Association of incident fragility fractures in patients hospitalised due to unexplained syncope and orthostatic hypotension

Background Fragility fractures are caused by low-energy insults such as falls from standing height or less and pose a growing health challenge as their incidence rises with increasing age. Impaired orthostatic blood pressure response and a number of cardiovascular biomarkers have been previously identified as risk factors for fractures. It is likely that severe episodes of syncope and orthostatic hypotension increase the risk of subsequent fragility fractures, however this relationship has not been thoroughly examined.PurposeTo investigate the relationship of hospital admissions due to unexplained syncope and OH with incident fragility fractures in a middle-aged population.MethodsWe analysed a large population-based prospective cohort of 30,446 middle-aged individuals (age, 57.5 ± 7.6; men, 39.8%). We included patients hospitalised due to unexplained syncope and OH. Cox regression analysis adjusted for age, sex, prevalent fractures, body mass index (BMI) were applied to assess the impact of unexplained syncope/OH hospitalisations on subsequent incident fragility fractures. Prevalent fractures occurring before syncope/OH hospitalisation were excluded (n = 39) as well as cases with no follow-up time after the event of syncope/OH (n= 8).ResultsThe mean follow-up from baseline to first incident fracture or end of follow-up was 17.8 + 6.5 years, and 8201 (27%) suffered incident fracture. The mean age of patients with unexplained syncope (n = 493) and OH patients (n = 406) at baseline was 61.5 ± 7.1 years (50.1%, male) and 62.6 ± 6.6 years (49.8% male), respectively. The mean time between baseline and first admission for syncope and OH was 12.3 ± 4.5 years, and the mean age at first hospitalisation was 74.4 ± 7.6 years. In the multivariable-adjusted Cox regression, the risk of subsequent incident fractures was increased among patients hospitalised due to unexplained syncope (HR: 1.20; 95% CI 1.03–1.40; p < 0.02) and OH (HR: 1.40; 95% CI 1.20–1.64; p < 0.001), respectively (Kaplan-Meier curves; Figure 1).ConclusionsPatients hospitalised due to unexplained syncope and OH demonstrate increased risk of subsequent fragility fractures. We suggest that patients who are hospitalised for unexplained syncope and OH should be clinically assessed for true syncope aetiology, systematically treated against fall risk, and evaluated for additional risk factors for fragility fractures

Syncope : new solutions for an old problem

Syncope is a frequent event in the general population. Approximately 1%-2% of all emergency department admissions are due to syncope and at least one-third of all people experience fainting in their life. Although consequences of cardiac syncope are generally feared, non-cardiac syncope is much more common and may be associated with severe injuries and quality-of-life impairment, particularly in older adults. Various diagnostic and therapeutic strategies have been created and implemented over decades, leading to significant improvements in diagnostic accuracy and treatment effectiveness. In recent years, diagnosis and treatment have further evolved according to an innovative approach focused on the hemodynamic mechanism underlying syncope, based upon the assumption that knowledge of the syncope mechanism is a prerequisite for effective syncope prevention and treatment. Therefore, a new classification of syncope has been proposed, which defines two main syncope phenotypes with different predominant mechanisms: the hypotensive phenotype, where hypotension or vasodepression prevails, and the bradycardic phenotype, where cardioinhibition prevails. Identification of syncope phenotype - bradycardic or hypotensive/vasodepressive - represents the first step towards personalized management of syncope, characterized by customized interventions for prevention. The present review aims to illustrate these new developments in the diagnosis and therapy of non-cardiac syncope within a mechanism-based perspective. Diagnosis and therapy of bradycardic and hypotensive phenotypes are discussed, with a focus on recent evidence

History of syncope predicts loss of consciousness after head trauma: Retrospective study

Background: Head trauma may present as transient loss of consciousness (TLOC) currently classified as traumatic in origin, in contrast to non-traumatic forms, such as syncope. Whether past history of syncope predisposes to loss of consciousness after head injury has been poorly studied. Methods: A retrospective analysis of data obtained from 818 consecutive patients admitted to Emergency Departments was conducted. Face-to-face semi-structured interviews were performed, where patients’ past history of syncope and head injury were explored. Head injury events were stratified as high- or low-energy trauma. Data regarding past syncopal events were explored in regard to number, age at the first occurrence, and syncope circumstances. Multivariate logistic regression model was applied to assess the relationship between loss of consciousness during head injury and past history of syncope. Results: Both past history of non-traumatic TLOC (odds ratio [OR] 3.78; 95% confidence interval [CI] 2.13–6.68, p &lt; 0.001) and high-energy mechanism (OR 3.84; 95% CI 2.35–6.28, p &lt; 0.001) predicted TLOC after head trauma. This relationship was even stronger when past episodes of TLOC were limited to those typical for reflex syncope (OR 4.34; 95% CI 2.34–7.89, p &lt; 0.001). Further, the number of non-traumatic TLOC episodes in the patient’s history was also predictive of TLOC after head injury (OR per 1 episode: 1.24; 95% CI 1.04–1.48, p = 0.015). Conclusions: Syncope in a patient’s history predicts loss of consciousness after head injury. The clinical importance of this finding merits further investigation

Effect of aging on cerebral tissue oxygenation in relation to reflex syncope

Background: There is an increased susceptibility to syncope with aging attributed to age-related physiological impairments. Cerebral oxime-try non-invasively measures cerebral tissue oxygenation (SctO2) and has been shown to be valuable in syncope evaluation. SctO2 has beenfound to decrease with aging but it is unknown whether the decrease in SctO2 is related to increased susceptibility to syncope during ortho-static provocation. By measuring SctO2 during head up tilt test (HUT) we can study age-related differences in SctO2 and their impact ondeveloping reflex syncope.Purpose: To investigate the effect of age on the cerebral tissue oxygenation threshold for syncope and presyncope among patients withvasovagal syncope.Methods: Non-invasive haemodynamic monitoring and near-infrared spectroscopy (NIRS) were applied during head-up tilt (HUT) in 139vasovagal syncope patients (mean [SD] 45[17] years, 60% female), and 82 control patients with a normal response to HUT (45[18] years,61% female). Group differences in SctO2 and systolic blood pressure (SBP) during HUT in supine position, after 3 and 10 min of HUT, 30seconds prior to syncope ("presyncopal phase") and during syncope in different age groups (60 years) were comparedusing one-way ANOVA and Tukey"s multiple comparison test. Associations between age and SctO2 were studied using linear regressionmodels adjusted for sex and concurrent SBP.Results: Lower SctO2 in supine position was associated with increasing age among controls (B=-0.085, p = 0.010) but not among VVS pa-tients (B=-0.036, p = 0.114). No age-related differences in SctO2 were found after 3 and 10 minutes of HUT and during syncope. MeanSctO2 (%) during the presyncopal phase decreased over the advancing age groups (60: 62.2 ± 5.8; p = 0.009 for inter-group comparison). In contrast, mean SBP during the presyncopal phase did not differ by age groups (60: 77.6 ± 20.8 mmHg, p = 0.133). Age was associated with lower SctO2 during the presyncopal phase after adjusting for sexand SBP (B = 0.096, p = 0.001).Conclusion: Older VVS patients have lower cerebral tissue oxygenation in the presyncopal phase compared with younger patients inde-pendently of systolic blood pressure. These results suggest either that with imminent reflex syncope cerebral tissue oxygenation diminishesmore with advancing age or that cerebral deoxygenation is better tolerated by older reflex syncope patients

Members of the emergency medical team may have difficulty diagnosing rapid atrial fibrillation in Wolff-Parkinson-White syndrome

Background: Atrial fibrillation (AF) in patients with Wolff-Parkinson-White (WPW) syn­drome is potentially life-threatening as it may deteriorate into ventricular fibrillation. The aim of this study was to assess whether the emergency medical team members are able to diagnose AF with a rapid ventricular response due to the presence of atrioventricular bypass tract in WPW syndrome. Methods: The study group consisted of 316 participants attending a national congress of emergency medicine. A total of 196 questionnaires regarding recognition and management of cardiac arrhythmias were distributed. The assessed part presented a clinical scenario with a young hemodynamically stable man who had a 12-lead electrocardiogram performed in the past with signs of pre-excitation, and who presented to the emergency team with an irregular broad QRS-complex tachycardia. Results: A total of 71 questionnaires were filled in. Only one responder recognized AF due to WPW syndrome, while 5 other responders recognized WPW syndrome and paroxysmal su­praventricular tachycardia or broad QRS-complex tachycardia. About 20% of participants did not select any diagnosis, pointing out a method of treatment only. The most common diagnosis found in the survey was ventricular tachycardia/broad QRS-complex tachycardia marked by approximately a half of the participants. Nearly 18% of participants recognized WPW syn­drome, whereas AF was recognized by less than 10% of participants. Conclusions: Members of emergency medical teams have limited skills for recognizing WPW syndrome with rapid AF, and ventricular tachycardia is the most frequent incorrect diagnosis.

Serum biomarkers and clinical outcomes in heart failure patients treated de novo with carvedilol

Background: The role of infl ammatory and hemodynamic stress biomarkers in heart failure(HF) patients treated de novo with beta-blockers has been poorly studied.Methods: A total of 86 patients (age 56 ± 9 years, 81 men) with left ventricular ejection fraction(LVEF) &lt; 40% and previously not treated with beta-blockers were initiated on carvedilol.At baseline and 12 months later we performed echocardiography, cardiopulmonary exercisetesting, and determined serum levels of B-type natriuretic peptide (BNP), endothelin-1 (ET-1),C-reactive protein (CRP), interleukin-6, and tumor necrosis factor alpha (TNF -a). Patientswere followed up over a total period of 9 ± 3 years from baseline.Results: Increased baseline CRP and its on-treatment decrease were associated with improvementof LVEF (est. coeffi cient per one SD: 1.6; 95% CI: –0.05,3.28; p = 0.056, and –1.80;–3.43, –0.18; p = 0.030, respectively) and diminishing of LV end-systolic volume index[mL/m2] (–6.83; –11.32; –2.34; p = 0.003, and 5.85; 1.23; –10.46; p = 0.014, respectively).Higher baseline ET-1 and on-treatment increase in TNF-a predicted frequent admissions(&gt; 1) for cardiac complications (odds ratio per one SD: 1.98; 95% CI: 1.09–3.59;p = 0.025, and 2.07, 1.12–3.84, p = 0.021, respectively) whereas higher baseline BNP wasasociated with increased mortality (hazard ratio per one SD: 2.09, 95% CI: 1.26–3.45;p = 0.004).Conclusions: Serum biomarkers may have different roles in prediction of clinical outcomesamong HF patients treated de novo with carvedilol

Proconvertase Furin Is Downregulated in Postural Orthostatic Tachycardia Syndrome.

Background: Postural Orthostatic Tachycardia Syndrome (POTS) is a cardiovascular autonomic disorder characterized by orthostatic intolerance and high prevalence among young women. The etiology of POTS is uncertain, though autoimmunity and inflammation may play an important role. We aimed to identify novel inflammatory biomarkers associated with POTS. Methods and Results: In the Syncope Study of Unselected Population in Malmö (SYSTEMA) cohort, we identified 396 patients (age range, 15-50 years) with either POTS (n = 113) or normal haemodynamic response during passive head-up-tilt test (n = 283). Blood samples were analyzed using antibody-based Proximity Extension Assay technique simultaneously measuring 57 inflammatory protein biomarkers. The discovery algorithm was a sequential two-step process of biomarker signature identification by supervised, multivariate, principal component analysis and verification by univariate ANOVA with Bonferroni correction. POTS patients were younger (26 vs. 31 years; p < 0.001) and there was no significant difference in sex distribution (74% vs. 67% females, p = 0.24). PCA and Bonferroni-adjusted ANOVA identified proconvertase furin as the most robust biomarker signature for POTS. Plasma level of proconvertase furin was lower (6.38 vs. 6.58 of normalized protein expression units (NPX); p < 0.001 in POTS, compared with the reference group. Proconvertase furin met Bonferroni-adjusted significance criteria in both uni- and multivariable regression analyses. Conclusion: Patients with POTS have lower plasma level of proconvertase furin compared with individuals with normal postural hemodynamic response. This finding suggests the presence of a specific autoimmune trait with disruption of immune peripheral tolerance in this hitherto unexplained condition. Further studies are needed for external validation of our results.This study was supported by grants from the Swedish Heart-Lung Foundation, the Swedish Heart and Lung Association, the Medical Faculty of Lund University, ALF funds, Skne University Hospital Funds, Crafoord Foundation, Ernhold Lundstrms Research Foundation, Region Skåne, Hulda and Conrad Mossfelt Foundation, and Anna-Lisa and Sven Eric Lundgrens Foundation for Medical Research