Syncope — Clinical Practice Review

Authors, Journal, Affiliations, Type, DOI

• Author: Rose Anne Kenny, M.D., D.Sc.
• Affiliations: School of Medicine, Trinity College Dublin; St. James Hospital Dublin
• Journal: New England Journal of Medicine (NEJM) 2026;395:582-591
• Type: Clinical Practice review article (NEJM series)
• DOI: 10.1056/NEJMcp2517255

Overview

Kenny's 2026 NEJM Clinical Practice review provides a contemporary, clinically oriented framework for syncope evaluation and management. The review emphasizes several important updates: syncope frequently presents as unexplained falls in older adults — a critical diagnostic pitfall; carotid sinus syndrome accounts for up to 30% of otherwise-unexplained falls in older patients; structured ED observation protocols are effective and reduce unnecessary admissions; implantable loop recorders (ILRs) enable symptom–rhythm correlation over up to 4 years; management is mechanism-specific — targeting hypotension, bradycardia, or tachycardia; and cardioneural ablation is emerging as a promising therapy for vagally-mediated syncope. The review aligns more closely with ESC 2018 guidelines (syncope units, early ILR use, emphasis on patient education) than ACC/AHA/HRS 2017.

Keywords

Syncope, transient loss of consciousness, cerebral hypoperfusion, reflex syncope, vasovagal syncope, orthostatic hypotension, cardiac syncope, unexplained falls, carotid sinus syndrome, cardioneural ablation, implantable loop recorder

Key Takeaways

Definition and Classification

• Syncope: Transient loss of consciousness + inability to maintain postural tone → temporary cerebral hypoperfusion → rapid spontaneous recovery. Episodes typically <1 minute.
• Three-category classification: (1) Reflex syncope — vasovagal, situational, carotid sinus syndrome; (2) Syncope due to orthostatic hypotension; (3) Cardiac syncope — bradyarrhythmias, tachyarrhythmias, structural heart disease, pulmonary hypertension, acute vascular disorders (PE, aortic dissection).

Epidemiology

• Affects one-third to one-half of the general population during their lifetime.
• Women report syncope more frequently than men (22% vs 15% prevalence).
• Cumulative incidence increases markedly with age: ~5% among women 20–29 years → nearly 50% among women ≥80 years.
• Lifetime cumulative incidence in women is nearly twice that in men.
• Recurrent syncope occurs in up to 20% of affected persons; associated with greater risks of death (HR 1.87) and MACE (HR 2.69) over 24 months vs nonrecurrent syncope.
• Falls account for ~15% of ED visits among older adults; 20–30% of such falls may be unexplained, potentially reflecting underlying syncope.
• Incidence of unexplained falls increases with age: ~4%/year at 50–60yr → ~8%/year at ≥70yr.

Etiology by Age

• Younger adults: Reflex syncope accounts for >90% of cases (generally benign prognosis but injury in >30% of episodes; major injury in ~15%).
• Older adults: Reflex ~40%, cardiac ~30%, orthostatic hypotension prevalent (>20% aged >70yr; up to 50–68% in institutional settings).
• Complex syncope: Multiple coexisting mechanisms in up to one-third of older adults.
• Unexplained syncope has declined from ~37% (early studies) to <10% in recent cohorts using structured diagnostic pathways and prolonged rhythm monitoring.

Reflex Syncope Subtypes

• Vasovagal syncope (VVS): Most common type; vasodepressor hypotension (SBP ≤80 mmHg) + HR <40 bpm or asystole ≥3s.
• Carotid sinus syndrome: Reflex syncope associated with carotid sinus hypersensitivity (pause ≥3s or SBP decrease ≥50 mmHg during carotid sinus massage). Accounts for 9–17% of syncope, up to 30% of otherwise-unexplained falls in older adults. Carotid sinus massage should be performed supine AND upright in patients >40yr with suspected reflex syncope, syncope on head turning, or unexplained falls.
• Situational syncope: Micturition, defecation, cough, swallow, emotional stress.

Orthostatic Hypotension

• Definition: SBP reduction ≥20 mmHg or DBP reduction ≥10 mmHg on standing.
• Initial OH: Transient decrease within 15 seconds after standing (generally benign; detected by beat-to-beat BP recording).
• Classic OH: Sustained decrease within 3 minutes after standing (≥30 mmHg SBP if supine hypertension present).
• Delayed OH: BP decrease after prolonged upright posture.
• Neurogenic OH: Due to autonomic nervous system dysfunction from central/peripheral neurologic disease.
• Postprandial hypotension: SBP decrease ≥20 mmHg within 2 hours after a meal; often co-occurs with OH.

Cardiac Syncope

• Rare in younger adults (~5%); increases with age, reaching 30% of syncopal events in older patients.
• Higher morbidity and mortality than reflex syncope.
• Causes: bradyarrhythmias, tachyarrhythmias, structural heart disease with outflow obstruction, pulmonary hypertension, PE, aortic dissection.
• High-risk features: age >60, known cardiac disease, male sex, brief/no prodrome, palpitations/chest pain before syncope, exertional syncope, syncope while seated/supine, abnormal ECG, family history of inheritable conditions or premature SCD (<50 years), known congenital heart disease.

Syncope Mimics

• Most common mimic: epilepsy.
• Urinary incontinence does NOT distinguish syncope from epilepsy (occurs in 10–20% of syncopal events, particularly in older adults).
• Tongue biting, jerking movements, and post-event drowsiness also occur in syncope.
• Other TLOC mimics: hypoglycemia, metabolic, drug/alcohol intoxication, concussion, TIA (rarely causes LOC).

Evaluation (Fig. 2 diagnostic algorithm)

1. History + physical examination + ECG + orthostatic BP measurements (supine and standing) — identifies the cause in most patients.
2. Risk stratification determines urgency and setting of further investigation.
3. Carotid sinus massage (supine + upright) in patients >40yr with suspected reflex syncope or unexplained falls.
4. Echocardiogram if known heart disease or evidence suggestive of structural heart disease.
5. Ambulatory cardiac monitoring: Duration guided by symptom frequency; up to 4 weeks for monthly events. ILR (battery life up to 4 years) for infrequent events.
6. Head-up tilt-table testing: When reflex syncope suspected but not confirmed after initial assessment.
7. Ambulatory BP monitoring: Identifies daytime hypotensive episodes; daytime SBP <90 mmHg has 91% specificity/32% sensitivity for reflex syncope diagnosis (SynABPM 1 study).
8. Blood tests: When clinically indicated (troponin for suspected ischemia, d-dimer/CT for suspected PE, hematocrit/hemoglobin for suspected hemorrhage).

Risk Stratification

• Short-term prognosis (ED → 30 days): Related to cause of syncope and reversibility of underlying condition.
• Long-term prognosis (up to 12 months): Related to effectiveness of therapy, severity/progression of underlying disease, and injury risk.
• Risk scores (San Francisco Syncope Rule, OESIL, STePS, ROSE, Boston Syncope Rule): validated but have NOT outperformed unstructured clinical judgment.
• Features increasing injury probability: Unexplained falls, recurrent falls, brief/absent prodrome, osteoporosis, cognitive impairment, polypharmacy. Culprit medications: diuretics, antianginals, psychotropics, anticholinergics, opioids, anticoagulants, antiplatelets; recent introduction of antihypertensives/antiarrhythmics.

Syncope in the Older Patient — KEY MESSAGE

• Approach similar to other age groups but complex syncope (>1 mechanism) occurs in >25%.
• Syncope frequently presents as unexplained falls — must consider syncope in any older patient with unexplained/recurrent falls.
• Orthostatic BP measurements, carotid sinus massage, and tilt-table testing can be performed even in frail patients with cognitive impairment.
• Multifactorial evaluation and intervention recommended.

Management and Treatment (Mechanism-Specific)

Disposition

• Outpatient: Presumptive reflex-mediated syncope without serious conditions or injury risk (reasonable in most cases).
• Structured ED observation protocol (6–12 hours cardiac monitoring): Intermediate-risk patients with unclear cause; reduces hospitalization without harm (RCT: n=124, similar serious outcomes at 30 days/6 months, lower costs).
• Hospital admission: Only in high-risk patients.
• Dedicated syncope management unit: Enables definitive diagnosis, additional testing (carotid sinus massage, tilt, ambulatory monitoring), personalized treatment plan, and follow-up.

Hypotension Management

• Conservative: increased fluid/electrolyte intake, trigger avoidance, deprescribing culprit medications.
• Antihypertensives with lowest hypotensive risk: ACE inhibitors (OR 0.85) and calcium-channel blockers (OR 0.81) per systematic review of 78 studies in older adults.
• Pharmacotherapy: droxidopa, midodrine (most consistent evidence for OH); atomoxetine, fludrocortisone (moderate efficacy); pyridostigmine + octreotide (refractory OH, limited evidence).
• Fludrocortisone for VVS: POST 2 RCT — HR 0.69 (95% CI 0.46–1.03; P=0.07) — marginally nonsignificant.

Bradycardia Management

• Cardiac pacing is the most effective therapy for symptomatic bradycardia, particularly in older patients.
• Meta-analysis of pacing RCTs in recurrent reflex syncope with documented bradycardia: >50% reduction in syncope recurrence.
• Continued presyncope/syncope despite pacing = clinically significant hypotension independent of bradycardia.
• Cardioneural ablation: Newer intervention — ablation of epicardial ganglionated plexuses reduces vagal activity; promising for bradycardic reflex syncope. Multiple RCTs ongoing (NCT03903744, NCT05573178, NCT05803148, NCT05461859, NCT04642976).

Tachycardia Management

• Depends on specific arrhythmia subtype, symptom severity, hemodynamic stability, and underlying cause.
• Management: reversible cause correction, antiarrhythmic medications, catheter ablation, ICD, emergency defibrillation.

Guidelines

• Two principal contemporary guidelines: ESC 2018 (Brignole et al.) and ACC/AHA/HRS 2017 (Shen et al.).
• Key differences:
  • ESC strongly recommends specialized syncope units; ACC/AHA/HRS do not.
  • ESC recommends earlier ILR use for unexplained syncope and unexplained falls.
  • ESC places stronger emphasis on patient education and behavioral lifestyle changes for reflex syncope.
• This review aligns more closely with ESC guidelines.

Areas of Uncertainty

• Optimal management of unexplained falls and complex syncope in older adults.
• Appropriate service models for syncope assessment and care.
• Effective approaches to BP reduction in frail older adults with hypertension.
• Fludrocortisone for OH — widely used despite non-definitive evidence.

Limitations

• Single-author narrative review — selection and interpretation reflect author's expertise and perspective.
• Not a systematic review or meta-analysis — evidence weighting is qualitative.
• Aligned with ESC 2018 over ACC/AHA/HRS 2017, which may reflect European vs North American practice divergence rather than evidence-based superiority.
• Cardioneural ablation evidence remains preliminary (RCTs ongoing); presented as promising but unproven.

Key Concepts Mentioned

• concepts/Syncope — comprehensive syncope framework updated with 2026 NEJM review
• concepts/Vasovagal-Syncope — fludrocortisone POST 2 data, cardioneural ablation
• concepts/Orthostatic-Hypotension — classification (initial/classic/delayed/postprandial), treatment evidence
• concepts/Carotid-Sinus-Syndrome — up to 30% of unexplained falls; pacing benefit

Key Entities Mentioned

• entities/ICD — cardiac syncope with ventricular arrhythmias
• entities/Implantable-Loop-Recorder — 55% diagnostic yield; battery life up to 4 years

Wiki Pages Updated

• wiki/sources/Syncope-Kenny-NEJM-2026.md — created (this page)
• wiki/concepts/Syncope.md — updated with Kenny 2026 data (epidemiology, falls overlap, cardioneural ablation, ED protocols)
• wiki/concepts/Vasovagal-Syncope.md — fludrocortisone POST 2 updated, cardioneural ablation added
• wiki/sourceindex.md — source entry added
• log.md — ingest entry appended