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Delirium tremens is a risk factor for Takotsubo cardiomyopathy
International Journal of Cardiology 191 (2015) 185–186
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Delirium tremens is a risk factor for Takotsubo cardiomyopathy Parijat S. Joy a,⁎, Gagan Kumar b a b
Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, United States Department of Critical Care, Phoebe Putney Memorial Hospital, Albany, GA 31701, United States
a r t i c l e
i n f o
Article history: Received 12 April 2015 Accepted 30 April 2015 Available online 1 May 2015 Keywords: Takotsubo Alcohol Withdrawal Cardiomyopathy Delirium tremens
of coexisting TCMP was 1.53 times higher (95% confidence interval 1.03–2.29) in alcohol withdrawal and 4.38 times higher (95% CI 2.91– 6.59) in delirium tremens. The presence of TCMP did not affect mortality in AWS. Alcohol consumption adversely affects the cardiovascular system and causal association with dilated cardiomyopathy is known. To develop cardiomyopathy, prolonged duration of alcohol consumption of 5– 9 years is necessary [5]. Binge drinking that has higher likelihood for AWS increases risk for ischemic heart disease but has not been
Table 1 Demographical and clinical characteristics of Takotsubo cardiomyopathy in alcoholism.
Takotsubo cardiomyopathy (TCMP) is often precipitated by acute emotional or physical stress. Exact etiology of TCMP is unknown but catecholamine surge is implicated [1]. Alcohol withdrawal syndromes (AWSs) also cause catecholamine surge [2]. We hypothesize that AWSs are risk factors for TCMP. To test this hypothesis, we analyzed discharge data for patients (age ≥18 years) from the year 2008 to 2010, from the Nationwide Inpatient Sample, Healthcare Cost and Utilization Project (HCUP), Agency for Healthcare Research and Quality [3]. We used ICD-9-CM codes to identify alcoholism, alcohol withdrawal, delirium tremens and TCMP (429.83) [4]. We compared alcohol withdrawal and delirium tremens (DT) to those who consume alcohol but did not have a history of AWS. The primary outcome studied was frequency of TCMP in the three groups. The chi squared test was used to compare categorical variables and Wilcoxon rank test was used to compare continuous variables. Since two comparisons were made, P value was kept at 0.025. We used multivariable logistic regression to examine if AWS was independently associated with increased frequency of TCMP. We adjusted the model for age, gender, race and comorbidities associated with TCMP. We also examined whether, TCMP in AWS was associated with higher in-hospital mortality or inpatient length of stay. There were an estimated 885 patients with TCMP in patients with alcoholism. Demographical and clinical details are shown in Table 1. Frequency of TCMP in alcohol withdrawals (0.023%) and delirium tremens (0.059%) was significantly higher than those with alcoholism alone (0.016%). On adjusting for age, gender and risk factors, the odds ⁎ Corresponding author at: 200 Hawkins Drive, Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, United States. E-mail address: [email protected] (P.S. Joy).
http://dx.doi.org/10.1016/j.ijcard.2015.04.251 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
Alcoholism
Alcohol withdrawal
Delirium tremens
3,418,903 559 (0.016%) 41.1 78.3
774,481 177 (0.023%) 50.9 62.7
254,855 149 (0.059%) 32.4 56.7
69.8 8.8 3.1 2.6 15.6
52.1 11.4 5.5 5.9 25.2
72.8 0 0 3.3 23.9
35.1 31.1 17.1 14 2.6 62.4 90.1
48.4 26.1 11.7 13.8 0 68.3 97.2
30.3 37.2 6.2 13.3 12.9 60.7 94.3
13.8 9.2 0.9 55.3
15.2 5.5 2.7 28.6
6.9 0 0 40.3
Outcomes In hospital mortality Length of hospital stay⁎, median days
1.8 4 (2–7)
2.9 7 (4–11)
0 10.5 (7–14)
(IQR) Disposition⁎ Home Homecare Skilled nursing facilities Others
68.2 9.0 20.2 2.6
71.2 16.9 8.8 3.0
36.8 20.9 42.3 0
Total cases Takotsubo CMP Age b 55 years (%) Females (%) Race (%) White Black Hispanic Others Unknown Insurance⁎ (%) Private Medicare Medicaid Uninsured Others Teaching hospitals⁎ (%) Urban hospitals⁎ (%) Co-morbidities (%) Anxiety BMI N 40 Hyperthyroid Smoking⁎
⁎ P-value b 0.025.
186
P.S. Joy, G. Kumar / International Journal of Cardiology 191 (2015) 185–186
investigated for cardiomyopathy [6]. However, in rats, “binge” exposure to ethanol activates protein kinases causing cardiomyocyte death and catecholamine exposure initiates cardiomyocyte apoptosis within 1 h. Elevated epinephrine level triggers a reversible depression in contractility of the apical region of the heart coupled with basal hypercontractility due to switching of epinephrine signaling through the beta-2-adrenoceptor from Gs-activated cardiostimulant to Gi-activated cardiodepressant pathways [7]. In humans with TCMP, high levels of epinephrine, norepinephrine and dopamine have been measured [1]. In patients undergoing AWS too, high levels of catecholamines have been measured in the plasma and CSF [8]. Barring some case reports, it has never been shown that AWS is associated with TCMP. AWS can present with “heartburn” and nausea but there is only one case report of AWS leading to acute coronary syndrome (ACS). Often, TCMP presents with chest pain, ST elevation (90%), Q-waves (27%) and T-wave inversion (97%), resembling ACS [9]. Therefore in some patients presenting with AWS, symptoms resembling ACS could possibly be related to TCMP. This study highlights the importance of considering TCMP as a possibility in patients with AWS particularly DT which is associated with a mortality of 5% [10]. Conflict of interest None of the authors have any conflict of interest.
References [1] I.S. Wittstein, Neurohumoral features of myocardial stunning due to sudden emotional stress, N. Engl. J. Med. 352 (2005) 539–548. [2] A.A. Patkar, R. Gopalakrishnan, P.C. Naik, H.W. Murray, M.J. Vergare, C.A. Marsden, Changes in plasma noradrenaline and serotonin levels and craving during alcohol withdrawal, Alcohol Alcohol. 38 (May-Jun 2003) 224–231. [3] HCUP Nationwide Inpatient Sample (NIS). Healthcare Cost and Utilization Project (HCUP). 2011. Agency for Healthcare Research and Quality, Rockville, MD. [Online]. Available: www.hcup-us.ahrq.gov/nisoverview.jsp. [4] A. Elixhauser, C. Steiner, D.R. Harris, R.M. Coffey, Comorbidity measures for use with administrative data, Med. Care 36 (Jan 1998) 8–27. [5] L. Fauchier, D. Babuty, P. Poret, D. Casset-Senon, M.L. Autret, P. Cosnay, et al., Comparison of long-term outcome of alcoholic and idiopathic dilated cardiomyopathy, Eur. Heart J. 21 (Feb 2000) 306–314. [6] M. Roerecke, J. Rehm, Irregular heavy drinking occasions and risk of ischemic heart disease: a systematic review and meta-analysis, Am. J. Epidemiol. 171 (Mar 2010) 633–644. [7] H. Paur, P.T. Wright, M.B. Sikkel, M.H. Tranter, C. Mansfield, P. O'Gara, et al., High levels of circulating epinephrine trigger apical cardiodepression in a beta2adrenergic receptor/Gi-dependent manner: a new model of Takotsubo cardiomyopathy, Circulation, vol. 126 2012, pp. 697–706 United States. [8] R.J. Hawley, C.B. Nemeroff, G. Bissette, A. Guidotti, R. Rawlings, M. Linnoila, Neurochemical correlates of sympathetic activation during severe alcohol withdrawal, Alcohol. Clin. Exp. Res. 18 (Dec 1994) 1312–1316. [9] K. Tsuchihashi, K. Ueshima, T. Uchida, N. Oh-mura, K. Kimura, M. Owa, et al., Transient left ventricular apical ballooning without coronary artery stenosis: a novel heart syndrome mimicking acute myocardial infarction, J. Am. Coll. Cardiol. 38 (Jul 2001) 11–18. [10] D.A. Yost, Alcohol withdrawal syndrome, Am. Fam. Physician 54 (Aug 1996) 657–664 (669).
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Delirium tremens is a risk factor for Takotsubo cardiomyopathy Parijat S. Joy a,⁎, Gagan Kumar b a b
Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, United States Department of Critical Care, Phoebe Putney Memorial Hospital, Albany, GA 31701, United States
a r t i c l e
i n f o
Article history: Received 12 April 2015 Accepted 30 April 2015 Available online 1 May 2015 Keywords: Takotsubo Alcohol Withdrawal Cardiomyopathy Delirium tremens
of coexisting TCMP was 1.53 times higher (95% confidence interval 1.03–2.29) in alcohol withdrawal and 4.38 times higher (95% CI 2.91– 6.59) in delirium tremens. The presence of TCMP did not affect mortality in AWS. Alcohol consumption adversely affects the cardiovascular system and causal association with dilated cardiomyopathy is known. To develop cardiomyopathy, prolonged duration of alcohol consumption of 5– 9 years is necessary [5]. Binge drinking that has higher likelihood for AWS increases risk for ischemic heart disease but has not been
Table 1 Demographical and clinical characteristics of Takotsubo cardiomyopathy in alcoholism.
Takotsubo cardiomyopathy (TCMP) is often precipitated by acute emotional or physical stress. Exact etiology of TCMP is unknown but catecholamine surge is implicated [1]. Alcohol withdrawal syndromes (AWSs) also cause catecholamine surge [2]. We hypothesize that AWSs are risk factors for TCMP. To test this hypothesis, we analyzed discharge data for patients (age ≥18 years) from the year 2008 to 2010, from the Nationwide Inpatient Sample, Healthcare Cost and Utilization Project (HCUP), Agency for Healthcare Research and Quality [3]. We used ICD-9-CM codes to identify alcoholism, alcohol withdrawal, delirium tremens and TCMP (429.83) [4]. We compared alcohol withdrawal and delirium tremens (DT) to those who consume alcohol but did not have a history of AWS. The primary outcome studied was frequency of TCMP in the three groups. The chi squared test was used to compare categorical variables and Wilcoxon rank test was used to compare continuous variables. Since two comparisons were made, P value was kept at 0.025. We used multivariable logistic regression to examine if AWS was independently associated with increased frequency of TCMP. We adjusted the model for age, gender, race and comorbidities associated with TCMP. We also examined whether, TCMP in AWS was associated with higher in-hospital mortality or inpatient length of stay. There were an estimated 885 patients with TCMP in patients with alcoholism. Demographical and clinical details are shown in Table 1. Frequency of TCMP in alcohol withdrawals (0.023%) and delirium tremens (0.059%) was significantly higher than those with alcoholism alone (0.016%). On adjusting for age, gender and risk factors, the odds ⁎ Corresponding author at: 200 Hawkins Drive, Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, United States. E-mail address: [email protected] (P.S. Joy).
http://dx.doi.org/10.1016/j.ijcard.2015.04.251 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
Alcoholism
Alcohol withdrawal
Delirium tremens
3,418,903 559 (0.016%) 41.1 78.3
774,481 177 (0.023%) 50.9 62.7
254,855 149 (0.059%) 32.4 56.7
69.8 8.8 3.1 2.6 15.6
52.1 11.4 5.5 5.9 25.2
72.8 0 0 3.3 23.9
35.1 31.1 17.1 14 2.6 62.4 90.1
48.4 26.1 11.7 13.8 0 68.3 97.2
30.3 37.2 6.2 13.3 12.9 60.7 94.3
13.8 9.2 0.9 55.3
15.2 5.5 2.7 28.6
6.9 0 0 40.3
Outcomes In hospital mortality Length of hospital stay⁎, median days
1.8 4 (2–7)
2.9 7 (4–11)
0 10.5 (7–14)
(IQR) Disposition⁎ Home Homecare Skilled nursing facilities Others
68.2 9.0 20.2 2.6
71.2 16.9 8.8 3.0
36.8 20.9 42.3 0
Total cases Takotsubo CMP Age b 55 years (%) Females (%) Race (%) White Black Hispanic Others Unknown Insurance⁎ (%) Private Medicare Medicaid Uninsured Others Teaching hospitals⁎ (%) Urban hospitals⁎ (%) Co-morbidities (%) Anxiety BMI N 40 Hyperthyroid Smoking⁎
⁎ P-value b 0.025.
186
P.S. Joy, G. Kumar / International Journal of Cardiology 191 (2015) 185–186
investigated for cardiomyopathy [6]. However, in rats, “binge” exposure to ethanol activates protein kinases causing cardiomyocyte death and catecholamine exposure initiates cardiomyocyte apoptosis within 1 h. Elevated epinephrine level triggers a reversible depression in contractility of the apical region of the heart coupled with basal hypercontractility due to switching of epinephrine signaling through the beta-2-adrenoceptor from Gs-activated cardiostimulant to Gi-activated cardiodepressant pathways [7]. In humans with TCMP, high levels of epinephrine, norepinephrine and dopamine have been measured [1]. In patients undergoing AWS too, high levels of catecholamines have been measured in the plasma and CSF [8]. Barring some case reports, it has never been shown that AWS is associated with TCMP. AWS can present with “heartburn” and nausea but there is only one case report of AWS leading to acute coronary syndrome (ACS). Often, TCMP presents with chest pain, ST elevation (90%), Q-waves (27%) and T-wave inversion (97%), resembling ACS [9]. Therefore in some patients presenting with AWS, symptoms resembling ACS could possibly be related to TCMP. This study highlights the importance of considering TCMP as a possibility in patients with AWS particularly DT which is associated with a mortality of 5% [10]. Conflict of interest None of the authors have any conflict of interest.
References [1] I.S. Wittstein, Neurohumoral features of myocardial stunning due to sudden emotional stress, N. Engl. J. Med. 352 (2005) 539–548. [2] A.A. Patkar, R. Gopalakrishnan, P.C. Naik, H.W. Murray, M.J. Vergare, C.A. Marsden, Changes in plasma noradrenaline and serotonin levels and craving during alcohol withdrawal, Alcohol Alcohol. 38 (May-Jun 2003) 224–231. [3] HCUP Nationwide Inpatient Sample (NIS). Healthcare Cost and Utilization Project (HCUP). 2011. Agency for Healthcare Research and Quality, Rockville, MD. [Online]. Available: www.hcup-us.ahrq.gov/nisoverview.jsp. [4] A. Elixhauser, C. Steiner, D.R. Harris, R.M. Coffey, Comorbidity measures for use with administrative data, Med. Care 36 (Jan 1998) 8–27. [5] L. Fauchier, D. Babuty, P. Poret, D. Casset-Senon, M.L. Autret, P. Cosnay, et al., Comparison of long-term outcome of alcoholic and idiopathic dilated cardiomyopathy, Eur. Heart J. 21 (Feb 2000) 306–314. [6] M. Roerecke, J. Rehm, Irregular heavy drinking occasions and risk of ischemic heart disease: a systematic review and meta-analysis, Am. J. Epidemiol. 171 (Mar 2010) 633–644. [7] H. Paur, P.T. Wright, M.B. Sikkel, M.H. Tranter, C. Mansfield, P. O'Gara, et al., High levels of circulating epinephrine trigger apical cardiodepression in a beta2adrenergic receptor/Gi-dependent manner: a new model of Takotsubo cardiomyopathy, Circulation, vol. 126 2012, pp. 697–706 United States. [8] R.J. Hawley, C.B. Nemeroff, G. Bissette, A. Guidotti, R. Rawlings, M. Linnoila, Neurochemical correlates of sympathetic activation during severe alcohol withdrawal, Alcohol. Clin. Exp. Res. 18 (Dec 1994) 1312–1316. [9] K. Tsuchihashi, K. Ueshima, T. Uchida, N. Oh-mura, K. Kimura, M. Owa, et al., Transient left ventricular apical ballooning without coronary artery stenosis: a novel heart syndrome mimicking acute myocardial infarction, J. Am. Coll. Cardiol. 38 (Jul 2001) 11–18. [10] D.A. Yost, Alcohol withdrawal syndrome, Am. Fam. Physician 54 (Aug 1996) 657–664 (669).