12 Year Old Asthmatic with Intermittent Dyspnea Unresponsive to Albuterol---What is it, and Why Now?

This case was written by one of our great Hennepin 2nd year residents, Aaron Robinson, with lots of comments and edits by Smith.

Thanks to Dr. Smith and Dr. Travis Olives for being part of this case. 

A 12 year old girl with a history of mild intermittent asthma presented to the emergency department with worsening shortness of breath over the past couple of days. She is up to date on her vaccinations and has no PMHx besides asthma and a noncontributory family history. She does not identify any specific triggers for her asthma. Initial screen in triage revealed normal vitals signs and a normal temperature. Upon interviewing the patient and her mother, they state that the patient has been having worsening shortness of breath in the past week, but her neb treatments (which typically eliminate her issues) haven't been working. The child appeared anxious, but overall nontoxic during her initial emergency department evaluation. Her mother had given her two albuterol neb treatments prior to arrival, without improvement. 

What was puzzling to the emergency physicians was the history and physical. On first glance, things seemed consistent with worsening asthma, but there was something that didn't fit. The child didn't have any wheezing on exam, but but this was not so unusual in that asthma frequently lacks wheezing. What was more unusual for asthma was that there was also no history of cough, (which is almost universally present in asthma).  

It was further digging in the history that piqued the emergency physicians' interest: the abrupt onset of the shortness of breath, with no apparent trigger, as well as the lack of even minimal improvement with albuterol. When questioned further, the patient said "I feel like I need to keep taking a deep breath and I get really nervous, then it goes away." These episodes have increased in frequency over the past few weeks. This unusual history prompted the emergency physician to broaden the differential and consider other pathology.

So, an ECG was ordered and is pictured below.

What do you see?

There is a short PR interval at 101 ms, even for a 12 year old.  Normal PR for a 12 year old ranges from 106 ms to 176 ms.  Here it is 101 ms.  

Furthermore, the computer reads a QRS duration of 117 ms, which is long even for an adult, but far too long for a 12 year old (normal = 87 ms).

In this case, the computer did interpret "ventricular pre-excitation/WPW [Delta Waves]"

But it might not always do so.

This is a textbook example of Wolff-Parkinson-White (Type B, see below). 

The PR interval is short (101 ms) and there are obvious delta waves, most notable in leads I, II, V1, V5, and V6. This is a pre-excitation syndrome, which predisposes the patient to runs of SVT (AVRT). The black arrows indicate the delta waves in the annotated ECG below.

With this finding, the ED physicians were immediately concerned that this patient wasn't having worsening asthma but was in fact having runs of symptomatic SVT. The patient was placed on the cardiac monitor. CXR was within normal limits, and bedside cardiac ultrasound did not reveal any grossly noticeable abnormalities. Initial troponin was negative, and chemistry was remarkable for hypokalemia (K=2.8), which places the patient at increased risk of dysrhythmia (how does it do so?  see below). Magnesium was normal. Potassium chloride supplementation was given PO. 

The hospital caring for her did not have advanced pediatric cardiac care and there was concern given the patient being increasingly symptomatic. The decision was made to transfer her to the nearby university hospital that had advanced pediatric cardiology for definitive care. She was transferred in stable condition. She never had any runs of SVT during her ED stay.

Follow up:

Follow up on the patient's transfer to a pediatric hospital with cardiac specialists:

The patient had a repeat chest XR and a formal echocardiogram the day of transfer, both of which were negative. No sign's of Ebstein's anomaly on echo. Why did they look for this? See below for an explanation. She was discharged with 24-hour Holter monitoring. She had multiple runs of SVT as well as multiple triplets and quadruplets of PACs that correlated with her symptoms. They took her to EP lab, where they performed a small ablation. Post-ablation, no further runs of SVT were seen and she no longer met criteria on ECG for WPW. No further AVRT could be induced in EP lab. The hypokalemia, as described above, was likely secondary to her albuterol use as we suspected. She is doing very well. 

Why did they look for Ebstein's anomaly?

Ebstein's Anomaly: Basically, it's a critical congenital heart defect that causes "atrialization" of the right ventricle. The atrioventricular valve is displaced inferiorly and the RV size is very small. The valve leaflets are abnormal, and describes as "plastered" to the RV. About half of patients also have an ASD or PFO. 

Why does this matter in our patient? About half of patients with Ebstein's also show evidence of WPW on ECG. Cardiac physicians were screening for this in this case. Remember cardiac anatomy: a thick, fibrous ring known as the anuli fibrosi cordis electrically insulates the atria from the ventricles. In MOST patients, the AV node is the limiting factor with its refractory period, and why atrial fibrillation usually can't degenerate into ventricular fibrillation. This is, of course, barring the fact that no accessory pathways exist, unlike our patient. Because of the severely displaced right-sided AV valve, the anuli fibrosi cordis is at risk of being disrupted, and why ~50% of patients with Ebstein's have WPW. 

Learning Point

In this case, the ECG is not at all difficult.  The computer even accurately diagnosed it.  

The learning point is that even children's symptoms may sometimes be explained by the ECG.  I (Smith) always obtain and ECG on children with chest pain that does not have a clear explanation, as they may have myocarditis and even myocardial infarction (from coronary dissection, previous Kawasaki's disease (which may be unknown), coronary anomalies).  And I even get just one troponin in these cases.  

Any child (just like adults) with episodes of palpitations, lightheadedness, syncope, or pre-syncope could have any of WPW, HOCM, long QT, Brugada, or Arrhythmogenic RV dysplasia.  Any child with unexplained dyspnea could have MI, myocarditis, congenital heart disease, RV hypertrophy from pulmonary hypertension, and more.  The ECG is simple, cheap, and non-invasive.  Nevertheless, in one major study of syncope in children in the ED, 58% did not get an ECG recorded!

Just this week, the New England Journal of Medicine [379(6):524-534; Aug 9, 2018] published an article which found that 42 of 11,168 asymptomatic adolescents screened for athletic activity had a variety of disorders that are associated with sudden death (36 detected by ECG, for 0.32%, or 1 in 300), including 5 HOCM, 2 Arrhythmogenic RV dysplasia, 1 dilated cardiomyopathy, 3 long QT, 2 with coronary anomaly, 3 with dangerous bicuspid aortic valve, and 26 with WPW (1 in 400).

If asymptomatic children have this many significant abnormalities, then children with unexplained symptoms would have many more, though this number is not known (as far as I can tell).

The only danger to recording an ECG is misinterpretation.  Especially not recognizing normal variants as normal.  

Here are a variety of cases of children with important ECG findings.

Wolff-Parkinson-White Syndrome

The Wolff-Parkinson-White Syndrome is a pre-excitation syndrome that is manifested by dysrhythmias due to an accessory pathway between the atria and the ventricles (i.e. The Bundle of Kent, or atrioventricular bypass pathway). It is more grossly typed as an Atrio-Ventricular Reentrant Tachycardia, or AVRT. It's classically defined by the appearance of the "delta wave" on EKG, which is the slurred upstroke of the QRS and the presence of a short PR interval. Because the accessory pathway goes through abnormal tissue, the conduction is not fast like the AV node/Purkinje network. When the SA node fires, the slowed conduction through the accessory pathway initially is responsible for the delta wave. Generally, the AV pathway predominates overall, and the patient is without issue. However, when a reentrant circuit is formed between the AV node and accessory pathway, a patient can enter SVT and be stable or symptomatic/unstable. Conduction occurs in orthodromic (most cases) or antidromic (~5% of WPW) conduction. 

Orthodromic

Orthodromic (latin "correct") conduction is conduction anterograde the AV node (the normal way) and retrograde up the accessory pathway. This causes the QRS to be narrow because the initial depolarization is as it usually is.

Antidromic

Much less commonly, antidromic reentry is exactly the opposite: anterograde conduction through the accessory pathway and retrograde up the AV node. This abnormal conduction causes the QRS to be wide and can be difficult to distinguish from ventricular tachycardia. Thankfully, it is less common. 

Depending on the location of the accessory pathway, the sinus EKG manifestations of WPW will vary. 

Type A Wolff-Parkinson-White. An example is below:

Photo from LITFL: Wolff-Parkinson-White Type AType A Wolff-Parkinson-White has a dominant R wave in V1, indicating a left-sided accessory pathway.
How can you tell?The large upright R-wave in V1 is analogous to a right bundle branch block.
The initial depolarization is on the left (left sided pathway, just like in RBBB when the left bundle is the only working fascicle, the depolarization is from left to right)

Type B Wolff-Parkinson-White. Another example from the fantastic LITFL example is below:

Type B Wolff-Parkinson-White has a "negative delta wave" in V1 and a predominant S wave, indicating a right-sided accessory pathway. The patient in this case appears to have a Type B WPW.

In this case, it has an LBBB-type morphology, with monophasic R-waves in I, V5 and V6.
This is because the right sided pathway leads to right to left activation, as you get in LBBB.

Notice also that in both types, there are ST-T abnormalities that could mimic ischemia.  These are "secondary" ST-T abnormalities, secondary to an abnormal QRS.  Whenever you see abnormal ST-T, you should ascertain whether the QRS is the source (secondary) or whether the QRS is relatively normal (ST-T are "primary", due to pathology such as ischemia.

How did hypokalemia affect this case? 

This patient has had an accessory pathway for some time.  It did not just suddenly appear.  So why did she start having symptoms?  Most likely, it was due to hypokalemia.  Hypokalemia can trigger premature atrial beats (PAB).  The initiation of a re-entrant rhythm, whether in AVNRT or AVRT (atrio-ventricular reciprocating tachycardia, in WPW), is through a PAB.  Normally, in sinus rhythm, the beat is conducted down BOTH the AV node and the accessory pathway.  The 2 together create a fusion beat, the delta wave the result of conduction down the accessory pathway, and the remaining narrow complex beat the result of conduction down the Purkinje fibers.  If there is a PAB which occurs when one of these pathways is refractory, then it will be blocked in that pathway and proceed down the other.  Then it will be able to travel back UP the pathway that was initially blocked as that one will no longer be refractory.  Then it can make an endless loop.  PABs do not require hypokalemia but can happen for many reasons.  Beta blockers are fairly good at suppressing PABs and therefore may be used to prevent initiation of SVT.

"Concealed WPW"

Interestingly, the delta wave may not always be seen! If the accessory pathway is far enough from the SA node, the depolarization from the SA node may not reach the accessory pathway by the time the AV node depolarizes. This results in no delta wave! However, you can "uncover" the accessory pathway by slowing the rate down in these patients. Another way that WPW can be concealed is in the very rare (~15% of all WPW patients) retrograde-only conduction, in which the accessory pathway ONLY allows retrograde conduction, which obviously wouldn't show a delta wave on sinus EKG but still predisposes the patient to re-entry tachycardias. 

For more on concealed conduction:

Wide Complex Tachycardia

A large R-wave in lead V1. And why is the PR interval not short?

A Very Fast Regular Narrow Complex, Followed by an Equally Fast Regular Wide Complex

Treatment in the acute setting is largely focused on SVT and electrolyte optimization. Vagal maneuvers and/or chemical conversion can be attempted in stable patients (adenosine, CCB, etc) in SVT. Unstable patients should get DC cardioversion immediately. If the patient has antidromic conduction, extreme caution must be taken as to not mistake this for ventricular tachycardia (it's VT until proven otherwise). In the most recent ACLS update, the AHA states that one may "Consider adenosine ONLY if the patient is in a stable, wide complex, REGULAR, MONOMORPHIC tachycardia." This is because adenosine will break antidromic WPW (or SVT with aberrancy), but obviously will NOT correct ventricular tachycardia. Adenosine should NEVER be tried in a patient with a WIDE complex IRREGULAR rhythm. This may be the feared atrial fibrillation with WPW, a rhythm that, if AV nodal blockade occurred, the fibrillation waves from the atria will be directed solely down the accessory pathway, and the patient will very likely decompensate into ventricular fibrillation. 

Definitive treatment of WPW can be through radio-frequency ablation of the accessory pathway in the electrophysiology lab or medical management. More can be found below.

Life in the Fast Lane does an outstanding job reviewing WPW and can be found here, including examples of WPW Type A and Type B EKGs. 

https://lifeinthefastlane.com/ecg-library/pre-excitation-syndromes/

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Comment by KEN GRAUER, MD (8/7/2018):

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Our thanks to Drs Robinson, Olives and Smith for this thought-provoking case. As per Dr. Smith — one of the KEY points is that certain symptoms in children may be explained by an ECG. Clinicians have been fascinated by WPW for years. Many aspects of diagnosis and management remain controversial. In the interest of academic pursuit — I’ll add the following comments.

• As noted — the diagnosis of WPW in this case is not difficult. There is obvious PR interval shortening — and, prominent delta waves are seen in virtually every lead on this tracing. But the diagnosis of WPW is often much more subtle. Delta waves are not always seen in as many leads as we do here. Some patients (especially older adults) develop some initial slurring of the QRS complex in a number of leads without there being any AP (Accessory Pathway). And, most importantly — is appreciation that in patients with WPW, conduction may be entirely down the AP — entirely down the normal AV nodal pathway — or — any relative percentage amount between these 2 possibilities. For example, if the relative amount of preexcitation is minimal (say 80-90% of impulses travel down the normal AV nodal pathway) — then delta waves may be difficult to recognize, and the QRS complex may not be overly wide (See ECG Blog #121).
• Conduction properties of the AP may vary for a variety of reasons. These include decreased ability to conduct in one or both directions over the AP as the patient ages — certain medications — autonomic stimuli, among others. This changing propensity to conduct over the AP is a major reason why risk of a potentially life-threatening WPW-related tachyarrhythmia is clearly less in adults over 35-40 with WPW who had not had previous symptomatic arrhythmias. As a result — older adults who have remained asymptomatic from their WPW over the balance of their lives do not necessarily need referral to a cardiologist. In contrast, given recent advancements in technology and the continually enhanced diagnostic and therapeutic prowess of experienced EP cardiologists — infants and children, and probably also teenage and young adult competitive athletes merit referral for full assessment in 2018, even when the patient is asymptomatic. NOTE: For more on assessment and management considerations in patients with asymptomatic WPW (including risk stratification) — Click HERE: ECG Blog #153.

Clinical Relevance of PR Interval Shortening:

The reason the PR interval is short with WPW — is that the AV node is bypassed.

• With normal conduction in sinus rhythm — the electrical impulse slows down as it passes through the AV node on its way to the ventricles. As a result — most of the PR interval normally consists of the time it takes for the impulse to traverse the AV node. The electrical impulse arrives at the ventricles sooner with WPW — because the relative delay that occurs when passing through the AV node is avoided by conduction over the AP.
• This is the reason the QRS complex with WPW will usually be wide when the rhythm is AFib or AFlutter — because in both of these arrhythmias, the impulse does not have to travel through the normal AV nodal pathway. Instead, entry into the ventricles can be accomplished much faster traveling anterograde over the AP. Absence of passage through the AV node with AFib and AFlutter also enables much faster ventricular rates to be achieved (depending on the refractory period of the AP — and not dependent on the refractory period of the AV node).
• In contrast, ~95% of AVRT is orthodromic — because the path to the ventricles passes over the normal AV nodal pathway. As a result — the QRS complex will usually be narrow in AVRT.

How to Recognize WPW in Patients with AFIB:

As alluded to above — the principal WPW-related Arrhythmias are: i) A regular reentry SVT = AVRT (AtrioVentricular Reciprocating Tachycardia); ii) AFib; and iii) AFlutter. While some WPW patients may be extremely symptomatic with episodes of AVRT — it is especially AFib (and not AVRT) that is most likely to be potentially life-threatening.

• Adenosine is potentially problematic if given to a patient with WPW who is in AFib — but, Adenosine IS useful to treat WPW patients with AVRT. The “good news” — is that you’ll often be able to recognize that a patient with AFib has WPW. This facilitates knowing when to avoid Adenosine (and when to also avoid Verapamil/Diltiazem).

For example — How would you interpret the arrhythmia shown in Figure-1?

Figure-1: How would you interpret this arrhythmia? (See text).

ANSWER: The rhythm is irregularly irregular. No P waves are seen. The QRS complex is wide. Therefore, even without seeing a complete 12-lead ECG — the above findings are virtually diagnostic of AFib.

• How fast is the rate of this AFib?

ANSWER: In places — the rate of the AFib seen in Figure-1 is between 250-300/minute (ie, the R-R interval in places is barely more than 1 large box in duration — which corresponds to a ventricular rate ~300/minute). The only way AFib results in a ventricular response this fast — is if impulses are bypassing the longer refractory period of the AV node — which means that there must be an AP!

• Recognition of the ECG features in Figure-1 are virtually diagnostic of AFib + WPW. These features are: i) exceedingly rapid AFib (over 220/minute in parts of the tracing); ii) QRS widening (due to anterograde conduction over the AP); and, iii) marked variability in the R-R intervals over this rhythm strip.
• For more on the basics of WPW-related arrhythmias — Click HERE: Section 12.
• Excellent teaching points made by this case include the likelihood that the cause of this 12-year old girl's shortness of breath was not asthma. And, while transfer to a facility with expertise in pediatric cardiology is the intervention of choice — it should be emphasized that we’ve not yet proved a sustained arrhythmia (AVRT, AFib, AFlutter) is the cause of this patient’s symptoms. Holter studies have demonstrated that not only sustained tachyarrhythmias — but also brady rhythms and isolated PACs and PVCs may also be the cause of palpitations. Comprehensive risk assessment by EP cardiology is needed to determine if AP ablation is or is not the recommended management for this patient at this time.

Beyond-the-Core: A number of ways for classifying WPW types have been proposed. A step beyond division into Types A & B — is to use morphology of delta waves in multiple leads on the ECG to predict the probable location of the AP. Having studied numerous proposed algorithms for predicting localization of the AP — I synthesized those I found most helpful into a user-friendly method that is surprisingly accurate (though clearly not perfect). My method takes minimal time.

• I do not try to memorize the Algorithm in my method. Instead — I simply turn to ECG BLOG #76 whenever I want to attempt my prediction.

Take another look at the initial ECG in this case (Figure-2):

Figure-2: Initial ECG on the 13yo girl in this case (See text).

• Click on the link to ECG Blog #76.
• The 1st Step in the Algorithm depends on where Transition occurs (ie, where the QRS complex in the chest leads becomes more positive than negative).
• Transition in Figure-2 occurs between leads V4-to-V5. This means that we begin with STEP B-5 — which immediately tells us we are dealing with a right-sided AP.
• We now need to measure the delta wave frontal plane axis — which we do by looking at delta wave polarity in leads I and aVF. Note that the delta wave in both leads I and aVF is positive — which means that the delta wave frontal plane is positive. According to the Algorithm — this predicts the AP will be localized to the Anterolateral RV Free Wall.
• 
  
• NOTE: I labeled this last set of comments as “Beyond-the-Core” — because precise localization of the AP is not critical information for providers who are not the EP cardiologist caring for the patient. But: i) It’s fun to be able to quickly and with surprisingly good accuracy predict localization of the AP; and, ii) I think it helpful to appreciate how the EP cardiologist knowing the likely location of the AP prior to performing EP study can facilitate more rapid isolation of the AP during EP study.