Background It is generally believed that cerebral hypoperfusion in patients with vasovagal syncope (VVS) is secondary to hypotension; however, current evidence suggests that this is not always the case. Thus, this study aimed to analyze the hemodynamic characteristics of patients with VVS and dynamic cerebral autoregulation (CA) dysfunction (referred to as CA-impaired VVS) to improve the diagnosis and treatment of this VVS subtype. Methods This retrospective study included 143 patients with VVS who underwent the head-up tilt test (HUTT) using transcranial Doppler (TCD). Patients were divided into two groups based on pathogenesis: CA-impaired VVS and blood pressure drop-dominant VVS. Hemodynamic parameters, including systolic and diastolic blood pressure, heart rate, and cerebral blood flow velocity (CBFV), were compared between the two groups to further analyze the differences in cardiocerebral hemodynamic indices. Results CA-impaired VVS accounted for 58% of the cases. During basic HUTT in the upright tilt position, the minimum systolic blood pressure (SBP), minimum diastolic blood pressure (DBP), and minimum mean arterial pressure (MAP) were significantly higher in the CA-impaired group than in the blood pressure drop-dominant group ( p < 0.05). Similarly, during the sublingual nitroglycerin HUTT in the upright tilt position, the minimum SBP, DBP, and MAP were significantly higher in the CA-impaired group than in the blood pressure drop-dominant group ( p < 0.05). After returning to the supine position, the mean SBP, DBP, and MAP remained significantly higher in the CA-impaired group than in the blood pressure drop-dominant group ( p < 0.05). In addition, the positivity rates for orthostatic tachycardia in the CA-impaired and blood pressure drop-dominant VVS groups were 73.5 and 65.0%, respectively. The incidence of neurogenic orthostatic hypotension was 2.4% in the CA-impaired group, which was significantly lower than the 16.7% in the blood pressure drop-dominant group ( p = 0.002). Conclusion This study reveals the characteristics and differences in cardiocerebral hemodynamics between CA-impaired and blood pressure drop-dominant subtypes of VVS, deepens the understanding of VVS pathogenesis, facilitates the accurate diagnosis of VVS, and enhances the ability to interpret its results.

Background: shock is a critical condition resulting from circulatory failure and is commonly observed in intensive care settings. It arises from four primary mechanisms, including hypovolemic, cardiogenic, distributive, and obstructive shock. However, some cases lack an identifiable cause or present with conditions mimicking sepsis. Rare causes, such as autonomic dysfunction, manifest through cardiovascular abnormalities like orthostatic hypotension and abnormal vasovagal responses. We reported here a case of autonomic dysfunction with amyloidosis due to its uncommon nature and significant influence on mortality rates. Timely and precise diagnosis, coupled with effective treatment, has the potential to be life-saving for the patient. Case presentation: A 73-year-old female with a past medical history of curative breast cancer 15 years ago, sick sinus syndrome status post DDDR 3 years ago, and previous heart failure with an unremarkable coronary angiography result, presented for evaluation of progressive dysphagia. Following admission for esophagogastroduodenoscopy, she developed clinical symptoms consistent with septic shock and acute kidney injury with volume overload, which resolved after appropriate treatment. Subsequently, the patient experienced unexplained hypotension accompanied by periorbital ecchymosis, prompting a skin biopsy, serum protein electrophoresis, and free light chain testing, ultimately leading to a diagnosis of AL amyloidosis. After discussing the treatment plan, the patient opted for palliative care, and pharmacotherapy was provided as part of supportive management. Conclusion: Refractory hypotension in AL amyloidosis poses a multifaceted clinical challenge, requiring a thorough and individualized treatment approach that considers the unique circumstances and therapeutic requirements of each patient.

Reflex syncope is the most frequent cause of transient loss of consciousness in the pediatric population. A structured diagnostic approach based on clinical evaluation and 12-lead ECG is mandatory to exclude the cardiac causes of syncope. Additional cardiac investigations, such as echocardiography, a stress test, or 24H Holter ECG monitoring, are needed in case of suspected cardiac syncope at initial evaluation. Cardiovascular autonomic function assessment, including ambulatory blood pressure monitoring and a tilt test, is useful for phenotyping syncope (hypotensive or bradycardic mechanism). In case of unexplained syncope after a comprehensive evaluation and high-risk criteria, an implantable loop recorder is indicated. The management is primarily based on reassurance, education, hydration, increased salt intake, and counter-pressure maneuvers. Pharmacological therapies and intervention strategies may be considered for patients with recurrent or disabling forms that are not responsive to lifestyle modifications.Conclusion: Reflex syncope in the pediatric population should be managed through a structured diagnostic pathway focused on excluding cardiac causes and guiding mechanism-based treatment. Education and lifestyle measures remain the cornerstone of management, while pharmacological or invasive strategies should be reserved for selected patients with recurrent or disabling symptoms. What is Known: • Reflex syncope is the most common cause of transient loss of consciousness in children and adolescents, and initial evaluation should rely on careful history taking, physical examination, and a 12-lead ECG to exclude cardiac causes. • Most pediatric reflex syncope can be managed conservatively through education and reassurance, together with adequate hydration, increased salt intake, and physical counter-pressure maneuvers. What is New: • This review proposes a structured stepwise diagnostic pathway that starts with clinical evaluation and ECG and escalates only when cardiac syncope is suspected or the presentation is high-risk. • It emphasizes the role of brief cardiovascular autonomic assessment (ambulatory blood pressure monitoring and tilt testing) to distinguish hypotensive from bradycardic mechanisms and guide individualized management.

The case of a36-year-old female patient with recurrent reflex syncope characterized by predominant cardioinhibition and episodes of asystole lasting up to 9s, as documented by an implantable loop recorder, is reported. Given her young age and symptomatic burden, cardioneuroablation (CNA) was performed without complications as an alternative to pacemaker implantation, in accordance with European Heart Rhythm Association (EHRA) recommendations. In this case, CNA has shown to be an effective and safe treatment option for managing recurrent cardioinhibitory reflex syncope. CNA should particularly be considered and offered in specialised centres for symptomatic patients under 40years of age, in which treatment options beyond conservative measures remain limited.

STRETCH-INDUCED SYNCOPE: AN EXAMINATION OF A RARELY RECOGNIZED CONDITION.

Deceleration capacity as a predictor of vasovagal syncope subtypes.

Objectives: This study aimed to assess the influence of standardized patient and student gender on the undergraduate medical students’ performance during the interview station of Objective Structured Clinical Examinations (OSCE). Methods: This study was conducted among fourth-year medical students during an OSCE at the University of Toulouse, France. Standardized patients, examiners, and students were blinded to the study design. Four gender-neutral clinical cases were developed, involving cardiac diagnoses: case 1: acute coronary syndrome; case 2: musculoskeletal chest pain; case 3: cardiac arrhythmias with acute coronary syndrome; case 4: vasovagal syncope. The primary outcome was the diagnostic hypothesis proposed by the student at the end of the standardized patient interview. Results: A total of 357 fourth-year students were assessed. The mean age of the students was 22 years (±2.6) and 225 (63.0%) were female. Ten standardized patients were involved, (7 female, median age: 51 [IQR 44–60]; 3 male, median age: 55 [IQR 50–59]). The rate of correct diagnostic hypotheses was significantly higher with male standardized patients (64.9% [95% CI, 55.0%-73.7%]) than with female standardized patients (45.6% [95% CI, 39.5%-51.8%]; p = 0.002). Female students were also less likely to propose correct diagnoses with female standardized patients (40% vs. 66.2%, p = 0.003) compared to male students (50% vs. 62%, p = 0.25). Conclusion: Our study supports that diagnostic hypothesis proposed by undergraduate medical students at the interview station during OSCEs is influenced by standardized patient gender, with a higher likelihood of incorrect diagnoses when the standardized patient is female, despite gender-neutral clinical cases. Diagnostic accuracy may also be influenced by student gender. These findings suggest that gender bias exists from the early stages of medical training.

Autonomic nervous system (ANS) imbalance may contribute to functional pelvic disorders such as overactive bladder (OAB). Transcutaneous tibial nerve stimulation (TTNS) is a non-invasive therapy for OAB; however, its autonomic modulation mechanisms remain unclear. This exploratory study evaluated the acute effects of TTNS on ANS activity in healthy volunteers using heart rate variability (HRV) to model neuroautonomic pathways relevant to OAB. In this open-label, prospective, exploratory, single-arm study, 20 healthy volunteers (11 women; median age 31 years) underwent three 10-min phases: baseline rest, continuous submotor TTNS via surface electrodes on the left tibial nerve, and post-stimulation recovery. HRV was recorded using a Polar H10 sensor and analyzed with Kubios software. Time-domain (SDNN, RMSSD, pNN50), frequency-domain (LF, HF, LF/HF), and additional indices (PNS, SNS, Stress indices) were assessed in standardized 5-min windows. Friedman and Wilcoxon tests with Bonferroni correction were applied. A vagal-oriented composite response score (z-delta mean) was correlated with age and BMI (Spearman, permutation-based p values). Significant phase effects were observed for PNS index, SNS index, Stress index, SDNN, and RMSSD (p < 0.05). Post-hoc analyses confirmed increases in PNS index, SDNN, and RMSSD, and decreases in SNS and Stress indices during stimulation compared with baseline. Partial post-stimulation persistence was noted for SDNN and Stress index, although these changes did not remain significant after Bonferroni correction. The composite response score correlated negatively with age (ρ = -0.52; p = 0.019; permutation p = 0.016) and showed a non-significant positive trend with BMI (ρ = 0.38; p = 0.10). Acute TTNS enhances parasympathetic and suppresses sympathetic activity, with partially sustained effects after stimulation. Younger age predicts stronger vagal responsiveness, suggesting age-dependent neuromodulatory efficacy. Validation in OAB populations is warranted.

Background Postural Orthostatic Tachycardia Syndrome (POTS) and Neurally-Mediated Hypotension (NMH) are heterogeneous syndromes characterized by dysautonomia and multisystem symptoms. Mast cell activation, often manifesting as hives, has been proposed as a contributing mechanism, but its prevalence and clinical relevance in POTS and NMH are poorly defined. Method Patients from the Johns Hopkins POTS Clinic completed surveys assessing hives frequency and symptom burden using the Malmö POTS, the Composite Autonomic Symptom Score (COMPASS)-31, and a pain questionnaire. Associations between hives and clinical features were evaluated among patients with confirmed POTS, NMH, or clinically diagnosed orthostatic intolerance. Result Among 188 respondents, 80 (42.6%) reported hives sometimes and 33 (17.6%) reported hives often or always. Increasing hives frequency was associated with higher Malmö POTS scores and greater autonomic symptom burden across multiple COMPASS-31 subdomains, including gastrointestinal, bladder, and vasomotor symptoms (all p < 0.05). Hives was also associated with pain (OR 3.47, 95% CI 1.54–7.77, p = 0.002) and tingling (OR 5.73, CI 2.15–15.26, p < 0.001), but not orthostatic symptoms. These associations persisted after multivariable adjustment. Conclusion Hives are common in orthostatic intolerance syndromes and are associated with increased symptom burden. Future studies are needed to clarify the role of mast cell activation and evaluate mast cell-targeted therapies.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long COVID share clinical features including persistent fatigue, post-exertional malaise (PEM), and gastrointestinal (GI) dysfunction. Growing evidence implicates brain-gut axis dysregulation, characterized by dysbiosis, neuroinflammation within the central nervous system (CNS), increased intestinal permeability, and microbial translocation in their pathophysiology. However, therapeutic strategies targeting these pathways remain poorly defined. We report a case of post-COVID ME/CFS successfully treated with electroacupuncture (EA)-based deep peroneal nerve stimulation which was employed to potentiate the vagal reflex. Fatigue trajectories were assessed using the Multidimensional Fatigue Inventory over 12 weeks. Based on the case, a systematic review of randomized controlled trials (RCTs) evaluating brain-gut axis-modulating interventions in ME/CFS or Long COVID was conducted. The patient exhibited a significant reduction in total fatigue, with early improvements in motivation and mental fatigue, and delayed improvement in physical fatigue following transient systemic symptom flares. Across included RCTs (n = 8, 790 participants), four investigated gut microbiome-modulating therapies and four employed nerve stimulation. Synbiotic and herbal interventions demonstrated benefits for fatigue or PEM, accompanied by alterations in specific bacterial populations or CNS metabolisms. Regarding nerve stimulation, transcranial direct current stimulation (tDCS) combined with exercise program improved fatigue, whereas standalone tDCS, auricular or peripheral TENS showed limited efficacy. Brain-gut axis-based interventions may alleviate fatigue in ME/CFS and Long COVID by potentially modulating neuroinflammation, restoring microbiome balance, and improving epithelial barrier function. EA-based vagal stimulation represents a feasible option for patients with severe or treatment-resistant symptoms. Larger mechanistic studies and rigorously designed RCTs are needed to establish therapeutic targets and optimize intervention strategies.

The rapid heart rate increase during the first seconds of exercise is primarily mediated by cardiac vagal withdrawal, which can be assessed by the 4-s exercise test (4sET), a pharmacologically validated and highly reliable procedure. However, the need for a cycle ergometer limits its applicability. Thus, we aimed to test the validity of a modified 4sET using wheelchair propulsion simulation (WPS) by comparing it with the traditional cycle ergometer protocol. Sixty healthy adults (30 men, 30 women; 22 ± 2years) performed, in randomized order, three repetitions each of the traditional (LEG 4sET) and modified (WPS) protocols. RR intervals were recorded via electrocardiography, and the cardiac vagal index (CVI) was calculated as the ratio of the last pre-exercise RR interval (RRB) to the shortest exercise RR interval (RRC). Mean CVI was lower for WPS compared with LEG (1.42 ± 0.03 vs. 1.48 ± 0.03; P = 0.001). Based on identity plots, a correction equation was derived for WPS values < 1.50: y = 0.7706x + 0.3861 (r2 = 0.63; P < 0.001). After correction, CVI did not differ between protocols (1.48 ± 0.17 vs. 1.48 ± 0.20; P = 0.854). Furthermore, a high and significant intraclass correlation coefficient (ICC) was found for the CVI between the protocols (ICC = 0.87; [0.74-0.93]; P < 0.05), and Bland-Altman analysis showed negligible bias and acceptable limits of agreement for the corrected WPS CVI. The WPS shows strong agreement with the traditional cycle ergometer 4sET, supporting its validity as a simpler and more accessible method for assessing dynamic cardiac vagal control.

Vasovagal responses (VVR) are common transient autonomic reactions to invasive procedures such as injections or needling, characterized by bradycardia, hypotension, and transient loss of consciousness; however, their occurrence and underlying autonomic mechanisms during dry needling (DN) for myofascial pain syndrome (MPS) remain poorly understood. This study aimed to determine the frequency of VVR during DN in patients with MPS and to compare autonomic parameters-heart rate variability (HRV), pupil diameter, and skin perfusion-between those with and without VVR. Prospective observational study. In total, 100 adults with acute cervical MPS underwent a standardized DN procedure. Outcomes included pressure pain threshold (PPT), heart rate (HR), blood pressure (BP), HRV indices [average NN interval (AVNN), standard deviation of NN intervals (SDNN), low-frequency (LF)/high-frequency (HF) ratio], pupil diameter, and skin perfusion, assessed at baseline, 5 min, and 30 min post-intervention. Participants were classified post hoc as VVR positive (VVR+) or VVR negative (VVR-) based on clinical signs of vasovagal reaction. No significant changes in skin perfusion or BP were found over time or between groups (p > 0.05). Significant main effects of time and Time × Group interactions were observed for PPT (p < 0.001), HR (p < 0.001), AVNN (p < 0.001), SDNN (p < 0.001), LF/HF ratio (p < 0.001), and pupil diameter (p < 0.001). Post hoc analyses revealed that only the VVR+ group showed significant increases in PPT (p < 0.001), AVNN (p < 0.001), SDNN (p < 0.001), and pupil diameter (p < 0.001), alongside decreases in HR (p < 0.001) and LF/HF ratio (p < 0.001) from baseline to post-intervention. The VVR- group showed no significant changes. Patients experiencing VVR during DN demonstrated distinct autonomic modulation with parasympathetic predominance, pupil dilation, and increased pain threshold. These findings suggest individual variability in autonomic reactivity during DN and suggest the need for awareness and monitoring of susceptible patients. The clinical registration number is ISRCTN16484644, date: January 28, 2025.

The orthostatic tolerance of service personnel of the Household Division of the British Army.

Background: The aim of this study was to compare emergency physician discharge decisions for syncope patients in the emergency department (ED) with two established risk stratification tools: the Osservatorio Epidemiologico sulla Sincope nel Lazio (OESIL) score and the San Francisco Syncope Rule (SFSR). Methods: We retrospectively reviewed medical records of adult patients presenting to a university hospital ED with syncope from 2013 to 2017. High-risk classification was defined as an OESIL score ≥2 or at least one positive SFSR criterion. Physician decisions were categorized as high-risk if the patient was hospitalized. Patients were classified as having reflex, cardiac, or orthostatic hypotension syncope. The discharge decisions made by physicians were compared with OESIL and SFSR scores. Sensitivity, specificity, and predictive values for 1-year mortality were calculated. Results: Among 457 patients included (median age 36, 95% reflex syncope), 411 (89.9%) were discharged from the ED. Based on risk scores, 114 (OESIL) and 139 (SFSR) patients were categorized as high risk. Concordance between physician decisions and risk scores was low (Kappa = 0.09 for OESIL, 0.12 for SFSR). The OESIL score demonstrated the highest sensitivity (77.8%) for predicting 1-year mortality, while the physician’s decision showed the highest specificity (91%). Conclusions: While physician decisions showed higher specificity, OESIL scores were more sensitive in identifying highrisk patients. In young, low-risk populations, reliance on clinical judgment may be reasonable, but a combined use of scoring tools and physician assessment could improve patient safety.

Goring during bullfights represents a penetrating trauma with a high risk of muscular, vascular, and vital injuries. Despite its frequency and severity, limited information is available on the immediate physiological response of the bullfighter at the moment of trauma. This case report describes the heart rate of a professional bullfighter who was gored during a bullfight, underwent surgery, and returned to fight the next bull. During the first fight, the bullfighter suffered a penetrating goring wound to the inner side of the lower third of his right thigh and a fracture of the ninth rib with intercostal rupture. Upon standing, he experienced a marked drop in heart rate and a feeling of loss of consciousness, possibly associated with vasovagal presyncope. He was transferred to the infirmary in hemodynamically stable condition. He was given local anesthesia, followed by surgical exploration, cleaning, and layered closure of the wound. After surgery, the bullfighter experienced a gradual increase in heart rate upon standing, possibly due to postural changes and postoperative sympathetic activation. He then returned to the bullring to resume activity. This case report highlights a possible vasovagal response to penetrating trauma, which may be relevant for trauma care, as a vasovagal or parasympathetic-predominant autonomic response could influence early clinical assessment.

Reflex bradyarrhythmias and syncope related to excessive vagal tone may be refractory to conservative therapy and significantly impair quality of life. Cardioneuroablation (CNA) has emerged as a device-sparing alternative, but real-world outcome data remain limited. We retrospectively evaluated 12 consecutive patients (aged 23-55 years) with drug-refractory, vagally mediated bradyarrhythmias confirmed by tilt-table testing. All underwent biatrial CNA guided by ultra-high-density electroanatomical mapping with automated fragmented-electrogram detection and robotic magnetic navigation. A contemporaneous cohort of medically managed patients with comparable clinical profiles (n = 10) served as a control group. The primary outcome was freedom from syncope or clinically significant bradyarrhythmia without pacemaker implantation. Secondary outcomes included procedural metrics, heart-rate changes, and recurrence during follow-up. All CNA procedures were completed without acute complications and with minimal fluoroscopy exposure. Resting sinus rate increased substantially after ablation. Over a mean follow-up of approximately 12 months, most CNA-treated patients remained free of symptomatic bradyarrhythmia or syncope without requiring pacemaker implantation, whereas recurrence and pacemaker placement were less frequent compared with controls. No delayed complications were observed. In this small, retrospective real-world cohort, biatrial CNA guided by automated electrogram analysis and robotic navigation was feasible, safe, and associated with short-term autonomic modulation and symptomatic improvement over approximately 12 months of follow-up in selected patients with vagally mediated bradyarrhythmias. These findings are exploratory and warrant confirmation in larger, prospective studies with longer follow-up to assess durability and reinnervation risk.

Asymptomatic Asystolic Carotid Sinus Hypersensitivity Predicts Asystolic Events During ILR Monitoring in Reflex Syncope Patients.

Objective: Syncope, a temporary loss of consciousness caused by cerebral hypoperfusion, is often benign but can signal serious neurological or cardiac issues. We retrospectively analyzed pediatric syncope cases in this study. Material and Methods: We analyzed 514 patients aged 6–18 years who presented with syncope to a pediatric neurology outpatient clinic. Results: Most patients (36.7%) had a single episode, though recurrent cases were also common. The primary triggers were prolonged standing (17.2%) and sudden postural changes (14.4%). Prodromal symptoms such as dizziness, visual disturbances, and nausea were reported in 69.5% of cases. Electroencephalography (EEG) was performed in 72.2% of patients, revealing epileptiform activity in 27 individuals. EEG requests increased significantly in patients with recurrent syncope episodes (p&lt;0.010). Cranial MRI was performed in 37.5% of the patients, and abnormalities were detected in 16.6%, most commonly arachnoid cysts. However, no statistically significant correlation was found between MRI utilization and the frequency of syncope episodes. Final diagnoses were predominantly vasovagal syncope (75.6%), followed by psychogenic syncope (10.3%), seizures (8.75%), cardiogenic syncope (4.5%), and hypoglycemia (0.85%). Conclusion: These results highlight the mostly benign nature of pediatric syncope, with vasovagal syncope as the most frequent diagnosis. EEG is useful for identifying underlying epilepsy, while neuroimaging should be reserved for selected cases.

Introduction Fludrocortisone and midodrine are frequently used to raise blood pressure (BP) in patients with vasovagal syncope (VVS)/low BP phenotype and orthostatic hypotension (OH), despite limited supporting evidence. This study assesses changes in Ambulatory Blood Pressure Monitor (ABPM) biomarkers and symptoms of syncope after commencing/increasing fludrocortisone or midodrine. Methods Patients attending a tertiary-referral falls & syncope unit and prescribed fludrocortisone/midodrine were included. ABPM at index visit and follow-up (after commencing/increasing fludrocortisone/midodrine) were analysed, with specific focus on biomarkers of syncope risk: overall systolic BP (sBP), minimum sBP, and ‘dips’ in sBP <100 mmHg. Symptoms of presyncope and syncope were assessed at follow-up. These variables were compared pre and post medication changes using paired t-tests. Results 110 patient reviews (median age 57.0 (95%CI 46.4–63.8) years, 77% female) were followed for median 4.0 (IQR 2.0–8.0) months. Of these, 52% (57/110) commenced/increased fludrocortisone, and 48% (53/110) commenced/increased midodrine. Fludrocortisone use was associated with significant increases in overall sBP, minimum sBP and reduction in sBP dips <100mmHg. Symptoms of presyncope improved in 73.7% participants commencing/increasing fludrocortisone. Only 9/27 outcomes reached statistical significance in participants commencing/increasing midodrine: overall sBP increase commencing midodrine, overall sBP increase increasing midodrine (including subgroup ≥65 years), overall sBP increase commencing/increasing midodrine (including subgroup ≥65 years), minimum sBP increase commencing midodrine (including subgroup <65 years), decrease in sBP dips <100mmHg in subgroup aged ≥65 years increasing midodrine, and decrease in sBP dips <100mmHg in subgroup ≥65 years commencing/increasing midodrine. Symptoms of presyncope improved in 64.2% participants commencing/increasing midodrine. Conclusion This study provides clinical data on the effectiveness of fludrocortisone and midodrine in patients with VVS/low BP phenotype and OH. Both fludrocortisone and midodrine significantly improved markers of future syncope risk, with fludrocortisone use showing a relatively greater effect.

Drug-induced baroreceptor dysfunction represents an underrecognized mechanism contributing to cardiovascular adverse drug reactions, including reflex tachycardia, bradycardia, syncope, orthostatic hypotension, and arrhythmias. However, despite the critical role played by the baroreflex arc in short-term blood pressure regulation through rapid autonomic adjustments, pharmacological impairment of this reflex has not been systematically evaluated in pharmacovigilance systems. This review synthesizes the current evidence on drug-induced baroreceptor dysfunction, discusses the limitations of spontaneous reporting databases, identifies potential pharmacovigilance signal detection methods, and points out major gaps in current knowledge. It also discusses opportunities opened by emerging tools, such as digital health technologies, computational modelling, and real-world evidence to strengthen the early detection of baroreflex related cardiovascular ADRs. We conclude that integrating baroreceptor-specific endpoints into pharmacovigilance frameworks might improve the prediction, detection, and prevention of serious cardiovascular drug reactions. Peer Review History: Received 8 October 2025; Reviewed 11 November 2025; Accepted 20 December; Available online 15 January 2026 Academic Editor: Dr. Sally A. El-Zahaby, Pharos University in Alexandria, Egypt, sally.elzahaby@yahoo.com Reviewers: Dr. Nada Farrag, Misr International University, Egypt, Nada_Hazem87@hotmail.com Dr. Mujde Eryilmaz, Ankara University,Turkey, meryilmaz@ankara.edu.tr