Syncope of unclear cause (SUC) presents a significant diagnostic challenge, with a considerable proportion of patients remaining without a definitive diagnosis despite comprehensive clinical evaluation. This study aims to explore the potential of unsupervised machine learning (ML), specifically clustering algorithms, to identify clinically meaningful subgroups within a cohort of 123 patients with SUC. Patients were prospectively recruited from the cardiology, neurology, and emergency departments, and clustering was performed using the k-prototypes algorithm, which is suitable for mixed-type data. The number of clusters was determined through cost function analysis and silhouette index, and visual validation was performed using UMAP. Five distinct patient clusters were identified, each exhibiting unique profiles in terms of age, comorbidities, and symptomatology. After clustering, nocturnal cardiorespiratory polygraphy and heart rate variability (HRV) parameters were analyzed across groups to uncover potential physiological differences. The results suggest distinct autonomic and respiratory patterns in specific clusters, pointing toward possible links among sympathetic dysregulation, sleep-related disturbances, and syncope. While the sample size imposes limitations on generalizability, this pilot study demonstrates the feasibility of applying unsupervised ML to complex clinical syndromes. The integration of clinical, autonomic, and sleep-related data may provide a foundation for future, larger-scale studies aiming to improve diagnostic precision and guide personalized management strategies in patients with SUC.

Background and Objectives: The association between syncope and sleep apnea (SA) has been scarcely investigated. Dysfunction of the autonomic nervous system (ANS) may represent a shared pathophysiological mechanism. This study aimed to determine the prevalence of SA in patients with syncope of unclear cause (SUC), identify potential associated factors, and evaluate nocturnal heart rate variability (HRV) as a marker of ANS function. Materials and Methods: A prospective cohort study was conducted in adult patients diagnosed with SUC. Nocturnal cardiorespiratory polygraphy was performed to detect the presence of SA. A range of variables potentially associated with SA was collected. Both SA diagnosis and HRV parameters were assessed using the Embletta^® MPR polygraph system. Results: A total of 156 patients were enrolled (57% male), with a mean age of 64 years and a mean body mass index of 27.5 kg/m² (range: 24.8–32.2). Hypertension was present in 46% of the cohort. The overall prevalence of SA was 78.2% (95% CI: 71.7–84.4%), with 28.7% classified as severe. Age (OR = 1.04; 95% CI: 1.01–1.07) and BMI (OR = 1.17; 95% CI: 1.06–1.28) were independent predictors of SA. Mean RR interval was significantly lower in patients with SA compared to those without (942 ms vs. 995 ms; p = 0.04). No significant differences in HRV parameters were observed between the two groups. Conclusions: This study found a high prevalence (nearly 78%) of SA among adult patients with SUC, particularly in individuals over 50 years of age and those who were overweight. However, this association could not be predicted based on clinical variables alone. No significant differences in nocturnal HRV were detected between patients with SUC with and without SA.

Background/Objectives: Heart rate variability (HRV) reflects autonomic nervous system modulation and may be altered in both unexplained syncope and obstructive sleep apnea (OSA). However, the nocturnal autonomic patterns underlying these conditions and their coexistence remain poorly understood. This study aimed to characterize nocturnal autonomic modulation in patients with unexplained syncope, OSA, or both, compared with individuals without these conditions. Methods: In this multicenter, cross-sectional, comparative study, 304 adults were assigned to four groups: controls (no syncope or OSA), OSA without syncope, syncope without OSA, and syncope with OSA. Time- and frequency-domain HRV parameters were derived from overnight respiratory polygraphy and compared across groups. Results: OSA was associated with increased root mean square of successive differences (RMSSD) and reduced low-frequency (LF) power, indicating enhanced vagal activity and lower nocturnal sympathetic tone. Syncope was characterized by further reductions in sympathetic indices (LF and very low frequency, VLF) with increased RMSSD, suggesting blunted sympathetic reserve. Patients with both conditions exhibited a mixed autonomic profile—elevated overall HRV with concurrent reductions in both sympathetic and parasympathetic components—indicating more profound dysautonomia despite milder OSA severity. Conclusions: OSA and syncope show distinct nocturnal autonomic patterns, and their coexistence leads to deeper autonomic imbalance. Incorporating nocturnal HRV analysis into routine polygraphy may improve pathophysiological stratification of unexplained syncope and identify clinically significant OSA.

Objectives: Unexplained syncope (US) persists despite extensive diagnostic evaluations, with autonomic dysfunction as a central mechanism. Sleep apnea (SA) may contribute through intermittent hypoxemia and autonomic imbalance. We evaluated the impact of SA treatment on syncope recurrence, nocturnal heart rate variability (HRV), and quality of life in patients with US. Methods: We conducted a prospective multicentre study in three hospitals in Galicia (Spain), including adults with US who underwent home respiratory polygraphy. SA was diagnosed according to guideline criteria, and treatment was prescribed when indicated (positive airway pressure therapy, positional therapy, and/or weight management). Symptoms, syncope burden, nocturnal heart rate variability derived from the ECG signal, and quality of life (SF-36 and a 0–100 visual analogue scale) were assessed at baseline and after 12 months. Results: Of 141 patients, 99 met treatment criteria, and 67 completed the 12-month follow-up. Mean age was 64.5 years; 59.6% were men; mean AHI was 25.9/h. After therapy, daytime sleepiness (Epworth score decreased from 8 to 5; p = 0.001), fatigue, nocturnal awakenings, and syncopal episodes decreased from 62.6% to 16.2%, 56.6% to 16.2%, and 3 to 0, respectively (all p < 0.001). HRV showed increased RR interval (p < 0.001) and RMSSD (p = 0.04). Quality of life improved in vitality (SF-36 vitality domain increased from 44 to 50; p = 0.02) and on the visual analogue scale (0–100: 50 to 70; p = 0.002). Conclusions: In this prospective cohort of patients with US and SA, therapy for SA was associated with fewer syncope recurrences, improvements in nocturnal respiratory indices, and selected heart rate variability measures, and better self-reported fatigue and vitality. Given the single-arm design and potential adherence and selection biases, these findings should be interpreted with caution and warrant confirmation in controlled studies.

Introduction: Syncope may be preceded by an ANS (autonomic nervous system) dysregulation that can be measured by heart rate variability (HRV). Changes have been seen in HRV of patients with sleep apnea (SA). Prevalence of SA in patients with recurrent syncope of unknown cause (SUC) and the relationship with HRV are unknown. Material and Methods: Descriptive, observational study in a tertiary hospital. Adults between 30-70 years old with SUC were included. All patients underwent home respiratory polygraphy (RP) including EKG channel with night HRV analysis. Clinical, epidemiological and polygraphic parameters were analyzed. All participants signed a informed consent. Study protocol was aproved by the Clinical Research Ethic Comittee. Results: 17 patients (58.8% women) with SUC were included. Mean age: 56.4 years. 14 (82.4%) were diagnosed with SA (35.3% mild, 23.5% moderate and 23.5% severe). Patients with SUC + SA were older. Changes in nocturnal HRV parameters were observed, but without reaching statistical significance (figure 1). Conclusion: - Prevalence of AS is increased in patients with recurrent SUC, so a RP should be performed in the study of syncope in patients older than 60y. - Nocturnal HRV could be a biological marker in patients with AS and syncope. - Studies are needed to increase the sample size and evaluate whether treatment of AS improves HRV and reduce the occurrence of syncope