e/ou parassimpático. Pode ser idiopática, como a atrofia multissistêmica ou a falência autonômica pura, ou secundária a patologias sistêmicas como diabetes mellitus, doenças neurodegenerativas, doença de Parkinson, síndromes demenciais, insuficiência renal crônica, amiloidose, podendo também acometer idosos. A presença de neuropatia autonômica cardiovascular (NAC) implica em maior gravidade e pior prognóstico em diversas situações clínicas. A detecção de hipotensão ortostática (HO) é um sinal tardio e significa maior gravidade no contexto das disautonomias, definida como hipotensão ortostática neurogênica (HON). Deve ser diferenciada das hipotensões por hipovolemia ou medicamentosas, chamadas de hipotensão ortostática não neurogênica (HONN). A HO pode decorrer de causas benignas, como a hipovolemia aguda, crônica, ou ao uso de diversos fármacos. Esses fármacos podem, entretanto, apenas desmascarar quadros subclínicos de disautonomia. Deve-se reavaliar todos os fármacos de pacientes com quadros disautonômicos. O diagnóstico preciso de NAC e a investigação do envolvimento de outros órgãos ou sistemas é de extrema importância na suspeita clínica de uma pandisautonomia. No diabético, além da idade e do tempo de doença, outros fatores estão associados a maior ocorrência de NAC, como descontrole glicêmico, hipertensão, dislipidemia e obesidade. Entre os pacientes diabéticos, 38­44% podem evoluir com disautonomia, com implicações prognósticas e maior mortalidade cardiovascular. Nas etapas iniciais da DM, a disfunção autonômica envolve o sistema parassimpático, posteriormente o simpático e mais tardiamente manifesta-se com hipotensão ortostática. Os testes de Valsalva, respiratório e ortostático (30:15) são os métodos de padrão ouro para o diagnóstico de NAC. Eles podem ser associados aos testes de variabilidade RR no domínio do tempo, e principalmente da frequência, para aumento da sensibilidade (protocolo dos 7 testes). Esses testes podem detectar alterações iniciais ou subclínicas e avaliar a gravidade e o prognóstico. O teste de inclinação (tilt test) não deve ser o exame de escolha para investigação de NAC em fase inicial, pois detecta casos em fases mais avançadas. A resposta no tilt com padrão disautonômico (queda gradativa da pressão arterial sem aumento da frequência cardíaca) pode sugerir NAC. O tratamento dos pacientes em fases moderadas a avançadas das disautonomias é bastante complexo e muitas vezes refratário, necessitando de avaliação especializada e multidisciplinar. Não há cura para a maioria das disautonomias em fase tardia. Os pacientes com HON podem evoluir com hipertensão supina em mais de 50% dos casos, representando um grande desafio terapêutico. O risco imediato e as consequências da HO devem ter preferência sobre os riscos mais tardios da hipertensão supina e valores maiores que 160/90 mmHg são toleráveis. Medidas como dormir com a cabeceira elevada (20­30 cm), não levantar à noite, uso de anti-hipertensivo de ação curta noturna para casos mais severos, como a losartana, captopril, clonidina ou adesivos de nitratos, podem ser necessários e efetivos em alguns casos. As medidas preventivas como cuidados posturais, boa hidratação, maior ingesta de sal, uso de meias e cintas abdominais compressoras, refeições fracionadas, atividade física supervisionada principalmente sentada, deitada ou exercícios na água são etapas importantes no tratamento. Diversos fármacos podem ser usados para HON sintomática, principalmente a fludrocortisona, a midodrina e a droxidopa. Esses últimas não estão disponíveis no Brasil. O risco de exacerbação ou desencadeamento de hipertensão supina deve ser considerado. A síndrome da fadiga crônica representa uma forma de disautonomia e tem sido renomeada como doença sistêmica de intolerância ao exercício, com novos critérios diagnósticos: 1 - Fadiga inexplicada, levando a incapacidade para o trabalho por mais que 6 meses; 2 - Mal-estar após exercício; 3 - Sono não reparador; 4 - Mais um dos seguintes achados: comprometimento cognitivo ou intolerância ortostática. Várias patologias na atualidade têm evoluído com fadiga crônica, sendo denominadas de doenças crônicas associadas a fadiga crônica. A síndrome postural ortostática taquicardizante (SPOT), outra forma de apresentação das síndromes disautonômicas, é caracterizada por elevação sustentada da frequência cardíaca (FC) ≥30 bpm (≥40 bpm se <20 anos) ou FC ≥120 bpm, nos primeiros 10 minutos em posição ortostática ou durante o tilt test, sem hipotensão ortostática clássica associada. Pode ocorrer leve redução na pressão arterial. Os sintomas manifestam-se ou pioram em posição ortostática, sendo comuns a tontura, fraqueza, pré-síncope, palpitações, além de outros sintomas sistêmicos.