Sérgio Laranjo

Background/Objectives: Vasovagal syncope is the most common subtype of reflex syncope and a frequent cause of transient loss of consciousness. Although its prognosis is generally benign, recurrent episodes can cause injury, restrict daily activities, and impair quality of life; patients who remain symptomatic despite first-line measures present a therapeutic challenge. This review integrates current evidence on mechanisms, prediction, and treatment, examining whether arterial-pressure defence and baroreflex behaviour provide a useful physiological framework. Methods: We conducted a narrative integrative review of PubMed and ClinicalTrials.gov from inception to June 2026, prioritising randomised trials, meta-analyses, major observational studies, guidelines and multi-society statements. No formal risk-of-bias assessment or de novo quantitative synthesis was undertaken. Results: Current evidence supports a dynamic failure of cardiovascular compensation during orthostatic stress, with variable contributions from impaired vasoconstrictor support and cardioinhibition. Laboratory haemodynamic and autonomic markers may anticipate tilt-test outcome, but this should not be equated with prediction of spontaneous clinical recurrence. Tilt training may modify vasoconstrictor reserve and baroreflex indices, although clinical efficacy varies with protocol and adherence. Therapeutic options extend from counter-pressure manoeuvres and selected pharmacological agents to pacing in highly selected patients with documented clinically relevant asystole; cardioneuroablation remains an emerging intervention. Conclusions: The haemodynamic phenotype may inform treatment selection but should not be used as a stand-alone indication for invasive therapy. We propose an evidence-informed, mechanism-based model of care, incorporating patient-reported outcomes, shared decision-making and cautious evaluation of emerging predictive and interventional approaches.

Premature ventricular complexes (PVCs) are common cardiac arrhythmias that can lead to cardiomyopathy when frequent. Post-extrasystolic potentiation (PESP), which is the transient increase in contractility following a PVC, may serve as a predictive marker for heart failure risk; yet, the underlying calcium-mediated mechanisms and their relative contribution compared to loading conditions remain poorly understood. We integrated a mechanochemical model coupling intracellular calcium dynamics to sarcomere mechanics within the CircAdapt closed-loop cardiovascular framework. A novel calcium source model incorporating the force–interval relationship was calibrated using experimental canine data. We simulated single PVCs across varying coupling intervals and systematically investigated the contributions of calcium dynamics versus loading conditions to PESP, quantified as changes in systolic blood pressure (∆SBP), maximum rate of left ventricular pressure rise (∆max(d P _Lv /d t )), and left ventricular ejection fraction (∆LVEF). The calcium-based force–interval relationship reproduced experimental mechanical restitution curves with high accuracy (RMSE 9.59 ± 0.08%). Shorter coupling intervals reduced premature beat contractility while enhancing PESP in subsequent beats. Systematic variation of preload, afterload, and intrinsic contractility revealed that calcium dynamics reproduce the observed PESP patterns, with loading conditions as modulators. Notably, ∆max(d P _Lv /d t ) and ∆SBP responded differently, with ∆SBP exhibiting complex non-monotonic behavior. The model qualitatively reproduced pressure–volume patterns from a single clinical quadrigeminy case. This study demonstrates that a calcium-based force–interval formulation reproduces the qualitative features of PESP within this framework, with preload and afterload modulating the pattern of beat-to-beat pressure response. The divergent behavior among contractility metrics emphasizes the need for multimetric assessment. This framework enables distinguishing intrinsic myocardial dysfunction from extrinsic loading effects, facilitating patient-specific risk stratification in PVC-induced cardiomyopathy.

Introduction: Vasovagal syncope is a prevalent condition marked by transient loss of consciousness due to abrupt decreases in systemic blood pressure and/or heart rate. Despite its clinical impact, the underlying haemodynamic mechanisms remain poorly defined, and data on age-related differences are limited and sometimes contradictory. Objectives: This study aimed to characterise haemodynamic adaptation patterns during a head-up tilt (HUT) test in adult (≥18 years) and paediatric (n = 81, adult n = 106) and 108 non-fainters (including 30 healthy controls) were studied. Compared to adult fainters, paediatric fainters showed a 24% larger decline in CO from baseline (mean difference of 1.1 L/min [95% CI: 0.5–1.7], p = 0.003) and a 15–20 bpm higher peak HR (p = 0.001) during presyncope. Both subgroups experienced significant drops in TPR, which were more pronounced in paediatric fainters (effect size = 0.27, 95% CI: 0.12–0.42). Non-fainters (including controls) maintained relatively stable haemodynamics, with no significant decrease in CO or TPR (p > 0.05). Age-related comparisons indicated a heavier reliance on HR modulation in paediatric fainters, leading to an earlier transition from compensated to pre-syncopal states. Conclusions: These findings demonstrate that paediatric fainters exhibit more abrupt decreases in CO and TPR than adults, alongside higher HR responses during orthostatic stress. Targeted interventions that address this heightened chronotropic dependency—such as tilt-training protocols or strategies to improve venous return—may be particularly beneficial in younger patients. An age-specific approach to diagnosis and management could improve risk stratification, minimise recurrent episodes, and enhance patient outcomes.

Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia, presenting a significant global healthcare challenge due to its rising incidence, association with increased morbidity and mortality, and economic burden. This arrhythmia is driven by a complex interplay of electrical, structural, and autonomic remodelling, compounded by genetic predisposition, systemic inflammation, and oxidative stress. Despite advances in understanding its pathophysiology, AF management remains suboptimal, with ongoing debates surrounding rhythm control, rate control, and anticoagulation strategies. Animal models have been instrumental in elucidating AF mechanisms, facilitating preclinical research, and advancing therapeutic development. This review critically evaluates the role of animal models in studying AF, emphasizing their utility in exploring electrical, structural, and autonomic remodelling. It highlights the strengths and limitations of various models, from rodents to large animals, in replicating human AF pathophysiology and advancing translational research. Emerging approaches, including optogenetics, advanced imaging, computational modelling, and tissue engineering, are reshaping AF research, bridging the gap between preclinical and clinical applications. We also briefly discuss ethical considerations, the translational challenges of animal studies and future directions, including integrative multi-species approaches, omics technologies and personalized computational models. By addressing these challenges and addressing emerging methodologies, this review underscores the importance of refining experimental models and integrating innovative technologies to improve AF management and outcomes.

Background and Objectives: Despite advances in the surgical management of patients with Fontan circulation, their exercise capacity and quality of life remain significantly impaired. Exercise-based cardiac rehabilitation (CR) offers promising improvements in these areas, but the implementation and adherence to these programmes are often inconsistent. This systematic review and meta-analysis aimed to evaluate the safety, efficacy, and optimal exercise modalities for Fontan patients. Materials and Methods: A systematic search of PubMed, Scopus, Web of Science, and Cochrane Library was conducted on 24 August 2023. Studies were screened and assessed for quality using the Cochrane RoB Tool 2 and STROBE checklist. Meta-analysis was performed using a continuous random-effects model to determine the effectiveness of various CR interventions, including aerobic exercise training (AET), resistance training, and inspiratory muscle training (IMT). Results: A total of 26 studies (7 RCTs, 19 cohorts) comprising 22 distinct cohorts were included, with a total sample size of 428 Fontan patients. The interventions ranged from 4 weeks to 24 months and included AET (18 studies), resistance training (11 studies), and IMT (6 studies). The meta-analysis revealed significant improvements in exercise capacity, with a pooled mean difference in peak VO₂ of 1.947 (95% CI: 1.491 to 2.402, p < 0.001). Subgroup analyses showed that combined AET and resistance training had the most robust effect, with a mean difference of 2.11 (95% CI: 1.57 to 2.65, p < 0.001). Home-based interventions showed significant benefits, while supervised and hybrid interventions did not show statistically significant differences. Publication bias was identified, particularly in home-based interventions, where smaller studies demonstrated larger effect sizes, as confirmed by Egger’s test (Intercept = 2.417, 95% CI: 1.498 to 3.337, p = 0.001). However, no significant bias was detected in supervised or hybrid interventions, which displayed symmetrical distributions in funnel plots and non-significant Egger’s test results. Conclusions: CR appears to be an effective intervention for improving exercise capacity in Fontan patients, particularly when combining AET with resistance training. Home-based programmes offer promising results, though the potential for publication bias, especially in smaller studies, warrants cautious interpretation of these findings. Further research is needed to refine protocols, explore long-term outcomes, and determine the underlying mechanisms, particularly for patients with more severe clinical presentations. The low incidence of adverse events across the studies reinforces the safety of these interventions.

Background: Catheter ablation (CA) is a well-established treatment for atrial fibrillation (AF). However, its effects on autonomic function and underlying mechanisms remain poorly understood. This study investigated autonomic and haemodynamic changes following CA and explored their potential implications for patient outcomes. Methods: Seventy-eight patients with AF underwent CA and were followed up at one, three, and six months. Autonomic function was assessed using a combination of head-up tilt (HUT), handgrip (HG), and deep breathing (DB) manoeuvres along with baroreflex sensitivity (BRS) and baroreflex effectiveness index (BEI) evaluation. Heart rate (HR), blood pressure (BP), and their variability were measured at each time point. Results: Significant autonomic alterations were observed after ablation, particularly at one month, with reductions in parasympathetic tone and baroreflex function. These changes gradually normalised by six months. Both pulmonary vein isolation (PVI) and cryoablation (CryO) had similar effects on autonomic regulation. Improvements in quality of life, measured by the AFEQT scores, were consistent with these physiological changes. Conclusions: CA for AF induces significant time-dependent autonomic and haemodynamic changes with recovery over six months. These findings underscore the need for ongoing monitoring and personalised post-ablation management. Further research is required to explore the mechanisms driving these alterations and their long-term impacts on patient outcomes.

Sleep is a complex biobehavioural process essential for overall health, with various dimensions including duration, continuity, timing, and satisfaction. This study investigated the intricate relationships between common sleep disorders such as insomnia and obstructive sleep apnoea (OSA) and their impact on atrial fibrillation (AF), a prevalent arrhythmia with significant health implications. Using a comprehensive review of the current literature, this study examined the pathophysiological mechanisms linking sleep disorders to cardiovascular risks, focusing on autonomic nervous system disturbances, inflammation, and oxidative stress associated with OSA. These findings indicate that sleep disorders significantly elevate the risk of AF through mechanisms such as increased sympathetic activity and structural cardiac remodelling. Additionally, this study highlights the potential benefits of treating sleep disorders, particularly with continuous positive airway pressure (CPAP) therapy, in reducing AF recurrence and improving cardiovascular outcomes. This conclusion emphasises the importance of integrated therapeutic approaches that address both sleep disorders and AF to enhance patient outcomes and quality of life. Future research should explore these connections to develop more effective and holistic treatment strategies.

Background and Objectives: The Fontan procedure, a palliative surgery for univentricular heart physiology, often reduces exercise capacity and quality of life. This study aimed to evaluate the impact of cardiac rehabilitation (CR) on improving outcomes in Fontan patients to inform evidence-based care. Materials and Methods: Fontan patients aged 8–30 participated in a structured CR program for at least three months. The program included weekly aerobic and resistance training sessions with educational and nutritional guidance. Baseline and post-CR assessments included cardiac function, fitness, daily activity, and health-related quality of life (HRQOL). Results: The cohort included ten Fontan patients, of whom six had a right systemic ventricle. CR significantly improved cardiorespiratory fitness, as seen in VO2 max (from 27.92 ± 5.15 to 34.69 ± 1.14 mL/kg/min, p = 0.0089) and percent predicted VO2 (from 0.67 ± 0.18 to 0.90 ± 0.02, p = 0.005). VCO2 increased by +8.68 ± 8.59 mL/kg/min but did not reach statistical significance (p = 0.05). Most haemodynamic and ventilatory parameters showed no significant improvement. All the SF-36 questionnaire domains showed significant HRQOL gains (p < 0.001). High adherence (85–93%), no adverse events, and reduced NT-proBNP levels supported the program’s safety. Conclusions: This study’s findings have important implications for the care of Fontan patients. CR significantly improved exercise capacity and HRQOL in Fontan patients across various anatomies, particularly in the right systemic ventricle. Integrating physical conditioning into standard care could reduce long-term morbidity and mortality; however, further research is needed to refine the protocols and confirm sustained benefits.