Asystole after Exercise in Healthy Persons

Case Reports

Patient 1

A 34-year-old man had atypical chest pain and a history of multiple episodes of syncope and presyncope, all related to physical stress. Two syncopal episodes occurred immediately after weight lifting. Submaximal exercise test results did not indicate ischemia. However, 1.5 minutes into recovery, the patient developed sudden asystole (lasting for 32 seconds) with rare ventricular escape beats (Figure 1). This resulted in respiratory arrest, and chest massage was initiated by the supervising physician; the patient recovered just before being intubated. Fifteen months later, he had another syncopal episode while walking into the bathroom at night. A chest radiograph, a 12-lead electrocardiogram, 24-hour Holter monitoring, and an echocardiogram all yielded normal test results. Head-up tilt testing was done, and, after 4 minutes in the upright position, the patient became abruptly asystolic for 23 seconds without previous symptoms or hypotension (blood pressure before asystole, 123/92 mm Hg; heart rate, 92 beats per minute). He lost consciousness and made a slow recovery after returning to the supine position. With avoidance of strenuous exercise, the patient has remained free of syncope without drug or pacemaker therapy during 9 months of follow-up surveillance.

Patient 2

A 22-year-old man had four episodes of syncope in a 1-year period, all occurring during or immediately after playing basketball. During warm-up before a game, he had a syncopal spell while standing still after running. He reported several similar episodes that he shortened by lying supine. Echocardiography showed moderate concentric left ventricular hypertrophy without evidence of outflow tract obstruction and showed a left ventricular ejection fraction of 75%. The surface electrocardiogram was consistent with left ventricular hypertrophy, but arterial blood pressure measurements were repeatedly normal. One minute after maximal exercise testing, he developed a sudden onset of bradycardia associated with near syncope, and several 4- to 6-second periods of asystole were documented followed by sinus bradycardia with first-degree atrioventricular block. Thallium imaging results were normal. The results of a comprehensive electrophysiologic study were also normal. Ten minutes into head-up tilt table testing, the patient had vasodepressor syncope (systolic blood pressure, 60 mm Hg) accompanied by mild bradycardia (43 beats per minute). A repeated exercise test, with a scopolamine patch in place, showed normal results. Scopolamine was prescribed but was subsequently discontinued because of side effects. The patient has taken oral disopyramide for 38 months and has had an uneventful course during this time; he continues to play basketball.

Patient 3

A 35-year-old man had two presyncopal episodes, one immediately after strenuous exercise and the second after fighting a fire. His clinical evaluation was unremarkable. Echocardiographic results showed mild mitral valve prolapse without mitral regurgitation and showed normal left ventricular function. Exercise radionuclide ventriculographic results were normal. Eight minutes into recovery, while seated, the patient had sudden asystole for 15 seconds with a brief loss of consciousness followed by a slow sinus recovery at a rate of 10 to 20 beats per minute. Respiratory arrest occurred, but cardiac and respiratory function returned spontaneously. Comprehensive electrophysiologic study results were entirely normal. Head-up tilt table testing at baseline was unremarkable, but repeated testing using intravenous isoproterenol (0.025 µg/kg per minute) provoked vasodepressor syncope (blood pressure, 80/60 mm Hg) with relative bradycardia (heart rate decrease from 120 to 64 beats per minute) after 15 minutes in the upright position. The patient started receiving atenolol (25 mg per day); repeated head-up tilt test and exercise test results (maximal heart rate, 148 beats per minute; Bruce stage 8) were normal. While receiving atenolol, the patient has remained free of recurrent syncope after 9 months of follow-up.

Discussion

Single cases of asystole after exercise have been described previously, but the underlying mechanisms have been uncertain [4-7]. Our findings of positive head-up tilt test results in all three patients suggest that a variant of neurocardiogenic syncope may be one mechanism of asystole after exercise, but additional abnormalities in the autonomic control of the cardiovascular system seem to be involved.

Blood pressure control at rest and also in response to changing posture is mainly regulated through the baroreceptor reflex [8]. The response to exercise involves additional mechanisms [9] (such as increased sympathetic activity) that have been partly ascribed to the so-called “metaboreflex” activated by metabolites from ischemic muscles [10, 11]. After exercise, the heart rate decreases to baseline, although the blood pressure remains increased, despite continuing activation of this reflex by ongoing muscle ischemia. This phenomenon has been attributed to an exercise-induced up-regulation of the parasympathetic efferent tone, which, in the period after exercise, selectively depresses the heart rate without affecting the vascular bed and blood pressure [9, 11].

The mechanisms provoking neurocardiogenic syncope are probably initiated by a progressive decrease in venous return in the upright position, which is responsible for maximal stimulation of the sympathetic system. Echocardiographic studies have documented a progressive decrease in end-diastolic and end-systolic volumes during head-up tilt table testing, with a maximal increase in fractional shortening before syncope [12]. The strong sympathetic drive in the setting of a relatively empty heart leads to vigorous myocardial contraction, which, in susceptible persons, activates mechanoreceptors in the left ventricular wall (C-fibers) and causes a profound response of the afferent vagal nerve [13]. This vagal stimulus may trigger a sudden withdrawal of the neural efferent sympathetic activity (negative feedback loop) and may increase the efferent parasympathetic tone with subsequent vasodilation and progressive hypotension [14]. Because arterial hypotension usually precedes bradycardia, inactivation of the sympathetic efferent tone and consequent vasodilation may be the primary mechanism of syncope [15]. Bradycardia and asystole, as markers of the increased parasympathetic tone, play only a secondary role in most patients with vasodepressor syncope. This view is further supported by the fact that, in most patients, hypotension and syncope cannot be avoided by atrioventricular sequential pacing [15]. Infrequently, however, cardioinhibition leading to profound bradycardia or asystole may be the dominant mechanism responsible for symptoms.

In our patients, syncope and asystole typically occurred in the recovery period of exercise, when venous return was diminished (sitting position). The findings of positive results from head-up tilt testing suggest that all three patients had a low threshold to trigger an abnormal afferent parasympathetic response to decreased venous return, suggesting that venous pooling after exercise may have been one of the mechanisms triggering their asystole. However, the long latency between maximal activation of the mechanoreceptors (peak exercise) and the onset of syncope during late recovery in one of our patients (8 minutes after exercise) and in another of the previously reported patients (10 minutes after exercise) suggests that other mechanisms, such as inappropriate control of the sympathetic tone after exercise (for example, diminished sympathetic response to muscle ischemia after exercise), may play an additional role in some patients.

Based on these patients and the current understanding of neurocardiogenic syncope, it appears that asystole after exercise in otherwise healthy persons may represent a variant of this syndrome, in which the effect of increased efferent parasympathetic tone predominates over the effect of sympathetic withdrawal. The optimal management of patients with vasodepressor syncope is unknown. In theory, if initiation of the vasodepressor reflex can be prevented, the hypotension and bradycardia that follow its activation should be eliminated. Accordingly, therapy is generally directed at the underlying mechanisms rather than at the outcome. Although several drugs (including β-blockers [16], disopyramide [17], and scopolamine [18]) have been used, no consensus exists about whether drug therapy or implantation of pacemakers is beneficial in treating patients with this condition [19].