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- Orthostatic stress and baroreflex sensitivity: a window into autonomic dysfunction in lone paroxysmal atrial fibrillationPublication . Ferreira, Mónica; Laranjo, Sergio; Cunha, Pedro; Geraldes, Vera; Oliveira, Mario; Rocha, IsabelThe abnormal neural control of atria has been considered one of the mechanisms of paroxysmal atrial fibrillation (PAF) pathogenesis. The baroreceptor reflex has an important role in cardiovascular regulation and may serve as an index of autonomic function. This study aimed to analyze the baroreceptor reflex's role in heart rate regulation during upright tilt (HUT) in patients with lone PAF. The study included 68 patients with lone PAF and 34 healthy individuals who underwent baroreflex assessment. Parameters such as baroreflex sensitivity (BRS), number of systolic blood pressure (BP) ramps, and the baroreflex effectiveness index (BEI) were evaluated. The study found that PAF patients had comparable resting BPs and heart rates (HRs) to healthy individuals. However, unlike healthy individuals, PAF patients showed a sustained increase in BP with an upright posture followed by the delayed activation of the baroreceptor function with a blunted HR response and lower BEI values. This indicates a pronounced baroreflex impairment in PAF patients, even at rest. Our data suggest that together with BRS, BEI could be used as a marker of autonomic dysfunction in PAF patients, making it important to further investigate its relationship with AF recurrence after ablation and its involvement in cardiovascular autonomic remodeling.
- Insights into the background of autonomic medicinePublication . Laranjo, Sergio; Geraldes, Vera; Oliveira, Mário; Rocha, IsabelKnowledge of the physiology underlying the autonomic nervous system is pivotal for understanding autonomic dysfunction in clinical practice. Autonomic dysfunction may result from primary modifications of the autonomic nervous system or be secondary to a wide range of diseases that cause severe morbidity and mortality. Together with a detailed history and physical examination, laboratory assessment of autonomic function is essential for the analysis of various clinical conditions and the establishment of effective, personalized and precise therapeutic schemes. This review summarizes the main aspects of autonomic medicine that constitute the background of cardiovascular autonomic dysfunction.
- Epicardial adipose tissue volume assessed by cardiac CT as a predictor of atrial fibrillation recurrence following catheter ablationPublication . Teixeira, Bárbara Lacerda; Cunha, Pedro; Jacinto, Ana Sofia; Portugal, Guilherme; Laranjo, Sergio; Valente, Bruno; Lousinha, Ana; Cruz, Madalena Coutinho; Delgado, Ana Sofia; Brás, Manuel; Paulo, Margarida; Guerra, Cátia; Ramos, Ruben; Fontes, Iládia; Ferreira, Rui Cruz; Oliveira, MarioIntroduction: In patients with atrial fibrillation (AF), up to one third have recurrence after a first catheter ablation (CA). Epicardial adipose tissue (EAT) has been considered to be closely related to AF, with a potential role in its recurrence. We aimed to evaluate the association between the volume of EAT measured by cardiac computed tomography (CT) and AF recurrence after CA. Methods: Consecutive AF patients underwent a standardized cardiac CT protocol for quantification of EAT, thoracic adipose volume (TAV) and left atrium (LA) volume before CA. An appropriate cut-off of EAT was determined and risk recurrence was estimated. Results: 305 patients (63.6 % male, mean age 57.5 years, 28.2 % persistent AF) were followed for 24 months; 23 % had AF recurrence at 2-year mark, which was associated with higher EAT (p = 0.037) and LAV (p < 0.001). Persistent AF was associated with higher EAT volumes (p = 0.010), TAV (p = 0.003) and LA volumes (p < 0.001). EAT was predictive of AF recurrence (p = 0.044). After determining a cut-off of 92 cm3, survival analysis revealed that EAT volumes > 92 cm3 showed higher recurrence rates at earlier time points after the index ablation procedure (p = 0.006), with a HR of 1.95 (p = 0.008) of AF recurrence at 2-year. After multivariate adjustment, EAT > 92 cm3 remained predictive of AF recurrence (p = 0.028). Conclusion: The volume of EAT measured by cardiac CT can predict recurrence of AF after ablation, with a volume above 92 cm3 yielding almost twice the risk of arrhythmia recurrence in the first two years following CA. Higher EAT and TAV are also associated with persistent AF.
- Vascular function after acute aerobic exercise in adults with and without type 2 diabetes mellitusPublication . Marôco, João Luís; Arrais, Inês; Silvestre, Tiago; Pinto, Marco; Laranjo, Sergio; Magalhães, João P.; Santa-Clara, Helena; Fernhall, Bo; Melo, XavierIt is unknown whether type 2 diabetes mellitus (T2DM) influences the vascular function response to aerobic exercise. We examined brachial artery flow-mediated dilation (FMD) and flow-mediated slowing (FMS) of pulse wave velocity (PWV), 10-and 60-min after a high-intensity interval exercise (HIIE) and moderate-intensity continuous exercise (MICE) in adults with and without T2DM. Twelve older male adults with T2DM (57-84 years), and twenty-four healthy young and older adults (12 per group, aged 20-40 years and 57-76 years, respectively), completed an acute bout of HIIE, MICE, and a non-exercise condition. FMD was evaluated by the same researcher following standardized guidelines. FMS was calculated from the manufacturer's PWV beta formulas. Central arterial stiffness was estimated via carotid-femoral PWV (cfPWV). %FMD was reduced (d= - 5.94%, 95% CI: - 10.50 to - 1.38%, p = 0.002), whereas %FMS increased (d = 4.55%, 95% CI: 0.62 to 8.48%, p = 0.01), 10-min after HIIE only in adults with T2DM, normalizing 60-min into recovery. Conversely, %FMD was increased (d = 5.33%, 95% CI: 0.76 to 9.89%, p = 0.009) 10-min after MICE only in adults with T2DM. cfPWV remained unchanged following HIIE and MICE in all groups. We report disease-associated vascular function responses to aerobic exercise suggesting both HIIE and MICE uncover transient vascular alterations in older adults with T2DM.
- Reflex syncope : an integrative physiological approachPublication . Laranjo, Sergio; Rocha, Maria Isabel de Sousa; Oliveira, Mario João MartinsSíncope, a forma mais comum de perda temporária de consciência é responsável por até 5% das idas aos serviços de emergência e até 3% dos internamentos hospitalares. É um problema médico frequente, com múltiplos gatilhos, incapacitante, potencialmente perigoso e desafiante em termos diagnósticos e terapêuticos. Assim, é necessária uma anamnese detalhada para primeiro estabelecer a natureza da perda de consciência, mas, após o diagnóstico, as medidas terapêuticas existentes são pouco eficazes. Embora a fisiopatologia da síncope vasovagal ainda não tenha sido completamente esclarecida, alguns mecanismos subjacentes foram já desvendados. Em última análise, a síncope depende de uma falha transitória na perfusão cerebral pelo que qualquer factor que afecte a circulação sanguínea cerebral pode determinar a ocorrência de síncope. Assim, o objectivo do presente estudo é caracterizar o impacto hemodinâmico e autonómico nos mecanismos subjacentes à síncope reflexa, para melhorar o diagnóstico, o prognóstico e a qualidade de vida dos doentes e dos seus cuidadores. Para isso, desenhámos e implementámos novas ferramentas matemáticas e computacionais que permitem uma avaliação autonómica e hemodinâmica integrada, de forma a aprofundar a compreensão do seu envolvimento nos mecanismos de síncope reflexa. Além disso, refinando a precisão do diagnóstico, a sensibilidade e a especificidade do teste de mesa de inclinação (“tilt test”), estabelecemos uma ferramenta preditiva do episódio iminente de síncope. Isso permitiu-nos estabelecer alternativas de tratamento eficazes e personalizadas para os doentes refractários às opções convencionais, sob a forma de um programa de treino de ortostatismo (“tilt training”), contribuindo para o aumento da sua qualidade de vida e para a redução dos custos directos e indirectos da sua assistência médica. Assim, num estudo verdadeiramente multidisciplinar envolvendo doentes com síncope reflexa refractária à terapêutica, conseguimos demonstrar uma assincronia funcional das respostas reflexas autonómicas e hemodinâmicas, expressas por um desajuste temporal entre o débito cardíaco e as adaptações de resistência total periférica, uma resposta baroreflexa atrasada e um desequilíbrio incremental do tónus autonómico que, em conjunto, poderão resultar de uma disfunção do sistema nervoso autónomo que se traduz por uma reserva simpática diminuída. Igualmente, desenhámos, testámos e implementámos uma plataforma computacional e respectivo software associado - a plataforma FisioSinal –incluindo novas formas, mais dinâmicas, de avaliação integrada autonómica e hemodinâmica, que levaram ao desenvolvimento de algoritmos preditivos para a estratificação de doentes com síncope. Além disso, na aplicação dessas ferramentas, comprovámos a eficácia de um tratamento não invasivo, não disruptivo e integrado, focado na neuromodulação das variáveis autonómicas e cardiovasculares envolvidas nos mecanismos de síncope. Esta terapêutica complementar levou a um aumento substancial da qualidade de vida dos doentes e à abolição dos eventos sincopais na grande maioria dos doentes envolvidos. Em conclusão, o nosso trabalho contribuiu para preencher a lacuna entre a melhor informação científica disponível e sua aplicação na prática clínica, sustentando-se nos três pilares da medicina translacional: investigação básica, clínica e comunidade.
- The contribution of genetics to the understanding and management of cardiomyopathies: part 1Publication . Cardoso, Isabel; Nunes, Sofia; Brás, Pedro; Viegas, José Miguel; Marques Antunes, Miguel; Ferreira, André; Almeida, Inês; Custódio, Inês; Trigo, Conceição; Laranjo, Sergio; Graça, Rafael; Ferreira, Rui Cruz; Oliveira, Mario; Aguiar Rosa, Sílvia; Antunes, DianaGenetics has assumed a pivotal role in clarifying the pathophysiology of cardiomyopathies, facilitating molecular diagnosis, and enabling effective family screening. The advent of next-generation sequencing has revolutionized genetic testing by enabling cost-effective, high-throughput analysis. It is imperative for cardiovascular physicians to mainstream genetic testing into their clinical decision-making. Although a definitive genotype-phenotype correlation may not always be evident, several genotypes have emerged as valuable risk predictors for disease severity and progression. European guidelines emphasize the importance of genetic tests for predicting clinical outcome in cardiomyopathies. While further research is essential to bridge existing gaps in the genetic evidence on cardiomyopathies, there is considerable potential for significant advancements.
- Hypothalamic control of sleep-wake circadian cyclePublication . Meira e Cruz, Miguel; Laranjo, Sérgio; Rocha, IsabelSleep-wake cycle is probably the most truthful signature of life. These unavoidable interchangeable states are together the matrix for all that occurs in physiology, and its rhythms are regulated by homeostatic and circadian processes involving different neuronal structures and distinct neural substrates. Hypothalamic regulation of sleep-wake cycle becomes of relevance as several neuropeptide-producing neurons involved in sleep and wakefulness regulation are located there. In this chapter, we provide a review of the hypothalamic regulation of sleep-wake cycle, focusing on the hypocretin system and melanin-concentrating hormone (MCH)-producing neurons located in the lateral hypothalamic area (LHA).
- Acute vagal modulation of electrophysiology of the atrial and pulmonary veins increases vulnerability to atrial fibrillationPublication . Oliveira, Mario; da Silva, M. Nogueira; Geraldes, Vera; Xavier, Rita; Laranjo, Sergio; Silva, Vitor; Postolache, Gabriela; Ferreira, Rui; Rocha, IsabelVagal activity is thought to influence atrial electrophysiological properties and play a role in the initiation and maintenance of atrial fibrillation (AF). We evaluated the effects of acute vagal stimulation on atrial conduction, refractoriness of atrial and pulmonary veins (PVs) and inducibility of AF. An open-chest epicardial approach was performed in New Zealand White rabbits with preserved autonomic innervation. Atrial electrograms were obtained with four unipolar electrodes placed epicardially along the atria (n = 22) and an electrode adapted to the proximal left PV (n = 10). The cervical vagus nerve was stimulated with bipolar platinum electrodes (20 Hz). Epicardial activation was recorded in sinus rhythm, and effective refractory periods (ERPs), dispersion of refractoriness and conduction times from high-lateral right atrium (RA) to high-lateral left atrium (LA) and PVs assessed at baseline and during vagal stimulation. Burst pacing (50 Hz, 10 s), alone or combined with vagal stimulation, was applied to the right (RAA) and left atrial appendage (LAA) and PVs to induce AF. At baseline, ERPs were lower in PVs than in LA and LAA, but did not differ significantly from RA and RAA, and there was a significant delay in the conduction time from RA to PVs compared with the activation time from RA to LA (P < 0.01). During vagal stimulation, ERP decreased significantly at all sites, without significant differences in the dispersion of refractoriness, and the atrial conduction times changed from 39 ± 19 to 49 ± 9 ms (RA to PVs; n.s.) and from 14 ± 7 to 28 ± 12 ms (RA to LA; P = 0.01). Induction of AF was reproducible in 50% of cases with 50 Hz and in 82% with 50 Hz combined with vagal stimulation (P < 0.05). During vagal stimulation, AF cycle length decreased at all sites, and AF duration changed from 1.0 ± 0.9 to 14.0 ± 10.0 s (P < 0.01), with documentation of PV tachycardia in three cases. In 70% of the animals, AF ceased immediately after interruption of vagal stimulation. We conclude that in the intact rabbit heart, vagal activity prolongs interatrial conduction and shortens atrial and PV ERP, contributing to the vulnerability to the induction and maintenance of AF. This model may be useful in the assessment of the autonomic influence in the mechanisms underlying AF.
- Hypothalamic Ion channels in hypertensionPublication . Geraldes, Vera; Laranjo, Sergio; Rocha, IsabelHypertension is a prevalent and major health problem, involving a complex integration of different organ systems, including the central nervous system (CNS). The CNS and the hypothalamus in particular are intricately involved in the pathogenesis of hypertension. In fact, evidence supports altered hypothalamic neuronal activity as a major factor contributing to increased sympathetic drive and increased blood pressure. Several mechanisms have been proposed to contribute to hypothalamic-driven sympathetic activity, including altered ion channel function. Ion channels are critical regulators of neuronal excitability and synaptic function in the brain and, thus, important for blood pressure homeostasis regulation. These include sodium channels, voltage-gated calcium channels, and potassium channels being some of them already identified in hypothalamic neurons. This brief review summarizes the hypothalamic ion channels that may be involved in hypertension, highlighting recent findings that suggest that hypothalamic ion channel modulation can affect the central control of blood pressure and, therefore, suggesting future development of interventional strategies designed to treat hypertension.
- O treino de ortostatismo (tilt training) aumenta a reserva vasoconstritora em doentes com síncope reflexa neurocardiogénicaPublication . Laranjo, Sergio; Oliveira, Mario; Tavares, Cristiano; Geraldes, Vera; Santos, Sofia; Oliveira, Eunice; Ferreira, Rui; Rocha, IsabelNeurocardiogenic syncope (NCS) is a common clinical entity resulting from an excessive reflex autonomic response, particularly during orthostatism. Treatment options are controversial and of limited effectiveness. Tilt training (TT) is a promising option to treat these patients. However, its mechanism of action and clinical impact remain unclear. Objective: To characterize hemodynamic and autonomic responses during a TT program in patients with NCS refractory to conventional measures. Methods: We studied 28 patients (50% male, mean age 41±14 years) without structural heart disease, with NCS documented by tilt testing. The TT program included 9 tilt sessions (3 times a week, 30 min) (60° - 6 sessions, 70° - 3 sessions), under ECG and blood pressure monitoring combined with home orthostatic self-training and 10° head-up during sleep. Systolic volume, cardiac output, total peripheral resistance, baroreflex sensitivity and heart-rate variability were computed. Patients were reassessed at 1 month and every 6 months for a maximum of 36 months (24±12 months). Results: Over the course of the TT program there was a significant increase in total peripheral resistance (1485±225 vs. 1591±187 dyn·s·cm(-5), p<0.05), with a decrease in standard deviation (206±60 vs. 150±42, p<0.05). During follow-up, syncope recurred in five patients (19%), with a significant reduction in the number of episodes (4.0±3.2/patient in the 12 months before TT vs. 1.4±0.8/patient post-TT, p<0.05). Conclusion: In refractory NCS, TT may be an effective therapeutic option, with long-term benefits. These results appear to be due to an increase in vasoconstrictor reserve combined with a reduction in its variance.