Biology of The Sinus Node

The atria are normally activated via the sinus node. The subset of rhythms originating from the sinus node are called sinus rhythms. Now's as good a time as ever to talk briefly about sinus node biology. 

The sinus node (a.k.a. sinoatrial node, SA node, or SAN) is a group of cells located in the upper right atrium. It's organized as a central cluster of P cells ("pacemaker cells") that have physiologic automaticity and generate the sinus impulse. These P cells are surrounded by a transitional zone of T cells ("perinodal" or "transitional cells") that transmit the impulse generated by P cells to the atrial myocardium. 

The P cells within the central cluster are not homogeneous either. They are organized in groups with slightly differing electrophysiologic properties.  

Cells higher up in the SA node fire intrinsically faster (greater automaticity) but tend to have increased acetylcholine sensitivity when compared to cells lower down, which tend to fire at slower rates. Higher vagal tone tends to suppress the higher cells preferentially, causing the slower lower cells to dominate, leading to bradycardia (the desired vagal response). Nonetheless, the default "leading pacemaker" is typically located superiorly in the SAN. 

Looking at the heart from the viewpoint of the right shoulder. Red = P cells. Blue = T cells.

https://www.mdpi.com/2308-3425/9/11/402 

The Sinus Impulse

As demonstrated above, the sinus impulse flows from the P cells, through the T cells, to the right atrial myocardium. From here, it spreads towards the AV node via the internodal tracts and towards the left atrium via Bachmann's bundle. 

On an ECG, atrial activation is represented as a p wave [read more here: Link to Normal p wave]. The vector of atrial depolarization that arises from activation via the sinus node is as follows, and is typically positive in leads I, II, and aVF while negative in aVR.  

I'll emphasize again that p waves are a result of atrial myocardial depolarization. The p wave does not represent P or T cell activity of the sinus node. Since the mass of these cells is so low, the voltage generated by their activated is too low to be appreciated on a surface ECG. It is impossible to detect P or T cell activation directly on an ECG. That being said, the general idea is that P cell activation would occur first, then a small pause delineating transit time through T cells, followed by the atrial depolarization represented by the p wave. 

Needs formal image (this particular image is protected by copyright) 

Normal Sinus Rhythm

For normal sinus rhythm (NSR), you need to meet the following criteria: 

Of course, this is a very stringent set of criteria, and this doesn't mean that someone who doesn't fit these criteria isn't "normal". There are many variations to the sinus rhythm that can be "normal", "benign", "physiologic" or however you want to put it. For example, respiratory sinus arrhythmias, sinus bradycardia, premature complexes, etc. But to be strict, to be NSR you need to fulfill the above criteria. 

Normal sinus rhythm in a 23 year old male patient. 

Sinus Bradycardia

When sinus impulses occur at a slower rate of <60 bpm, the rhythm is called sinus bradycardia. The most common cause of sinus bradycardia is increased vagal tone (i.e. during sleep, athletes with high baseline vagal tone), whereas non-physiologic causes include: 

Differential Diagnoses of Sinus Bradycardia

2:1 Sinoatrial Exit Block

Without other contextual clues or longer strips, sinus bradycardia is indistinguishable from 2:1 sinoatrial exit block.  


For example, the strip below appears to sinus bradycardia at around 30 bpm. (Note that the top strip is from lead II, and the bottom strip is from lead V1.) 

However, when you look at a longer strip, it appears that the sinus rate rapidly goes up to about 60 bpm. This is suggestive of the bradycardic period being a result of every other p waves being transiently dropped (a transient sinoatrial exit block at a 2:1 ratio).  

Sinus Rhythm with 2:1 AV Block

This arrhythmia is merely a mimic of sinus bradycardia and can potentially be distinguished with a close enough eye. For example, the strip below appears to be sinus bradycardia at a rate of roughly 53 bpm. 

However, on closer review, there are hidden positive deflections inside the T waves, located exactly halfway between the visible p waves. This is suggestive of non-conducting sinus impulses (i.e. an AV block). The actual rhythm is sinus tachycardia at a rate of roughly 106 bpm with 2:1 AV block. 

Source: modified from https://ecg.bidmc.harvard.edu/maven/dispcase.asp?rownum=367&ans=1&caseid=368 

Blocked Atrial Bigeminy

Along the same lines as the example above, this rhythm is also a mimic of sinus bradycardia. 

Source: modified from https://doi.org/10.1111/j.1747-0803.2012.00646.x 

Upon closer review, however, it appears that there is a sharp deflection in the T waves representative of PACs. There is an alternating pattern of sinus p wave and PAC, which makes this an example of atrial bigeminy. However, all of the PACs occur early and are blocked as the AV junction is likely still refractory to impulses. Additionally, the PACs themselves are blocking an in-between sinus impulse. 

Sinus Tachycardia

When sinus impulses occur at a rate >100 bpm, the rhythm is known as sinus tachycardia. This is usually secondary to an increase in sympathetic tone from some sort of physiologic stressor, in the body's attempt to increase cardiac output. This includes, but isn't limited to: 

An example of sinus tachycardia at 102 bpm. Other findings in the ECG unrelated to the rhythm: left atrial enlargement. 

Sometimes, associated with sinus tachycardia and the associated sympathetic tone, we might see prominent Ta waves (atrial repolarization waves). We may also see shortened PR intervals due to the sympathetic tone enhancing AV nodal conduction. Also note in the example below how the p wave appears to be "fusing" with the preceding T wave due to the high heart rate. This is sinus tachycardia at a rate of 114 bpm. 

Sometimes in sinus tachycardia, the p wave can be hidden under the preceding T wave, especially when combined with a first degree AV block (prolonged PR interval). This can actually make it difficult to identify the sinus rhythm. This can be seen in the example below: 

The clues that this is a sinus rhythm:  

Differential Diagnoses of Sinus Tachycardia

Sinoatrial Nodal Reentrant Tachycardia (SANRT)

Without any contextual clues, sinus tachycardia is indistinguishable from SANRT.  

SANRT is a rare rhythm wherein an aberrant micro-reentrant circuit within the sinus node causes paroxysmal tachycardia. Since the rhythm is originating from the sinus node, it still produces p waves just like any other sinus tachycardia. There is no evidence on the surface ECG of the micro-reentrant circuit. 

Some contextual clues that may help identify SANRT:  

An example of SANRT below in an infant with hypoplastic left heart syndrome, with positive p waves in I, II, III, and aVF and negative p waves in aVR. The p waves are highlighted in red in the limb leads. Source: modified from https://doi.org/10.1016/S0002-9149(01)01992-0

Apart from the very high rate (216 bpm), there isn't much distinguishing this from very fast sinus tachycardia. However, when administering adenosine, there was the following response: 

Abrupt termination of the rhythm with administration of adenosine. The preserved p wave morphology post-conversion suggests SANRT. Note: although the p waves look taller during the SANRT, it's because they are "sitting" atop the T waves, accentuating their amplitude. Note that, even though the baseline heart rate appears quite fast, it is still within normal range since the patient is an infant. 

In the same patient, there was an ECG captured of the abrupt initiation of SANRT. We can see the patient's sinus rhythm at ~150 bpm (highlighted in red), followed by a PAC (highlighted green) that initiates a short run of non-sustained SANRT ~200 bpm (highlighted in blue) which spontaneously and abrupt terminates, returning to sinus rhythm at ~150 bpm.  

Right Atrial Ectopic Tachycardia

Some atrial ectopic tachycardias originating near the sinus node can be indistinguishable from sinus tachycardia from just the surface ECG. Contextual clues, the same as those needed for identifying SANRT, are often also necessary here if the p wave morphologies cannot be differentiated. 

Note the ECG below, from a 6 year old with ectopic atrial tachycardia originating from the fossa ovalis in the RA. The p wave morphology and polarity meets criteria for sinus p wave, even though in reality this is not a sinus rhythm. 

Source: https://www.thecardiologyadvisor.com/home/decision-support-in-medicine/cardiology/atrial-tachycardia-diagnosis-and-treatment/ 

Sinus Arrhythmia

Rhythms that originate from the sinus node with irregular atrial rates (with P-P interval variations) are called sinus arrhythmias. Essentially, the generation or transmission of sinus impulses varies from beat to beat, resulting in the irregularity. 

There are several types of sinus arrhythmias: 

Respiratory Sinus Arrhythmia

In respiratory sinus arrhythmia, the heart rate varies in relation to the respiratory cycle, and is a physiologic rhythm that tends to occur in younger individuals. This variability tends to diminish with age and tachycardia. 

During inspiration, the increased venous return during inspiration is sensed by stretch receptors and baroreceptors, which then lower the vagal tone, causing an increase in heart rate. Conversely, expiration results in higher vagal tone, causing a decrease in heart rate. Because of this relationship, we tend to see gradual changes in the P-P intervals that are dependent on the respiratory cycle. 

Source: modified from https://upload.wikimedia.org/wikipedia/commons/a/a4/Respiratory_sinus_arrhythmia.jpg 

The ECG above demonstrates more subtle respiratory sinus arrhythmia.  

Non-Respiratory Sinus Arrhythmia

In this non-respiratory sinus arrhythmia, the heart rate varies independent of the respiratory cycle. Unlike respiratory sinus arrhythmia, this rhythm tends to be pathologic (as a result of heart disease or digoxin) and tends to occur in the elderly. This rhythm is due to intrinsic dysfunction of the sinus node as opposed to external influences (i.e. vagal tone) causing variations. 

Non-respiratory sinus arrhythmia is characterized by sudden and seemingly random changes in the P-P interval irrespective of the respiratory cycle. 

Ventriculophasic Sinus Arrhythmia

This is a special type of sinus arrhythmia that occurs in conjunction with AV blocks, where not every sinus impulse is conducted to the ventricles.  

In ventriculophasic sinus arrhythmia, the P-P intervals containing a QRS complex (a.k.a. a conducted beat) tend to be shorter than the P-P intervals not containing a QRS complex (a.k.a. a non-conducted beat). This is because the increase in intracardiac pressures related to ventricular systole (which happens with the QRS complex) leads to the activation of baroreceptors that then decrease the vagal tone, consequently increasing sinus nodal recovery and excitability. 

Notice how, in the ECG strip above, that the P-P intervals containing a conducted beat are shorter than those not containing one. This is demonstrated more clearly with labeling below.

Differential Diagnoses of Sinus Arrhythmia

Sometimes sinoatrial exit blocks, as discussed in the following section, can cause P-P interval variability that may be mistaken for one of the types of sinus arrhythmia discussed above. 

Sinus rhythms may appear irregular if there are several PACs closely resembling sinus p waves interspersed within the rhythm. These PACs may originate from sites in the RA near the SA node, or may rarely originate from the SA node itself (sinus nodal extrasystole). 

Sinoatrial Exit Blocks

Sinoatrial exit blocks (SAEB) are a group of cardiac conduction disorders related to sinus nodal T cell dysfunction. Recall that the T cells (transitional cells) are important for transmitting signals generated by the P cells to the surrounding atrial myocardial. 

When T cells malfunction, even if the P cells are properly generating sinus impulses, the transmission of these impulses to the atrial cardiomyocytes is either slowed down or blocked completely.  

SAEB are categorized in the following way, in order of severity: 

1st Degree SAEB 

In 1st degree SAEB, the T cells still conduct all the impulses through to the atria, though it takes them longer to do so. 

On the ECG diagram below, notice that the end result of 1st degree SAEB is indistinguishable from normal sinus rhythm. Since we cannot pick up P or T cell activity on the ECG, we can't really appreciate the delay in sinus impulse transmission, and so it doesn't outwardly look any different from NSR. 

The only way to identify 1st degree SAEB is through invasive electrophysiologic studies. 

2nd Degree SAEB, Type 1 

In 2nd degree Type 1 SAEB, also known as sinoatrial Wenckebach, the T cells become progressively slower at conducting sinus impulses until eventually an impulse is blocked, after which conduction returns to normal and the cycle repeats. 

The slowed conduction happens because T cells pathologically become more fatigued (refractory) after each consecutive sinus impulse, so it takes longer to activate them. The T cells create a "delay" in conduction that progressively lengthens. The dropped beat at the end of the cycle provides the T cells enough time to recuperate fully so that the next cycle can begin with normal conduction. This is an example of decremental conduction.  

The above is an example of SA Wenckebach. I've notated the P cell (red) and T cell (blue) activity. Note the progressively slowing T cell transmission time leading to transmission failure, and recovery following the blocked beat. Also note that the blocked beat is lacking both a p wave and QRS complex. 

Source: modified from https://ecg.utah.edu/lesson/6 

An important property of the progressive T cell delay in SA Wenckebach is that the increment in the T cell delay decreases with progressive beats, until the dropped beat. So, in the example above

ECG Manifestations of 2nd Degree Type 1 SAEB

Since we cannot directly observe the T cell delay progressively lengthening on a surface ECG, the diagnosis of 2nd degree Type 1 SAEB is determined by recognizing the impact that progressive T cell delay has on the other elements on the ECG (most importantly the p waves).  

The prolonging T cell delay can cause a progressive shortening of the p-p interval leading up to the blocked beat, which can be measured on the ECG. This may also lead to the appearance of clustering of the QRS complexes prior to the dropped beat. 

Notice the shortening of the p-p intervals leading up to the dropped beat. Notice as well that the QRS complexes look like they're clustering together prior to the dropped beat. 

Source: modified from https://litfl.com/wp-content/uploads/2018/08/ECG-SA-Block-type-1.jpg 

To throw a wrench into things, there may some cases (like to the left) where the p-p interval shortening is not clear, even in true SA Wenckebach. 

There's a slight decrease in the p-p interval (from 26 mm to 25 mm) but how can you be confident that the 1 mm decrease in p-p intervals is significant? In these cases, we can use another trick to uncover the diagnosis.  

Source: modified from https://ecg.utah.edu/lesson/6 

If the p-p interval across the blocked beat is less than twice the original p-p interval, then it is likely SA Wenckebach.  

In the case above, the “original” p-p interval at the beginning of the sequence is 26 mm. Across the blocked beat, the p-p interval is 47 mm. Since 47 is less than 2 x 26 = 52, we can say this is 2nd degree SAEB, Type 1. 

Summary of ECG findings of 2nd degree Type 1 SAEB

2nd Degree SAEB, Type 2 

In 2nd degree Type 2 SAEB, the T cells sporadically fail to transmit impulses without progressive slowing of conduction. 

As mentioned to the left, the lack of progressive T cell delay means no QRS clustering and a p-p interval over the blocked beat that's a multiple of the normal p-p interval. 

Sometimes, you may even see multiple blocked beats, as shown above. The p-p interval is still a multiple of the normal p-p interval. 

Examples - 2nd degree Type 2 SAEB

Example #1 of 2nd degree Type 2 SAEB

Above is an example of a 2nd degree Type 2 SAEB with a junctional escape. 

Source: modified from https://litfl.com/wp-content/uploads/2018/08/ECG-Sino-atrial-block-Type-II.jpg 

When trying to conceptualize what is happening in the heart of this patient, we have the following: 

Example #2 of 2nd degree Type 2 SAEB

Another example of 2nd degree Type 2 SAEB, with the p-p interval across the dropped beat being 2000 ms (twice the normal p-p interval of 1000 ms). Also, there is no progressive decrease in the p-p interval. 

Example #3 of 2nd degree Type 2 SAEB

Summary of ECG findings of 2nd degree Type 2 SAEB 

2nd degree 2:1 sinoatrial block 

The 2:1 SAEB is a special form of the 2nd degree SAEB, with an alternating pattern of conducted beat and blocked beat. Again, without contextual clues, it is impossible to distinguish from sinus bradycardia from an ECG alone. Additionally, even though the underlying pathophysiology may be from either a Type 1 or Type 2 mechanism, due to an inability to analyze consecutive p-p intervals, it is not possible to tell whether it is a Type 1 or Type 2 SAEB from the surface ECG alone. 

3rd degree sinoatrial block 

In 3rd degree SAEB, there’s a complete inability of T cells to transmit sinus impulses to the atria.  

On an ECG, there will be no p waves with or without an escape rhythm. This is indistinguishable from sinus arrest (P cell failure) on the ECG, and you need an invasive electrophysiologic study to delineate the two conditions. 

Differential diagnoses of sinoatrial exit blocks 

AV Blocks

Similar to SAEB, AV blocks involved blocked beats (albeit we should see p waves). AV Wenckebach can also demonstrate QRS clustering.  

It's important to identify if the blocked beats involve blocked p waves (which would support SAEB) or just blocked QRS complexes with intact p waves (which would support AV block). This differentiation is made harder if the p waves are harder to visualize. 

In the case above, you can see P waves prior to each QRS complex, although the PR intervals are progressively lengthening. This in itself is suggestive of AV Wenckebach. However, the 4th p wave in this sequence is hidden by the end of the T wave, and also obscured by ECG noise. From this alone, it may be misleading and suggest a blocked p wave and QRS although that is not the case. The p wave is more visible at the second blocked beat near the end of the strip. 

Blocked PACs 

A non-conducted PAC that's hidden under a T wave can sometimes be confused for a dropped sinus p wave and SAEB. Observe the example below.

Source: modified from https://litfl.com/wp-content/uploads/2018/08/Blocked-Premature-Atrial-Complex-PAC-1.jpg 

In fact, if we were to measure the P-P intervals, we would get the following: 

This looks like it perfectly fits the definition of SA Wenckebach. The P-P interval is decreasing (from 685 to 677) until a dropped beat with no p waves or QRS complexes. The P-P interval over the dropped beat (1251) is less than twice the original P-P interval (685).  

However, a diagnosis of SA Wenckebach would be incorrect because we would be missing a subtle blocked PAC, circled below. 

We can recognize that there is a hidden PAC there by comparing the shape of this T wave with the others, and noticing there is more of a "peak" to the wave, suggestive of a superimposed p wave.  

Additionally, the fact that this hidden p wave occurs before you would expect the next sinus p wave suggests that it is a PAC. 

Sinus Rhythm with U waves

****************************

Sinus Pause/Arrest

Sinus pause and sinus arrest occur when there are long absences of sinus impulses. A sinus pause is any absence (i.e. could encapsulate a single dropped beat), whereas a sinus arrest is a pause lasting > 3 seconds. We think of sinus arrest being a result of sinoatrial P cell dysfunction, and the loss of the ability to generate sinus impulses. However, the exact mechanism cannot often be determined, and sinus pauses may be a result of T cell dysfunction and high degree sinoatrial exit blocks as well. In fact, as mentioned previously, a 3rd degree SAEB is indistinguishable from a sinus pause or arrest. 

Short sinus pauses can happen from time to time in a healthy heart and don't last long before P cells start working again. Usually this is asymptomatic and doesn't cause disease. 

There are several pathologies that can lead to malfunction of the sinus node, leading to pauses. This includes, but isn't limited to: 

Oftentimes, the heart can compensate for pauses using escape rhythms. However, sometimes the same disease that affects P cells affects the secondary pacemakers, leading to a lack of appropriate escape rhythm; this can lead to cardiac syncope or death. 

An example of sinus pause, in which P cell dysfunction is leading to a lack of sinus p waves. Some additional points: 

Source: modified from https://www.researchgate.net/figure/Sinus-pause-followed-by-a-junctional-escape-beat_fig1_294104585 

Sinus Pause

The following ECG shows a patient with several sinus pauses on one ECG. 

Sinus Arrest

Below is an example of sinus bradycardia devolving into sinus arrest, leading to a long period of asystole prior to an escape beat.

Source: https://litfl.com/wp-content/uploads/2018/08/ECG-Sinus-Arrest-1-strip-3.jpg 

Below is another example of a shorter sinus arrest lasting 4.5 seconds in one patient: 

Post-Conversion Pause

Sometimes, after the termination of rapid supraventricular tachycardias (such as atrial fibrillation, atrial flutter, SVT, etc.) there might be a post-conversion pause wherein the sinus node takes a while to recover from overdrive suppression. This recovery period is longer the more intrinsic damage the sinus node has. Various medications and high parasympathetic tone can also contribute to longer sinus node recovery time. The sinus node dysfunction may also manifest as a bradycardic rhythm following the termination of the tachycardia. This phenomenon is known as tachycardia-bradycardia syndrome, and is a cause of sick sinus syndrome

The above strip shows alternating paroxysmal supraventricular tachycardia and long post-conversion pauses/sinus arrest. 

Source: https://litfl.com/wp-content/uploads/2018/08/Brady-Tachy-Brady-Syndrome.jpg 

The above strip shows atrial fibrillation with sinus arrest following termination of the rhythm. There are a few junctional escape beats prior to resumption of sinus rhythm. The prolonged post-conversion pause is suggestive of sinus node dysfunction. 

Source: https://doi.org/10.1161/circulationaha.116.018011 

The above is another example of tachycardia-bradycardia syndrome with post-conversion pauses. It begins with SVT (4 beats) followed by a post-conversion pause and a stretch of sinus beats (from beat 5 to 11) with significant intermittent pauses (longest one lasting 2.8 seconds, between beats 7-8). It then ends with another run of SVT (from beat 12 to 25). 

Differential Diagnoses of Sinus Pause

Sinoatrial Exit Block

A sinus exit block can be indistinguishable from a short sinus pause, and practically speaking, differentiating the two may not be clinically important. 

That being said, analyzing and comparing different stretches of pauses can help identify relationships between pauses and regular p-p intervals. This may help narrow the ECG diagnosis for the keen interpreter. 

For example, consider the rhythm strip below: 

Note that the p-p interval across the sinus pause (3275 ms) is roughly 4 times the normal p-p interval (800 ms). Given that the p-p interval across the blocked beat is roughly equal to a multiple of the normal p-p interval, this raises suspicion about a 2nd degree Type 2 SAEB with essentially 3 non-conducted p waves, as follows: 

By examining another sinus pause that the patient had, shown below, we can further support this suspicion. 

For the same patient, just a few moments later, there was an 1800 ms pause (whereas the regular p-p interval was 900 ms).  Again, the p-p interval across the blocked beat is a multiple of the normal p-p interval, suggesting a 2nd degree Type 2 SAEB with a single blocked p wave this time. 

Vasovagal Reflex

Typically, the term "sinus pauses" refers to pathologic circumstances related to malfunction of the sinus node. Sometimes, the sinus node can be suppressed due to high vagal tone, causing sinus pauses.  

Notably, this is not PRIMARY sinus nodal dysfunction, but rather SECONDARY sinus nodal suppression due to vagal tone. 

The vasovagal reflex is an increase in vagal tone in response to some physiologic stimulus (i.e. fear, pain, etc.) that can have transient hemodynamic consequences.  

These include either a cardioinhibitory response (i.e. decrease in cardiac output via vagally-mediated bradycardia) or vasodepressor response (i.e. vagally-mediated decrease in systemic vascular resistance). Sometimes we see both mechanisms in the same patient.  

With the vasovagal reflex, cerebral perfusion can be transiently decreased, leading to presyncope or syncope.  There is no permanent damage or dysfunction of the conduction system from vagal stimuli.

ECG manifestations of vasovagal syncope typically involve:

This strip shows a gradual increase in the P-P interval as the sinus node slows down, leading to a sinus pause. The PR interval also progressively prolongs, although this is more subtle. This occurred in the context of vasovagal syncope. 

Source: modified from https://www.jacc.org/doi/10.1016/j.jacc.2017.08.025 

Fine Atrial Fibrillation

Fine atrial fibrillation can mimic sinus pauses, especially when there is a slow ventricular rate.  

This diagnosis does NOT insinuate sinus nodal dysfunction on its own (even though there is often a correlation between atrial fibrillation and sinus node disease). The lack of sinus p waves is because of continual SA nodal suppression by rapid and indefatigable atrial depolarization waves created by fibrillatory conduction. 

The difference is that there are usually rapid but low-voltage fibrillatory waves present, suggesting continued atrial depolarization (albeit in a disorganized manner). 

Source: https://litfl.com/wp-content/uploads/2018/08/ECG-Atrial-Fibrillation-Slow-Ventricualr-response.jpg

In the ECG above, that long R-R interval in the middle of the ECG strip (lasting just over 2.6 seconds) is not a sinus pause, as the underlying rhythm is atrial fibrillation (note the irregularly irregular rhythm with low-voltage fibrillatory waves best observed in lead V1). This is representative of slow atrial fibrillation, which is likely a combination of atrial fibrillation and a high degree of AV nodal block causing intermittent non-conduction. This will be discussed further in the [Atrial fibrillation] section. 

Note that this pause is different than the post-conversion pause seen when atrial fibrillation ENDS and the sinus node is allowed a chance to regain automaticity 

Practically speaking, in the clinical setting, you can enhance the appearance of underlying fibrillatory waves by either: