The Exercise Stress Test: An Electrophysiologist's Perspective (Part 1)

I received an email from Singapore today, which I found quite interesting:

"Hi Eric, I think some of the CAs are not entirely sure what to look out for when running a treadmill with a modified protocol, such as those for WPW, Brugada, etc. I don't blame them, even I am not sure exactly what to look out for in such instances. Do you guys have any materials/resources that could help? The SRs would probably find it quite useful too. Thanks!"

Although treadmill stress tests are, of course, most often used to look for myocardial ischaemia, they also have utility in a number of EP contexts, most notably:

1. To assess robustness (or otherwise) of AV nodal conduction
2. To assess robustness (or otherwise) of antegrade accessory pathway conduction (i.e. WPW) 
3. For risk stratification in Brugada syndrome 
4. To aid in the diagnosis and risk stratification of long QT syndrome
5. Very occasionally, to assess implanted device function

Lets take a look at these in turn.

1. To assess the robustness of AV nodal conduction

EP is often referred patients who are bradycardic and appear to have some problem with AV conduction, and the issue is: (1) is impaired AV conduction pathological? and (2) if so, does it merit anti-bradycardia device implantation? In such cases, it is very useful to be able to assess whether AV conduction "gives up" as the atrial rate increases. From a teleological perspective, AV conduction which is unreliable with increasing atrial rates must clearly be pathological. Put another way, it makes no sense for AV conduction to worsen as the sinus rate increases e.g. with exercise, since this implies that with exertion, the ventricular rate falls. Remembering this simple rule is frequently enough to deduce whether a pacemaker implant is likely to be helpful.

In fact, exercise stress testing can often be taken further and used to localise the level of AV block to either the AV nodal level, or the infra-nodal level. With sympathetic stimulation, AV nodal conduction is improved. However, this is not the case for infra-nodal conduction, and indeed, as atrial impulses reach the infra-nodal conduction system faster and faster, successive impulses encroach more and more on the refractory period. The most usual pattern of infra-nodal block then is abrupt loss of AV conduction, otherwise commonly referred to as Mobitz type II block. In severe cases, it is even possible to observe higher degrees of AV block and complete heart block. Such cases will always require a pacemaker implant, unless some reversible cause for the impaired AV conduction can be found.

2. To assess the robustness (or otherwise) of antegrade accessory pathway conduction

Some folks are born with so-called accessory pathways. These are basically connections between the atrium and ventricle at a point other than the AV node, and are generally composed of working myocardial cells. In some cases, accessory pathways conduct only in the antegrade direction (i.e. A→V), in others they conduct in the retrograde direction (V→A), and in still others, they are bidirectional. When they conduct in the antegrade direction, accessory pathways may activate the ventricular myocardium earlier than conduction through the AV node would - this is then known as pre-excitation and on the surface ECG, this is manifested as a delta wave. We would call this a Wolff-Parkinson-White pattern ECG, and if the patient were symptomatic, we would say the patient had Wolff-Parkinson-White syndrome.

Why would an exercise test be helpful in this context? It is helpful to think through this in a few steps:

(i) The feared complication of WPW is that of ventricular fibrillation (and therefore, sudden death). The reason for this is that in a normal individual, AV conduction is regulated by the AV node - the AVN has a property called decremental conduction, where the faster atrial impulses reach the node, the slower conduction through the node. This is why in a normal individual, atrial fibrillation (where atrial impulses may reach the AVN at rates of 600/min) does not translate into ventricular fibrillation and sudden death. In contrast, for patients with WPW, accessory pathway conduction is usually not decremental (since the pathways are composed of normal, working myocardial cells). Therefore, in such individuals, AF can result in VF. This is especially unfortunate as individuals with accessory pathways are also more prone to AF.

(ii) Therefore, risk stratification for SCD in WPW patients basically boils down to evaluating whether  the accessory pathway allows robust antegrade conduction. If the accessory pathway allows very rapid antegrade conduction, then the risk of AF degenerating into VF (and therefore sudden death) is higher.

Accurate assessment of the electrophysiological properties of accessory pathways can only be made in the EP lab. However, the exercise stress test can sometimes be useful as a non-invasive alternative. The idea is to evaluate the point at which accessory pathway conduction is lost when the atrial rate increases (as a result of exercise) - if this occurs easily, then the risk of ventricular fibrillation and sudden death will be low, and vice-versa.

This theory has been tested.  Daubert and colleagues demonstrated that (only) abrupt and complete loss of preexcitation during exercise confirms poor antegrade accessory pathway conduction a long anterograde APERP. In EP-speak, what they showed, in a predominantly adult prospective study, was that persistence of preexcitation during exercise stress showed a sensitivity of 96% (but a specificity of only 17%) in predicting either a SPERRI in AF of  less than 250ms or an APERP of less than 250ms. What this means is that while the exercise test has a reasonable negative predictive value (about 88%), it has quite poor positive predictive value (about 17%).

So, to summarise the above:

a) Report whether there is abrupt and complete loss of pre excitation during the exercise test. I would also state the maximum heart rate reached.

b) If there is abrupt and complete loss of pre excitation during the exercise test, and the patient is clinically asymptomatic (no faints / loss of consciousness), then the patient is most likely to be low risk for ventricular fibrillation.

c) However, the converse is not true - just because pre-excitation persists throughout the exercise test does not mean that the patient is high risk.

I think that's probably enough for a single post. I'll post some examples of (1) and (2) in the future, and also discuss more about (3) to (5).