Syncope diagnostic evaluation in a southern European population: patterns of clinical practice and cost implications

Abstract

Background

Syncope is a common cause of emergency department visits and is associated with heterogeneous clinical practice and substantial hospital resource use. We primarily aimed to quantify the direct per-patient hospital costs of syncope. Secondary aims were to characterize patterns of resource utilization, determine the cost structure by care pathway and functional component, and identify determinants of total per-patient cost. Additionally, we estimated the potential emergency department cost savings resulting from adherence to the 2018 European Society of Cardiology syncope guidelines.

Methods

We conducted an observational, retrospective cohort study at a private hospital in Lisbon, Portugal, from 1 January to 31 December 2023, including pediatric (< 18 years) and adult (≥ 18 years) patients with a principal emergency department diagnosis of syncope (ICD-9-CM 780.2/992.1). Direct costs were assessed by micro-costing (bottom-up approach) from the hospital perspective (base year 2023), with patient-level analysis. Total per-patient cost was modeled using a generalized linear model as a function of age, sex, etiology, and total number of comorbidities as predictors. Potential emergency department savings were estimated using a counterfactual simulation of guideline-concordant diagnostic testing.

Results

We analyzed 375 patients (mean age 49.4 ± 26.5 years; 60.3% female). Etiology was established in 41.1% of the cohort, with reflex syncope predominating (32.3%), whereas 58.1% remained unexplained. Aggregate total cost was €661,992.74, with a mean of €1,765.31 per patient. Costs ranged from €408 per patient for emergency department-only management to €13,048 for episodes requiring hospitalization. Diagnostic testing accounted for 63.3% of total cost. In multivariable analysis, age ≥ 80 years, male sex, higher comorbidity burden and cardiac etiology were associated with significantly higher hospital costs. Potential emergency department diagnostic-testing savings were €80,228.28, corresponding to €213.94 per patient.

Conclusion

Syncope was associated with substantial hospital costs in a context of marked practice variation and intensive diagnostic testing. Structured, guideline-aligned care pathways may support more selective diagnostic evaluation and efficient use of healthcare resources.

Clinical trial number

Not applicable.

Graphical Abstract

Supplementary Information

The online version contains supplementary material available at https://doi.org/10.1186/s12913-026-14945-w.

Introduction

Syncope is defined by the European Society of Cardiology (ESC) as a transient loss of consciousness (TLOC) due to cerebral hypoperfusion, characterized by abrupt onset, short duration, and complete spontaneous recovery [1]. Although often benign, syncope may be the first manifestation of a serious condition with potentially fatal implications [1, 2]. From an organizational standpoint, it represents a growing concern for healthcare systems [3, 4] and constitutes a clinically challenging presentation in the Emergency Department (ED), accounting for 3% to 6% of admissions [5, 6].

Despite evidence-based international guidelines [1, 7], syncope assessment remains fragmented and heterogeneous [8–10]. Current recommendations discourage low-yield strategies and prioritize diagnostic testing with the highest likelihood of establishing an etiologic diagnosis [11]. However, dissemination and effective integration into clinical practice remain limited, and adoption is often slow and incomplete [10, 12–15].

At the same time, an estimated 30–50% of patients are discharged without a conclusive diagnosis [6, 16], a pattern associated with decentralized diagnostic evaluation, frequent use of low-yield tests, and referrals across multiple specialty clinics [8, 9, 17–20]. In the context of increasing pressure on health systems to optimize resource use [21], syncope represents an important area for improving the appropriateness and efficiency of diagnostic evaluation.

Portugal has a mixed healthcare system in which a universal, tax-funded public National Health Service, the Serviço Nacional de Saúde (SNS), operates alongside a substantial private healthcare sector [22]. In 2023, private current health expenditure represented 36.1% of total current health expenditure [23], and private hospitals accounted for 11.5 thousand of the 35.7 thousand hospital beds in Portugal [24]. This mixed public–private context should be considered when interpreting resource use and cost estimates from a private hospital setting.

Against this health-system background, syncope is associated with substantial resource use and costs. In the United Kingdom, the median per-patient cost of diagnostic testing was £1,114, with a mean of £1,613 [11]. In Italy, the mean cost was estimated at €1,394 per patient, rising to €2,785 among inpatients [8]. In Portugal, a Markov model based on transition probabilities derived from the literature and cost data from the SNS estimated a mean cost per syncope episode of €1,760–2,800 [25].

However, real-world evidence on clinical practice, resource use, and costs in syncope remains limited, and no such data are currently available for Portugal, where the literature has thus far been restricted to model-based estimates for the SNS.

This study first quantifies the direct per-patient hospital costs associated with the evaluation of syncope, using clinical registry data from a private multispecialty hospital in Portugal in 2023. Second, it characterizes the patterns of resource utilization, determines the cost structure by care pathway and functional component, and identifies determinants of total per-patient cost. Finally, it estimates the potential ED cost savings that would result from adherence to the 2018 ESC guidelines [1].

Methods

Study design

We conducted a retrospective observational cohort study in a single private multispecialty healthcare group in the Lisbon region, drawing on data from its two highest-volume hospitals. In 2023, these institutions jointly recorded 167,862 emergency visits across general, pediatric, and obstetric emergency care.

Population and inclusion criteria

We considered pediatric (< 18 years) and adult (≥ 18 years) patients treated in the ED between January 1 and December 31, 2023, in whom syncope was coded as the primary diagnosis according to the International Classification of Diseases, 9th Revision – Clinical Modification (ICD-9-CM): 780.2 (“Syncope and collapse”) or 992.1 (“Heat syncope”). A total of 386 eligible patients were initially identified.

Exclusion criteria

Exclusion criteria were as follows: hospital discharge against medical advice (n = 5), refusal of admission after a proposal for hospitalization (n = 1), transfer to a SNS institution before completion of the diagnostic evaluation (n = 4), and incomplete clinical or financial information (n = 1). After application of these criteria, the final analytical cohort comprised 375 patients. Three additional patients were excluded from the multivariate analysis after being classified as differential diagnoses (see Section “Determinants of total hospital cost per patient”). Study population selection and exclusions are summarized in Supplementary Fig. 1 (Additional file 1).

Data sources and collection procedures

Clinical and administrative data were extracted from an institutional data warehouse that centralizes and organizes information (Glintt^® electronic information system).

At the patient level, the following variables were collected: age; sex; number and type of pre-existing comorbidities; frequency and type of diagnostic tests; frequency and type of invasive therapeutic procedures; number and specialty of follow-up consultations; occurrence, duration, and type of inpatient unit, and syncope etiology.

Comorbidity information was obtained from routine clinical documentation in the medical records, including recorded past medical history and usual medication, rather than from ICD-coded administrative data. Repeated performance of the same diagnostic test in the same patient was recorded as separate occurrences. Etiological attribution was likewise based exclusively on routine clinical documentation recorded by attending physicians, without research adjudication of diagnostic judgment.

For episodes involving an ED stay of less than 24 h and no subsequent follow-up, the etiology recorded for the index ED visit was used. For hospitalized patients, the etiology stated in the discharge summary was adopted. For episodes with outpatient follow-up, etiological attribution was based on clinical records, diagnostic tests, and specialty consultations documented within 60 days of the index ED visit, irrespective of the date of presentation. The same 60-day observation window was applied across all patients for care pathway classification, including those initially classified as ED only, in order to determine whether any subsequent outpatient consultations or diagnostic tests occurred within the study institution. Accordingly, follow-up was defined relative to the index episode and, when necessary, was allowed to extend beyond December 31, 2023, so that all patients had the same 60-day opportunity for outpatient follow-up ascertainment.

After this period, cases with no determined cause were classified as unexplained syncope, defined by the 2017 joint American College of Cardiology (ACC), American Heart Association (AHA), and Heart Rhythm Society (HRS) (ACC/AHA/HRS) guideline as TLOC whose cause remains undetermined after an adequate initial evaluation by an experienced health care professional [7]. This evaluation includes, but is not limited to, a detailed medical history, a complete physical examination, and a 12-lead electrocardiogram (ECG). By contrast, cases initially included in the cohort under the primary ED code for syncope and collapse but subsequently found, after clinical evaluation, not to represent true syncope were classified as differential diagnoses.

Readmissions for syncope occurring within the same calendar year (ICD-9-CM 780.2 or 992.1) were identified and considered new episodes, each initiating a new 60-day follow-up window. For patient-level etiologic characterization, the etiology assigned to the most recent episode was retained, thereby ensuring single-patient inclusion in the main analyses. For patient-level cost analyses, all hospital resource use and corresponding costs accrued across episodes during the available observation period were aggregated at the patient level, including diagnostic tests, consultations, and other care components incurred during readmissions and their associated follow-up.

Cost measurement

A cost measurement from the hospital perspective was conducted using bottom-up micro-costing on a per-episode basis, with subsequent aggregation at the patient level. The valuation used internal unit costs provided by the Institution’s Processes and Information Department.

Overhead costs were considered to be the set of indirect costs attributable to the hospital activity of each patient. It included administrative and support service charges (cleaning and maintenance), infrastructures (building maintenance, electricity, water, and air conditioning), equipment (depreciation and maintenance of medical equipment not directly used on patients), and non-medical human resources (security team, IT technicians, and administrative staff). The calculation was based on unit reference values defined by the Planning and Management Control Department, applied as proportional multipliers to the following operational allocators: minutes spent in the emergency room, days of hospitalization adjusted to the type of unit, minutes in the operating room, number of consultations performed and, in the case of diagnostic tests, a fixed percentage applied to the billed value of the exam.

The cost was then measured for each of the four mutually exclusive care trajectories:

Exclusive ED, evaluation only in the ED, without hospitalization and without outpatient follow-up;

ED with outpatient, assessment in the ED with subsequent outpatient follow-up (consultations and/or diagnostic tests), without hospitalization;

ED with hospitalization, evaluation in the ED with hospitalization on the same admission, without outpatient follow-up;

ED with hospitalization and outpatient, assessment in the emergency department with hospitalization on the same admission, followed by outpatient follow-up.

Costs were allocated per episode, according to a sequential and cumulative logic, with subsequent aggregation at the patient level, determining the total individual cost for the period under review.

The institution provided unit costs derived from the measurement and valuation of the following functional components:

ED – medical fees, cost of goods sold (COGS), diagnostic tests, and overhead calculated based on length of stay in the ED;

Hospitalization – daily hospital rate adjusted to the type of service (general hospitalization, special care unit for newborns, intermediate care unit, or multipurpose intensive care unit), medical fees, COGS, invasive therapeutic procedures, diagnostic tests, and overhead proportional to the days of hospitalization and time in the operating room;

Outpatient (external consultations) – medical fees, COGS, medical specialty consultations, diagnostic tests, and overhead proportional to the total number of consultations performed.

The diagnostic tests were valued as a separate item, including medical fees, COGS and overhead, and were subsequently allocated to the care setting in which they occurred.

One-way sensitivity analyses were performed to assess the robustness of the micro-costing estimates. Specifically, diagnostic test costs and overhead costs were varied by ± 10% and ± 20% relative to the base-case estimates, and total hospital cost per patient was recalculated for each scenario.

Determinants of total hospital cost per patient

Total hospital cost per patient was modeled using a generalized linear model (GLM) with gamma distribution and logarithmic link function, given the non-negative, right-skewed distribution of cost data. The following predictor variables were included: (i) age, categorized into five groups (< 18 years, 18–39 years, 40–59 years, 60–79 years, and ≥ 80 years); (ii) sex; (iii) syncope etiology, categorized into four clinically interpretable groups (reflex, orthostatic hypotension, cardiac, and unexplained); and (iv) total number of comorbidities per patient.

Cases ultimately classified as differential diagnoses were retained in the descriptive cohort but excluded from the etiologic predictor in the GLM, as they did not represent confirmed syncope etiologies and could not be meaningfully modeled as a separate analytic category. Of the 375 patients in the full analytical cohort, three were excluded from the GLM on this basis. No additional cases were excluded because of missing predictor or cost data, resulting in a final GLM analytic sample of 372 patients. Care pathway was not included as an independent variable in the model because it is a post-baseline mediator that directly shapes patterns of resource use and the composition of total hospital costs, and adjusting for it would therefore risk overadjustment.

Estimation of potential savings in the emergency department by counterfactual simulation

A counterfactual simulation based on risk stratification was performed to compare observed ED practice with an idealized scenario defined by full adherence to the 2018 ESC guidelines [1] for syncope management in the ED.

The simulation was deliberately restricted to the ED, as this was the only setting in which guideline-based recommendations could be operationalized in a standardized manner for the index acute episode. In other care settings, the indication for diagnostic testing is contingent on subsequent clinical evolution and suspected etiology.

The observed ED diagnostic testing and corresponding costs reflected actual emergency physician practice. To construct the guideline-concordant counterfactual scenario, two cardiologist coauthors with expertise in syncope and arrhythmology independently reviewed the clinical information available from the index ED episode, including age, sex, presenting features, and other details relevant to risk stratification. To preserve an assessment anchored to the initial ED presentation, reviewers were not provided with information obtained after the initial evaluation, including subsequent diagnostic findings and the diagnostic tests actually ordered in the ED.

Based on the 2018 ESC recommendations applicable to the initial ED evaluation [1], each reviewer assigned patients to a risk category (low, intermediate, or high) and identified the diagnostic tests that would have been expected under full guideline adherence. In cases of disagreement, the case was jointly re-reviewed and the final classification was established through discussion-based consensus.

The potential savings per patient were calculated as the difference between observed and expected ED diagnostic costs.

Results

We identified 386 patients who presented to the ED in 2023 with a primary diagnosis of syncope (ICD-9-CM codes 780.2 or 992.1). After applying the exclusion criteria, 11 patients were excluded, leaving 375 patients for analysis.

Among the 375 analyzed patients, the mean age was 49.4 ± 26.5 years and 60.3% were female. Baseline demographic and clinical characteristics are presented in Table 1. Overall, 59.5% had at least one comorbidity, most commonly hypertension, dyslipidemia, neoplasia, and depressive disorder.

Table 1.

Baseline characteristics of patients with syncope evaluated in the emergency department (n = 375)

Characteristic
Age, mean ± SD (years)	49.4 ± 26.5
Sex	n (%)
Female	226 (60.3)
Male	149 (39.7)
Age group (years)
< 18	66 (17.6)
18–39	80 (21.3)
40–59	72 (19.2)
60–79	84 (22.4)
≥ 80	73 (19.5)
Most frequent comorbidities
Hypertension	114 (30.4)
Dyslipidemia	71 (18.9)
Neoplasia	64 (17.1)
Depression	41 (10.9)
Anxiety	25 (6.7)
History of arrhythmia	21 (5.6)
Ischemic heart disease	20 (5.3)
Thyroid disease	17 (4.5)
Cerebrovascular disease	16 (4.3)
Diabetes mellitus	10 (2.7)
≥ 1 comorbidity	223 (59.5)

SD, standard deviation

At the end of the follow-up period, the etiology was established in 41.1% of the cohort, with a predominance of reflex syncope (32.3%), followed by orthostatic hypotension (4.8%) and cardiac syncope (4%) (Table 2). In 58.1% of cases, the etiology remained undetermined and was classified as unexplained syncope. In the hospitalization subgroup (n = 33), 17 patients (51.5%) were discharged without a defined etiology.

Table 2.

Final etiology of syncope in the cohort (n = 375)

Etiology of syncope		n (%)
Reflex		121 (32.3)
Orthostatic hypotension		18 (4.8)
Cardiac	Arrhythmic	7 (1.9)	15 (4.0)
	Structural	6 (1.6)
	Cardiopulmonary and great vessels	2 (0.5)
Unexplained		218 (58.1)
Differential diagnosisa		3 (0.8)

^aCases initially coded in the emergency department as “syncope and collapse” (ICD-9-CM 780.2) reclassified after clinical evaluation as differential diagnoses: transient ischemic attack (n = 1), epilepsy (n = 1), and psychogenic pseudosyncope (n = 1). ICD-9-CM, International Classification of Diseases, 9th Revision – Clinical Modification

In the ED, a mean of 2.70 ± 1.59 diagnostic tests per patient were performed (Supplementary Table 1, Additional file 2), predominantly laboratory tests (81.9%), 12-lead ECG (81.1%), and cranial computed tomography (CT) (37.3%) (Table 3). During hospitalization, the mean rose to 5.66 ± 1.79 diagnostic tests per patient, with emphasis on 24-hour Holter monitoring (78.8%), transthoracic echocardiography (72.7%), and carotid-vertebral Doppler ultrasound (66.7%). In the outpatient setting, a mean of 2.78 ± 1.60 diagnostic tests per patient were performed, with emphasis on 24-hour Holter monitoring (50.0%), transthoracic echocardiography (47.3%), and 12-lead ECG (33.6%).

Table 3.

Most commonly performed diagnostic tests and invasive therapeutic procedures by care setting

Examination/Procedure	n (%)
ED (n = 375)
Diagnostic tests
Laboratory tests	307 (81.9)
12-lead ECG	304 (81.1)
Cranial CT scan	140 (37.3)
Chest X-ray	83 (22.1)
Thoracic aorta CT angiography	20 (5.3)
Pulmonary arteries CT angiography	18 (4.8)
Chest CT	9 (2.4)
Cerebral CT angiography	6 (1.6)
Cervical spine CT scan	6 (1.6)
Transthoracic echocardiogram	5 (1.3)
Hospitalization ( n  = 33)
Diagnostic tests
24-hour Holter monitoring	26 (78.8)
Transthoracic echocardiogram	24 (72.7)
Carotid-vertebral Doppler ultrasound	22 (66.7)
12-lead ECG	19 (57.6)
Laboratory tests	16 (48.5)
Electroencephalogram	15 (45.5)
Chest X-ray	8 (24.2)
Cranial CT scan	5 (15.2)
Lower-extremity Doppler ultrasound	5 (15.2)
Cardiac MRI	4 (12.1)
Invasive therapeutic procedures
Cardiac catheterization	2 (6.1)
Cardiac device implantation	1 (3.0)
Examination/Procedure	n (%)
Outpatient ( n  = 146)
Diagnostic tests
24-hour Holter monitoring	73 (50.0)
Transthoracic echocardiogram	69 (47.3)
12-lead ECG	49 (33.6)
Electroencephalogram	39 (26.7)
Carotid-vertebral Doppler ultrasound	21 (14.4)
Laboratory tests	24 (16.4)
Stress test	21 (14.4)
24-hour ABPM	16 (11.0)
Cranial CT scan	12 (8.2)
Chest X-ray	9 (6.2)
Tilt test	9 (6.2)
Invasive therapeutic procedures
Cardiac catheterization	2 (1.37)
Cardiac device implantation	1 (0.7)

ED, emergency department; ECG, electrocardiogram; CT, computed tomography; MRI, magnetic resonance imaging. ABPM, ambulatory blood pressure monitoring

Among hospitalized patients (n = 33), the mean length of stay was 6.70 days, predominantly on general wards (93.9%) (Supplementary Table 2, Additional file 3). During the follow-up period, the specialties most involved in care were cardiology (43.2%), neurology (29.5%), and internal medicine (20.5%) (Supplementary Table 3, Additional file 4). During the same calendar year, the readmission rate for syncope was 1.6% (n = 6), occurring a mean of 25 days after the initial episode, with a new etiological determination in two cases.

The total hospital cost for the cohort of 375 patients with syncope was €661,992.74. In the aggregate analysis by care pathway (Table 4), the mean total cost per patient was €1,765.31 and the median was €369.07.

Table 4.

Costs per patient by care pathway

Care pathway	n	Mean (€)	95% CI of mean	SD (€)	Median [IQR] (€)
Exclusive EDa	204	408.22	[272.81–543.63]	980,91	165.35 [65.50–429.24]
ED with outpatientb	138	1,202.94	[642.77–1,763.11]	3,327.81	603.50 [337.51–1,014.64]
ED with hospitalizationc	25	13,047.91	[8,685.01–17,410.81]	10,569.56	10,440.44 [4,506.21–‍20,511.20]
ED with hospitalization and outpatient cared	8	10,814.08	[2,547.53–19,080.62]	9,887.96	7,216.59 [6,824.21–‍11,083.67]
Total cost	375	1,765.31	[1,258.02–2,272.61]	4,995.96	369.07 [122.70–896.31]

Mutually exclusive care pathway categories – ^a assessment only in the ED, without hospitalization and without outpatient follow-up. ^b assessment in the ED with outpatient follow-up (consultations and/or diagnostic tests), without hospitalization. ^c assessment in the ED with hospitalization on the same admission, without outpatient follow-up. ^d assessment in the ED with hospitalization, followed by outpatient follow-up. CI, confidence interval; ED, emergency department; SD, standard deviation; IQR, interquartile range [P25–P75]

By functional component (Table 5), diagnostic tests constituted the main cost item, with a mean cost of €1,118.40 per patient and a median of €248.02, followed by hospitalization, with a mean cost of €529.99 and a median of €0, and by the ED, with a mean cost of €105.66 and a median of €71.92. In aggregate terms, diagnostic tests accounted for 63.3% of the total cost, hospitalization for 30.0%, and the ED for 6.0%. Specialist consultations were not reported separately in the table, as they represented < 1% of total cost.

Table 5.

Costs by functional component: disaggregated analysis (n = 375)

Functional component	Mean (€)	95% CI of mean (€)	SD (€)	Median [IQR] (€)
Emergency departmenta	105.66	[94.28–117.05]	112.14	71.92 [49.40–115.71]
Diagnostic testsb	1,118.40	[797.19–1,439.61]	3,163.37	248.02 [45.65–758.91]
Hospitalizationc	529.99	[238.23–821.75]	2,873.33	0 [0–0]

^a Includes medical fees, COGS, and overhead, calculated based on length of stay in the ED; ^b Includes all diagnostic tests performed in different contexts (ED, hospitalization, and outpatient), with costs calculated based on medical fees, COGS, and respective overhead; ^c Includes daily hospital fees adjusted to the type of service, medical fees, COGS, therapeutic procedures, and overhead proportional to the number of days of hospitalization and operating room time. Specialized consultations were not included in the table as they represent a residual fraction of the total cost (< 1%). CI, confidence interval; SD, standard deviation; IQR, interquartile range [P25–P75]; COGS, cost of goods sold; ED, emergency department

One-way sensitivity analyses varying diagnostic test costs and overhead costs by ± 10% and ± 20% produced the expected changes in absolute total cost estimates, but did not materially alter the overall interpretation of the cost profile. Across all scenarios, the resulting changes in total hospital cost were proportionally smaller than the variations applied to the individual cost components, and the main pattern of findings remained stable, supporting the robustness of the micro-costing results to plausible variation in key costing assumptions (Supplementary Tables 4 and 5, Additional file 5).

Using the < 18 years group as the reference, the ≥ 80 years group showed costs 9.6 times higher (Exp(B) = 9,672; p < 0,001), with an increasing gradient in the other age groups (Table 6). Compared to females, males had costs 37% higher cost (Exp(B) = 1,372; p = 0,020). Regarding etiology, compared to reflex syncope, cardiac etiology was associated with 3.12 times higher costs (Exp(B) = 3,123; p = 0,001). We estimated a 15% increase in cost per additional comorbidity (Exp(B) = 1,152; p = 0,002).

Table 6.

Determinants of total hospital cost per patient (n = 372): generalized linear model with gamma distribution and logarithmic link function

Variables	Variable categories	Exp(B)	Lower limit of CI (95%)	Upper limit of CI (95%)	p-value
Age (age groups, years)	≥ 80	9.672	5.925	15.789	< 0.001
	60–79	5.832	3.610	9.420	< 0.001
	40–59	3.677	2.438	5.546	< 0.001
	18–39	1.653	1.115	2.451	0.012
	< 18 (ref.)	1	–	–	–
Sex	Male	1.372	1.051	1.790	0.020
	Female (ref.)	1	–	–	–
Etiology	Cardiac	3.123	1.552	6.282	0.001
	OH	2.231	1.181	4.215	0.013
	Unexplained	1.518	1.147	2.009	0.003
	Reflex (ref.)	1	–	–	–
Comorbidities	–	1.152	1.055	1.257	0.002

Generalized linear model with gamma distribution and logarithmic link, estimated by maximum likelihood. Dependent variable: total cost per patient (€). Predictors: age, sex, etiology of syncope, and total number of comorbidities (continuous). Ref. – reference category/comparison denominator. p-value – obtained in the Wald test. CI (95%) – 95% confidence interval for Ex(B). OH, orthostatic hypotension

The cost in the observed scenario was €133,241.54, compared to €53,013.26 in the ideal scenario, aligned with the 2018 ESC guidelines [1], resulting in potential diagnostic testing savings of €80,228.28 (60.2%). The mean cost per patient was €355.31 in the observed scenario and €141.37 in the ideal scenario. The mean savings per patient was €213.94, corresponding to a relative reduction of 60.2% compared to the observed mean cost per patient.

Discussion

Key findings

In 2023, reflecting the clinical practice captured in this study, the total cost of syncope diagnosis and treatment in the cohort was €661,992.74, corresponding to a mean per-patient cost of €1,765.31 and a median of €369.07. Costs varied markedly across mutually exclusive care pathways, ranging from €408 per patient for those managed exclusively in the ED to €13,048 for those requiring hospitalization. Diagnostic testing was the largest cost driver, accounting for 63.3% of total expenditure. In multivariable regression, age ≥ 80 years, male sex, higher comorbidity burden and cardiac etiology were independently associated with higher adjusted per-patient hospital costs. In a counterfactual simulation restricted to ED diagnostic testing and assuming full adherence to the 2018 ESC guidelines [1], we estimated total potential savings of €80,228.28 and a mean per-patient saving of €213.94.

Interpretation of results

Cost measures

Despite limitations to direct comparability arising from methodological heterogeneity, differences across healthcare systems, and variation in analytic perspectives, the available evidence consistently indicates that syncope management imposes a substantial economic burden [8, 11]. In a prospective, multicenter study conducted in Italian public hospitals, Brignole et al. estimated a mean cost per episode of €1,394 for the management of 929 patients using conventional pathways [8]. Similarly, Providência et al., using a Markov model applied to a simulated cohort of patients with unexplained syncope, estimated a mean cost for Portugal between €1,760 and €2,800 [25]. The mean cost observed in the present study was within the range of previous estimates, although toward its upper bound, reinforcing the relevance of syncope as a resource-intensive condition across different healthcare settings.

Care pathways and cost components

Care pathways involving hospitalization were associated with substantially higher mean per-patient costs and, when aggregated across patients, accounted for 62.3% of total cohort expenditure. This finding reinforces the central role of hospitalization as the main driver of direct costs, in line with published evidence. It is estimated that 40–50% of syncope presentations to the ED result in hospitalization [1, 19, 26], with this component accounting for > 75% of the total cost [8, 12, 27]. Similarly, in the Italian multicenter study by Brignole et al. [8], the total aggregate cost for the cohort of 929 patients was €1,295,000, of which 78% corresponded to hospitalization. Sandhu et al., in a Canadian population-based study of 51,831 patients, estimated a mean inpatient cost of C$30,000–C$40,000, equivalent to 69–74% of the total hospital cost [4].

It should be noted that, whereas many studies aggregate diagnostic test costs within hospitalization costs, our analysis disaggregated expenditure into its individual components. Under this framework, although hospitalization remained the trajectory with the highest mean cost per patient, diagnostic tests constituted the largest cumulative component of expenditure across the cohort, irrespective of the setting in which they were performed. In economic terms, this shifts attention away from hospitalization as the sole cost driver and toward the cross-sectional use of diagnostic tests throughout the care pathway, suggesting that budgetary pressure stemmed less from hospitalization per se than from a systematically intensive and not always selective diagnostic approach.

Three factors directly related to the institutional setting and the profile of the study sample may help explain this result. First, the hospitalization rate in the cohort was particularly low (8.8%), thereby reducing the relative weight of this component. Second, diagnostic activity was substantial, with a mean of approximately three diagnostic tests per patient across the care pathway, as well as occasional instances of particularly intensive use. Third, in the private sector, diagnostic tests tend to have higher unit costs due to the inclusion of professional fees, fixed operating costs, and depreciation of advanced technology.

Among these factors, the relatively low hospitalization rate observed in our cohort is particularly relevant to interpretation. Admission rates for syncope are known to vary widely across healthcare systems and organizational settings, with published estimates ranging from approximately 12% to 86% [6]. This difference likely reflects a combination of contextual and methodological factors. In particular, the study population was restricted to ED encounters in which syncope was recorded as the primary diagnosis, which may have excluded more clinically complex presentations in which syncope occurred secondarily in the context of another acute condition and which might be associated with a higher probability of admission. In addition, the organizational characteristics of the study setting, including relatively streamlined access to outpatient specialty evaluation, may have facilitated ambulatory management or deferred investigation for selected patients. Variation in local admission thresholds, organizational processes, and patient case mix may also have contributed. The lower proportion of ED encounters coded as syncope compared with some international reports [5, 6] should also be interpreted in light of the deliberately specific case definition used in this study, which was restricted to episodes in which syncope was coded as the primary ED diagnosis, and the broad institutional denominator, which comprised general, pediatric, and obstetric emergency activity.

This overall cost pattern is further contextualized by evidence showing that intensive diagnostic testing in syncope may generate substantial expenditure without proportionate gains in etiologic clarification. Johnson et al., in a retrospective study based on hospital billing data, reported a cumulative total cost of $305,530.00, of which only $5,851.00 corresponded to examinations that actually contributed to identification of the cause of syncope (1.9%) [28]. Similarly, Edvardsson et al. conducted a micro-costing analysis in 570 patients with unexplained syncope at a university hospital in the United Kingdom, reporting a median per-patient diagnostic testing cost of £1,114 (95% CI: 995–1,233) and a mean of £1,613 (95% CI: 1,494–1,732). Despite this spending, no etiologic diagnosis was established, suggesting low diagnostic yield and limited clinical value of unstructured testing [11].

Sociodemographic and clinical determinants

Multivariate regression analysis revealed systematic differences in total per-patient hospital costs across sociodemographic and clinical profiles. First, costs increased with age, mirroring previous evidence that related advanced age to greater clinical complexity, higher comorbidity burden and polypharmacy, higher risk of adverse events, and longer length of stay [7, 29–31]. In addition, evaluating syncope in older adults is clinically challenging, marked by a higher prevalence of cardiac causes, orthostatic hypotension, and drug interactions, while the absence or brevity of prodromes and amnesia of the event favor presentations as falls, making identification of a TLOC more difficult [32–36]. By contrast, reflex syncope, predominant in younger patients [36–38], is generally benign, more straightforward to diagnose, typically requiring less extensive investigation.

Male patients also experienced higher total hospital costs, which may reflect greater comorbidity burden and higher hospitalization rates previously reported among men presenting with syncope, despite the higher frequency of ED presentations among women [39].

Statistically significant higher total costs were observed for cardiac, orthostatic hypotension, and unexplained syncope, with the most pronounced effect in the cardiac group. This pattern is also consistent with the literature: cardiac syncope is associated with a higher risk of adverse events, prolonged hospitalization, a need for continuous monitoring, and increased use of invasive therapeutic procedures [19]. Moreover, this etiology carries an approximately twofold higher risk of mortality than the remaining etiologies [12, 40], warranting more cautious and intensive clinical approaches. These findings are consistent with Barón-Esquivias et al., who, in a retrospective study of 203 patients, identified cardiac syncope as the most expensive (€5,679 per patient) compared with the substantially lower costs for reflex syncope (€1,436 per patient) [41]. In line with this framework, reflex syncope, particularly in younger individuals without heart disease, is associated with lower risk, reduced clinical complexity, and consequently lower consumption of hospital resources [12, 42, 43].

In orthostatic hypotension, common in older adults [12, 33] and often associated with cardiovascular disease, autonomic dysfunction, or pharmacologic iatrogenesis [32], the need for targeted evaluation and therapeutic adjustments tends to increase the use of diagnostic testing, placing this etiology at an intermediate expenditure level. In addition, the risk of mortality is approximately twice that of the general population [12, 44]. Unexplained syncope often entails multiple diagnostic tests using a diagnostic exclusion (“shotgun”) approach [12], with low diagnostic yield [11, 25, 45]. This broad, resource-dispersing strategy, combined with the substantial proportion of inconclusive cases in the present cohort, may account for a comparatively high-cost profile.

Finally, the number of comorbidities was significantly associated with total hospital cost per patient, with costs increasing for each additional comorbidity. This finding is consistent with previous evidence linking greater comorbidity burden to higher hospital costs, longer length of stay, and increased resource use in patients presenting with syncope [4, 46].

Comparison with guidelines and potential savings

Our data revealed extensive use of diagnostic tests in the assessment of syncope, including laboratory testing, imaging, and neurological examinations. This practice contrasts with the rationale endorsed by current guidelines, which recommend an initial syncope evaluation centered on a detailed medical history, physical examination, and a 12-lead ECG [1, 7], an approach that alone can establish the diagnosis in 50–90% of cases [47–49].

Furthermore, scientific evidence has reinforced the role of comorbidities and pharmacologic iatrogenesis as relevant underlying causes of syncope [7], with medications implicated in an estimated 5–15% of episodes [50], particularly antihypertensive and psychotropic agents [12]. In this context, international guidelines emphasize selective use of diagnostic tests: laboratory studies should be reserved for specific clinical contexts – hematocrit or hemoglobin in suspected hemorrhage; oxygen saturation and arterial blood gas analysis in suspected hypoxia; troponin when syncope associated with cardiac ischemia is suspected; and D-dimer testing in suspected pulmonary embolism [1]. Similarly, chest X-rays and several neurological tests, such as an electroencephalogram (EEG), carotid and vertebral Doppler ultrasound, cranial CT, and brain magnetic resonance imaging (MRI), are not recommended for the routine assessment of syncope [1]. Instead, these tests should be reserved for specific clinical scenarios, such as clinical signs suggestive of seizure, focal neurological findings warranting further investigation, or suspected traumatic brain injury [1, 7].

This guidance has been repeatedly supported by evidence highlighting the low diagnostic yield and high marginal cost associated with indiscriminate test ordering in syncope [1, 7, 12]. Within this framework, the present findings suggest that current testing patterns may not always be optimally targeted and that some areas of resource use warrant closer value-based scrutiny [48].

Empirical evidence likewise shows that several investigations frequently used in syncope care provide limited immediate diagnostic return. In a retrospective study of 2,106 patients aged ≥ 65 years admitted for syncope, Mendu et al. reported that cranial CT was performed in 63% of cases but contributed to the diagnosis in only 2%; 95% of patients underwent cardiac biomarker testing, with a significant troponin I elevation in only 5% [31]. Ruwald et al. analyzed 570 hospital readmissions for syncope and found that although every patient underwent testing, no clinically relevant changes informing the diagnosis were identified [45]. Similarly, Johnson et al. evaluated 1,038 patients and observed that none of the obtained chest radiographs contributed to establishing the etiology of syncope [28]. Finally, a systematic review cited by the ACC/AHA/HRS noted that, although head CT was performed in 57% of 2,728 patients, only 1% had a direct diagnostic yield. In the same review, EEG had a diagnostic utility of just 0.7% despite being ordered in more than half of the cases in a sample of 2,084 patients [7, 51].

Within this broader pattern of resource-intensive and not always selective diagnostic evaluation, hospitalization, although less frequent in absolute terms, still accounted for a substantial share of total costs, while its diagnostic yield remained limited. Notably, 51.5% of hospitalized patients in our cohort were discharged without an established etiology, raising questions about whether admission patterns were consistently aligned with risk-stratified management. These findings are particularly relevant in light of international recommendations that emphasize early risk stratification. Not all patients classified as high risk require hospitalization, whereas admitting low-risk patients may lead to avoidable costs, prolonged care pathways, and increased iatrogenic risk [52]. The absence of standardized clinical protocols likely contributed to the observed heterogeneity in practice and incomplete alignment with available evidence.

This limited diagnostic resolution extended beyond the hospitalized subgroup and was evident across the cohort. Indeed, 58.1% of patients were discharged without an established etiologic diagnosis, making this one of the most salient findings of the study. Although concerning, this proportion is broadly consistent with the literature, as multiple observational studies and systematic reviews report that 20–60% of syncope presentations remain without definitive etiologic clarification [6, 8, 52]. Yet, in the present study, the persistence of etiologic uncertainty is particularly striking when considered alongside the intensity of diagnostic testing. This suggests that the challenge lay not only in the inherent complexity of syncope, but also in the limited discriminative efficiency of the diagnostic process as implemented in routine care. Because syncope is a transient clinical event and potentially informative findings may no longer be evident at the time of evaluation, a degree of diagnostic uncertainty is often unavoidable [53]. Nevertheless, the coexistence of extensive testing and a high proportion of unexplained cases suggests that the diagnostic pathway remained more expansive than discriminative, with investigations not always sufficiently selective, sequentially integrated, or closely aligned with the most informative clinical hypotheses. This may also have been reflected in the limited use of targeted investigations with potentially greater diagnostic value in appropriately selected patients, an issue that is further considered below.

In line with this interpretation, Numeroso et al., in a cross-sectional survey of 102 ED directors in Italy [54], found that despite the existence of reference guidelines, approximately 43.6% of centers lacked structured protocols for syncope evaluation, favoring empirical and individualized approaches [19, 54].

Taken together, these findings suggest that low etiologic resolution arose from the interplay between the intrinsic complexity of syncope and a broader set of individual, organizational, and structural constraints. In particular, incomplete application of guideline-based risk stratification and the absence of coordinated models capable of integrating the different stages of the clinical pathway may have contributed to a diagnostic process that remained insufficiently selective and only partially structured. Additional contributing factors likely included operational and behavioral determinants such as limited familiarity with guideline recommendations among clinicians, defensive decision-making oriented toward error avoidance, and the absence of protocols, clinical pathways, routine auditing, and shared case-management mechanisms [14, 55]. Collectively, these factors may have reinforced practice variation, reduced diagnostic selectivity and pathway integration, and promoted intensive, not always optimally targeted, testing.

Implications for practice

Within this broader context of substantial diagnostic expenditure, marked cost heterogeneity across patient profiles, and potential ED cost savings from guideline-concordant diagnostic testing, organizational strategies such as Syncope Units (SUs) emerge as particularly promising models for standardizing syncope care in line with contemporary guideline recommendations [56]. Ghariq et al., for example, in a prospective multicenter study across five tertiary hospitals in the Netherlands, demonstrated that implementing an SU alongside the systematic application of guidelines significantly increased diagnostic accuracy (86% vs. 69%) and diagnostic yield (89% vs. 76%), while generating a mean savings of €908 per patient compared with the conventional model [15]. Similarly, Ammirati et al. reported an 85% reduction in hospital costs and an increase in the etiologic diagnosis rate to 82% in a cohort of 741 patients consecutively referred to SUs for unexplained syncope [27]. In a prospective, randomized clinical trial, Shen et al. observed a significantly higher diagnosis rate among patients evaluated in an ED-associated SU (67% vs. 10%; p < 0.001) [57]. Torabi et al. likewise demonstrated, in a cohort of 2,663, that a protocol-driven autonomic evaluation in an SU, including head-up tilt testing, active standing test, carotid sinus massage, and the Valsalva maneuver, enabled determination of the etiology in approximately 80% of cases initially classified as unexplained syncope [58].

Despite evidence supporting SUs as a more structured model of care, their implementation remains limited [19, 46, 59]. In a prospective multinational study of 952 patients across 41 EDs in 14 European countries, only 13% were referred for SU evaluation [10], highlighting a disruptive gap between available evidence and current practice. A similar pattern may be observed in our cohort. Despite institutional availability, the tilt test was performed in only nine patients. This is clinically relevant because contemporary recommendations support tilt testing after a non-diagnostic initial evaluation, particularly when reflex syncope or orthostatic hypotension is suspected [1, 7]. Similarly, although 24-hour Holter monitoring was frequently used in the present cohort, current guidelines increasingly emphasize individualized ambulatory rhythm monitoring strategies, including external and implantable loop recorders in selected patients with recurrent or unexplained syncope, given their greater diagnostic yield for intermittent arrhythmic events [1]. Rather than indicating lack of diagnostic activity, this pattern suggests that syncope-specific investigations with potentially greater value in appropriately selected patients were not consistently integrated into the diagnostic pathway, likely reflecting the absence of a structured algorithm and of a fast-track referral pathway to a SU.

ACC/AHA/HRS guidelines acknowledge the potential benefits of SUs, whereas ESC guidelines explicitly recognize their central role as specialized organizational structures [1, 7] with demonstrated capacity to increase diagnostic effectiveness [9, 49, 57, 60], reduce unnecessary hospitalizations [8, 27, 49, 57] and optimize resource utilization [11, 15, 27, 61].

Strength and limitations

This study has several important strengths. To our knowledge, it is the first Portuguese study to characterize syncope-related diagnostic and treatment patterns and their associated hospital costs using real-world data. It draws on detailed clinical registries, enabling a granular characterization of diagnostic procedures, patient trajectories, and patterns of service use across distinct care pathways. Furthermore, by comparing observed costs with those expected under a guideline-concordant scenario, the study provides a quantitative estimate of potentially avoidable ED diagnostic expenditure and underscores the importance of reassessing current care practices.

These strengths should, however, be interpreted in light of several limitations. First, the study was conducted within a single private-sector institution comprising two hospital units, which may constrain the generalizability of the findings. External validity may therefore be influenced by organizational specificities, the demographic and clinical profile of the population served, local patterns of resource utilization, and differences in clinical practice and adherence to guideline-based care.

A further limitation relates to the absence of follow-up for patients evaluated exclusively in the ED, either within or outside the institution. It remains unknown whether these patients subsequently underwent diagnostic testing elsewhere, received additional clinical follow-up, or experienced adverse outcomes after discharge. Although this does not compromise in-hospital cost estimation, it limits a more integrated understanding of the full clinical pathway and may result in underestimation of costs incurred beyond the index hospital episode.

An additional limitation concerns the capture of syncope-related readmissions within the study year. Patients presenting earlier in the year had a greater opportunity for one or more subsequent readmissions to be captured than those presenting later. This may have resulted in incomplete capture of readmissions and associated cost accumulation among patients with late-year index presentations. Nevertheless, the likely effect on the overall findings was limited, given the small number of readmissions observed in the cohort (n = 6).

Representativeness of the study cohort should also be considered. The study population was derived from ED encounters in which syncope was recorded as the primary diagnosis. Accordingly, encounters in which syncope was recorded only as secondary diagnosis were not included in the study population. This restriction was adopted to preserve a clinically coherent population centered on presentations in which syncope itself constituted the primary reason for ED evaluation and the main driver of diagnostic work-up and cost attribution. Nevertheless, it may limit the generalizability of the findings to the broader spectrum of ED encounters in which syncope is documented secondarily, particularly when occurring in the context of another acute primary condition.

Finally, the estimate of potential savings associated with adherence to international guidelines in the ED should be interpreted with caution. The simulated estimates were not prospectively validated against clinical outcomes, and no sensitivity analysis was undertaken specifically for the counterfactual savings analysis. More broadly, the study does not constitute a formal economic evaluation or cost-effectiveness analysis. Accordingly, higher costs or limited diagnostic yield should not, in and of themselves, be taken as definitive evidence of low-value care, as some higher-cost strategies may still be justified if associated with improved outcomes in selected patients.

Conclusions

Syncope was associated with substantial hospital costs, marked practice variation, and intensive use of diagnostic procedures, imposing a considerable burden on hospital care. Its management remained both clinically complex and organizationally fragmented, reinforcing the need for more structured, risk-stratified, and guideline-aligned models of care. Against this background, the systematic implementation of SUs and standardized clinical protocols, aligned with recommendations from international scientific societies, may provide an important opportunity to enhance diagnostic consistency, strengthen care coordination, and promote more efficient use of healthcare resources.

Supplementary Information

Below is the link to the electronic supplementary material.

Abbreviations

ACC/AHA/HRS

American College of Cardiology, American Heart Association, Heart Rhythm Society

COGS

Cost of goods sold

CI

Confidence interval

CT

Computed tomography

ECG

Electrocardiogram

ED

Emergency department

EEG

Electroencephalogram

ESC

European Society of Cardiology

GLM

Generalized linear model

ICD-9-CM

International Classification of Diseases, 9th Revision, Clinical Modification

IQR

Interquartile range

MRI

Magnetic resonance imaging

SD

Standard deviation

SNS

Serviço Nacional de Saúde

SUs

Syncope Units

TLOC

Transient loss of consciousness

Author contributions

Conceptualization, C.A., J.P., M.O. and S.L.; Methodology, C.A., J.P., M.O. and S.L.; Validation, J.P., M.O. and S.L.; Formal analysis, C.A.; Investigation, C.A.; Data curation, C.A.; Writing—original draft preparation, C.A. and J.P.; Writing—review and editing, J.P., C.A., M.O. and S.L.; Visualization, C.A.; Supervision, J.P. and M.O. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding. The article processing charge (APC) for this publication was supported by Medtronic. Medtronic had no role in the conception, design, conduct, data collection, data analysis, data interpretation, drafting, review, or approval of the manuscript, nor in the decision to submit the article for publication. The authors retain full academic independence and assume sole responsibility for the integrity, accuracy, and content of the work.

Data availability

The patient-level dataset analyzed in this study contains confidential information and is subject to institutional data-use restrictions. In accordance with the EU General Data Protection Regulation (GDPR) and the terms of the data-use agreement with CUF (Portugal), the data are not publicly available and cannot be shared, including upon reasonable request. Aggregated results supporting the findings are provided in the article and its supplementary material.

Declarations

Ethics approval and consent to participate

The study was conducted in accordance with the Declaration of Helsinki, and approved by the Ethics Committee of CUF (CES n. º 10/2024/47600232, Approval Date 07 January 2025). The requirement for informed consent was waived by the Committee because the research involved analysis of deidentified clinical and administrative records, posed no more than minimal risk, and obtaining individual consent was not practicable.

Consent for publication

Not applicable.

Competing interests

C.A., M.O. and S.L. are professionally affiliated with CUF – José de Mello Saúde. The institution provided access to deidentified clinical and administrative records and had no role in study design, data collection, analysis or interpretation, manuscript preparation, or the decision to submit for publication. J.P. declares no competing interests. The authors declare no other competing interests.