Approach Considerations
See also the Guidelines section for recommendations from the American College of Cardiology, the American Heart Association, and the Heart Rhythm Society for the evaluation and management of bradycardia and disorders of cardiac conduction delay.
For patients in whom sinus node dysfunction (SND) is clinically suspected but not confirmed by electrocardiography (ECG) and/or exercise stress test findings, a number of different modalities may be helpful. In most patients, ambulatory ECG monitoring for an extended period of time (typically 2-4 weeks but potentially longer) has the greatest yield and allows for correlation with symptoms. In select patients in whom the diagnosis remains uncertain, other diagnostic testing options include adenosine administration, carotid sinus massage, and invasive electrophysiologic (EP) studies.
The introduction of the implantable loop monitor has also enhanced the diagnostic yield of the clinical evaluation if symptoms are intermittent, extending over weeks to months.
Laboratory studies
Because hypothyroidism and electrolyte imbalances can contribute to SND, thyroid function testing and serum electrolyte testing (Na+, K+, Ca2+) can be useful. Infiltrative cardiomyopathies (eg, amyloid, sarcoid) can present with evidence of diffuse conduction system disease, but screening is typically reserved for patients in whom specific clinical factors suggest the diagnosis.
Echocardiography
No specific imaging studies are required in the initial workup of SND. However, an echocardiogram should be considered because it can document the presence of underlying valvular or ischemic heart disease and may suggest the diagnosis of amyloid when diffuse conduction system findings are present.
Transesophageal atrial pacing
Transesophageal atrial pacing is reserved mainly for pediatric patients. It may be performed safely to determine sinus node recovery time in children who present with dizziness, syncope, or palpitations.
Exercise stress testing
Exercise stress testing helps in identifying abnormal sinus node function. A subnormal increase in heart rate after exercise (ie, chronotropic incompetence) can help identify individuals with SND who may benefit from a pacemaker implantation.
Electrocardiography
The diagnosis of sinus node dysfunction (SND) in patients with suggestive symptoms is often made on the basis of surface electrocardiographic (ECG) features. Manifestations seen on ECG may include the following:
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Periods of inappropriate and often severe bradycardia, with heart rate of below 50 beats per minute (bpm)
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Sinus pauses, arrest, and sinoatrial (SA) exit block with, and often without, appropriate atrial and junctional escape rhythms
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Alternating bradycardia and atrial tachyarrhythmias; atrial fibrillation is the most common arrhythmia, but atrial flutter and paroxysmal supraventricular tachycardias (ie, due to atrial tachycardia) may also occur
See the images below.
This 12-lead electrocardiogram (ECG) is from an asymptomatic girl aged 10 years, which was brought to our attention because of the irregularity of the P-P intervals. This ECG shows sinus arrhythmia at a rate of 65-75 beats per minute. The P waves all originate from the sinus node (SN) because they have a positive axis (upright) in leads I, II, and aVF. The PR interval is 104ms, and the QRS is narrow at 86ms, with a normal axis of 64°. The corrected QT (QTc) interval measures 402ms. Therefore, this is a normal ECG.
Below is an electrocardiogram (ECG) of a girl aged 2 years who was referred to the clinic by a pediatrician for evaluation of a heart murmur. This ECG shows atrial rhythm originating most likely from the lower left atrium (P waves are inverted in lead I and are positive in II and aVF, with a frontal axis of 124°). The PR interval measures 113 ms, and the QRS is narrow at 90 ms. Right ventricular (RV) conduction delay is shown and is best seen in the precordial leads V1 and V2. The QRS frontal axis shows right axis deviation (reference range for a child aged 2 years is 0-110°). The patient does not have RV hypertrophy by voltage criteria. The inverted T waves in V1 are a normal finding at this age. An echocardiogram showed a moderately sized atrial septal defect. Nonsinus atrial rhythm is not a synonym of sinus node dysfunction.
This is a 12-lead electrocardiogram (ECG) from a boy aged 12 years with a history of syncope. This patient was healthy until 1 month earlier, when he started to experience episodes of lightheadedness. The ECG shows sinus arrhythmia (bradycardia) at a rate of 50-79 beats per minute, with a PR interval of 136 ms. Two junctional escape beats are present after a prolonged pause. The QRS is narrow at 85 ms, with a normal frontal axis of 70°. The corrected QT interval (QTc) is 411 ms. A later electrophysiologic study showed prolonged sinus node recovery time (SNRT) and sinoatrial conduction time (SACT). Because of the patient's symptoms and his sinus node (SN) dysfunction, he received an atrial pacemaker. If this 12-lead ECG had been recorded from an asymptomatic patient, the findings would be considered within normal limits and no further workup would be indicated. In this case, the lightheadedness and, ultimately, the syncope defined sick sinus syndrome, with the patient requiring pacemaker therapy.
Ambulatory ECG (Holter) Monitoring and Event Recording
For patients with clinically suspected sinus node dysfunction (SND) in whom the initial electrocardiogram (ECG) and monitoring are not diagnostic, ambulatory ECG monitoring or long-term event monitoring (eg, 7 or 30 days) is useful in the assessment of SND [30] and for correlation with symptoms.
The specificity of a direct observation of spontaneous (ie, not provoked by an electrophysiologic [EP] study) SND is 100%, and an EP study is not required. Therefore, cardiac monitoring, rather than EP study, is the method of choice to assess SND.
A 24-hour Holter study also has the advantage of revealing whether SND produces symptoms such as dizziness, presyncope, or syncope; these cannot be determined during an EP study, because the patient is heavily sedated. Therefore, a 24-hour Holter study can help decide if pacemaker therapy is required.
Pharmacologic Stimulation Tests
This section outlines steps to allow systematic evaluation of sinus node (SN) function.
Calculating the intrinsic heart rate (IHR)
The IHR is the heart rate in the presence of complete pharmacologic denervation of the SN. This is achieved with the simultaneous use of beta blockers and atropine. The calculation of the IHR following simultaneous administration of beta blockers and atropine is largely of historical interest and is rarely performed in the modern evaluation of patients with suspected SN dysfunction (SND). The IHR in a healthy person is approximately equal to 117.2 – (0.53 × age in years).
Sinus node response to pharmacologic challenge
A number of drugs have been used in to aid in the diagnosis of SND. The pharmacologic protocols are briefly described below.
Atropine and isoproterenol
Atropine (1 or 2 mg) and isoproterenol (2-3 mcg/minute) may be useful, because both agents normally increase the sinus rate. A suggested abnormal response is an increase in the sinus rate of less than 25% above the baseline, or to a sinus rate below 90 beats per minute. [31] Due to fact that in most cases the diagnosis of SND can be achieved by establishing a symptom-rhythm correlation with the use of ambulatory monitoring in conjunction with a comprehensive history and physical examination, testing with these agents is rarely necessary.
Adenosine
Adenosine has been proposed as an alternative to invasive electrophysiology studies, but its routine use is not yet established.
Electrophysiologic Studies
Invasive electrophysiologic (EP) studies are rarely used for the evaluation of sinus node dysfunction (SND) because of their limited sensitivity in eliciting bradyarrhythmias as well as due to the widespread availability of diagnostic options for long-term monitoring. However, in patients with suspected SND who also describe sustained episodes of tachyarrhythmias, EP studies may be helpful in an effort to identify a tachycardia (eg, atrial tachycardia) that would be potentially curable with ablation. [28] Nevertheless, invasive EP studies may be performed in the following situations involving symptomatic patients [28] :
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Those without ECG findings suggestive of SND and no other evident cause for their symptoms
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Those in whom ECG events are compatible with SND but fail to correlate with symptoms
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Those with SND who have sustained episodes of tachycardia that may be amenable to ablation
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Those with syncope or near syncope who have bundle branch or bifascicular block; such patients may require invasive EP evaluation of the sinoatrial (SA) node, the atrioventricular (AV) node, and the infranodal His-bundle-Purkinje system function. EP testing that shows SA nodal dysfunction allows for the selection of appropriate therapy in up to 50% of these patients.
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Those with syncope or near syncope who have ventricular arrhythmias may require EP study to assess for inducibility of ventricular tachyarrhythmias
The salient aspects of EP studies that aid in eliciting a bradyarrhythmic abnormality include assessment of the SA node recovery time, SA conduction time (SACT), and the SN and atrial tissue refractory periods.
Classic EP criteria for SND include the presence of 1 or more of the following:
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Corrected SN recovery time (CSNRT) greater than 275 milliseconds (ms)
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SA conduction time greater than 200 ms
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SA node arrest
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SA exit block
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SN reentry tachycardia
SN recovery time (SNRT)
EP studies can document SND when studying SN automaticity by directly recording electrical activity.
Measurement of SNRT is achieved by pacing the atrium. Pacing should be performed from a catheter placed in the high right atrium (HRA) near the SN at the junction of the superior vena cava (SVC) and the RA for 4-6 trials of 30 seconds each. Each trial should use successively shorter pacing cycle lengths (eg, 600 ms, 550 ms, 500 ms), beginning with a cycle length just shorter than the resting sinus cycle length. SNRT is the time interval between the last paced captured beat to the first spontaneous sinus beat.
Gradual return of the SN to its baseline rate occurs over 5-6 beats. Prolonged pauses (ie, secondary pauses) can occur after the initial recovery interval in SND.
If the longest interval for the recovery interval or secondary pause exceeds 1500 ms, the SNRT is prolonged.
To adjust for heart rate and before each pacing increase, the resting sinus cycle length (SCL) is measured. When the resting SCL is subtracted from the SNRT, the CSNRT is obtained. Its upper reference range limit is 525 ms; if the SNRT exceeds the SCL by more than 525 ms, the SNRT is abnormal. The same occurs if the ratio of SNRT to SCL (ie, SNRT/SCL × 100) is more than 160%.
Sinoatrial conduction time (SACT)
SACT is another parameter that can be used to assess SN function. It is defined as the time interval in milliseconds for an impulse that originates in the SN to conduct through the perinodal tissue to the adjacent RA tissue. (The tissue that surrounds the SN or perinodal tissue has characteristics that are similar to those of the AV node.)
Note the following:
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Eight premature atrial contractions (PACs) are fired in the HRA at 5-10 bpm faster than the SN rate before they are stopped abruptly.
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SACT represents the time in milliseconds that it takes for the PAC fired in the HRA to enter and reset the SN. It also represents the time for the new spontaneous SN impulse (ie, SCL) to reach the HRA. SACT is measured as the time in milliseconds from the last PAC to the first spontaneous sinus beat.
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When the time interval between the last spontaneous SN depolarization (ie, before the PAC) and the one that occurred after a PAC is less than twice the value of the 2 previous spontaneous SN depolarizations, reset of the SN by the PAC has occurred.
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SACT can be calculated as the interval from the PAC to the next spontaneous SN beat, which includes conduction through the perinodal tissue into the SN, resetting the SN, and conduction through the same perinodal tissue back into the HRA (ie, [return interval - SCL]/2). The reference range is 50-125 ms in children and 200-250 ms in adults.
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If the SN cannot produce a spontaneous impulse following PACs (ie, these have not reset the SN and, therefore, SACT cannot be calculated), SA entrance block is present. This block could be caused by a markedly prolonged SA conduction and/or an increased refractory period of the peri-SN or SN fibers, both of which indicate SND. SN entrance block alternating with reset responses also denotes SND.
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SN reentry tachycardia occurs when activation of the atrium during the supraventricular tachycardia is the same as sinus beats (ie, the P-wave axis and morphology are the same as those in the sinus rhythm). It is usually indicative of SND.
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This 12-lead electrocardiogram (ECG) is from an asymptomatic girl aged 10 years, which was brought to our attention because of the irregularity of the P-P intervals. This ECG shows sinus arrhythmia at a rate of 65-75 beats per minute. The P waves all originate from the sinus node (SN) because they have a positive axis (upright) in leads I, II, and aVF. The PR interval is 104ms, and the QRS is narrow at 86ms, with a normal axis of 64°. The corrected QT (QTc) interval measures 402ms. Therefore, this is a normal ECG.
-
Below is an electrocardiogram (ECG) of a girl aged 2 years who was referred to the clinic by a pediatrician for evaluation of a heart murmur. This ECG shows atrial rhythm originating most likely from the lower left atrium (P waves are inverted in lead I and are positive in II and aVF, with a frontal axis of 124°). The PR interval measures 113 ms, and the QRS is narrow at 90 ms. Right ventricular (RV) conduction delay is shown and is best seen in the precordial leads V1 and V2. The QRS frontal axis shows right axis deviation (reference range for a child aged 2 years is 0-110°). The patient does not have RV hypertrophy by voltage criteria. The inverted T waves in V1 are a normal finding at this age. An echocardiogram showed a moderately sized atrial septal defect. Nonsinus atrial rhythm is not a synonym of sinus node dysfunction.
-
This is a 12-lead electrocardiogram (ECG) from a boy aged 12 years with a history of syncope. This patient was healthy until 1 month earlier, when he started to experience episodes of lightheadedness. The ECG shows sinus arrhythmia (bradycardia) at a rate of 50-79 beats per minute, with a PR interval of 136 ms. Two junctional escape beats are present after a prolonged pause. The QRS is narrow at 85 ms, with a normal frontal axis of 70°. The corrected QT interval (QTc) is 411 ms. A later electrophysiologic study showed prolonged sinus node recovery time (SNRT) and sinoatrial conduction time (SACT). Because of the patient's symptoms and his sinus node (SN) dysfunction, he received an atrial pacemaker. If this 12-lead ECG had been recorded from an asymptomatic patient, the findings would be considered within normal limits and no further workup would be indicated. In this case, the lightheadedness and, ultimately, the syncope defined sick sinus syndrome, with the patient requiring pacemaker therapy.
