Internal Medicine/Syncope

Introduction to Syncope

Syncope is a transient loss of consciousness characterized by a rapid onset, short duration, and spontaneous complete recovery. It occurs due to a temporary reduction in blood flow to the brain, leading to a sudden loss of consciousness and postural tone. Syncope is a common clinical problem, affecting approximately 3–5% of the general population, and it accounts for 1–3% of all emergency department visits. This brief loss of consciousness can be caused by a variety of underlying conditions and triggers.

Neurally Mediated Syncope

Causes of Neurally Mediated Syncope: Neurally mediated syncope, often referred to as vasovagal syncope, can be provoked by a wide range of triggers. These triggers include provoking factors like fear, pain, anxiety, intense emotion, the sight of blood, and exposure to unpleasant sights and odors. Additionally, orthostatic stress, such as rapidly changing from a seated or supine position to an upright one, can also induce neurally mediated syncope. Furthermore, neurally mediated syncope can be categorized into several subtypes, including situational reflex syncope, pulmonary, urogenital, gastrointestinal, cardiac, and ocular syncope, each associated with specific events or conditions.

Treatment of Neurally Mediated Syncope: Managing neurally mediated syncope involves a multifaceted approach. Patients are often reassured about the benign nature of the condition and educated on potential triggers to avoid. Avoidance of provocative stimuli, such as prolonged standing or situations that induce anxiety, is recommended. Plasma volume expansion with increased fluid and salt intake can help stabilize blood pressure. Isometric counterpressure maneuvers involving the tensing of abdominal and leg muscles, handgrip exercises, and leg crossing may raise blood pressure by enhancing central blood volume and cardiac output. Among these maneuvers, abdominal muscle tensing is the most effective.

While there's limited evidence from randomized controlled trials, some experts may prescribe medications like fludrocortisone, vasoconstricting agents, and β-adrenoreceptor antagonists for patients who experience refractory symptoms. However, it's important to note that these pharmacological treatments should be used judiciously due to the lack of consistent evidence supporting their use. Cardiac pacemakers are rarely beneficial, except in specific cases involving older patients or those with documented asystole.

Orthostatic Hypotension

Causes of Orthostatic Hypotension: Orthostatic hypotension is defined as a significant drop in systolic blood pressure (at least 20 mmHg) or diastolic blood pressure (at least 10 mmHg) within 3 minutes of standing or head-up tilt on a tilt table. This condition often accompanies autonomic failure, which results in sympathetic vasoconstrictor dysfunction. Various underlying causes of orthostatic hypotension include primary autonomic failure due to neurodegenerative diseases like multiple system atrophy, Parkinson's disease, Lewy body dementia, pure autonomic failure, and secondary autonomic failure caused by conditions like diabetes, hereditary amyloidosis, and autoimmune disorders.

Orthostatic hypotension can also have iatrogenic causes, such as medications that lower peripheral resistance, diuresis, and volume depletion due to medical conditions like hemorrhage, vomiting, diarrhea, or reduced fluid intake. Additionally, there's a phenomenon known as "postprandial hypotension," where blood pressure falls significantly after meals, particularly large, carbohydrate-rich meals or alcohol consumption. The mechanism behind postprandial hypotension is not fully understood but is thought to involve autonomic dysregulation.

Treatment of Orthostatic Hypotension: Addressing orthostatic hypotension involves a stepwise approach. Initially, reversible causes, particularly vasoactive medications, should be identified and discontinued or adjusted. Patient education is crucial, emphasizing gradual changes from supine to upright positions and awareness of the hypotensive effects of large meals. Isometric counterpressure maneuvers and raising the head of the bed can also help alleviate symptoms. Increasing dietary fluid and salt intake can expand intravascular volume and improve orthostatic tolerance.

In cases where nonpharmacologic measures are ineffective, pharmacological interventions may be necessary. Medications such as fludrocortisone acetate and vasoconstricting agents like midodrine and l-dihydroxyphenylserine can be considered. Some patients with intractable symptoms may require additional therapies, including pyridostigmine, atomoxetine, yohimbine, octreotide, desmopressin acetate (DDAVP), and erythropoietin. The choice of treatment depends on the underlying cause and individual patient factors.

Cardiac Syncope

Causes of Cardiac Syncope: Cardiac syncope results from either arrhythmias or structural heart disease, and often, these two factors coexist. Bradyarrhythmias, which involve abnormally slow heart rhythms, can cause syncope. Examples include severe sinus node dysfunction (e.g., sinus arrest or sinoatrial block) and atrioventricular (AV) block (e.g., Mobitz type II, high-grade, and complete AV block). The tachyarrhythmias that cause syncope, particularly ventricular tachyarrhythmias, are also significant contributors. The likelihood of syncope in ventricular tachycardia is partly dependent on the ventricular rate, with rates less than 200 beats per minute being less likely to induce syncope. Ventricular tachycardia compromises hemodynamic function by causing ineffective ventricular contractions, reduced diastolic filling, loss of AV synchrony, and potential myocardial ischemia.

Several inherited disorders with cardiac electrophysiologic instability, often resulting from mutations in ion channel subunit genes, can lead to cardiac syncope. These disorders include the long QT syndrome, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia. Structural heart diseases, such as valvular disease, myocardial ischemia, hypertrophic cardiomyopathy, and cardiac masses like atrial myxoma, can also compromise cardiac output and lead to syncope. Importantly, structural heart disease can increase the risk of arrhythmias, contributing to syncope.

Treatment of Cardiac Syncope: The treatment of cardiac syncope depends on the underlying cardiac disorder. Patients with bradyarrhythmias often require cardiac pacing to correct abnormalities like sinus node dysfunction and AV block. For tachyarrhythmias, treatment options include ablation procedures, antiarrhythmic drugs, and implantable cardioverter-defibrillators (ICDs) to prevent life-threatening arrhythmias. It's essential to recognize that the management of these conditions is highly specialized and should be overseen by physicians with expertise in cardiac electrophysiology.

Structural heart diseases require tailored management approaches, which may involve medications to alleviate symptoms, valve repair or replacement, revascularization for myocardial ischemia, and surgical interventions to address structural abnormalities. Due to the complexity of these cases, consultation with a cardiologist or cardiac surgeon is often necessary to determine the most appropriate treatment plan for individual patients.

Initial Evaluation and Diagnosis

The initial evaluation of a patient who has experienced syncope is a crucial step in determining the cause, assessing the risk of future episodes, and ensuring patient safety. This comprehensive assessment includes the following components:

• Detailed History: A thorough history-taking is essential and should include a detailed account of the events leading up to the syncopal episode, including any prodromal symptoms, triggers, and patient-reported symptoms.
• Questioning of Eyewitnesses: Eyewitness accounts can provide valuable information regarding the circumstances of the episode, such as the patient's appearance, movements, and any unusual behaviors or sounds.
• Physical and Neurologic Examination: A complete physical examination, including a neurologic assessment, can reveal signs of underlying medical conditions or neurological abnormalities.
• Blood Pressure and Heart Rate Measurements: Blood pressure and heart rate should be measured in both the supine position and after 3 minutes of standing to assess for orthostatic hypotension.

High-risk features should be carefully evaluated during the initial assessment. These features include:

• The new onset of chest discomfort, abdominal pain, shortness of breath, or headache.
• Syncope occurring during exertion or while in a supine position.
• Sudden onset of palpitations followed by syncope.
• Known severe coronary artery disease or structural heart disease.

High-risk features on examination include:

• Unexplained systolic blood pressure of less than 90 mmHg.
• Suggestive signs of gastrointestinal hemorrhage.
• Persistent bradycardia (heart rate less than 40 beats per minute).
• An undiagnosed systolic murmur.

To further aid in diagnosis:

• An electrocardiogram (ECG) should be performed if an arrhythmia or underlying cardiac disease is suspected. Relevant ECG abnormalities include bradyarrhythmias, tachyarrhythmias, atrioventricular block, acute myocardial ischemia, old myocardial infarction, prolonged QT interval, and bundle branch block.
• Laboratory tests may be ordered selectively when specific disorders such as myocardial infarction, anemia, or secondary autonomic failure are suspected.
• Autonomic Nervous System Testing: Specialized autonomic testing, including tilt-table testing, can be performed in dedicated centers. These tests assess various aspects of autonomic function, such as heart rate variability, thermoregulatory sweat response, and blood pressure response to different maneuvers. They are helpful in identifying autonomic failure and demonstrating a predisposition to neurally mediated syncope.
• Carotid Sinus Massage: In patients with symptoms suggestive of carotid sinus syncope or in those over 40 years of age with recurrent unexplained syncope, carotid sinus massage may be considered. However, this test should be conducted with continuous ECG and blood pressure monitoring and avoided in patients with carotid bruits, known plaques, or stenosis.
• Cardiac Evaluation: For patients with a high pretest probability of arrhythmia as the cause of syncope, ECG monitoring is indicated. Hospital-based monitoring is necessary when there is a high likelihood of a life-threatening arrhythmia, such as patients with severe coronary artery or structural heart disease, nonsustained ventricular tachycardia, supraventricular tachycardia, paroxysmal atrial fibrillation, trifascicular heart block, prolonged QT interval, Brugada syndrome ECG pattern, syncope during exertion, syncope while seated or supine, or a family history of sudden cardiac death.

Outpatient Holter monitoring is recommended for patients who experience frequent syncopal episodes (e.g., one or more per week). Additionally, loop recorders, which continually record and erase cardiac rhythm data, may be used for patients with suspected arrhythmias and a lower risk of sudden cardiac death. These loop recorders can be either external or implantable, depending on the frequency of syncope episodes.

• Echocardiography should be performed in patients with a history of cardiac disease or if abnormalities are found on physical examination or the ECG. Echocardiographic diagnoses that may be responsible for syncope include aortic stenosis, hypertrophic cardiomyopathy, cardiac tumors, aortic dissection, and pericardial tamponade. Furthermore, echocardiography plays a role in risk stratification based on the left ventricular ejection fraction.
• Treadmill Exercise Testing: Patients who have experienced syncope during or shortly after exercise should undergo treadmill exercise testing with ECG and blood pressure monitoring. This testing can help identify exercise-induced arrhythmias, such as tachycardia-related atrioventricular block, and exaggerated vasodilation during exercise.
• Electrophysiologic Studies: In patients with structural heart disease and ECG abnormalities when noninvasive investigations have failed to yield a diagnosis, electrophysiologic studies may be considered. However, these studies have limited sensitivity and specificity and should only be performed when a high pretest probability of an arrhythmia exists. Currently, electrophysiologic studies are rarely used for the evaluation of syncope but may be considered in select cases.
• Psychiatric Evaluation: In patients with recurrent unexplained syncope episodes, screening for psychiatric disorders may be appropriate. Tilt-table testing, which can reproduce syncope in the absence of hemodynamic changes, may be useful in confirming psychogenic syncope when psychiatric causes are suspected.

Treatment and Management of Syncope

The treatment and management of syncope depend largely on the underlying cause identified through the initial evaluation. Below are some key approaches to managing syncope based on its etiology:

• Neurally Mediated Syncope:
  • Education and Trigger Avoidance: Patients with neurally mediated syncope should be educated about the condition's benign nature and potential triggers. Avoidance of known triggers, such as prolonged standing or anxiety-inducing situations, is advised.
  • Volume Expansion: Increasing fluid and salt intake can help stabilize blood pressure, improving orthostatic tolerance.
  • Isometric Counterpressure Maneuvers: Techniques like tensing abdominal and leg muscles, handgrip exercises, and leg crossing may elevate blood pressure by enhancing central blood volume and cardiac output.
  • Medications: In some cases of refractory symptoms, medications like fludrocortisone, vasoconstricting agents, or β-adrenoreceptor antagonists may be considered. However, these should be used judiciously due to limited supportive evidence.
  • Cardiac Pacemakers: Rarely, cardiac pacing may be recommended, especially in older patients or those with documented asystole.
• Orthostatic Hypotension:
  • Identifying and Addressing Reversible Causes: The first step is to identify and address any reversible causes, particularly medications or conditions contributing to orthostatic hypotension.
  • Patient Education: Patients should be educated about the importance of gradual position changes and awareness of postprandial hypotension. They should also be advised to maintain an adequate fluid and salt intake.
  • Isometric Counterpressure Maneuvers: Similar to neurally mediated syncope, these maneuvers can be employed to improve blood pressure stability.
  • Pharmacological Interventions: In cases where non-pharmacologic measures are ineffective, pharmacological interventions may be considered. Medications such as fludrocortisone acetate, midodrine, l-dihydroxyphenylserine, pyridostigmine, atomoxetine, yohimbine, octreotide, desmopressin acetate (DDAVP), and erythropoietin might be used depending on the underlying cause.
• Cardiac Syncope:
  • Treatment of Arrhythmias: Addressing the underlying arrhythmias is critical. This may involve interventions such as cardiac pacing for bradyarrhythmias and ablation, antiarrhythmic drugs, or implantable cardioverter-defibrillators (ICDs) for tachyarrhythmias.
  • Structural Heart Disease Management: Structural heart diseases require a tailored approach, including medical therapy to alleviate symptoms, valve repair or replacement, revascularization for myocardial ischemia, and surgical interventions to address structural abnormalities. Consultation with a cardiologist or cardiac surgeon is often necessary.

Prognosis and Follow-Up

The prognosis of syncope depends largely on its underlying cause and the effectiveness of treatment. Patients with neurally mediated syncope generally have a favorable prognosis as the condition is benign and rarely life-threatening. Effective trigger avoidance and symptom management can significantly improve their quality of life.

Orthostatic hypotension outcomes vary depending on the underlying etiology. In cases where reversible causes are identified and managed, patients can experience significant improvement in symptoms and functional status. However, those with progressive neurodegenerative diseases may have a less favorable long-term prognosis.

The prognosis of cardiac syncope is highly dependent on the specific arrhythmia or structural heart disease responsible for the syncope. Prompt diagnosis and appropriate treatment are essential in preventing recurrent syncope and associated complications. Some arrhythmias, if left untreated, can lead to sudden cardiac death, highlighting the importance of accurate diagnosis and timely intervention.

Follow-up care for patients who have experienced syncope is essential. Regular monitoring, especially for those with cardiac or neurologic disorders, helps assess treatment effectiveness and prevent recurrence. Medication adjustments, further diagnostic tests, or changes in treatment strategies may be necessary during follow-up visits.

Conclusion

Syncope is a complex clinical syndrome with various potential causes, including neurally mediated syncope, orthostatic hypotension, and cardiac syncope. The initial evaluation is critical for determining the underlying etiology and guiding treatment decisions. Management strategies range from trigger avoidance and lifestyle modifications to pharmacological interventions and surgical procedures, depending on the specific cause of syncope.

Patient education plays a crucial role in syncope management, as understanding the condition and its triggers empowers individuals to take measures to prevent future episodes. While most cases of syncope have a benign prognosis, some can be associated with life-threatening arrhythmias or structural heart diseases. Therefore, prompt diagnosis and appropriate treatment are essential in ensuring the best outcomes for patients who experience syncope.

Continued research and advances in diagnostic techniques and therapies are improving our understanding of syncope and enhancing our ability to provide effective care to affected individuals. Clinicians and researchers continue to work together to refine our approach to the evaluation and management of syncope, ultimately improving the quality of life and outcomes for those who experience this challenging clinical condition.