- Email: [email protected]
Takotsubo syndrome presenting as syncope in a patient with permanent pacemaker
Takotsubo syndrome presenting as syncope in a patient with permanent pacemaker Bharatraj Banavalikar, Sivasankaran Sivasubramonian, Narayanan Namboodiri, Krishna Kumar Mohanan Nair, Dibya Ranjan Behera, Ajitkumar Valaparambil PII: DOI: Reference:
S0022-0736(17)30131-0 doi: 10.1016/j.jelectrocard.2017.05.005 YJELC 52415
To appear in:
Journal of Electrocardiology
Please cite this article as: Banavalikar Bharatraj, Sivasubramonian Sivasankaran, Namboodiri Narayanan, Nair Krishna Kumar Mohanan, Behera Dibya Ranjan, Valaparambil Ajitkumar, Takotsubo syndrome presenting as syncope in a patient with permanent pacemaker, Journal of Electrocardiology (2017), doi: 10.1016/j.jelectrocard.2017.05.005
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT TITLE: Takotsubo syndrome presenting as syncope in a patient with permanent pacemaker
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Bharatraj Banavalikar*1 MBBS, MD, DM, Sivasankaran Sivasubramonian* MBBS, MD, DM, Narayanan Namboodiri* MBBS, MD, DM, Krishna Kumar Mohanan Nair*
SC
MBBS, MD, DM, Dibya Ranjan Behera* MBBS, MD, Ajitkumar Valaparambil* MBBS, MD, DM.
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*Department of Cardiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, India - 695011 1
Corresponding author’s present address: Dr. Bharatraj Banavalikar, Cardiac
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Electrophysiology unit, Department of Cardiology, Sri Jayadeva Institute of Cardiovascular Sciences & Research, Bengaluru, India– 560069. E-mail: [email protected]
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Word count: 1246
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Telephone: +919745606590, Fax: +91-80-2653-4477
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Short title: Takotsubo syndrome Conflict of interest: The authors declare that they have no conflict of interest. Funding: None
ACCEPTED MANUSCRIPT
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ABSTRACT:
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Takotsubo syndrome is an acute reversible heart failure syndrome triggered by physical or emotional stress, especially in postmenopausal women. Herein, we describe a case of a 31-
SC
year-old pacemaker dependent lady who presented with syncope after she was bereaved of her father. Electrocardiogram at admission revealed ventricular paced rhythm at 60/min,
MA NU
prolonged QT interval and frequent runs of torsades de pointes. Transthoracic echocardiogram and left ventriculogram revealed findings typical of Takotsubo syndrome. QT prolongation and torsade de pointes in the context of fixed-rate ventricular pacing implies
PT
ED
direct catecholamine toxicity on the ventricular myocardium independent of heart rate.
Keywords: Takotsubo syndrome, Torsades de pointes, QT prolongation, paced rhythm,
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Pacemaker dysfunction
ACCEPTED MANUSCRIPT
Introduction:
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Takotsubo syndrome (TS) is an acute reversible heart failure syndrome triggered by physical or emotional stress, especially in postmenopausal women. Initially described in Japan, the
SC
condition has a worldwide distribution. Prognosis of this condition is generally favorable. Arrhythmic complications during the acute phase, however, may entail a worse prognosis.
MA NU
We report a case of recurrent torsades de pointes (TDP), complicating TS in a young female with a permanent pacemaker. Case report:
ED
A 31-year-old lady with a history of permanent pacemaker (VVI mode) implantation for congenital complete heart block 20years ago presented with syncope 2 days after the demise
PT
of her father. She had undergone one pulse generator replacement 9 years after pacemaker
CE
implantation. Her cardiac structure and function were normal on previous follow-up visits and was not on any medication. Electrocardiogram (ECG) on admission revealed right
AC
ventricular pacing at a rate of 60/min with concordant T wave inversions, corrected QT interval (QTc) of 630ms and frequent runs of nonsustained TDP (Figure 1A and 1B). Her QTc was 428ms when she was seen in our device clinic 2 weeks back for a routine check-up (Figure 1C). Device interrogation on admission revealed lower pacing rate of 60/min, pacing threshold of 2.4V at a pulse width of 0.4ms, pulse amplitude of 4V and battery life of 3 years. Pacing threshold was 1.8V when measured in the device clinic two weeks prior to syncope. Her N-terminal Pro-BNP and Troponin-T were 2214 and 136 pg/ml respectively. Serum electrolytes and renal parameters were normal. Transthoracic echocardiogram and left ventriculogram revealed hypokinesia and ballooning of apical segments along with preserved basal contraction with a left ventricular ejection fraction of 40% (Figure 2). Epicardial
ACCEPTED MANUSCRIPT coronaries were normal at coronary angiography. In view of repeated runs of TDP, pacing rate was increased to 80/min which led to prompt resolution of these episodes. One month
T
after discharge, her left ventricular function had normalized along with a reduction in QTc to
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440ms (Figure 3).
SC
Discussion:
To the best of our knowledge, this is the first report of Takotsubo syndrome (TS) associated
MA NU
with TDP in the context of ventricular paced rhythm. TS is an acute heart failure syndrome that typically presents with chest pain and breathlessness. Syncope is a rare but grave manifestation that could be due to ventricular tachycardia or fibrillation, bradyarrhythmia including pacemaker dysfunction, severe left ventricular outflow obstruction or cardiogenic
ED
shock. Up to 10% cases may involve young individuals as exemplified by our patient.
PT
Electrocardiographic changes of TS in patients with paced ventricular rhythm tends to be subtle and may not be easily discernible [1]. Transient prolongation of QTc and new
CE
concordant T wave inversions may be the only findings, both of which were observed in our
AC
patient. QTc prolongation is commonly noted but TDP is uncommon in TS. Madias et al. observed ventricular arrhythmias in 8% of their patients with TS and found that QTc was significantly prolonged in patients with ventricular arrhythmias compared to those without arrhythmias [2]. Rate adaptation of ventricular repolarisation is preserved in patients with TS in contrast to patients with myocardial infarction. Syed et al. retrospectively analyzed TS patients with ventricular arrhythmias and proposed that significant heart rate variation due to conduction system disease or atrial fibrillation may predispose to arrhythmias [3]. Pacemaker dysfunction with loss of capture is a rare complication in patients with TS which may be due to myocardial edema causing electrophysiological perturbations at the right ventricular apex. Wissner et al. [4] described transient pacemaker dysfunction in a
ACCEPTED MANUSCRIPT patient with biventricular TS which normalized following the recovery of mechanical function.
T
Our patient had significant prolongation of QT interval with frequent runs of TDP on
RI P
presentation. She was on fixed-rate ventricular pacing for complete heart block thereby precluding RR interval variation. This implies that QT prolongation was caused by
SC
catecholamine toxicity directly on the ventricular myocardium independent of heart rate. No
MA NU
other cause of QT prolongation was observed. Syncope in our patient could be due to TDP or pacemaker dysfunction. There was an acute increase in pacing threshold from 1.8V to 2.4V suggesting electrophysiological perturbations at the apical septum. Nevertheless, her pacing threshold was well below the pulse amplitude (4V), making capture failure unlikely. In fact,
ED
increasing the pacing rate to 80/min led to successful resolution of TDP.
PT
Exaggerated sympathetic activation is the underlying factor in the pathophysiology of TS. Apical ballooning and acute heart failure also occur in other hyperadrenergic states such as
CE
pheochromocytoma and subarachnoid hemorrhage. Experimental studies have implicated sympathetic overactivity in causing QT prolongation and dispersion of repolarisation
AC
although the exact mechanism has not been elucidated [5]. On the other hand, myocardial edema during the acute phase may cause transient electrical inhomogeneity and apicobasal dispersion of repolarisation [6]. In some patients, acute autonomic dysfunction merely unmasks the reduced repolarisation reserve due to preexisting subclinical mutations affecting ion channels [7]. Future studies should focus on elucidating the molecular mechanisms of QT prolongation in TS. To summarize, new onset concordant T wave inversions and QT prolongation are notable ECG findings of TS in patients with paced ventricular rhythm. Electrical complications such as TDP or pacemaker dysfunction can lead to syncope and sudden cardiac
ACCEPTED MANUSCRIPT death. QT prolongation and TDP in the context of fixed-rate ventricular pacing implies direct catecholamine toxicity on the ventricular myocardium independent of chronotropic effects.
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T
‘Conflicts of Interest: none declared.’ References:
SC
[1] Chauhan K, Sontineni SP, Alla VM, Holmberg MJ. Electrocardiographic abnormalities of takotsubo cardiomyopathy in a patient with paced ventricular rhythm. Cardiology research
MA NU
and practice. 2010 Jun 8;2010. doi:10.4061/2010/643832
[2] Madias C, Fitzgibbons TP, Alsheikh-Ali AA, et al. Acquired long QT syndrome from stress cardiomyopathy is associated with ventricular arrhythmias and torsades de pointes.
ED
Heart Rhythm. 2011;8:555-61. doi:10.1016/j.hrthm.2010.12.012
PT
[3] Syed FF, Asirvatham SJ, Francis J. Arrhythmia occurrence with takotsubo
CE
cardiomyopathy: a literature review. Europace. 2011;13:780-8. doi:10.1093/europace/euq435 [4] Wissner E, Fortuin FD, Scott LR, et al. Reversible pacemaker dysfunction in a patient
AC
with transient cardiac apical ballooning syndrome: a case report. Europace. 2008;10:1105-7. doi:10.1093/europace/eun174 [5] Schwartz PJ, Malliani A. Electrical alternation of the T-wave: clinical and experimental evidence of its relationship with the sympathetic nervous system and with the long QT syndrome. American heart journal. 1975;89:45-50. doi:10.1016/0002-8703(75)90008-3 [6] Marra MP, Zorzi A, Corbetti F, et al. Apicobasal gradient of left ventricular myocardial edema underlies transient T-wave inversion and QT interval prolongation (Wellens’ ECG pattern) in Tako-Tsubo cardiomyopathy. Heart Rhythm. 2013;10:70-7. doi:10.1016/j.hrthm.2012.09.004
ACCEPTED MANUSCRIPT [7] Behr ER, Mahida S. Takotsubo cardiomyopathy and the long-QT syndrome: an insult to
RI P
T
repolarization reserve. Europace. 2009;11:697-700. doi:10.1093/europace/eup081
SC
FIGURE LEGENDS:
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Figure 1A. Rhythm strip showing runs of Torsade-de-pointes on admission. 1B. Electrocardiogram at admission showing paced rhythm at a rate of 60/min with prolonged QT interval and concordant T wave inversions. 1C. Electrocardiogram 2 weeks prior to hospitalization showing paced rhythm at 60/min with
PT
ED
normal QT interval and absence of concordant T wave inversions.
Figure 2. Echocardiogram and left ventriculogram illustrating apical ballooning in Takotsubo
CE
syndrome. A-D show the diastolic frames and E- H show the systolic frames where the basal
AC
contractions are preserved with ballooning out of apex. Figure 3A- Electrocardiogram at 1-month follow-up showing resolution of T wave changes and a normal QTc ( 440ms). Figures 3B and 3C show systolic and diastolic frames in parasternal long axis view revealing normalization of LV contractile function at 1-month follow-up.
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ACCEPTED MANUSCRIPT
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Fig. 1
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Fig. 2
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Fig. 3
ACCEPTED MANUSCRIPT HIGHLIGHTS
Concordant T wave inversions & prolonged QT typical of Takotsubo syndrome with
T
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paced rhythm
Electrical complications such as torsades de pointes can lead to syncope and sudden
MA NU
Prolonged QT & TDP in the context of paced rhythm implies direct adrenergic
CE
PT
ED
toxicity independent of heart rate
AC
SC
cardiac death
S0022-0736(17)30131-0 doi: 10.1016/j.jelectrocard.2017.05.005 YJELC 52415
To appear in:
Journal of Electrocardiology
Please cite this article as: Banavalikar Bharatraj, Sivasubramonian Sivasankaran, Namboodiri Narayanan, Nair Krishna Kumar Mohanan, Behera Dibya Ranjan, Valaparambil Ajitkumar, Takotsubo syndrome presenting as syncope in a patient with permanent pacemaker, Journal of Electrocardiology (2017), doi: 10.1016/j.jelectrocard.2017.05.005
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT TITLE: Takotsubo syndrome presenting as syncope in a patient with permanent pacemaker
RI P
T
Bharatraj Banavalikar*1 MBBS, MD, DM, Sivasankaran Sivasubramonian* MBBS, MD, DM, Narayanan Namboodiri* MBBS, MD, DM, Krishna Kumar Mohanan Nair*
SC
MBBS, MD, DM, Dibya Ranjan Behera* MBBS, MD, Ajitkumar Valaparambil* MBBS, MD, DM.
MA NU
*Department of Cardiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, India - 695011 1
Corresponding author’s present address: Dr. Bharatraj Banavalikar, Cardiac
ED
Electrophysiology unit, Department of Cardiology, Sri Jayadeva Institute of Cardiovascular Sciences & Research, Bengaluru, India– 560069. E-mail: [email protected]
CE
Word count: 1246
PT
Telephone: +919745606590, Fax: +91-80-2653-4477
AC
Short title: Takotsubo syndrome Conflict of interest: The authors declare that they have no conflict of interest. Funding: None
ACCEPTED MANUSCRIPT
T
ABSTRACT:
RI P
Takotsubo syndrome is an acute reversible heart failure syndrome triggered by physical or emotional stress, especially in postmenopausal women. Herein, we describe a case of a 31-
SC
year-old pacemaker dependent lady who presented with syncope after she was bereaved of her father. Electrocardiogram at admission revealed ventricular paced rhythm at 60/min,
MA NU
prolonged QT interval and frequent runs of torsades de pointes. Transthoracic echocardiogram and left ventriculogram revealed findings typical of Takotsubo syndrome. QT prolongation and torsade de pointes in the context of fixed-rate ventricular pacing implies
PT
ED
direct catecholamine toxicity on the ventricular myocardium independent of heart rate.
Keywords: Takotsubo syndrome, Torsades de pointes, QT prolongation, paced rhythm,
AC
CE
Pacemaker dysfunction
ACCEPTED MANUSCRIPT
Introduction:
RI P
T
Takotsubo syndrome (TS) is an acute reversible heart failure syndrome triggered by physical or emotional stress, especially in postmenopausal women. Initially described in Japan, the
SC
condition has a worldwide distribution. Prognosis of this condition is generally favorable. Arrhythmic complications during the acute phase, however, may entail a worse prognosis.
MA NU
We report a case of recurrent torsades de pointes (TDP), complicating TS in a young female with a permanent pacemaker. Case report:
ED
A 31-year-old lady with a history of permanent pacemaker (VVI mode) implantation for congenital complete heart block 20years ago presented with syncope 2 days after the demise
PT
of her father. She had undergone one pulse generator replacement 9 years after pacemaker
CE
implantation. Her cardiac structure and function were normal on previous follow-up visits and was not on any medication. Electrocardiogram (ECG) on admission revealed right
AC
ventricular pacing at a rate of 60/min with concordant T wave inversions, corrected QT interval (QTc) of 630ms and frequent runs of nonsustained TDP (Figure 1A and 1B). Her QTc was 428ms when she was seen in our device clinic 2 weeks back for a routine check-up (Figure 1C). Device interrogation on admission revealed lower pacing rate of 60/min, pacing threshold of 2.4V at a pulse width of 0.4ms, pulse amplitude of 4V and battery life of 3 years. Pacing threshold was 1.8V when measured in the device clinic two weeks prior to syncope. Her N-terminal Pro-BNP and Troponin-T were 2214 and 136 pg/ml respectively. Serum electrolytes and renal parameters were normal. Transthoracic echocardiogram and left ventriculogram revealed hypokinesia and ballooning of apical segments along with preserved basal contraction with a left ventricular ejection fraction of 40% (Figure 2). Epicardial
ACCEPTED MANUSCRIPT coronaries were normal at coronary angiography. In view of repeated runs of TDP, pacing rate was increased to 80/min which led to prompt resolution of these episodes. One month
T
after discharge, her left ventricular function had normalized along with a reduction in QTc to
RI P
440ms (Figure 3).
SC
Discussion:
To the best of our knowledge, this is the first report of Takotsubo syndrome (TS) associated
MA NU
with TDP in the context of ventricular paced rhythm. TS is an acute heart failure syndrome that typically presents with chest pain and breathlessness. Syncope is a rare but grave manifestation that could be due to ventricular tachycardia or fibrillation, bradyarrhythmia including pacemaker dysfunction, severe left ventricular outflow obstruction or cardiogenic
ED
shock. Up to 10% cases may involve young individuals as exemplified by our patient.
PT
Electrocardiographic changes of TS in patients with paced ventricular rhythm tends to be subtle and may not be easily discernible [1]. Transient prolongation of QTc and new
CE
concordant T wave inversions may be the only findings, both of which were observed in our
AC
patient. QTc prolongation is commonly noted but TDP is uncommon in TS. Madias et al. observed ventricular arrhythmias in 8% of their patients with TS and found that QTc was significantly prolonged in patients with ventricular arrhythmias compared to those without arrhythmias [2]. Rate adaptation of ventricular repolarisation is preserved in patients with TS in contrast to patients with myocardial infarction. Syed et al. retrospectively analyzed TS patients with ventricular arrhythmias and proposed that significant heart rate variation due to conduction system disease or atrial fibrillation may predispose to arrhythmias [3]. Pacemaker dysfunction with loss of capture is a rare complication in patients with TS which may be due to myocardial edema causing electrophysiological perturbations at the right ventricular apex. Wissner et al. [4] described transient pacemaker dysfunction in a
ACCEPTED MANUSCRIPT patient with biventricular TS which normalized following the recovery of mechanical function.
T
Our patient had significant prolongation of QT interval with frequent runs of TDP on
RI P
presentation. She was on fixed-rate ventricular pacing for complete heart block thereby precluding RR interval variation. This implies that QT prolongation was caused by
SC
catecholamine toxicity directly on the ventricular myocardium independent of heart rate. No
MA NU
other cause of QT prolongation was observed. Syncope in our patient could be due to TDP or pacemaker dysfunction. There was an acute increase in pacing threshold from 1.8V to 2.4V suggesting electrophysiological perturbations at the apical septum. Nevertheless, her pacing threshold was well below the pulse amplitude (4V), making capture failure unlikely. In fact,
ED
increasing the pacing rate to 80/min led to successful resolution of TDP.
PT
Exaggerated sympathetic activation is the underlying factor in the pathophysiology of TS. Apical ballooning and acute heart failure also occur in other hyperadrenergic states such as
CE
pheochromocytoma and subarachnoid hemorrhage. Experimental studies have implicated sympathetic overactivity in causing QT prolongation and dispersion of repolarisation
AC
although the exact mechanism has not been elucidated [5]. On the other hand, myocardial edema during the acute phase may cause transient electrical inhomogeneity and apicobasal dispersion of repolarisation [6]. In some patients, acute autonomic dysfunction merely unmasks the reduced repolarisation reserve due to preexisting subclinical mutations affecting ion channels [7]. Future studies should focus on elucidating the molecular mechanisms of QT prolongation in TS. To summarize, new onset concordant T wave inversions and QT prolongation are notable ECG findings of TS in patients with paced ventricular rhythm. Electrical complications such as TDP or pacemaker dysfunction can lead to syncope and sudden cardiac
ACCEPTED MANUSCRIPT death. QT prolongation and TDP in the context of fixed-rate ventricular pacing implies direct catecholamine toxicity on the ventricular myocardium independent of chronotropic effects.
RI P
T
‘Conflicts of Interest: none declared.’ References:
SC
[1] Chauhan K, Sontineni SP, Alla VM, Holmberg MJ. Electrocardiographic abnormalities of takotsubo cardiomyopathy in a patient with paced ventricular rhythm. Cardiology research
MA NU
and practice. 2010 Jun 8;2010. doi:10.4061/2010/643832
[2] Madias C, Fitzgibbons TP, Alsheikh-Ali AA, et al. Acquired long QT syndrome from stress cardiomyopathy is associated with ventricular arrhythmias and torsades de pointes.
ED
Heart Rhythm. 2011;8:555-61. doi:10.1016/j.hrthm.2010.12.012
PT
[3] Syed FF, Asirvatham SJ, Francis J. Arrhythmia occurrence with takotsubo
CE
cardiomyopathy: a literature review. Europace. 2011;13:780-8. doi:10.1093/europace/euq435 [4] Wissner E, Fortuin FD, Scott LR, et al. Reversible pacemaker dysfunction in a patient
AC
with transient cardiac apical ballooning syndrome: a case report. Europace. 2008;10:1105-7. doi:10.1093/europace/eun174 [5] Schwartz PJ, Malliani A. Electrical alternation of the T-wave: clinical and experimental evidence of its relationship with the sympathetic nervous system and with the long QT syndrome. American heart journal. 1975;89:45-50. doi:10.1016/0002-8703(75)90008-3 [6] Marra MP, Zorzi A, Corbetti F, et al. Apicobasal gradient of left ventricular myocardial edema underlies transient T-wave inversion and QT interval prolongation (Wellens’ ECG pattern) in Tako-Tsubo cardiomyopathy. Heart Rhythm. 2013;10:70-7. doi:10.1016/j.hrthm.2012.09.004
ACCEPTED MANUSCRIPT [7] Behr ER, Mahida S. Takotsubo cardiomyopathy and the long-QT syndrome: an insult to
RI P
T
repolarization reserve. Europace. 2009;11:697-700. doi:10.1093/europace/eup081
SC
FIGURE LEGENDS:
MA NU
Figure 1A. Rhythm strip showing runs of Torsade-de-pointes on admission. 1B. Electrocardiogram at admission showing paced rhythm at a rate of 60/min with prolonged QT interval and concordant T wave inversions. 1C. Electrocardiogram 2 weeks prior to hospitalization showing paced rhythm at 60/min with
PT
ED
normal QT interval and absence of concordant T wave inversions.
Figure 2. Echocardiogram and left ventriculogram illustrating apical ballooning in Takotsubo
CE
syndrome. A-D show the diastolic frames and E- H show the systolic frames where the basal
AC
contractions are preserved with ballooning out of apex. Figure 3A- Electrocardiogram at 1-month follow-up showing resolution of T wave changes and a normal QTc ( 440ms). Figures 3B and 3C show systolic and diastolic frames in parasternal long axis view revealing normalization of LV contractile function at 1-month follow-up.
PT
ED
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ACCEPTED MANUSCRIPT
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Fig. 1
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Fig. 2
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ACCEPTED MANUSCRIPT
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Fig. 3
ACCEPTED MANUSCRIPT HIGHLIGHTS
Concordant T wave inversions & prolonged QT typical of Takotsubo syndrome with
T
RI P
paced rhythm
Electrical complications such as torsades de pointes can lead to syncope and sudden
MA NU
Prolonged QT & TDP in the context of paced rhythm implies direct adrenergic
CE
PT
ED
toxicity independent of heart rate
AC
SC
cardiac death