Civilian and military aviation programs require crewmembers to undergo flight physicals before their training and at regular intervals while continuing their flight duties. These physicals are similar to sports or occupational physicals in their intent to identify those individuals who might be at higher risk of negative personal or societal outcomes from their participation in related activities. The hypobaric environment encountered with flying creates many unusual demands on a person's cardiovascular and pulmonary systems, and several conditions can increase the risk of developing dysbarisms in that environment. This case presentation describes a routine flight physical performed for clearance of a young man to complete hypobaric chamber training in the U.S. Navy.
C.S. is a 26-yr-old male Naval officer who presented for a routine Navy flight physical. He denied any history of cardiac disease in his family as well as a personal history of drug or tobacco use. His review of systems was negative, and his past medical history and surgical history were unremarkable. He denied any history of cardiac disease in his family and any history of drug or tobacco use. His physical examination also was unremarkable, with normal cardiovascular and pulmonary examinations. His resting heart rate was in the high 40s, but he was asymptomatic, and he said that he was "pretty athletic."
As part of a Navy flight physical, some routine labs, a chest x-ray, and an electrocardiogram (ECG) were performed. His urinalysis, complete blood cell count, and basic chemistries were all within normal limits. His chest x-ray was reported as being normal. His ECG is shown in the Figure.
As a reminder, there are two major pacemakers in the heart. The sinoatrial (SA) node paces the atria and, in most cases, the ventricles through the internal conduction system of the heart. If the SA node's discharge rate slows too much or conduction is blocked, the ventricles can be paced by their own intrinsic pacemaker cells located within the atrioventricular (AV) junction. Rhythms paced from this anatomic area are known as "junctional rhythms" with a rate of 40-60 bpm. In the presence of a normal conduction system, impulses can be propagated in a retrograde direction to cause atrial contraction.
Introduction: AV Dissociation
AV dissociation should not be confused with AV block. AV block is a complete dissociation of atrial and ventricular activity. Causes of true AV dissociation include sinus bradycardia (usually below the patient‘s intrinsic AV escape rate), acceleration of an alternate pacemaker, or pause producers (16). AV dissociation is considered a symptom of an underlying rhythm disturbance, not a primary dysrhythmia (3). The overall incidence of AV dissociation is somewhere between approximately 0.5% and 1.4% (1). The incidence of isorhythmic dissociation only makes up a fraction of these cases. The incidence increases with general anesthesia exposure, digitalis intoxication, rheumatic heart disease, and recent myocardial infarction (1), as well as the use of antiarrhythmic therapies like procainamide, quinidine, and calcium-channel blockers (13). In fact, isorhythmic dissociation occurs in approximately 15% of patients who undergo enflurane anesthesia (1) and has been reported with other anesthetic agents such as halothane, nitrous oxide, and fentanyl (5). Advancing age and heart disease were predictors of its occurrence during anesthesia (1), and, possibly as a consequence of these factors, hypotension develops in some anesthetized patients who develop isorhythmic dissociation (8). When prolonged or clinically significant, the hypotension may need to be treated. Discontinuation of the anesthetic agent will reverse the hypotension and the dissociation (1), as do many other medications or simply ``waiting it out'' with spontaneous return to sinus rhythm (15). Calcium chloride (4), propranolol (5), and esmolol (15) all have been used successfully to break this rhythm. Epinephrine and atropine, like the inhaled anesthetics, are known to induce isorhythmic dissociation, possibly through an imbalance between the parasympathetic and sympathetic system control of heart rate and blood pressure (1,15), but they also may be effective treatments for isorhythmic dissociation conversion because of their sinus rate acceleration (5). However, please remember that, most times, no treatment is needed.
Isorhythmic dissociation occurs only when the sinus rate is close to a ventricular escape rate (6). Because sinus bradycardia with rates into the 40s is common in well-conditioned athletes, this is a population in which this finding may be seen more frequently (13). It often is found incidentally on resting ECGs, and the finding will resolve with increasing the heart rate above that of a typical escape rhythm. In contrast, in patients with complete AV block, the junctional escape rhythm typically will accelerate with exercise instead of converting to sinus rhythm as in isorhythmic dissociation (10). Isorhythmic dissociation occurs in up to 20% of endurance athletes (17).
There are two patterns of isorhythmic dissociation on ECG: Pattern I and II.
Pattern I has a P wave that ``wanders'' through the QRS and thus can be located to the right, to the left, or within the QRS, as if ``marching through it and back.'' Pattern II has a P wave that is fairly constant in its position relative to the QRS, usually within it or after it in the ST or T portions (7). Pattern I seems to be mediated by a biologic feedback loop responding to the heart rate, filling pressure/stroke volume, and its relation to arterial pressure. The mechanism for Pattern II is less clearly understood (1). It may represent transient isorhythmic dissociation in the presence of a more prolonged AV junctional rhythm with retrograde atrial conduction as proposed by Waldo (18) and possibly demonstrated by the cases in Levy and Edflstein's study (7).
Waldo and associates (18) conclude that true AV dissociation only occurs transiently when there is a junctional rhythm with retrograde capture of the atria. However, one would expect to see P wave inversion if there was retrograde capture of the atria. Unlike true AV junctional rhythms where the atria are depolarized by the AV junction because of a lack of sinus node activity, the P waves are not inverted but typically upright (5). In Waldo's series of patients, all the P waves were positive or biphasic in leads II, III, and aVF (18). They point to the constant temporal relationship between the junctional beat and the P wave as a sign of this retrograde atrial capture. This demonstrated that the morphology of the P wave is an inaccurate reflection of whether retrograde activation of the atria was occurring because studies have shown that synchronization with P wave oscillation as described occurred in animals with or without intact retrograde conduction (11).
The salient ECG findings of isorhythmic dissociation are 1) similar atrial and ventricular rates, in contrast to AV block where the atrial rate is usually faster than the ventricular rate; 2) varying P wave locations: before, within, or after the QRS complex, but always closely approximated (12) and appearing to oscillate slowly and rhythmically about the QRS complex (9); 3) no signs of ischemic ST-T changes or other arrhythmias (13); and 4) P waves are usually upright or biphasic in leads II, III, and aVF. If one sees atrial fusion beats, AV block is ruled out.
The demonstration of isorhythmic dissociation on ECG is dependent on many factors - fortuitous timing might be the most consistent variable. In this often intermittent finding, many variables determine the particular pattern on ECG, including the relative discharge rates of the pacemakers, the presence or absence of retrograde conduction, the hemodynamic consequences of atrial contraction timing and the body's response mechanism to its consequences, the response from atrial stretch mechanisms, the baroreceptor mediated responses, and the responsiveness of the sinus node to these forces (11).
Pathophysiology/Mechanism of Pattern I Isorhythmic Dissociation
AV dissociation is marked by separate atrial and ventricular electrical activity or ``beating'' with different pacemakers driving each of them separately. However, in isorhythmic dissociation there appears to be some dependency of one on the other despite appearing "dissociated" on first glance. Review of longer rhythm strips will elucidate this intrinsic relationship. So, what is the mechanism of this relationship? Many researchers have looked at this.
When two tissues with inherent electrical pulsativity are in contact, it has been shown that the two tissues will tend to develop synchronous rhythms, especially when their inherent rates are very similar because the slower tissue will accelerate to the rate of the faster tissue (14). In the heart, the atria and the ventricles represent these two tissues; both have intrinsic pacemakers that can cause asynchronous contractility in the presence of a block or when the rates of the two are vastly different such as in atrial fibrillation, represent these two tissues.
Isorhythmic dissociation occurs during periods when the rhythm alternates between the atrial rate and the junctional rate because the sinus pacemaker has slowed or the junctional pacemaker has accelerated (18). Levy and Zieske (8) felt that the most potent mechanism causing synchronization was caused by heart rate fluctuations induced by responses to arterial blood pressure fluctuations. Diederich (2) proposed that the proper mechanism for the sinus rate acceleration was not the baroreceptor response feedback but the stretching of sinus node fibers by atrial contraction against the closed tricuspid valve. Patel (11) further concluded that right atrial stretch might be an additional factor causing sinus acceleration.
Pauley and associates demonstrated the systematic slowing and accelerating of the atrial cycle in relation to a junctional rhythm in dogs. They showed that with the onset of a junctional rhythm, AV dissociation would start when the ventricular rate exceeded the sinus atrial rate. The sinus node would be captured in a retrograde fashion, synchronizing the ventricular and atrial rates. The sinus node would then accelerate, escaping from retrograde capture, and taking over as the pacing force as the rate increases above the junctional rate (12). This cycle may repeat over and over (12). This cycling can be correlated with respiratory cycling which increases and decreases venous return to the heart, thus affecting the stroke volume, which responsively increases and decreases the P-P interval, thus inducing an inherent sinus arrhythmia. The junctional R-R interval remains constant because it is unaffected by the respiratory cycle. This is what allows for the development of AV dissociation because as the sinus intervals get longer, a ventricular escape rhythm will develop. The P wave can be seen before, within, or after the QRS but often will eventually synchronize with the ventricle in a consistent pattern for many seconds at a time. The apparent oscillation of the P wave through the QRS complex occurs within a limited range of PR and RP intervals (11). There may be a period of a fixed RP period, after which the P-P interval shortens and the P wave again appears to the left of the QRS (as a PR interval instead of RP) (11).
The improper timing of atrial contraction in relation to ventricular contraction induced in isorhythmic dissociation, in addition to the shortening P-P cycle, which decreases atrial filling, may cause cardiac output reductions of up to 25% (1). Hypotension was seen when the P waves were located within the QRS complexes or were to the right of the QRS (1). Furthermore, AV valve regurgitation can occur when the atria and ventricles contract simultaneously, thus further reducing the cardiac output and exacerbating the blood pressure fall (1). This rhythm may occur intermittently with sinus rhythm or may be persistent, especially at rest, until higher heart rates are achieved, which breaks the relative synchronization (13). Prolonged Valsalva maneuvers often can "break" the AV synchronization and temporarily restore sinus rhythm, but many times, sinus rhythm is restored spontaneously (14).
In isorhythmic dissociation, as the PR interval shortens and the P wave appears within or after the QRS complex, ventricular filling decreases, which decreases cardiac output with a resulting decline in arterial pressure. This decline in pressure activates the baroreceptors that inhibit vagal stimulation of the heart, thus causing a rise in heart rate through SA node disinhibition. The P wave then begins to move to the left of the QRS and the PR interval lengthens, thus causing increased filling times, resulting in increased cardiac output and subsequent increased blood pressure. Increases in blood pressure are perceived in the baroreceptors that then stimulate the vagus to slow the heart rate to maintain a homeostatic state (15). Isorhythmic dissociation causes a marked unstabilizing effect on sinus rate as the blood pressure fluctuations cause just enough signal delay or lag to cause continual oscillation back and forth across the QRS axis (6). Thus this rhythm pattern can be viewed as a "negative feedback controlled physiological arrhythmia" (6). In the vast majority of younger persons who present with this ECG finding, they will be asymptomatic and the disorder will cause no significant physiologic effects. This control loop works well in young, healthy individuals, but it may not work as well in the elderly or those with other comorbid diseases, such as heart disease or those taking certain medications.
Management and Outcomes
C.S. was sent to a cardiologist for further evaluation. The cardiologist performed an exercise stress test (EST). The EST was conducted according to a Bruce protocol, during which the patient exercised for 15 min. He reached 17.50 metabolic equivalents (METs) and achieved 92% of his maximal heart rate. The exercise was stopped secondary to fatigue only. The test was negative for significant dysrhythmias or ST changes. The patient's AV dissociation resolved with higher heart rates than captured on his initial ECG. The cardiologist diagnosed the patient with isorhythmic dissociation of no clinical significance and cleared him for all flight duties.
Isorhythmic dissociation often is found only transiently on ECG, and in the vast majority of cases, it is a benign finding. However, caution should be exercised in calling this finding benign in those patients who are symptomatic, on cardiac medications, or have a history of significant cardiovascular disease without further cardiology consultation. In a young, otherwise healthy population with the salient ECG features and no historical clues to suspect otherwise, isorhythmic dissociation should be considered a benign form of AV dissociation (13). Patients with normal diastolic relaxation and ventricular compliance usually are not affected by the decreases in cardiac output and thus most often this condition is clinically insignificant (15). Have your patient do some flutter kicks for a minute or two (or other exercise) and repeat the ECG - the isorhythmic dissociation should resolve, and the patient should be cleared for flight duties and sports participation.
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