What are the key diagnoses not to miss in a patient presenting with syncope?

Critical Life-Threatening Diagnoses Not to Miss in Syncope

The key diagnoses not to miss in syncope are cardiac causes—particularly arrhythmias, structural heart disease, and acute coronary syndromes—as these carry 18-33% one-year mortality compared to 3-4% for non-cardiac causes, making cardiac syncope an independent predictor of death even after adjusting for comorbidities. 1

High-Risk Cardiac Conditions Requiring Immediate Recognition

Arrhythmic Causes (ECG-Diagnosed)

• Severe bradyarrhythmias: Persistent sinus bradycardia <40 bpm, repetitive sinoatrial blocks or sinus pauses >3 seconds, Mobitz II second-degree or third-degree AV block 1
• Tachyarrhythmias: Rapid paroxysmal supraventricular tachycardia, ventricular tachycardia, or non-sustained polymorphic VT 1
• Conduction abnormalities: Alternating left and right bundle branch block, bifascicular block, or any intraventricular conduction delay with QRS ≥120 ms 1
• Pacemaker/ICD malfunction with cardiac pauses 1

Primary Electrical Disease

• Long QT syndrome: Prolonged QT interval predisposing to torsades de pointes 1, 2
• Brugada syndrome: Type I pattern with coved ST-elevation in V1-V3 1, 2
• Wolff-Parkinson-White syndrome: Pre-excited QRS complexes 1, 2
• Arrhythmogenic right ventricular dysplasia: Epsilon waves, negative T waves in right precordial leads, ventricular late potentials 1, 2

Structural Heart Disease

• Severe aortic stenosis or other significant valvular disease 1
• Hypertrophic cardiomyopathy: Especially dangerous in young patients with exertional syncope 1, 2
• Acute myocardial infarction/ischemia: ECG evidence of acute ischemia with or without infarction 1
• Atrial myxoma: Prolapsing tumor causing obstruction 1

Vascular Catastrophes

• Pulmonary embolism: Massive PE causing obstructive shock 1
• Acute aortic dissection: Tearing chest/back pain with syncope 1
• Ruptured abdominal aortic aneurysm 1

High-Risk Clinical Features Mandating Admission

Level B Recommendations (Strong Evidence)

Admit immediately if any of the following are present: 1

• History of congestive heart failure or ventricular arrhythmias
• Associated chest pain or symptoms compatible with acute coronary syndrome
• Physical examination findings of significant CHF or valvular heart disease
• ECG findings of ischemia, arrhythmia, prolonged QT, or bundle branch block

Level C Recommendations (Moderate Evidence)

Strongly consider admission for: 1

• Age >60 years (some risk scores use >45 years or >65 years) 1
• History of coronary artery disease or congenital heart disease
• Family history of unexpected sudden death
• Exertional syncope in younger patients without obvious benign etiology

Special Populations at Extreme Risk

Young Patients with Exertional Syncope

Syncope during exercise is a red flag for potentially fatal conditions: 1

• Hypertrophic cardiomyopathy (most common cause of sudden death in young athletes)
• Congenital heart disease
• Anomalous origin of left coronary artery
• Myocarditis
• Idiopathic prolonged QT interval
• Cystic medial necrosis

While syncope in children, adolescents, and young adults is generally benign, exercise-related syncope must be assumed cardiac until proven otherwise. 1

Patients with Known Cardiac Disease

Those with history of angina, myocardial infarction, ventricular arrhythmia, or CHF have significantly higher likelihood of cardiac-related syncope and carry 18-33% one-year mortality. 1 Any abnormality on baseline ECG is an independent predictor of cardiac syncope or increased mortality. 1

Risk Stratification Using Validated Predictors

Multivariate Predictors of Adverse Outcomes

The four strongest predictors of 72-hour to 1-year adverse events are: 1

• History of ventricular arrhythmias
• Abnormal ECG in the emergency department
• Age >45 years
• History of congestive heart failure

Patients with zero risk factors have 0% 72-hour cardiac mortality and 0.7% risk of arrhythmia, while those with 3-4 risk factors have 57.6-80.4% risk of 1-year mortality or significant arrhythmia. 1

Additional High-Risk Features from Multiple Risk Scores

• Abnormal ECG (defined as anything other than normal sinus rhythm, including Q waves, ST abnormalities, conduction delays) 1
• Systolic blood pressure <90 mmHg 1
• Dyspnea or signs of heart failure 1
• Elevated troponin or BNP (though usefulness is uncertain) 1
• Anemia requiring transfusion 1

Critical Pitfalls to Avoid

Don't Be Falsely Reassured By:

• Normal ECG: While a normal ECG suggests low risk for most cardiac causes, it does not exclude paroxysmal atrial tachyarrhythmias, intermittent AV block, or early channelopathies 1
• Young age alone: Exertional syncope in the young demands cardiac evaluation regardless of age 1
• Single episode: Even one syncopal event with high-risk features warrants full evaluation 1

Don't Over-Rely On:

• Routine laboratory testing: Comprehensive labs have no diagnostic utility in syncope evaluation 1
• Neuroimaging: Brain CT/MRI has extremely low yield unless focal neurologic deficits are present 1
• Prodromal symptoms: While typical vasovagal prodrome suggests benign etiology, cardiac syncope can occasionally present with warning symptoms 1

Immediate Life-Threatening Conditions Beyond Cardiac

Neurologic

• Subarachnoid hemorrhage: Sudden severe headache with syncope 1
• Stroke/TIA: Though rare cause of true syncope, must exclude with focal deficits 1

Hemorrhagic

• Significant anemia from GI bleeding: Positive fecal occult blood, low hemoglobin 1
• Ruptured ectopic pregnancy in women of childbearing age

Metabolic/Toxic

• Severe hypoglycemia (though technically not true syncope)
• QT-prolonging medications or drug toxicity 1

Hospital evaluation and treatment are recommended (Class I) for patients with any serious medical condition potentially relevant to syncope identified during initial evaluation. 1 Conversely, patients with presumptive reflex-mediated syncope and no serious medical conditions can reasonably be managed outpatient. 1