Prolonged Asystole during Head-Up Tilt Test in a Patient with Malignant Neurocardiogenic Syncope

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1 Case Report Prolonged Asystole during Head-Up Tilt Test in a Patient with Malignant Neurocardiogenic Syncope Takashi Tokano MD 1, Yuji Nakazato MD 2, Akitoshi Sasaki MD 3, Gaku Sekita MD 3, Masayuki Yasuda MD 3, Masataka Sumiyoshi MD 4, Hiroyuki Daida MD 3 1 Department of Cardiology, Juntendo Shizuoka Hospital 2 Department of Cardiology, Juntendo Urayasu Hospital 3 Department of Cardiology, Juntendo University School of Medicine 4 Department of Cardiology, Juntendo Nerima Hospital A 27 year-old man was taken to our emergency room after collapsing during a conference. The patient had a history of syncope twice since age 15. A marked sinus bradycardia and asystole were induced causing the patient to collapse when tested to stand up in the emergency room. Cardioinhibitory type neurocardiogenic syncope was considered to be the cause of the syncope. Therefore the patient was treated with oral disopyramide at a daily dose of 150 mg. Three weeks later, a head-up tilt test was performed for evaluation of drug effectiveness. However, a prolonged asystole for 24 seconds due to sinus arrest without escape beat was induced 7 minutes after starting the tilt at 80 degrees. Although the tilt table was returned to the flat position immediately, it took an additional 30 seconds for complete recovery of the patient s consciousness. Malignant cardioinhibitory type neurocardiogenic syncope with a prolonged asystole such as was found in this patient has rarely been observed. Treatment options should be discussed if the patient refuses pacemaker implantation. (J Arrhythmia 2008; 24: 76 80) Key words: Asystole, Neurocardiogenic syncope, Head-up tilt test Introduction Head-up tilt test (HUT) is useful for diagnosis of neurocardiogenic syncope and classification for the subtype of neurocardiogenic syncope. 1) A markedly prolonged asystole accompanied with syncope and convulsion is occasionally observed during HUT. We present a case in which a patient with neurocardiogenic syncope showed a prolonged asystole for over 20 seconds during HUT and had poor recovery after discontinuation of tilting while taking oral disopyramide. Case Report The patient was a healthy-appearing 27 year-old male. The patient was taken to our emergency care unit due to syncope in October, He had lost consciousness for a couple of minutes just after seeing one of his colleagues collapse during a Received 30, July, 2007: accepted 18, April, Address for Correspondence: Takashi Tokano MD, Department of Cardiology, Juntendo Shizuoka Hospital, 1129, Izunagaoka, Izunokunishi, Shizuoka, , Japan. TEL: , ext FAX: taka@med.juntendo.ac.jp 76

2 Tokano T Prolonged asystole during head-up tilt test conference. He had no previous history of illness; however he had a history of syncope twice since age 15. The first episode occurred when the patient witnessed his father receiving a head-injury. The second episode occurred during an argument with his father. In the emergency room, no abnormality was found on physical examinations, chest X-ray, electrocardiogram, routine blood tests and echocardiography (Figure 1). However, a marked sinus bradycardia and asystole were induced and the patient collapsed when being tested to stand up after these examinations (Figure 2). Cardioinhibitory type neurocardiogenic syncope was considered to be the cause of this episode. The patient had been treated with oral disopyramide at a daily dose of 150 mg since this episode. We also gave him general information to prevent syncope in case of neurocardiogenic syncope. Three weeks later, the patient visited our clinic without any symptoms, and head-up tilt testing (HUT) was performed for evaluation of drug effectiveness. However, a prolonged asystole of 24 seconds due to sinus arrest without escape beat was induced 7 minutes after starting the tilt at 80 degrees, although the tilt table was resumed to the flat position immediately after the bradycardia was induced (Figure 3). The patient showed syncope, apnea and convulsion at that time, and we needed to resuscitate him and give intravenous atropine sulfate at a dose of 0.5 mg. After administration of atropine sulfate, escape beats and then sinus beats were shown, and the blood pressure slowly recovered. It took more than 30 seconds for complete recovery of the patient s consciousness and spontaneous respiration due to low blood pressure. We recommended pacemaker implantation in this patient; however, the patient and his family strongly refused. Therefore, the patient has been treated with oral disopyramide again at a daily dose of 300 mg. The patient regularly visits our clinic, and has had no incidents of naturally-occurring syncope. Discussion Neurocardiogenic syncope has been considered to be the cause of recurrent unexplained syncope in some patients. HUT is useful for diagnosis and classification of the subtype of neurocardiogenic syncope. 1) The classification of neurocardiogenic syncope is helpful for considering the treatment for each case, and HUT guided therapy for neurocardiogenic syncope has been considered to be reasonable. 2) Patients with neurocardiogenic syncope who also show HUT-induced markedly prolonged asystole (over 3 seconds), so-called malignant neurocardiogenic syncope, are only reported in 1 9% of patients who have undergone HUT. 3 8) The presented case is a patient diagnosed with malignant neurocardiogenic syncope because he had asystole for 24 seconds during HUT and his recovery after discontinuation of tilting was extremely poor. I V1 II V2 III V3 avr V4 avl avf V5 V6 Figure 1 The 12 lead electrocardiogram just after arriving in the emergency room. No arrhythmia, ST-T change and the other specific abnormality was noted. 77

3 Just after standing 4 minutes after standing Asystole: 17.8 seconds Figure 2 The monitor electrocardiogram in the emergency room. A marked sinus bradycardia progressing to asystole with duration of 17.8 seconds was shown when the patient stood up after taking basic examinations. The patient collapsed at this time. The issues of malignant neurocardiogenic syncope are its reproducibility of syncope during HUT, treatment and outcome. The reproducibility of tiltinduced asystole was unexpectedly poor in previous reports. 9) In addition, Dhala A, et al. have shown that the asystolic response during HUT may occur in 4% of normal subjects. 9) In cases with cardioinhibitory type neurocardiogenic syncope, disopyramaide or beta receptor antagonists are empirically used; however, there is insufficient data for its effectiveness. 2,3,10 12) While medical therapy such as oral beta receptor antagonists and disopyramide has been a conventional treatment for prevention of syncope in cases with neurocardiogenic syncope, pacemaker implantation may provide further beneficial effects in cases with cardioinhibitory type neurocardiogenic syncope, especially for patients showing a prolonged asystole during HUT ) As described, the pacing therapy reduced the likelihood of syncope in patients with malignant neurocardiogenic syncope. However, the effectiveness of pacing therapy may not be predicted by the HUT induced bradycardia. 14) Pacemaker implantation was predominant over medical therapy; however, syncope still occurred after pacemaker implantation in 4 22% of such patients ) These results suggested that decision making for pacemaker implantation in patients with neurocardiogenic syncope must be carefully discussed in each case. Regarding previous reports, the prolonged asystole during HUT is considered to be non life-threatening and only affects quality of life 5,7) while Maloney JD et al. reported a case with the HUT induced asystole for 73 seconds 3) and Milstein S, et al. suggested the HUT induced prolonged asystole may cause sudden cardiac death. 4) In the present case, a prolonged asystole in the emergency room when standing up and HUTinduced prolonged asystole were documented; however, the spontaneous episodes of syncope seemed to be an emotional response. Therefore, in this case excessive vagal tone may have caused prolonged asystole especially when the patient underwent heavy stress. We explained to the patients about the possible mechanism of syncope and its prevention. Because emotional stress cannot be completely 78

4 Tokano T Prolonged asystole during head-up tilt test Tilt 0 degree 12.5 mm/sec ECG BP 100 mmhg 50 mmhg Asystole: 24 seconds Atropine sulfate 0.5 mg ECG 100 mmhg 50 mmhg BP 10 seconds Figure 3 The monitor electrocardiogram and blood pressure recorded by Task Force Monitor (TFM-3040, CNSystem Inc. Austria) during head-up tilt testing. Approximately 7 minutes after starting baseline tilt, a prolonged systole was shown. The patient had syncope, apnea and convulsion, therefore cardiopulmonary resuscitation was performed. After the administration of atropine sulfate at a dose of 0.5 mg, escape beats and then sinus beats were shown, however the hypotension continued and it took an additional 30 seconds for complete recovery of the cardiac rhythm, blood pressure and the patient s consciousness. ECG: electrocardiogram (lead II), BP: blood pressure eliminated from our daily life and this case showed extremely long asystole, disopyramide was given instead of beta receptor antagonists and sedatives. However, oral disopyramide at a daily dose of 150 mg could not prevent HUT-induced prolonged asystole in the presented case. Tilt training is expected to be an alternative and effective therapy as Reybrouck T, et al. reported that 95% of the patients with cardioinhibitory or mixed type neurocardiogenic syncope had no recurrence of syncope after this therapy. 18,19) In the present case, we will perform tilt training and psychological intervention 20) in addition to the medication. However a permanent pacemaker implantation seems to be the final option if the patient and his family would have agreed with the procedure considering the patient s condition. References 1) Sutton R, Petersen M, Brignole M, et al: Proposed classification for tilt induced vasovagal syncope. Eur J Cardiac Pacing Electrophysiol 1992; 2: ) Natale A, Sra J, Dhala A, et al: Different treatment strategies for neurocardiogenic syncope. PACE 1995; 18: ) Maloney JD, Jaeger FJ, Foud-Trazi FM, et al: Malignant vasovagal syncope: Prolonged asystole provoked by head-up tilt test. Cleve Clin J Med 1988; 55: ) Milstein S, Buetikofer J, Lesser J, et al: Cardiac asystole: A manifestation of neurally mediated hypotensio-bradycardia. J Am Coll Cardiol 1989; 14: ) Dahla A, Natale A, Sra J, et al: Relevance of asystole during head-up tilt testing. Am J Cardiol 1995; 75: ) Pentousis D, Cooper JP, Cobbe SM: Prolonged asystole induced by head up tilt test. Report of four cases and brief review of the prognostic significant and medical management. Haert 1997; 77: ) Baron-Esquivias G, Pedrote A, Cayuela A, et al: Longterm outcome of patients with asystole induced by headup tilt test. Eur Heart J 2002; 23: ) Chou HH, Lin KH, Luqman N, et al: Prolonged ventricular systole, sinus arrest, and paroxysmal atrial flutter-fibrillation: An uncommon presentation of vasovagal syncope. PACE 2003; 26: ) Manzillo GF, Romano M, Corrado G, et al: Reproducibility of asystole during head-up tilt testing in patients with neurally mediated sysncope. Europace 2002; 4: ) Morillo CA, Leitch JW, Yee R, et al: A placebocontrolled trial of intravenous and oral disopyramide for prevention of neurally mediated sysncope induced by 79

5 head-up tilt. J Am Coll Cardiol 1996; 22: ) Atiga WL, Rowe P, Calkins H, et al: Management of vasovagal syncope. J Cradiovasc Electrophysiol 1999; 10: ) Brignole M: Randomized clinical trial of neurally mediated syncope. J Cradiovasc Electrophysiol 2003; 14: S64 S69 13) Sra JS, Jazayeri MR, Avitall B, et al: Comparison of cardiac pacing with drug therapy in the treatment of neurocardiogenic (vasovagal) syncope with bradycardia or asystole. N Eng J Med 1993; 328: ) Sheldon R: Role of pacing in the treatmentof vasovagal syncope. Am J Cardiol 1999; 84: 26Q 32Q 15) Connolly SJ, Sheldon R, Roberts RS, et al: The North American vasovagal pacemaker study (VPS). Randomized trial of permanent cardiac pacing for the prevention of vasovagal syncope. J Am Coll Cadriol 1999; 33: ) Sutton R, Brignole M, Menozzi C, et al: Dual-chamber pacing in the treatment of neurally mediated tilt-positive cardioinhibitory syncope. Pacemaker versus no therapy: A multicenter randomized study. Circulation 2000; 102: ) Ammirati F, Colivicchi F, Santini M: Permanent cardiac pacing versus medical treatment for the prevention of recurrent vasovagal syncope: A multicenter, randomized, controlled trial. Circulation 2001; 104: ) Reybrouck T, Heidbruchel H, Werf FVD, et al: Tilt training: A treatment for malignant and recurrent neurocardiogenic syscope. PACE 2000; 23: ) Abe H, Sumiyoshi M, Kohshi K, et al: Effects of orthostatic self-training on head-up tilt testing for the prevention of tilt-induced neurocardiogenic sysncope: Comparison of pharmacological therapy. Clinical and Experimental Hypertension 2003; 25: ) Newton JL, Kenny RA, Baker CR: Cognitive behavioural therapy as a potential treatment for vasovagal/ neurocardiogenic syncope a pilot study. Europace 2003; 5: