Sinus node dysfunction: Clinical manifestations and diagnosis

INTRODUCTION — 

Sinus node dysfunction (SND) is characterized by age-related fibrosis of the sinoatrial (SA) nodal tissue and surrounding atrial myocardium. SND causes symptoms such as fatigue, dyspnea on exertion, lightheadedness, presyncope, and syncope.

The clinical manifestations and diagnosis of SND will be reviewed here. The epidemiology, etiology, natural history, and treatment of SND are discussed in detail separately. (See "Sinus node dysfunction: Epidemiology, etiology, and natural history" and "Sinus node dysfunction: Treatment".)

DEFINITION — 

While various definitions of sinus node dysfunction (SND) exist [1], we define SND as abnormal sinus node function that causes symptoms (eg, fatigue, dyspnea on exertion, lightheadedness, presyncope, syncope) and does not have a reversible cause (eg, acute myocardial infarction, sinoatrial [SA] nodal-blocking medications [eg, beta blockers, calcium channel blockers, ivabradine, digoxin, class I antiarrhythmics, amiodarone, acetylcholinesterase inhibitors]).

Abnormal sinus node function refers to the presence of one or more of the following:

●Sinus bradycardia with rate <50 bpm while awake

●Sinus pause >3 seconds while awake

●Sinus arrest

●Sinoatrial (SA) nodal exit block

●Inadequate heart rate response to physiological demands during activity (ie, chronotropic incompetence)

Sinus bradycardia and sinus pauses can occur during sleep in normal, healthy individuals.

Older patients may have evidence of abnormal sinus node function on electrocardiogram (ECG) without experiencing concurrent symptoms. Historically, these patients have been said to have “sick sinus syndrome,” a diagnosis that does not require symptoms to be present. This term is still used by some experts, who find it helpful for identifying patients at risk for symptomatic bradycardia. However, for the purposes of this discussion, we consider symptoms to be necessary for a diagnosis of SND. This definition is in agreement with the 2018 American College of Cardiology/American Heart Association (ACC/AHA) Guideline on the Evaluation and Management of Patients with Bradycardia and Cardiac Conduction Delay, which states “Correlation between symptoms and bradycardia is considered to be the ‘gold standard’ of diagnosis” of SND [1].

When SND occurs in a patient who also has a paroxysmal atrial tachyarrhythmia (eg, atrial fibrillation, atrial flutter, atrial tachycardia), the patient is considered to have tachycardia-bradycardia (ie, “tachy-brady”) syndrome.

CLINICAL PRESENTATION — 

Most patients with sinus node dysfunction (SND) present with one or more of the following nonspecific symptoms: fatigue, dyspnea on exertion, lightheadedness, presyncope, or syncope. Many patients with SND have preexisting cardiac conditions (eg, coronary artery disease, heart failure); the onset of bradycardia may lead to an exacerbation of symptoms (eg, chest pain, dyspnea) related to the underlying conditions. Patients with coexisting atrial tachyarrhythmias (ie, tachycardia-bradycardia syndrome) may notice intermittent palpitations.

Patients with SND often develop mild symptoms that gradually progress in frequency and severity. However, on occasion, patients may present with the sudden onset of more severe symptoms (eg, syncope). Rarely, patients may have signs and symptoms of hemodynamic instability (hypotension, altered mental status) or even cardiac arrest.

On physical examination, many patients with SND will have bradycardia; however, a normal heart rate at the time of the examination does not rule out SND because many patients with SND do not have sustained bradycardia. Other physical examination findings may include hypotension, altered mental status, or signs of acute heart failure.

EVALUATION AND DIAGNOSIS

When to suspect the diagnosis — The diagnosis of sinus node dysfunction (SND) should be suspected in patients ≥65 years of age (or younger patients with surgically corrected congenital heart disease) who present with any of the following symptoms or findings:

●Syncope without an apparent trigger, or syncope in a patient with known paroxysmal atrial fibrillation (because SND can cause post-conversion pauses).

●Exertional symptoms (eg, dyspnea, fatigue, lightheadedness), especially if the patient’s resting heart rate is <60 bpm in the absence of sinoatrial nodal-blocking agents. If the patient wears a heart-rate monitor (eg, smartwatch), they may report minimal acceleration of the heart rate with activity.

●Evidence of abnormal sinus node function on electrocardiogram (ECG), such as sinus bradycardia with heart rate <50 bpm, sinus pauses >3 seconds, or sinoatrial (SA) nodal exit block.

Evaluation — For all patients suspected of having SND, our initial evaluation consists of a history and physical examination and an assessment of the 12-lead ECG.

History and physical examination — We perform a history and physical to assess the patient’s symptoms and determine if they have a potentially reversible cause of abnormal sinus node function. We ask about the following:

●Symptoms with activity that may be due to chronotropic incompetence (ie, inadequate heart rate response to physiological demands during activity), such as fatigue, dyspnea, and lightheadedness.

●Symptoms at rest that may be due to bradycardia, such as fatigue, lightheadedness, and unexplained presyncope/syncope.

●History of presyncope or syncope when turning the head or looking upward, which suggests carotid sinus syndrome, a condition that can cause both syncope and bradycardia. (See 'Differential diagnosis' below.)

●Symptoms that may suggest a potentially reversible cause of abnormal sinus node function, including the following (see "Sinus node dysfunction: Epidemiology, etiology, and natural history", section on 'Etiology'):

•Chest pain or dyspnea at rest, which may be due to acute myocardial infarction.

•Cold intolerance, weight gain, or constipation, which may suggest the presence of hypothyroidism. Patients who report these symptoms should be evaluated for hypothyroidism. (See "Diagnosis of and screening for hypothyroidism in nonpregnant adults".)

●Palpitations, which may be due to an atrial tachyarrhythmia.

●History of cardiac conditions such as coronary artery disease or heart failure (either of which may be exacerbated by bradycardia) or atrial fibrillation (in which case the patient may have tachycardia-bradycardia syndrome).

●History of rigorous athletic training, which may cause sinus bradycardia that is physiological. (See 'Differential diagnosis' below.)

●Medications that may slow the sinus node rate (eg, beta blockers, nondihydropyridine calcium channel blockers, digoxin, certain antiarrhythmics).

We look for the following findings on physical examination:

●Hypothermia and hypoxemia, which can cause transient bradycardia.

●Jaundice, because hyperbilirubinemia can cause sinus bradycardia.

●Signs of heart failure (eg, elevated jugular venous pressure, lung crackles, leg edema) that may indicate reduced cardiac output secondary to bradycardia.

12-lead electrocardiogram and prior records — We obtain a 12-lead ECG and review any available prior ECGs or ambulatory rhythm monitor results. We look for any of the following findings:

●Evidence of abnormal sinus node function, including any of the following (see "Sinoatrial nodal pause, arrest, and exit block"):

•Periods of sinus bradycardia with heart rate <50 bpm [2,3]

•Sinus pauses >3 seconds or sinus arrest

•SA exit block (waveform 1)

●Evidence of ST-elevation myocardial infarction or myocardial ischemia, either of which can transiently impact the sinus node. (See "Diagnosis of acute myocardial infarction".)

●Alternating sinus bradycardia and atrial tachyarrhythmias (eg, atrial fibrillation, atrial flutter, paroxysmal supraventricular tachycardias) (waveform 2). More than 50 percent of patients with SND have atrial tachyarrhythmias [2,4-9], which may be the result of a progressive pathological process that affects both the SA node and the atrium [10-12]. The presence of tachyarrhythmias may impact the management of the patient who has SND.

Exclusion of reversible causes — For patients in whom a reversible cause of abnormal sinus node function (eg, sinoatrial nodal-blocking medications [beta blockers, calcium channel blockers, ivabradine, digoxin, class 1 antiarrhythmic drugs, amiodarone, acetylcholinesterase inhibitors], acute myocardial infarction or ischemia, hypothyroidism, hypothermia, hypoxemia, hyperbilirubinemia) has been found on history, physical, and 12-lead ECG, we address those conditions as needed and assess whether the patient has persistent abnormal sinus node function. If sinus activity returns to normal, the patient does not have SND. If the patient continues to have evidence of abnormal sinus node function, we proceed to further diagnostic testing. (See 'Correlation of rhythm and symptoms' below.)

Correlation of rhythm and symptoms — The history, physical examination, and 12-lead ECG do not usually provide enough information to diagnose or exclude SND because the duration of the rhythm assessment on the ECG is brief (ie, 10 seconds), making it unlikely that any manifestation of abnormal sinus node function other than sinus bradycardia will be captured. Most patients require further testing to determine whether they have abnormal sinus node function and, if so, whether the rhythm abnormality correlates with symptoms.

All patients — For patients with suspected SND, an ambulatory cardiac rhythm monitor (ie, ambulatory ECG) is indicated to determine whether the symptoms correlate with abnormal sinus node function [13]. We usually perform ambulatory monitoring for an extended period (eg, two to four weeks) [14,15]. For patients with frequent symptoms (eg, several times per week), a shorter monitoring duration (eg, 24 to 48 hours) is reasonable [16-19]. For patients with infrequent symptoms that are more severe (eg, syncope), we may choose long-term monitoring with an implantable (ie, insertable) loop recorder (ILR) [20]. (See "Ambulatory ECG monitoring".)

Patients should be educated about the importance of documenting the presence and nature of symptoms while being monitored. The most common method of indicating that symptoms are present involves pushing a button on the device or, in the case of ILRs, on the handheld activator. Examining the recorded rhythm during symptoms is a crucial step in diagnosing or excluding SND.

Digital health technologies (eg, smartwatches) with single- or multilead ECG capability are available for purchase. Some individuals may prefer them over prescription-grade monitors, or may use them for longer-term monitoring after the prescription-grade monitor has been returned.

Ambulatory monitoring has largely supplanted older methods of diagnosing SND such as pharmacologic challenges (eg, isoproterenol, atropine with or without beta blockers) and invasive electrophysiology study [21-25]. However, if the patient is suspected of having both SND and a tachyarrhythmia that may be curable with ablation [13], and ambulatory monitoring has not captured evidence of arrhythmia, electrophysiology study may be appropriate. (See "Invasive diagnostic cardiac electrophysiology studies".)

Patients with exertional symptoms — For most patients who experience symptoms primarily during activity, an exercise treadmill test (ETT) is a helpful supplemental test to evaluate for chronotropic incompetence (ie, inadequate heart rate response to physiological demands during activity). If we are also considering a diagnosis of myocardial ischemia, we perform the test with imaging (eg, echocardiography, radionuclide myocardial perfusion). If we do not suspect myocardial ischemia, an exercise stress test without imaging is sufficient. (See "Exercise ECG testing: Performing the test and interpreting the ECG results".)

While there are varying definitions of chronotropic incompetence, many clinicians consider an inability to achieve ≥80 percent of the maximum predicted heart rate as evidence of chronotropic incompetence [13]. However, the sensitivity and specificity of this criterion are uncertain, and the results of exercise testing may not be reproducible [26]. Furthermore, noncardiac conditions that impact exercise capacity (eg, chronic obstructive pulmonary disease [COPD], osteoarthritis) are common in older patients and may limit the utility of the ETT for many patients.

We interpret the results of the ETT as follows:

●For patients who achieve ≥80 percent of the maximum predicted heart rate on the ETT, SND is not the cause of their exertional symptoms. They do not require further testing for SND unless they develop symptoms at rest in the future. Evaluation for other causes of exertional symptoms (eg, myocardial ischemia, COPD, heart failure) may be indicated.

●For patients with bradycardia (ie, <60 bpm) at rest who experience minimal augmentation of the sinus rate (eg, ≤20 percent) with exercise, and who experience symptoms (eg, fatigue, dyspnea) during the test, SND is present. (See 'Establishing the diagnosis' below.)

●For patients who experience chest pain and/or ischemic ECG changes during the ETT, we pursue further evaluation for myocardial ischemia and treat as necessary. If symptoms and/or bradycardia persist after treatment, we order an ambulatory cardiac monitor. (See "Selecting the optimal cardiac stress test" and 'All patients' above.)

●For all other patients, the ETT results are not helpful for diagnosing or excluding SND.

Establishing the diagnosis — We use information obtained during our evaluation to diagnose or exclude SND. To receive a diagnosis of SND, a patient must have all three of the following features:

●Evidence of abnormal sinus node function (eg, sinus rate <50 bpm, sinus pause >3 seconds, sinus arrest, sinoatrial exit block, or chronotropic incompetence).

●Symptoms (eg, fatigue, dyspnea, lightheadedness, presyncope, syncope) that coincide with the ECG abnormalities.

●Absence of a reversible cause of abnormal sinus node function (eg, acute myocardial infarction, sinoatrial nodal-blocking medications, hypothyroidism, hypoxemia, hypothermia). (See "Sinus node dysfunction: Epidemiology, etiology, and natural history", section on 'Etiology'.)

If the diagnosis of SND is uncertain, referral to a cardiac electrophysiologist is indicated. In some cases, an electrophysiology study can be helpful.

DIFFERENTIAL DIAGNOSIS — 

The differential diagnosis for sinus node dysfunction (SND) includes the following conditions:

●Reversible sinus node disorder due to atrioventricular (AV) nodal-blocking medications or conditions such as acute myocardial infarction, myocardial ischemia, hypothyroidism, hypoxemia, and hypothermia. The history, physical, laboratory test results, and electrocardiogram (ECG) are helpful in excluding reversible causes. (See "Sinus node dysfunction: Epidemiology, etiology, and natural history", section on 'Etiology'.)

●Physiologically normal bradycardia in highly conditioned athletes. In contrast with patients with SND, these individuals are typically asymptomatic.

●Conditions that cause both symptoms (eg, syncope, presyncope) and bradycardia, such as carotid sinus syndrome and neurocardiogenic (ie, reflex) syncope. Patients with carotid sinus syndrome tend to experience symptoms when turning their head or looking upward, while patients with neurocardiogenic syncope tend to develop symptoms in response to certain physical or emotional triggers. Patients with SND, on the other hand, do not usually identify a specific trigger of their symptoms. (See "Carotid sinus hypersensitivity and carotid sinus syndrome" and "Reflex syncope in adults and adolescents: Clinical presentation and diagnostic evaluation".)

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Arrhythmias in adults" and "Society guideline links: Syncope" and "Society guideline links: Cardiac implantable electronic devices" and "Society guideline links: Supraventricular arrhythmias".)

INFORMATION FOR PATIENTS — 

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Sinus node dysfunction (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Definition – Patients with sinus node dysfunction (SND) have evidence of abnormal sinus node function (eg, sinus rate <50 bpm, sinus pause >3 seconds, sinus arrest, sinoatrial exit block, or chronotropic incompetence), symptoms (eg, fatigue, dyspnea, lightheadedness, presyncope, syncope) that coincide with the electrocardiogram (ECG) abnormalities, and absence of a reversible cause of abnormal sinus node function (eg, acute myocardial infarction, atrioventricular [AV] nodal-blocking medications, hypothyroidism, hypoxemia, hypothermia). (See 'Definition' above.)

●Clinical presentation – Symptoms of SND include fatigue, dyspnea on exertion, lightheadedness, presyncope, or syncope. Some patients may have palpitations due to paroxysmal atrial fibrillation, which is often present in patients with SND. (See 'Clinical presentation' above.)

●Evaluation and diagnosis – SND should be suspected in patients >65 years of age with unexplained syncope, exertional symptoms such as dyspnea or fatigue, or evidence of abnormal sinus node function on ECG such as sinus bradycardia or sinus pauses. (See 'When to suspect the diagnosis' above.)

•History, physical examination, and ECG – We perform a history and physical examination to assess the patient for symptoms and determine if a reversible cause of abnormal sinus node function (eg, acute myocardial infarction, sinoatrial nodal-blocking medications, hypothyroidism) is present. We examine the ECG for evidence of abnormal sinus node function or ST-elevation myocardial infarction. (See 'History and physical examination' above and '12-lead electrocardiogram and prior records' above.)

•Exclusion of reversible causes – If a reversible cause of abnormal sinus node function is identified, we address the condition as appropriate. If abnormal sinus node function persists, we proceed to further diagnostic testing. (See 'Exclusion of reversible causes' above and 'Correlation of rhythm and symptoms' above.)

•Testing to correlate rhythm and symptoms – For most patients, further testing is needed to establish a correlation between symptoms and bradycardia.

-For most patients, we order an ambulatory rhythm monitor and instruct patients to document the presence of symptoms while being monitored. (See 'All patients' above.)

-For patients with symptoms during activity, we also order an exercise treadmill test to evaluate for chronotropic incompetence (ie, inadequate heart rate response to physiological demands during activity). (See 'Patients with exertional symptoms' above.)

•Establishing the diagnosis – The diagnosis of SND is made based on the correlation of sinus dysfunction and symptoms in the absence of a reversible cause. (See 'Establishing the diagnosis' above.)

●Differential diagnosis – The differential diagnosis of SND includes reversible causes of abnormal sinus node function, physiologically normal bradycardia in highly conditioned athletes, and certain conditions (eg, carotid sinus syndrome, neurocardiogenic syncope) that can cause both symptoms and bradycardia. (See 'Differential diagnosis' above.)

ACKNOWLEDGMENT — 

The UpToDate editorial staff acknowledges Alan Cheng, MD, who contributed to earlier versions of this topic review.