- Email: [email protected]
Genetic basis of sudden cardiac death due to emotional trauma in apparently healthy individuals
518
Letters to the Editor
Table 1 Multivariate analysis of one- and 12-month major adverse cardiac events after acute myocardial infarction.
Gender Age IHD history Diabetes Hypertension Dyslipidemia Smoking Family history Killip class higher than II
One-month MACE
12-month MACE
p value
Odd ratio (95% CI)
p value
Odd ratio (95% CI)
0.85 b0.01 0.06 0.06 0.43 b0.05 b0.05 0.52 b0.01
1.03 (0.71–1.50) 1.03 (1.02–1.05) 1.46 (0.97–2.20) 1.37 (0.99–1.89) 1.13 (0.83–1.54) 2.28 (1.16–4.49) 1.54 (1.07–2.21) 1.26 (0.62–2.55) 3.63 (2.76–4.91)
0.78 b 0.01 b 0.01 b 0.01 0.32 b 0.01 0.06 0.34 b 0.01
0.96 (0.73–1.27) 1.02 (1.01–1.03) 1.55 (1.15–2.09) 1.37 (1.09–1.73) 1.11 (0.89–1.38) 1.94 (1.27–2.96) 1.28 (0.99–1.64) 1.23 (0.79–1.91) 2.10 (1.68–2.63)
MACE; major adverse cardiac event, IHD; Ischemic heart disease, CI; confidence interval.
in-hospital mortality in women compared with men. Even though the baseline characteristics were worse in women, the short- and longterm outcomes were not different between male and female patients undergoing PCI with DES.
This study was carried out with the support of the Korean Circulation Society (KCS) in the memorandum of the 50th Anniversary of the KCS. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [6]. References [1] Reina A, Colmenerom M, AguayodeHoyos E, et al. Gender differences in management and outcome of patients with acute myocardial infarction. Int J Cardiol 2007;16:389–95. [2] Lee KH, Jeong MH, Ahn YK, et al, Korea Acute Myocardial Infarction Registry (KAMIR) Investigators. Gender differences of success rate of percutaneous coronary intervention and short term cardiac events in Korea Acute Myocardial Infarction Registry. Int J Cardiol 2008;130:227–34. [3] Berger JS, Elliott L, Gallup D, et al. Sex differences in mortality following acute coronary syndromes. JAMA 2009;302:874–82. [4] Gan SC, Beaver SK, Houck PM, et al. Treatment of acute myocardial infarction and 30-day mortality among women and men. N Engl J Med 2000;343:8–15. [5] Chang WC, Kaul P, Westerhout CM, et al. Impact of sex on long-term mortality from acute myocardial infarction vs unstable angina. Arch Intern Med 2003;163:2476–84. [6] Coasts AJ. Ethical authorship and publishing. Int J Cardiol 2009;131:149–50.
0167-5273/$ – see front matter © 2010 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2010.02.028
Genetic basis of sudden cardiac death due to emotional trauma in apparently healthy individuals Kenan Yalta ⁎, Okan Onur Turgut, Mehmet Birhan Yilmaz, Ahmet Yilmaz, Izzet Tandogan Cumhuriyet University, Cardiology Department, Sivas, 58100, Turkey
a r t i c l e
i n f o
Article history: Received 12 November 2009 Accepted 30 November 2009 Available online 19 January 2010 Keywords: Emotional trauma Sudden cardiac death Ion channelopathy Genetic basis
In their recently published article, Babu V et al. reported several sudden deaths after the demise of a renowned politician in India [1]. The sudden deaths in this article were reported to be strongly associated with emotional trauma possibly leading to a variety of conditions described as heart attack etc. The authors particularly propounded TTC as the possible underlying etiology of sudden deaths [1]. However, TTC has been regarded as a typically benign and reversible entity of postmenopausal women with a recent history of emotional stress [2]. On the other hand, some authors reported higher rates of malign ventricular arrhythmias and mortality in patient series with TTC compared to previous reports [3]. Similarly a case with cardiac asystole due to TTC with successful resuscitation was also reported previously [4]. We agree with the
⁎ Corresponding author. E-mail address: [email protected] (K. Yalta).
authors that TTC might have led to SCDs in a group of victims. However, this might have constituted only a minority due to the generally accepted benign nature and female gender predilection of this entity (majority of victims reported in the article by Babu V et al. were male [1]). Several theories have been propounded regarding the exact mechanisms of SCD due to emotional trauma. Emotional stress is closely associated with sympathetic system hyperactivation that may trigger some fatal events including acute coronary syndromes or may induce malign ventricular arrhythmias in arrhythmia-prone patients. QT interval prolongation is well known to be associated with SCD. Emotional stress was reported to prolong corrected QT interval possibly in the setting of a congenital long QT syndrome (LQTS) with a borderline QT interval [5]. Significant QT interval prolongation was also demonstrated to occur by the onset of active mental stress indicating the effects of adrenergic activation on repolarization [6]. QT interval prolongation induced by active mental stress may help comprehend the link between sudden stress and malign arrhythmias [6]. Genetically determined arrhythmogenic entities (catecholaminergic ventricular tachycardia (VT), ion channelopathies including congenital LQTS etc.) have been considered as important etiologies of SCD, particularly in the young. Ion channelopathies may be overt or obscure with regard to resting ECG signs, and are accompanied by a spectrum of clinical symptoms (asymptomatic to syncopal attacks or SCD) that may emerge in the presence of some triggering factors. Subclinical mutations of LQTS genes have also been of clinical importance, and were found to account for drug- induced malign arrhythmic events [7]. Due to a compensated or a mild ion channelopathy (with a normal or borderline resting ECG), clinical manifestations may remain silent unless the patient encounters
Letters to the Editor
external triggering factors including QT interval prolonging drugs [7], severe emotional trauma etc. Therefore, some of the victims reported in the article by Babu V et al. [1] (particularly the relatively young ones in whom the SCDs were not clinically suggestive of any apparent etiology including acute coronary syndromes or other structural heart disease etc.) might have harboured some kind of genetically determined arrhythmogenic conditions including ion channelopathies (with normal or abnormal resting ECGs) that might lead to SCDs in response to a sudden and severe emotional trauma. Thorough analysis and genetic screening of families of these victims may confirm this suggestion, and may help take preventive measures for the family members against SCD. In conclusion, the first manifestation of a genetically determined ion channelopathy may be SCD. However, ion channelopathies may be easily ignored when they are not accompanied by ECG signs and clinical symptoms, and may remain clinically dormant unless the patient faces severe triggering factors (drugs, severe emotional stress etc.). A portion of sudden deaths due to emotional trauma may be attributable to genetically determined arrhythmogenic entities including ion channelopathies, particularly in relatively young and apparently healthy victims suggesting thorough examination and further analysis (including genetic screening) of the family members of these victims for prevention of SCD.
519
The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [8]. References [1] Babu V, Paul N. Sudden deaths following the unexpected demise of a popular politician in India. Int J Cardiol 2010;145(2):266–7. [2] Bybee KA, Kara T, Prasad A, et al. Systematic review: transient left ventricular apical ballooning: a syndrome that mimics ST-segment elevation myocardial infarction. Ann Intern Med 2004;141(11):858–65. [3] Bonello L, Com O, Ait-Moktar O, et al. Ventricular arrhythmias during Tako-tsubo syndrome. Int J Cardiol 2008;128(2):e50–3. [4] Bahlmann E, Krause K, Häerle T, van der Schalk H, Kuck KH. Cardiac arrest and successful resuscitation in a patient with Tako-Tsubo cardiomyopathy. Int J Cardiol 2008;130(1):e4–6. [5] Batchvarov VN, Bajpai A, Behr E. Prolongation of the QT interval and postextrasystolic augmentation of the TU-wave during emotional stress. Indian Pacing Electrophysiol J 2008;8(2):146–8. [6] Andrássy G, Szabo A, Ferencz G, Trummer Z, Simon E, Tahy A. Mental stress may induce QT-interval prolongation and T-wave notching. Ann Noninvasive Electrocardiol 2007;12(3):251–9. [7] Makita N, Horie M, Nakamura T, et al. Drug-induced long-QT syndrome associated with a subclinical SCN5A mutation. Circulation 2002;106(10):1269–74. [8] Coats AJ. Ethical authorship and publishing. Int J Cardiol 2009;131:149–50.
0167-5273/$ – see front matter © 2009 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2009.11.060
Genetic basis of sudden cardiac death due to emotional trauma in apparently healthy individuals: Commentary Varsha Babu a, Navin Paul b,⁎ a b
Bridgeport Hospital/Yale University Internal Medicine Residency Program, Bridgeport, CT, USA Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
a r t i c l e
i n f o
Article history: Received 31 December 2009 Accepted 4 April 2010 Available online 5 May 2010 Keywords: Sudden cardiac death Emotional trauma Genetic basis
In this issue of the journal, Yalta et al. [1] propose an elegant alternative solution to our report of the epidemic of sudden deaths caused by the demise of a popular politician in India [2]. Emotional trauma causing sudden deaths has been previously reported, although the reason behind such events has not been widely examined. Suggested causes include acute coronary events due to rupture of a previously silent atherosclerotic plaque, caused by stress-induced hemodynamic, autonomic and prothrombotic responses [3]. Alternative suggestions include stress-induced cardiomyopathy or, as Yalta et al. have suggested, congenital arrhythmogenic states. Whether
other factors are at play is currently unknown. It should also be noted that these entities are not mutually exclusive, as illustrated by a recent report of congenital long QT syndrome in a patient with takotsubo cardiomyopathy [4]. The possible interplay of drugs causing QT prolongation adds a further layer of complexity to this scenario. The racial profile of the population under study also needs to be considered. Congenital long QT syndromes or congenital arrhythmogenic states are rarely reported in literature from India. The true prevalence of such syndromes in the country is unknown, and possibly is due to the absence of adequate studies. While congenital arrhythmogenic states are likely to be responsible for some of the deaths, and takotsubo cardiomyopathy for some others, it is likely that other factors including acute coronary syndromes and other unexplained factors also contributed to the deaths. Since our report was based on second-hand observations of events occurring in another country, it is more than likely that other unknown factors were also at play. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [5]. References
⁎ Corresponding author. Department of Medicine, David Geffen School of Medicine at UCLA, 10833 Le Conte Ave, Los Angeles, CA, USA. E-mail address: [email protected] (N. Paul).
[1] Yalta K, Turgut OO, Yilmaz MB, Yilmaz A, Tandogan I. Genetic basis of sudden cardiac death due to emotional trauma in apparently healthy individuals. Int J Cardiol 2010;145(3):518–9.
Letters to the Editor
Table 1 Multivariate analysis of one- and 12-month major adverse cardiac events after acute myocardial infarction.
Gender Age IHD history Diabetes Hypertension Dyslipidemia Smoking Family history Killip class higher than II
One-month MACE
12-month MACE
p value
Odd ratio (95% CI)
p value
Odd ratio (95% CI)
0.85 b0.01 0.06 0.06 0.43 b0.05 b0.05 0.52 b0.01
1.03 (0.71–1.50) 1.03 (1.02–1.05) 1.46 (0.97–2.20) 1.37 (0.99–1.89) 1.13 (0.83–1.54) 2.28 (1.16–4.49) 1.54 (1.07–2.21) 1.26 (0.62–2.55) 3.63 (2.76–4.91)
0.78 b 0.01 b 0.01 b 0.01 0.32 b 0.01 0.06 0.34 b 0.01
0.96 (0.73–1.27) 1.02 (1.01–1.03) 1.55 (1.15–2.09) 1.37 (1.09–1.73) 1.11 (0.89–1.38) 1.94 (1.27–2.96) 1.28 (0.99–1.64) 1.23 (0.79–1.91) 2.10 (1.68–2.63)
MACE; major adverse cardiac event, IHD; Ischemic heart disease, CI; confidence interval.
in-hospital mortality in women compared with men. Even though the baseline characteristics were worse in women, the short- and longterm outcomes were not different between male and female patients undergoing PCI with DES.
This study was carried out with the support of the Korean Circulation Society (KCS) in the memorandum of the 50th Anniversary of the KCS. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [6]. References [1] Reina A, Colmenerom M, AguayodeHoyos E, et al. Gender differences in management and outcome of patients with acute myocardial infarction. Int J Cardiol 2007;16:389–95. [2] Lee KH, Jeong MH, Ahn YK, et al, Korea Acute Myocardial Infarction Registry (KAMIR) Investigators. Gender differences of success rate of percutaneous coronary intervention and short term cardiac events in Korea Acute Myocardial Infarction Registry. Int J Cardiol 2008;130:227–34. [3] Berger JS, Elliott L, Gallup D, et al. Sex differences in mortality following acute coronary syndromes. JAMA 2009;302:874–82. [4] Gan SC, Beaver SK, Houck PM, et al. Treatment of acute myocardial infarction and 30-day mortality among women and men. N Engl J Med 2000;343:8–15. [5] Chang WC, Kaul P, Westerhout CM, et al. Impact of sex on long-term mortality from acute myocardial infarction vs unstable angina. Arch Intern Med 2003;163:2476–84. [6] Coasts AJ. Ethical authorship and publishing. Int J Cardiol 2009;131:149–50.
0167-5273/$ – see front matter © 2010 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2010.02.028
Genetic basis of sudden cardiac death due to emotional trauma in apparently healthy individuals Kenan Yalta ⁎, Okan Onur Turgut, Mehmet Birhan Yilmaz, Ahmet Yilmaz, Izzet Tandogan Cumhuriyet University, Cardiology Department, Sivas, 58100, Turkey
a r t i c l e
i n f o
Article history: Received 12 November 2009 Accepted 30 November 2009 Available online 19 January 2010 Keywords: Emotional trauma Sudden cardiac death Ion channelopathy Genetic basis
In their recently published article, Babu V et al. reported several sudden deaths after the demise of a renowned politician in India [1]. The sudden deaths in this article were reported to be strongly associated with emotional trauma possibly leading to a variety of conditions described as heart attack etc. The authors particularly propounded TTC as the possible underlying etiology of sudden deaths [1]. However, TTC has been regarded as a typically benign and reversible entity of postmenopausal women with a recent history of emotional stress [2]. On the other hand, some authors reported higher rates of malign ventricular arrhythmias and mortality in patient series with TTC compared to previous reports [3]. Similarly a case with cardiac asystole due to TTC with successful resuscitation was also reported previously [4]. We agree with the
⁎ Corresponding author. E-mail address: [email protected] (K. Yalta).
authors that TTC might have led to SCDs in a group of victims. However, this might have constituted only a minority due to the generally accepted benign nature and female gender predilection of this entity (majority of victims reported in the article by Babu V et al. were male [1]). Several theories have been propounded regarding the exact mechanisms of SCD due to emotional trauma. Emotional stress is closely associated with sympathetic system hyperactivation that may trigger some fatal events including acute coronary syndromes or may induce malign ventricular arrhythmias in arrhythmia-prone patients. QT interval prolongation is well known to be associated with SCD. Emotional stress was reported to prolong corrected QT interval possibly in the setting of a congenital long QT syndrome (LQTS) with a borderline QT interval [5]. Significant QT interval prolongation was also demonstrated to occur by the onset of active mental stress indicating the effects of adrenergic activation on repolarization [6]. QT interval prolongation induced by active mental stress may help comprehend the link between sudden stress and malign arrhythmias [6]. Genetically determined arrhythmogenic entities (catecholaminergic ventricular tachycardia (VT), ion channelopathies including congenital LQTS etc.) have been considered as important etiologies of SCD, particularly in the young. Ion channelopathies may be overt or obscure with regard to resting ECG signs, and are accompanied by a spectrum of clinical symptoms (asymptomatic to syncopal attacks or SCD) that may emerge in the presence of some triggering factors. Subclinical mutations of LQTS genes have also been of clinical importance, and were found to account for drug- induced malign arrhythmic events [7]. Due to a compensated or a mild ion channelopathy (with a normal or borderline resting ECG), clinical manifestations may remain silent unless the patient encounters
Letters to the Editor
external triggering factors including QT interval prolonging drugs [7], severe emotional trauma etc. Therefore, some of the victims reported in the article by Babu V et al. [1] (particularly the relatively young ones in whom the SCDs were not clinically suggestive of any apparent etiology including acute coronary syndromes or other structural heart disease etc.) might have harboured some kind of genetically determined arrhythmogenic conditions including ion channelopathies (with normal or abnormal resting ECGs) that might lead to SCDs in response to a sudden and severe emotional trauma. Thorough analysis and genetic screening of families of these victims may confirm this suggestion, and may help take preventive measures for the family members against SCD. In conclusion, the first manifestation of a genetically determined ion channelopathy may be SCD. However, ion channelopathies may be easily ignored when they are not accompanied by ECG signs and clinical symptoms, and may remain clinically dormant unless the patient faces severe triggering factors (drugs, severe emotional stress etc.). A portion of sudden deaths due to emotional trauma may be attributable to genetically determined arrhythmogenic entities including ion channelopathies, particularly in relatively young and apparently healthy victims suggesting thorough examination and further analysis (including genetic screening) of the family members of these victims for prevention of SCD.
519
The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [8]. References [1] Babu V, Paul N. Sudden deaths following the unexpected demise of a popular politician in India. Int J Cardiol 2010;145(2):266–7. [2] Bybee KA, Kara T, Prasad A, et al. Systematic review: transient left ventricular apical ballooning: a syndrome that mimics ST-segment elevation myocardial infarction. Ann Intern Med 2004;141(11):858–65. [3] Bonello L, Com O, Ait-Moktar O, et al. Ventricular arrhythmias during Tako-tsubo syndrome. Int J Cardiol 2008;128(2):e50–3. [4] Bahlmann E, Krause K, Häerle T, van der Schalk H, Kuck KH. Cardiac arrest and successful resuscitation in a patient with Tako-Tsubo cardiomyopathy. Int J Cardiol 2008;130(1):e4–6. [5] Batchvarov VN, Bajpai A, Behr E. Prolongation of the QT interval and postextrasystolic augmentation of the TU-wave during emotional stress. Indian Pacing Electrophysiol J 2008;8(2):146–8. [6] Andrássy G, Szabo A, Ferencz G, Trummer Z, Simon E, Tahy A. Mental stress may induce QT-interval prolongation and T-wave notching. Ann Noninvasive Electrocardiol 2007;12(3):251–9. [7] Makita N, Horie M, Nakamura T, et al. Drug-induced long-QT syndrome associated with a subclinical SCN5A mutation. Circulation 2002;106(10):1269–74. [8] Coats AJ. Ethical authorship and publishing. Int J Cardiol 2009;131:149–50.
0167-5273/$ – see front matter © 2009 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2009.11.060
Genetic basis of sudden cardiac death due to emotional trauma in apparently healthy individuals: Commentary Varsha Babu a, Navin Paul b,⁎ a b
Bridgeport Hospital/Yale University Internal Medicine Residency Program, Bridgeport, CT, USA Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
a r t i c l e
i n f o
Article history: Received 31 December 2009 Accepted 4 April 2010 Available online 5 May 2010 Keywords: Sudden cardiac death Emotional trauma Genetic basis
In this issue of the journal, Yalta et al. [1] propose an elegant alternative solution to our report of the epidemic of sudden deaths caused by the demise of a popular politician in India [2]. Emotional trauma causing sudden deaths has been previously reported, although the reason behind such events has not been widely examined. Suggested causes include acute coronary events due to rupture of a previously silent atherosclerotic plaque, caused by stress-induced hemodynamic, autonomic and prothrombotic responses [3]. Alternative suggestions include stress-induced cardiomyopathy or, as Yalta et al. have suggested, congenital arrhythmogenic states. Whether
other factors are at play is currently unknown. It should also be noted that these entities are not mutually exclusive, as illustrated by a recent report of congenital long QT syndrome in a patient with takotsubo cardiomyopathy [4]. The possible interplay of drugs causing QT prolongation adds a further layer of complexity to this scenario. The racial profile of the population under study also needs to be considered. Congenital long QT syndromes or congenital arrhythmogenic states are rarely reported in literature from India. The true prevalence of such syndromes in the country is unknown, and possibly is due to the absence of adequate studies. While congenital arrhythmogenic states are likely to be responsible for some of the deaths, and takotsubo cardiomyopathy for some others, it is likely that other factors including acute coronary syndromes and other unexplained factors also contributed to the deaths. Since our report was based on second-hand observations of events occurring in another country, it is more than likely that other unknown factors were also at play. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [5]. References
⁎ Corresponding author. Department of Medicine, David Geffen School of Medicine at UCLA, 10833 Le Conte Ave, Los Angeles, CA, USA. E-mail address: [email protected] (N. Paul).
[1] Yalta K, Turgut OO, Yilmaz MB, Yilmaz A, Tandogan I. Genetic basis of sudden cardiac death due to emotional trauma in apparently healthy individuals. Int J Cardiol 2010;145(3):518–9.