© 2003 by European Society of Cardiology
CASE REPORT
Prolonged asystole during head-up tilt testing with clomipramine infusion
2nd Department of Cardiology, Onassis Cardiac Surgery Center Athens, Greece
Manuscript submitted 30 May 2002. Accepted after revision 19 March 2003.
Correspondence: Dionyssios I. Leftheriotis, MD, Onassis Cardiac Surgery Center, 2nd Department of Cardiology, 356 Syngrou Ave, 176 74 Athens, Greece. Tel.: +30-210-9493-372/000; Fax: +30-210-9493-373; E-mail: elbee{at}ath.forthnet.gr
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Abstract |
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This case report describes a patient with a history of neurocardiogenic syncope, who had had a negative head-up tilt test with isoprenaline, but he experienced a prolonged asystole during a head-up tilt test with clomipramine (serotonin reuptake inhibitor) 24 h later. This patient was successfully treated with fluoxetine.
Key Words: Neurocardiogenic syncope, clomipramine, tilt-test
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Introduction |
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Head-up tilt testing (HUT), with or without drugs, is the critical tool of choice for the diagnosis of the syndrome of neurocardiogenic syncope (NCS). Prolonged asystole during HUT has been reported to occur in 18% (>3 s) and 9.1% (>5 s) of patients with NCS[1,
2]. However, there are only a few reported cases describing asystole longer than 40 s during HUT or vasovagal syncope[3–6]. In this report, we describe a patient who experienced a 70 s long asystole during a HUT with clomipramine infusion (a serotonin reuptake inhibitor) and was successfully treated with fluoxetine. |
Case report |
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A 35-year-old man was referred because of two syncopal and three presyncopal episodes during the last 4 months, all preceded by nausea and sweating. The initial work-up including physical examination, chest X ray, electrocardiogram (ECG), complete blood count, serum electrolytes, fasting blood sugar, thyroid function studies, echocardiogram, stress test, neurological consultation and Holter ECG were normal. Then, the patient was subjected to a 30 min HUT at 60°, followed by isoprenaline infusion (2 µg/min of isoprenaline) for 15 more minutes[7]
. This test was negative for provocation of hypotension or syncope. On the following day, a second HUT at 60° was performed, using clomipramine as a challenge agent (5 mg infused during the first 5 min of the test)[8]. At the 10th minute of tilt, the patient suddenly lost consciousness and became pulseless and apnoeic. The patient was quickly returned to the supine position, atropine sulphate (1 mg) was intravenously administered and external cardiac massage was provided. Just before being intubated, he resumed sinus rhythm and regained consciousness a few seconds later. The ECG recording showed a prolonged asystole of 70 s, terminated by an escape beat. The duration of sinus pause was 72.5 s. Interestingly, the patient reported that this syncopal spell was a less dramatic experience than his two previous ones (Fig. 1).
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The patient was treated with fluoxetine hydrochloride for 6 months (20 mg daily). He was instructed to report any recurrence of symptoms, such as syncope or presyncope. Within this follow-up period, no presyncopal or syncopal episode was reported.
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Discussion |
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This case has several interesting issues. First of all, our patient demonstrated a long period of asystole (70 s) during clomipramine HUT. This is, to our knowledge, one of the longest asystoles ever reported during an episode of vasovagal syncope[3
–6]. Another remarkable observation is that although this patient had an asystolic response to the clomipramine HUT, he had a negative HUT with isoproterenol the day before. In our department, clomipramine is used as a challenge agent during HUT.
Clomipramine infusion causes an enhancement of central nervous system serotonergic activity by inhibiting serotonin reuptake in the synapse and increasing 5-HT1A receptors' stimulation. In a recent study, we have reported that clomipramine administration during the tilt test considerably increases its sensitivity, without loss of specificity and improves its diagnostic value[8]. As we have already shown, patients with neurocardiogenic syncope may have a more sensitive central serotonergic system than normal individuals[9].
Fluoxetine, that also inhibits serotonin reuptake and increases 5-HT receptors' stimulation, proved to be a successful treatment for our patient. During their chronic administration, serotonin reuptake inhibitors, such as fluoxetine, cause a continuous increase in extracellular serotonin concentration. The mechanism of their chronic action seems to be the downregulation of postsynaptic serotonin receptors. Their therapeutic efficacy is usually observed after 4 to 6 weeks of treatment, when serotonin receptors are downregulated[10–12]. In contrast to the acute inhibition of serotonin reuptake, that elicits the positive response to HUT, the chronic treatment with serotonin reuptake inhibitors seems to protect patients from stimulation of the serotonergic component of the vasovagal reflex.
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References |
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[1] Brignole M, Menozzi C, Gianfranchi L, et al. The clinical and prognostic significance of the asystolic response during the head-up tilt test. Eur J Card Pacing Electrophysiol 1992; 2: 109–113.
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[6] Baron-Esquivias G, Pedtrone A, Cayuelta A, et al. Long-term outcome of patients with asystole induced by head-up tilt test. Eur Heart J 2002; 23: 483–489.
[7] Task Force on Syncope. European Society of Cardiology. Guidelines on management (diagnosis and treatment) of syncope. Eur Heart J 2001; 22: 1256–1306.
[8] Theodorakis G, Markianos M, Zarvalis E, et al. Provocation of neurocardiogenic syncope by clomipramine administration during the head-up tilt test in vasovagal syndrome. J Am Coll Cardiol 2000; 36: 174–178.
[9] Theodorakis G, Markianos M, Livanis E, et al. Central serotonergic responsiveness in neurocardiogenic syncope. A clomipramine test challenge. Circulation 1998; 98: 2724–2730.
[10] Grubb BP and Kosinski DJ. Serotonin and syncope: an emerging connection? Eur J Card Pacing Electrophysiol 1995; 5: 306–314.
[11] Di Girolamo E, Di Iorio C, Sabatini P, et al. Effects of paroxetine hydrochloride, a selective serotonin reuptake inhibitor, on refractory vasovagal syncope: a randomized, double-blind, placebo-controlled study. J Am Coll Cardiol 1999; 33: 1227–1230.
[12] Rickels K and Schweizer E. Clinical overview of serotonin reuptake inhibitors. J Clin Psychiatry 1990; 51: 9–12.
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