2018 ESC Guidelines for the diagnosis and management of syncope

This is a clinical practice guideline, not an original experiment. The authors systematically reviewed the existing literature on syncope to produce evidence-based recommendations. The "interventions" tested across the underlying studies include:

**Diagnostic strategies:** History-taking, physical examination, electrocardiogram (ECG), carotid sinus massage, tilt-table testing, ambulatory ECG monitoring (Holter, event recorder, implantable loop recorder), and electrophysiological studies.

**Treatment approaches:**

- Physical counter-pressure manoeuvres (PCMs): leg crossing, arm tensing, squatting, hand-gripping.

- Lifestyle modifications: increased salt and fluid intake, avoidance of triggers (prolonged standing, hot environments, dehydration).

- Tilt-training (progressive exposure to upright posture).

- Medications: midodrine (a vasoconstrictor), fludrocortisone (a mineralocorticoid that expands blood volume), beta-blockers (controversial), and selective serotonin reuptake inhibitors (SSRIs).

- Cardiac pacing (for cardioinhibitory reflex syncope or bradyarrhythmias).

- Catheter ablation (for arrhythmias like atrial fibrillation or ventricular tachycardia).

**Comparators:** Placebo, no treatment, usual care, or alternative treatments (e.g., PCMs vs. no PCMs; pacing vs. no pacing).

**Outcome measures:** Recurrence of syncope, time to first recurrence, injury from syncope, quality of life, and adverse events from treatment.

The guideline is based on a synthesis of hundreds of studies involving tens of thousands of patients across multiple populations:

**General population:** Syncope has a lifetime prevalence of ~40% in the general population, with a peak incidence in adolescents (reflex syncope) and older adults (cardiac syncope).

**Emergency department patients:** ~1–3% of all ED visits are for syncope; ~10–20% of these have a cardiac cause.

**Specific subgroups:**

- Reflex syncope (vasovagal, situational, carotid sinus syndrome): predominantly young, healthy individuals (ages 10–30) with normal hearts.

- Cardiac syncope: older adults (mean age ~65–75) with structural heart disease (e.g., aortic stenosis, hypertrophic cardiomyopathy, ischaemic heart disease) or arrhythmias (e.g., sick sinus syndrome, AV block, ventricular tachycardia).

- Orthostatic hypotension: older adults, diabetics, Parkinson's disease patients, and those on vasoactive medications.

**Setting:** Outpatient clinics, emergency departments, and hospital wards across Europe, North America, and Asia.

The guideline does not use a single measurement instrument but instead defines diagnostic criteria and risk stratification tools:

**Syncope definition:** Transient loss of consciousness due to cerebral hypoperfusion, characterised by rapid onset, short duration, and spontaneous complete recovery.

**Diagnostic tests:**

- **ECG:** 12-lead resting ECG (abnormalities include bradycardia, heart block, ventricular arrhythmias, ischaemia).

- **Carotid sinus massage:** Performed supine and upright; positive if asystole >3 seconds or systolic BP drop >50 mmHg with symptom reproduction.

- **Tilt-table testing:** Patient tilted to 60–70° for 20–45 minutes; positive if syncope occurs with hypotension/bradycardia.

- **Ambulatory monitoring:** Holter (24–48 hours), event recorder (2–4 weeks), implantable loop recorder (up to 3 years).

- **Blood pressure measurement:** Orthostatic BP measurement (systolic BP drop ≥20 mmHg or diastolic drop ≥10 mmHg within 3 minutes of standing).

**Risk stratification tools:**

- **OESIL score** (0–4 points): age >65, history of cardiovascular disease, syncope without prodrome, abnormal ECG. 1-year mortality: 0% (0 points) to 57% (4 points).

- **San Francisco Syncope Rule:** abnormal ECG, heart failure, shortness of breath, haematocrit <30%, systolic BP <90 mmHg. Sensitivity 96%, specificity 62% for serious outcomes.

- **Canadian Syncope Risk Score:** 0–11 points; predicts 30-day serious adverse events.

### Study design

This is a **clinical practice guideline** developed by the European Society of Cardiology (ESC) Task Force for the Diagnosis and Management of Syncope. It follows a structured evidence-review process:

**Systematic literature search:** PubMed, EMBASE, and Cochrane databases were searched for studies published up to 2017. Keywords included syncope, vasovagal, orthostatic hypotension, cardiac syncope, and related terms.

**Evidence grading:** Each recommendation is assigned a class (I = recommended, IIa = should be considered, IIb = may be considered, III = not recommended) and a level of evidence (A = multiple RCTs or meta-analyses, B = single RCT or large observational studies, C = expert opinion or small studies).

**Consensus process:** Recommendations were drafted by the task force, reviewed by external experts, and approved by the ESC Committee for Practice Guidelines.

### What this design can and cannot prove

**What it can prove:**

Provides a comprehensive, evidence-based framework for clinical decision-making.

Identifies which diagnostic tests and treatments have the strongest evidence base.

Highlights gaps in the literature where evidence is weak or absent.

**What it cannot prove:**

It is not a single experiment, so no causal claims can be made from the guideline itself.

Recommendations are only as strong as the underlying studies; many are based on observational data or small RCTs.

The guideline reflects consensus opinion, which may be influenced by expert bias or cultural practice patterns.

It does not provide individualised predictions; risk scores are population-level tools.

### Major methodological weaknesses

**Heterogeneity of underlying studies:** The guideline synthesises studies with vastly different designs, populations, and outcome definitions.

**Publication bias:** Studies with positive results are more likely to be published, potentially inflating treatment effects.

**Lack of blinding in many studies:** Tilt-table testing and physical manoeuvres are difficult to blind, introducing potential bias.

**Industry funding:** Some recommendations (e.g., for implantable loop recorders) may be influenced by device manufacturers.

**Outdated evidence:** The guideline was published in 2018; newer studies (e.g., on wearable devices, smartphone-based monitoring) are not included.

### Diagnostic yield (from underlying studies)

**History and physical exam alone:** Identify cause in ~50% of cases (sensitivity 85%, specificity 99% for reflex syncope).

**ECG:** Abnormal in ~5–10% of syncope patients; identifies cardiac cause in ~2–5%.

**Carotid sinus massage:** Positive in ~10–20% of patients >40 years old with unexplained syncope.

**Tilt-table testing:** Positive in ~60–80% of patients with suspected reflex syncope; specificity ~90% (i.e., 10% false-positive rate).

**Implantable loop recorder:** Diagnostic yield of ~30–50% over 12–24 months in patients with recurrent unexplained syncope.

**Orthostatic blood pressure measurement:** Positive in ~10–20% of older adults with syncope.

### Treatment efficacy (from underlying RCTs)

**Physical counter-pressure manoeuvres (PCMs):** In a landmark RCT (n=223, mean age 38, 70% female), PCMs reduced syncope recurrence by 39% over 14 months (hazard ratio 0.61, 95% CI 0.41–0.91, p=0.014). Number needed to treat (NNT) = 5.

**Tilt-training:** In a small RCT (n=50, mean age 30), tilt-training reduced syncope recurrence from 70% to 20% over 12 months (p<0.001). However, compliance was poor (~50% dropped out).

**Midodrine:** In a meta-analysis of 5 RCTs (n=189), midodrine reduced syncope recurrence by 50% (relative risk 0.50, 95% CI 0.32–0.78, p=0.002). Side effects: supine hypertension in ~10%, urinary retention in ~5%.

**Fludrocortisone:** In a single RCT (n=210, mean age 30), fludrocortisone reduced syncope recurrence by 30% (hazard ratio 0.69, 95% CI 0.46–1.03, p=0.07 — not statistically significant). Side effects: hypertension, hypokalaemia.

**Cardiac pacing:** In patients with cardioinhibitory reflex syncope (asystole >3 seconds), pacing reduced syncope recurrence from 57% to 19% over 2 years (hazard ratio 0.25, 95% CI 0.13–0.48, p<0.001). NNT = 3.

**Beta-blockers:** No benefit over placebo in multiple RCTs (relative risk 1.0, 95% CI 0.7–1.4, p=0.9). Not recommended.

### Risk stratification

**OESIL score:** 1-year mortality 0% (0 points), 13% (1 point), 33% (2 points), 57% (3–4 points).

**San Francisco Syncope Rule:** Sensitivity 96% (95% CI 89–99%), specificity 62% (95% CI 58–66%) for predicting serious outcomes within 30 days.

**Canadian Syncope Risk Score:** 30-day serious adverse events: 0.4% (low risk, ≤0 points), 3.5% (medium risk, 1–3 points), 12.5% (high risk, ≥4 points).

**Physical counter-pressure manoeuvres:** Reduce syncope recurrence by about 40% — meaning if you faint 5 times per year, you might faint 3 times per year instead. This is roughly equivalent to the effect of midodrine but without side effects.

**Tilt-training:** Reduces recurrence by ~70% in those who comply, but compliance is a major issue (only ~50% complete the training). The effect is large but impractical for many.

**Midodrine:** Reduces recurrence by ~50%, but comes with a 10% risk of supine hypertension (dangerous if you lie down with high blood pressure).

**Cardiac pacing:** Reduces recurrence by ~75% in the specific subgroup with documented asystole — a very large effect, but only applicable to ~5–10% of syncope patients.

**Fludrocortisone:** A non-significant 30% reduction — not reliable enough to recommend as first-line therapy.

### What the authors acknowledge

Many recommendations are based on small, underpowered studies (level B or C evidence).

There is a lack of high-quality RCTs for many treatments (e.g., salt/fluid loading, compression stockings).

The guideline does not address paediatric syncope in detail.

Risk stratification tools have not been validated in all populations (e.g., primary care vs. ED).

### What a critical reader would note

**Publication bias:** Studies showing benefit of PCMs, midodrine, and pacing are more likely to be published than null results.

**Placebo effect:** Syncope recurrence rates in placebo groups range from 30–60%, suggesting a strong psychological component. Many treatments may work partly through expectation.

**Lack of blinding:** Tilt-training and PCMs cannot be blinded, so results may be inflated by patient expectation or investigator bias.

**Industry influence:** The guideline recommends implantable loop recorders (manufactured by Medtronic, Abbott, etc.) as a first-line diagnostic tool for unexplained syncope, despite limited cost-effectiveness data.

**Population limits:** Most studies excluded patients with structural heart disease, so results may not generalise to older adults with comorbidities.

**Duration:** Most RCTs followed patients for 12–24 months; long-term efficacy and safety beyond 2 years are unknown.

**Self-report bias:** Syncope recurrence is typically self-reported; patients may under- or over-report events.

For someone running their own n=1 experiment:

### What to test

**Primary intervention:** Physical counter-pressure manoeuvres (PCMs) — leg crossing, arm tensing, squatting, or hand-gripping at the first sign of prodrome (lightheadedness, visual changes, nausea).

**Dose:** Perform the manoeuvre immediately upon recognising prodrome and hold for 2–3 minutes until symptoms resolve. Practice 3–5 times per week to build muscle memory.

**Alternative interventions:**

- Increased salt intake: 3–5 grams of extra sodium per day (e.g., 1–2 teaspoons of salt, or salt tablets 500–1000 mg with meals).

- Increased fluid intake: 2–3 litres of water per day, with a bolus of 500 ml of cold water immediately upon prodrome.

- Tilt-training: Stand against a wall with feet 15–20 cm away for 10–30 minutes daily, gradually increasing duration.

### Minimum meaningful duration

**PCMs:** 4–6 weeks to learn the technique and assess feasibility; 3–6 months to see a reduction in syncope frequency.

**Salt/fluid loading:** 2–4 weeks to see if symptoms improve; longer (3–6 months) to assess recurrence rate.

**Tilt-training:** 4–8 weeks to see if tolerance improves; 3–6 months to see a reduction in syncope.

### What to measure

**Primary outcome:** Number of syncope episodes per month (count each event).

**Secondary outcomes:**

- Number of presyncope episodes (near-faints) per month.

- Prodrome duration (seconds from first symptom to loss of consciousness).

- Time to recovery (seconds from lying down to feeling normal).

- Injury from syncope (bruises, fractures, head trauma).

- Quality of life (e.g., using the Syncope Functional Status Questionnaire, or a simple 1–10 scale).

**Objective measures (if available):**

- Orthostatic blood pressure (sitting, then standing at 1, 3, and 5 minutes).

- Heart rate variability (using a wearable device like a Polar H10 or Apple Watch).

- Hydration status (urine colour, thirst level).

### Key confounds to control for

**Dehydration:** Track fluid intake (aim for 2–3 L/day). Avoid alcohol and caffeine, which are diuretics.

**Sleep deprivation:** Poor sleep increases vagal tone and syncope risk. Track sleep duration and quality.

**Heat exposure:** Hot environments cause vasodilation and reduce blood pressure. Avoid saunas, hot showers, and prolonged sun exposure.

**Prolonged standing:** Standing still pools blood in the legs. If you must stand, shift weight, contract leg muscles, or cross your legs.

**Medications:** Beta-blockers, diuretics, vasodilators, and antidepressants can worsen syncope. Do not stop prescribed medications without consulting a doctor.

**Menstrual cycle:** Syncope is more common in the luteal phase (days 14–28) due to progesterone-induced vasodilation. Track cycle phase.

**Psychological state:** Anxiety, panic attacks, and hyperventilation can mimic or trigger syncope. Consider a daily mood log (e.g., 1–10 anxiety scale).