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Acquired long QT syndrome and Torsades de Pointes related to donepezil use in a patient with Alzheimer disease
The Egyptian Heart Journal (2015) xxx, xxx–xxx
H O S T E D BY
Egyptian Society of Cardiology
The Egyptian Heart Journal www.elsevier.com/locate/ehj www.sciencedirect.com
CASE REPORT
Acquired long QT syndrome and Torsades de Pointes related to donepezil use in a patient with Alzheimer disease Ahmet Seyfeddin Gurbuz a,*, Semi Ozturk b, Emrah Acar c, Su¨leyman C¸agan Efe c, Taylan Akgun c, Alev Kilicgedik c, Ahmet Guler c, Cevat Kirma c a Kartal Kosuyolu Education and Research Hospital, Cardiology, Kozyatagı mah. Dr. Sukru kunt sok, No:4 Kadıkoy, Istanbul, Turkey b _ Turkey Haseki Education and Research Hospital, Cardiology, Denizer Caddesi, Cevizli Kavsßag˘ı, No:2 Kartal, Istanbul, c Kartal Kosuyolu Education and Research Hospital, Cardiology, Denizer Caddesi, Cevizli Kavsßag˘ı, _ No:2 Kartal, Istanbul, Turkey
Received 8 June 2015; accepted 24 July 2015
KEYWORDS Donepezil; AChIs; Torsades de Pointes; QT prolongation; Syncope
Abstract Acetylcholinesterase inhibitors are group of drugs commonly used in Alzheimer disease and have beneficial effects on treatment. Although they have many known side effects, cardiovascular side effects are rarely seen. We present a 84 year old female who was admitted to emergency service due to repetitive syncope episodes while taking donepezil. Her electrocardiogram showed QT prolongation and on follow-up a Torsades de Pointes episode occurred. Patient was discharged with normal corrected QT time after removal of donepezil. ª 2015 Production and hosting by Elsevier B.V. on behalf of Egyptian Society of Cardiology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
1. Introduction Donepezil is a widely used Acetylcholinesterase inhibitor (AChI) for Alzheimer’s disease treatment. It has remedial effects mainly on the cognitive functions and it increases patient compliance.1,2 It has gastrointestinal side effects such * Corresponding author. E-mail addresses: [email protected] (A.S. Gurbuz), [email protected] (S. Ozturk), dreacar44@ hotmail.com (E. Acar), [email protected] (S.C¸agan Efe), [email protected] (T. Akgun), [email protected] (A. Kilicgedik), [email protected] (A. Guler), ckirma@ hotmail.com (C. Kirma). Peer review under responsibility of Egyptian Society of Cardiology.
as nausea, vomiting, appetite loss, diarrhea albeit its beneficial effects. Rarely reported cardiac adverse effects were mainly bradycardia and related syncope.3 We reported a patient taking donepezil experienced syncope due to QT prolongation and subsequent Torsades de Pointes (TdP) not related to bradycardia. 2. Case report A 84 year old female patient was admitted to emergency service due to recurrent syncope episodes for two days. She mentioned palpitations beginning shortly before syncope. She described slowing down in her motor abilities, drowsiness, nausea and vomiting. She had been taking regularly donepezil
http://dx.doi.org/10.1016/j.ehj.2015.07.004 1110-2608 ª 2015 Production and hosting by Elsevier B.V. on behalf of Egyptian Society of Cardiology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Please cite this article in press as: Gurbuz AS et al. Acquired long QT syndrome and Torsades de Pointes related to donepezil use in a patient with Alzheimer disease, The Egypt Heart J (2015), http://dx.doi.org/10.1016/j.ehj.2015.07.004
2 10 mg for Alzheimer’s disease, ramipril 5 mg for hypertension and acetylsalicylic acid 100 mg for coronary artery disease. Her medical history revealed a thorough examination due to chest pain and syncope three years ago in another hospital. She had no history of antiarrhythmic drug use, family history of Long QT syndrome or sudden cardiac death. On admission, mean arterial pressure was 160/100 mmHg, mean heart rate was 65 bpm, and pulse oxygen saturation was 95%. ECG showed atrial fibrillation with deep T wave inversions on precordial derivations and QTc interval was measured 624 ms (calculated by Bazett’s formula) (Fig. 1A). Renal function tests, cardiac biomarkers and electrolytes were normal. Her carotid and vertebral arterial doppler ultrasonography were normal. Echocardiography showed normal left ventricular systolic function, left ventricular hypertrophy, mild mitral and tricuspid regurgitation. Cranial computed tomography showed only senile atrophy without any other pathologic signs. She was hospitalized in coronary care unit. During follow-up a sudden TdP episode occurred causing hemodynamic instability (Fig. 2). The rhythm spontaneously returned to her previous rhythm of atrial fibrillation. We removed donepezil out of treatment. We infused supplementary potassium and magnesium to prevent TdP recurrence. On 4th day, mean heart rate and QTc interval were measured 60 bpm and 500 ms respectively (Fig. 1B). On 10th day average heart rate and QTc interval were measured 70 bpm and 430 ms respectively (Fig. 1C). On follow-up there was no bradycardia or another TdP episode. She was discharged without donepezil. She did not have complaint of palpitations and syncope during follow-up for one year. Her ECG showed normal QTc values as well. We could have reached other hospital’s discharge reports during outpatient clinic follow-up. At the time of syncope three years ago, she had been taking donepezil for one year. Her coronary angiogram revealed 40% stenosis on left anterior descending artery. An electrophysiology study (EPS) was performed in order to clarify whether syncope was related to arrhythmia. EPS confirmed prolonged QRS and QT interval and revealed normal sinus and atrioventricular node functions. No arrhythmia was induced with programmed atrial and
Figure 1 At the time of admission ECG showed (A) atrial fibrillation and mean heart rate 65 bpm, and QTc interval was 624 msn on admission. (B) On 4th day average heart rate was 60 bpm, and QTc interval was 500 msn. (C) On 10th day mean heart rate was 70 bpm, and QTc interval was 430 msn.
A.S. Gurbuz et al.
Figure 2 rhythm.
Telemetry revealed Torsades de Pointes and follow-up
ventricular stimulation. 3 days after cessation of donepezil QT and QTc intervals were shortened 440 and 450 ms respectively (Fig. 3). She was discharged on 7th day of follow-up with a normal QTc interval and cautioned not to use donepezil three years ago. After two years of asymptomatic follow-up, another unaware neurologist prescribed donepezil for worsening of Alzheimer symptoms. She had been taking donepezil for one year at the time she was admitted to our emergency service due to syncope. 3. Discussion Alzheimer’s disease is the result of decrements in cognitive and intellectual functions and it causes impairments in memory, speech, sensation and thinking. Alzheimer drugs are more widely used owing to accrue of old aged population. AChIs are a promising drug group that are used for improvement in cognitive functions of Alzheimer patients.4 They inhibit acetylcholine disruption and thus increase intrasynaptic acetylcholine amount. Increased acetylcholine level also increases vagal activity via stimulating GABAergic and glycinergic inhibitory receptors.4,5 It is ineluctable that enhanced vagal activity affects gastrointestinal and cardiac functions. Despite their effects on amelioration of cognitive and intellectual functions, they have common gastrointestinal side effects and rare but serious cardiac side effects such as bradycardia, atrioventricular block, syncope and QT interval prolongation.6 Donepezil is an AChI and used in the treatment of Alzheimer disease. Long QT syndrome (LQTS) is characterized by prolongation of the corrected QT (QTc) interval on the surface electrocardiogram and is associated with precipitation of torsade de pointes (TdP) that may cause sudden death.7 It is mainly separated into acquired and congenital categories according to underlying etiology. Congenital LQTS was associated with many different gene mutations.8 Hypomagnesaemia, hypokalemia and specific drugs are the causes of acquired LQTS. Although it is accepted as an acquired syndrome, it is well known that silent K channel gene mutations could underlie or at least accompany the pathophysiology.9 The diagnosis of LQTS is facilitated with a probability score known as the ‘Schwartz score’ which takes ECG and familial and clinical features into account.10 In the literature, there are only five cases reporting QT prolongation associated with donepezil use.11–14 Being on 8th and 9th decades, possessing coronary atherosclerosis and risk
Please cite this article in press as: Gurbuz AS et al. Acquired long QT syndrome and Torsades de Pointes related to donepezil use in a patient with Alzheimer disease, The Egypt Heart J (2015), http://dx.doi.org/10.1016/j.ehj.2015.07.004
Long QT syndrome and Torsades de Pointes
3
Figure 3 ECG obtained in another hospital three years ago. Three days after syncope, ECG showed sinus rhythm and QTc interval was measured 450 msn.
factors, and multidrug usage are prominent and common features of patients experienced cardiovascular side effects in reported cases. Three cases experienced TdP. One of the cases with TdP had bradycardia and the other one had hypokalemia as a susceptibility factor. QT prolongation in two cases without TdP was attributed to concomitant benidipine and escitalopram usage with donepezil. We presented a patient experienced recurrent syncope episodes which are related to QT prolongation. In our case QT interval prolongation was confirmed by EPS. After donepezil usage for one year syncopes and palpitations suggesting arrhythmias recurred. Furthermore there was a two year symptom free interval after removing donepezil out of treatment. This observation suggested that donepezil is the likely cause of symptoms. Our patient’s Schwartz score was 6, confirming LQTS and suggesting a genetic surveillance. However, further investigation was not possible because of unavailability of genetic testing. The Naranjo probability scale confirmed that donepezil was the probable cause of QT interval prolongation, TdP and syncope in this patient.15 Although some studies did not find association of QT prolongation with donepezil, long-term use in a patient with risk factors including multidrug usage, advanced age, hypertension and related left ventricular hypertrophy could make prone to QT prolongation.16 Physicians should take these factors into account when prescribing donepezil and should keep in mind that QT prolongation and TdP may cause syncope apart from bradycardia in a patient taking AChIs. Conflict of interest
3.
4.
5.
6. 7.
8.
9. 10. 11.
12.
13.
Authors state that there is no conflict of interest in this article. 14.
References 15. 1. Haider B, Schmidt R, Schweiger C, Forstner T, Labek A, Lampl C. Medication adherence in patients with dementia: an Austrian cohort study. Alzheimer Dis Assoc Disord 2014;28(2):128–33. 2. Boada-Rovira M, Brodaty H, Cras P, Baloyannis S, Emre M, Zhang R, Bahra R, 322 Study Group. Efficacy and safety of donepezil in patients with Alzheimer’s disease: results of a global,
16.
multinational, clinical experience study. Drugs Aging 2004;21(1): 43–53. Gill SS, Anderson GM, Fischer HD, Bell CM, Li P, Normand SL, et al. Syncope and its consequences in patients with dementia receiving cholinesterase inhibitors: a population-based cohort study. Arch Intern Med 2009;169(9):867–73. Doody RS1, Ferris SH, Salloway S, Sun Y, Goldman R, Watkins WE, et al. Donepezil treatment of patients with MCI: a 48-week randomized, placebo-controlled trial. Neurology 2009;72(18): 1555–61. Wang J, Wang X, Irnaten M, et al. Endogenous acetylcholine and nicotine activation enhances GABAergic and glycinergic inputs to cardiac vagal neurons. J Neurophysiol 2003;89:2473–81. Howes LG. Cardiovascular effects of drugs used to treat Alzheimer’s disease. Drug Saf 2014;37(6):391–5. Kallergis EM, Goudis CA, Simantirakis EN, Kochiadakis GE, Vardas PE. Mechanisms, risk factors, and management of acquired long QT syndrome: a comprehensive review. Sci World J 2012;2012:212178. Schwartz PJ. Practical issues in the management of the long QT syndrome: focus on diagnosis and therapy. Swiss Med Wkly 2013;143:13843. Roden DM, Viswanathan PC. Genetics of acquired long QT syndrome. J Clin Invest 2005;115:2025–32. Schwartz PJ, Crotti L. QTc behavior during exercise and genetic testing for the long-QT syndrome. Circulation 2011;124:2181–4. Tanaka A, Koga S, Hiramatsu Y. Donepezil-induced adverse side effects of cardiac rhythm: 2 cases report of atrioventricular block and Torsade de Pointes. Intern Med 2009;48:1219–23. Takaya T, Okamoto M, Yodoi K, et al. Torsades de Pointes with QT prolongation related to donepezil use. J Cardiol 2009;54: 507–11. Shinozaki K. Shortening of donepezil-induced QTc prolongation with a change in the interacting drug, after electrocardiograph monitoring by community pharmacists: a case report. Yakugaku Zasshi 2012;132(2):237–41. Leitch A1, McGinness P, Wallbridge D. Calculate the QT interval in patients taking drugs for dementia. BMJ 2007;335(7619):557. Naranjo CA, Busto U, Sellers EM. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981;14:239–45. Igeta H, Suzuki Y, Tajiri M, Someya T. Cardiovascular pharmacodynamics of donepezil hydrochloride on the PR and QT intervals in patients with dementia. Hum Psychopharmacol 2014; 29(3):292–4.
Please cite this article in press as: Gurbuz AS et al. Acquired long QT syndrome and Torsades de Pointes related to donepezil use in a patient with Alzheimer disease, The Egypt Heart J (2015), http://dx.doi.org/10.1016/j.ehj.2015.07.004
H O S T E D BY
Egyptian Society of Cardiology
The Egyptian Heart Journal www.elsevier.com/locate/ehj www.sciencedirect.com
CASE REPORT
Acquired long QT syndrome and Torsades de Pointes related to donepezil use in a patient with Alzheimer disease Ahmet Seyfeddin Gurbuz a,*, Semi Ozturk b, Emrah Acar c, Su¨leyman C¸agan Efe c, Taylan Akgun c, Alev Kilicgedik c, Ahmet Guler c, Cevat Kirma c a Kartal Kosuyolu Education and Research Hospital, Cardiology, Kozyatagı mah. Dr. Sukru kunt sok, No:4 Kadıkoy, Istanbul, Turkey b _ Turkey Haseki Education and Research Hospital, Cardiology, Denizer Caddesi, Cevizli Kavsßag˘ı, No:2 Kartal, Istanbul, c Kartal Kosuyolu Education and Research Hospital, Cardiology, Denizer Caddesi, Cevizli Kavsßag˘ı, _ No:2 Kartal, Istanbul, Turkey
Received 8 June 2015; accepted 24 July 2015
KEYWORDS Donepezil; AChIs; Torsades de Pointes; QT prolongation; Syncope
Abstract Acetylcholinesterase inhibitors are group of drugs commonly used in Alzheimer disease and have beneficial effects on treatment. Although they have many known side effects, cardiovascular side effects are rarely seen. We present a 84 year old female who was admitted to emergency service due to repetitive syncope episodes while taking donepezil. Her electrocardiogram showed QT prolongation and on follow-up a Torsades de Pointes episode occurred. Patient was discharged with normal corrected QT time after removal of donepezil. ª 2015 Production and hosting by Elsevier B.V. on behalf of Egyptian Society of Cardiology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
1. Introduction Donepezil is a widely used Acetylcholinesterase inhibitor (AChI) for Alzheimer’s disease treatment. It has remedial effects mainly on the cognitive functions and it increases patient compliance.1,2 It has gastrointestinal side effects such * Corresponding author. E-mail addresses: [email protected] (A.S. Gurbuz), [email protected] (S. Ozturk), dreacar44@ hotmail.com (E. Acar), [email protected] (S.C¸agan Efe), [email protected] (T. Akgun), [email protected] (A. Kilicgedik), [email protected] (A. Guler), ckirma@ hotmail.com (C. Kirma). Peer review under responsibility of Egyptian Society of Cardiology.
as nausea, vomiting, appetite loss, diarrhea albeit its beneficial effects. Rarely reported cardiac adverse effects were mainly bradycardia and related syncope.3 We reported a patient taking donepezil experienced syncope due to QT prolongation and subsequent Torsades de Pointes (TdP) not related to bradycardia. 2. Case report A 84 year old female patient was admitted to emergency service due to recurrent syncope episodes for two days. She mentioned palpitations beginning shortly before syncope. She described slowing down in her motor abilities, drowsiness, nausea and vomiting. She had been taking regularly donepezil
http://dx.doi.org/10.1016/j.ehj.2015.07.004 1110-2608 ª 2015 Production and hosting by Elsevier B.V. on behalf of Egyptian Society of Cardiology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Please cite this article in press as: Gurbuz AS et al. Acquired long QT syndrome and Torsades de Pointes related to donepezil use in a patient with Alzheimer disease, The Egypt Heart J (2015), http://dx.doi.org/10.1016/j.ehj.2015.07.004
2 10 mg for Alzheimer’s disease, ramipril 5 mg for hypertension and acetylsalicylic acid 100 mg for coronary artery disease. Her medical history revealed a thorough examination due to chest pain and syncope three years ago in another hospital. She had no history of antiarrhythmic drug use, family history of Long QT syndrome or sudden cardiac death. On admission, mean arterial pressure was 160/100 mmHg, mean heart rate was 65 bpm, and pulse oxygen saturation was 95%. ECG showed atrial fibrillation with deep T wave inversions on precordial derivations and QTc interval was measured 624 ms (calculated by Bazett’s formula) (Fig. 1A). Renal function tests, cardiac biomarkers and electrolytes were normal. Her carotid and vertebral arterial doppler ultrasonography were normal. Echocardiography showed normal left ventricular systolic function, left ventricular hypertrophy, mild mitral and tricuspid regurgitation. Cranial computed tomography showed only senile atrophy without any other pathologic signs. She was hospitalized in coronary care unit. During follow-up a sudden TdP episode occurred causing hemodynamic instability (Fig. 2). The rhythm spontaneously returned to her previous rhythm of atrial fibrillation. We removed donepezil out of treatment. We infused supplementary potassium and magnesium to prevent TdP recurrence. On 4th day, mean heart rate and QTc interval were measured 60 bpm and 500 ms respectively (Fig. 1B). On 10th day average heart rate and QTc interval were measured 70 bpm and 430 ms respectively (Fig. 1C). On follow-up there was no bradycardia or another TdP episode. She was discharged without donepezil. She did not have complaint of palpitations and syncope during follow-up for one year. Her ECG showed normal QTc values as well. We could have reached other hospital’s discharge reports during outpatient clinic follow-up. At the time of syncope three years ago, she had been taking donepezil for one year. Her coronary angiogram revealed 40% stenosis on left anterior descending artery. An electrophysiology study (EPS) was performed in order to clarify whether syncope was related to arrhythmia. EPS confirmed prolonged QRS and QT interval and revealed normal sinus and atrioventricular node functions. No arrhythmia was induced with programmed atrial and
Figure 1 At the time of admission ECG showed (A) atrial fibrillation and mean heart rate 65 bpm, and QTc interval was 624 msn on admission. (B) On 4th day average heart rate was 60 bpm, and QTc interval was 500 msn. (C) On 10th day mean heart rate was 70 bpm, and QTc interval was 430 msn.
A.S. Gurbuz et al.
Figure 2 rhythm.
Telemetry revealed Torsades de Pointes and follow-up
ventricular stimulation. 3 days after cessation of donepezil QT and QTc intervals were shortened 440 and 450 ms respectively (Fig. 3). She was discharged on 7th day of follow-up with a normal QTc interval and cautioned not to use donepezil three years ago. After two years of asymptomatic follow-up, another unaware neurologist prescribed donepezil for worsening of Alzheimer symptoms. She had been taking donepezil for one year at the time she was admitted to our emergency service due to syncope. 3. Discussion Alzheimer’s disease is the result of decrements in cognitive and intellectual functions and it causes impairments in memory, speech, sensation and thinking. Alzheimer drugs are more widely used owing to accrue of old aged population. AChIs are a promising drug group that are used for improvement in cognitive functions of Alzheimer patients.4 They inhibit acetylcholine disruption and thus increase intrasynaptic acetylcholine amount. Increased acetylcholine level also increases vagal activity via stimulating GABAergic and glycinergic inhibitory receptors.4,5 It is ineluctable that enhanced vagal activity affects gastrointestinal and cardiac functions. Despite their effects on amelioration of cognitive and intellectual functions, they have common gastrointestinal side effects and rare but serious cardiac side effects such as bradycardia, atrioventricular block, syncope and QT interval prolongation.6 Donepezil is an AChI and used in the treatment of Alzheimer disease. Long QT syndrome (LQTS) is characterized by prolongation of the corrected QT (QTc) interval on the surface electrocardiogram and is associated with precipitation of torsade de pointes (TdP) that may cause sudden death.7 It is mainly separated into acquired and congenital categories according to underlying etiology. Congenital LQTS was associated with many different gene mutations.8 Hypomagnesaemia, hypokalemia and specific drugs are the causes of acquired LQTS. Although it is accepted as an acquired syndrome, it is well known that silent K channel gene mutations could underlie or at least accompany the pathophysiology.9 The diagnosis of LQTS is facilitated with a probability score known as the ‘Schwartz score’ which takes ECG and familial and clinical features into account.10 In the literature, there are only five cases reporting QT prolongation associated with donepezil use.11–14 Being on 8th and 9th decades, possessing coronary atherosclerosis and risk
Please cite this article in press as: Gurbuz AS et al. Acquired long QT syndrome and Torsades de Pointes related to donepezil use in a patient with Alzheimer disease, The Egypt Heart J (2015), http://dx.doi.org/10.1016/j.ehj.2015.07.004
Long QT syndrome and Torsades de Pointes
3
Figure 3 ECG obtained in another hospital three years ago. Three days after syncope, ECG showed sinus rhythm and QTc interval was measured 450 msn.
factors, and multidrug usage are prominent and common features of patients experienced cardiovascular side effects in reported cases. Three cases experienced TdP. One of the cases with TdP had bradycardia and the other one had hypokalemia as a susceptibility factor. QT prolongation in two cases without TdP was attributed to concomitant benidipine and escitalopram usage with donepezil. We presented a patient experienced recurrent syncope episodes which are related to QT prolongation. In our case QT interval prolongation was confirmed by EPS. After donepezil usage for one year syncopes and palpitations suggesting arrhythmias recurred. Furthermore there was a two year symptom free interval after removing donepezil out of treatment. This observation suggested that donepezil is the likely cause of symptoms. Our patient’s Schwartz score was 6, confirming LQTS and suggesting a genetic surveillance. However, further investigation was not possible because of unavailability of genetic testing. The Naranjo probability scale confirmed that donepezil was the probable cause of QT interval prolongation, TdP and syncope in this patient.15 Although some studies did not find association of QT prolongation with donepezil, long-term use in a patient with risk factors including multidrug usage, advanced age, hypertension and related left ventricular hypertrophy could make prone to QT prolongation.16 Physicians should take these factors into account when prescribing donepezil and should keep in mind that QT prolongation and TdP may cause syncope apart from bradycardia in a patient taking AChIs. Conflict of interest
3.
4.
5.
6. 7.
8.
9. 10. 11.
12.
13.
Authors state that there is no conflict of interest in this article. 14.
References 15. 1. Haider B, Schmidt R, Schweiger C, Forstner T, Labek A, Lampl C. Medication adherence in patients with dementia: an Austrian cohort study. Alzheimer Dis Assoc Disord 2014;28(2):128–33. 2. Boada-Rovira M, Brodaty H, Cras P, Baloyannis S, Emre M, Zhang R, Bahra R, 322 Study Group. Efficacy and safety of donepezil in patients with Alzheimer’s disease: results of a global,
16.
multinational, clinical experience study. Drugs Aging 2004;21(1): 43–53. Gill SS, Anderson GM, Fischer HD, Bell CM, Li P, Normand SL, et al. Syncope and its consequences in patients with dementia receiving cholinesterase inhibitors: a population-based cohort study. Arch Intern Med 2009;169(9):867–73. Doody RS1, Ferris SH, Salloway S, Sun Y, Goldman R, Watkins WE, et al. Donepezil treatment of patients with MCI: a 48-week randomized, placebo-controlled trial. Neurology 2009;72(18): 1555–61. Wang J, Wang X, Irnaten M, et al. Endogenous acetylcholine and nicotine activation enhances GABAergic and glycinergic inputs to cardiac vagal neurons. J Neurophysiol 2003;89:2473–81. Howes LG. Cardiovascular effects of drugs used to treat Alzheimer’s disease. Drug Saf 2014;37(6):391–5. Kallergis EM, Goudis CA, Simantirakis EN, Kochiadakis GE, Vardas PE. Mechanisms, risk factors, and management of acquired long QT syndrome: a comprehensive review. Sci World J 2012;2012:212178. Schwartz PJ. Practical issues in the management of the long QT syndrome: focus on diagnosis and therapy. Swiss Med Wkly 2013;143:13843. Roden DM, Viswanathan PC. Genetics of acquired long QT syndrome. J Clin Invest 2005;115:2025–32. Schwartz PJ, Crotti L. QTc behavior during exercise and genetic testing for the long-QT syndrome. Circulation 2011;124:2181–4. Tanaka A, Koga S, Hiramatsu Y. Donepezil-induced adverse side effects of cardiac rhythm: 2 cases report of atrioventricular block and Torsade de Pointes. Intern Med 2009;48:1219–23. Takaya T, Okamoto M, Yodoi K, et al. Torsades de Pointes with QT prolongation related to donepezil use. J Cardiol 2009;54: 507–11. Shinozaki K. Shortening of donepezil-induced QTc prolongation with a change in the interacting drug, after electrocardiograph monitoring by community pharmacists: a case report. Yakugaku Zasshi 2012;132(2):237–41. Leitch A1, McGinness P, Wallbridge D. Calculate the QT interval in patients taking drugs for dementia. BMJ 2007;335(7619):557. Naranjo CA, Busto U, Sellers EM. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981;14:239–45. Igeta H, Suzuki Y, Tajiri M, Someya T. Cardiovascular pharmacodynamics of donepezil hydrochloride on the PR and QT intervals in patients with dementia. Hum Psychopharmacol 2014; 29(3):292–4.
Please cite this article in press as: Gurbuz AS et al. Acquired long QT syndrome and Torsades de Pointes related to donepezil use in a patient with Alzheimer disease, The Egypt Heart J (2015), http://dx.doi.org/10.1016/j.ehj.2015.07.004