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Neurocrit Care DOI 10.1007/s12028-016-0334-y

PRACTICAL PEARL

Takotsubo in Traumatic Injury

1,2 1 1 1 Chun Fai Cheah • Mario Kofler • Alois Josef Schiefecker • Ronny Beer • 3 1 1 Gert Klug • Bettina Pfausler • Raimund Helbok

Ó The Author(s) 2017. This article is published with open access at Springerlink.com

Abstract Keywords Á Background Takotsubo cardiomyopathy (TC) is a well- Myocardial dysfunction Á Takotsubo cardiomyopathy Á known complication after aneurysmal subarachnoid hem- Monitoring Á Echocardiography orrhage and has been rarely described in patients with traumatic brain injury (TBI). Methods Case report and review of literature. Introduction Results Here, we report a 73-year-old woman with mild traumatic brain injury (TBI) presenting in cardiogenic Takotsubo cardiomyopathy (TC) is known to occur in shock. Takotsubo cardiomyopathy (TC) was diagnosed by patients with severe brain insult. It has been widely repeated echocardiography. Cardiovascular support by described after (SAH, inotropic agents led to hemodynamic stabilization after 1.2–28 %) [1–3]; however, it rarely occurs in patients initiation of levosimendan. Cardiac function fully recov- with , ischemic , and ered within 21 days. We performed an in-depth literature traumatic brain injury (TBI) [4]. In medical ICU review and identified 16 reported patients with TBI and patients, the incidence ranges between 5.7 and 28 % TC. Clinical course and characteristics are discussed in the [5, 6]. Here, we report a case of mild TBI with sec- context of our patient. ondary progression presenting with severe TC Conclusion Takotsubo cardiomyopathy is under-recog- and provide a comprehensive review of all reported TBI nized after TBI and may negatively impact outcome if left cases [7–19]. untreated.

Case Report

Electronic supplementary material The online version of this A previously healthy 73-year-old woman was admitted to article (doi:10.1007/s12028-016-0334-y) contains supplementary the trauma ward of our tertiary hospital with mild TBI. material, which is available to authorized users. On presentation, she was disoriented, had a Glasgow & Raimund Helbok Coma Scale (GCS) score of 14, and suffered from retro- [email protected] grade . Neurological examination revealed

1 bilateral gaze-evoked nystagmus, but no other focal neu- Department of , Neurological Intensive Care Unit, rological deficit and her vital signs were stable. Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria Laboratory workup revealed 0.21 % blood alcohol con- centration. Computed tomography (CT) scanning of the 2 Department of Neurology, Hospital Pulau Pinang, Jalan Residensi, 10990 Georgetown, Pulau Pinang, Malaysia brain showed right parieto-occipital and left temporo- parietal fractures with an subdural hematoma 3 University Clinic of Internal Medicine III, Cardiology and Angiology, Medical University of Innsbruck, Anichstrasse (ASDH) and traumatic SAH over the left hemisphere and 35, 6020 Innsbruck, Austria a small left frontal hemorrhagic contusion (Fig. 1, Panel 123 Neurocrit Care

Fig. 1 Neuroimaging and echocardiography Panel A indicate axial head computed tomography on admission and at follow-up 6 h later. Echocardiography on day 8 indicates moderate reduction in LVEF secondary to a persisting midventricular and apical hypo-/akinesia (arrows, Panel B). After 21 days (Panel C) LVEF nearly normalized and regional wall motion markedly improved (arrows) consistent with the typical presentation of a takotsubo cardiomyopathy. LV left ventricle, EF ejection fraction

A). Six hours later, the patient deteriorated and repeat Postoperatively the patient was on norepinephrine (0.073 head-CT showed a significant progression of the left mcg/kg/min), sufentanil (0.073 mcg/kg/min), and mida- frontal hemorrhage with intraventricular extension and a zolam (6 mcg/kg/min). Within the next 24 h, of 11 mm (Fig. 1, Panel A). Hematoma norepinephrine had to be continuously increased to 0.29 evacuation and placement of an external ventricular drain mcg/kg/min to achieve a cerebral perfusion pressure were immediately performed, and the patient was trans- (CPP) of >65 mmHg. In addition, dobutamine (6.038 ferred to the neurological intensive care unit. mcg/kg/min), phenylephrine (0.725 mcg/kg/min), and

123 Neurocrit Care hydrocortisone (1.933 mcg/kg/min, given to treat sec- ‘transient-left-ventricular ballooning syndrome,’ ‘apical bal- ondary adrenal insufficiency) were necessary to keep the looning syndrome,’ ‘myocardial dysfunction’ or ‘’ patient hemodynamically stable. together with ‘traumatic brain injury,’ ‘,’ and ‘poly- At this time, the electrocardiography showed sinus trauma.’ Only articles in English language were included. at a rate of 130 beats per minute (bpm) with non-specific repolarization abnormalities with no corre- spondence to a distinct coronary territory. Results Laboratory myocardial biomarkers exceeded pathologic thresholds: Troponin T levels peaked at 0.54 ng/mL (nor- Overall we identified 13 published articles involving 16 TBI mal range, <0.014 ng/mL) and NT-proBNP was 4690 ng/ patients with TC [7–19] (Table 1). Among these, 13 were L (normal range 0–303 ng/L). Creatinine kinase (CK) was adults and 3 of pediatric age. All patients (except 1 unchar- within normal range. Bedside transthoracic echocardiog- acterized) presented with impaired raphy demonstrated severe left ventricular (LV) necessitating mechanical ventilation. The brain injury pat- myocardial dysfunction (ejection fraction 35 %), marked tern was heterogeneous including various degrees of hypokinesia of the apical and midventricular portions of contusional hematoma, epidural hemorrhage (EDH), sub- the left ventricle suggestive of takotsubo cardiomyopathy dural hemorrhage (SDH), and traumatic SAH with 5 patients (TC). Only mild mitral regurgitation was detected. Invasive undergoing neurosurgical intervention. Six patients pre- coronary angiography was not performed because of typi- sented with polytrauma on admission. TC was diagnosed cal findings on echocardiogram and the limited therapeutic within 24 h in most patients (N = 10/16, 63 %); however, possibility due to intracranial bleeding. one patient developed TC 12 days after admission. In 4 As dobutamine was not improving the severe patients, coronary angiography was performed and con- myocardial dysfunction, levosimendan was added (initial firmed TC. Electrocardiography abnormalities were found in dose 0.03 mcg/kg/min, gradually increased to 0.12 mcg/ 9/16 patients (56 %) including ST segment and kg/min) and maintained for 28 h. After initiation, no changes, and 69 % (11/16) had elevated serum troponin increased dosage of norepinephrine was needed. The heart levels. Treatment differed; however, most received inotropic rate decreased to less than 100 bpm, dobutamine and support using dobutamine. In one patient, levosimendan at a phenylephrine could be withdrawn, and norepinephrine dose of 0.1 mcg/kg/min was used for 24 h. In addition, was slowly decreased over the following days without various drugs were used to sustain adequate blood pressure significant drops in blood pressure. Repeated transthoracic including epinephrine, norepinephrine, and vasopressin. echocardiography demonstrated improvement in LV Five patients needed extracorporeal life support to treat myocardial function on day 8 (ejection fraction 40 %) severe refractory cardiovascular shock. Echocardiography (Fig. 1, Panel B) and further recovery on day 21 (Fig. 1, revealed abnormal results in all patients (100 %) and was Panel C, ejection fraction 49.9 %, normal 54–74 %). reversible in the majority of patients within 7 days except in Coronary angiography was not performed as coronary 2 patients after 12 and 17 days, respectively. artery disease deemed unlikely due to recovery in cardiac In summary, (1) brain injury pattern in TBI patients function in repeated echocardiography suggestive for TC presenting with TC is heterogeneous and therefore as underlying pathology. The patient was successfully unspecific, (2) in the majority of patients inotropic sup- weaned on day 11 and discharged for neurorehabilitation port using dobutamine leads to improved cardiac function, 21 days after trauma. At this time, she was fully awake (3) patients presenting in severe refractory cardiovascular with a GCS score of 15, mildly disabled with a grade 4 shock may necessitate extracorporeal life support, and (4) brachio-facial left-sided and dysphagia. with adequate management of TC long-term is more dependent on the severity of brain injury.

Review of Literature Discussion

Methods Myocardial dysfunction in various degrees has been reported in patients with brain trauma [20–22] (Table 2), We performed a comprehensive literature search using the being more prevalent in severe TBI. TC represents a seri- search terms ‘Takotsubo cardiomyopathy,’ ‘Tako-tsubo car- ous manifestation of myocardial dysfunction and is defined diomyopathy,’ ‘stress cardiomyopathy,’ ‘stunned myocardium,’ as an acute, transient, and reversible heart failure syndrome

123 123 Table 1 Reported cases of takotsubo cardiomyopathy with traumatic brain injury in the literature References Number Admission Imaging TC Echocardiography ECG Laboratory Other Treatment (s) Functional of level of onset investigation (s) outcome/ patients consciousness, day cardiac GCS outcome

Palac et al. [7] 1 Unresponsive tSAH 1 EF 45 % NA CK max = 1244 NA Dopamine, Mortality: a LV hypokinesia U/L Norepinephrine, Yes sparing apex Troponin Vasopressin Echo the max = 1.4 ng/mL same day: (NR < 0.5 ng/mL) EF = 60 % Krishnamoorthy 1 Worsening SDH 2EF35% NA NA NA Phenylephrine: Mortality: et al. [8] somnolence Midline Basal hypokinesia 300 mcg No shift Ephedrine: 20 mg Echo the Craniectomy same day: EF = 55 % Divekar et al. [9] 1 Unresponsive SDH 1 EF 45 %. T wave inversion in I, CK max = 853 CAG: normal NA Mortality: a Apical akinesia aVL, and V4–V6 with U/L NA QT prolongation Troponin T Echo after max = 0.6 ng/mLa 3 days: normal Deleu et al. [10] 1 GCS 6 Contusion 6 EF 18 %, Diffuse , CK max = 311 NA Epinephrineb:up Mortality: EDH LV akinesia diffuse, symmetric T U/L (NR 39–238 to 3 mcg/min No wave inversion U/L) Norepinephrinec Echo after Troponin 12 days: max = 0.08 ng/ EF = 50 % mL (NR < 0.03 ng/ mL) Wippermann 1 NA Diffuse 1EF< 10 % Anterior myocardial Troponin I NA Inotropes, Mortality: et al. [11] max = 2.3 ng/ Craniotomy Yes LV akinesia a mL ECLS Echo after 2 days: EF = 50 % Mare´chaux et al. 1 Impaired tSAH 1 EF 20 % Diffuse T wave Troponin NA NA Mortality: [12] consciousness LV akinesia inversion with QT max = 1.6 ng/ Yes sparing apex prolongation mL Echo: NA (NR < 0.1 ng/ mL) erci Care Neurocrit erci Care Neurocrit Table 1 continued References Number Admission Imaging TC Echocardiography ECG Laboratory Other Treatment (s) Functional of level of onset investigation (s) outcome/ patients consciousness, day cardiac GCS outcome

Vergez 1 NA SDH, 2 Severe Marked ST Troponin I NA Norepinephrinec: 0.– Mortality: No et al. herniation LV hypokinesia elevation max = 3.2 ng/ 0.83 mcg/kg/min Echo after [13] (C2 mm) mL Dobutamine: 15 mcg/ 17 days: negative T waves (NR < 0.02 ng/ kg/min Improvement in left precordium mL) Craniotomy apical LV contractility Riera et al. 1 GCS 5 Contusion, 5 Moderate to Sinus tachycardia, CK max = 242U/ CAG: normal Norepinephrine: 0.8–1 Mortality: No [14] tSAH severe subendocardial L (NR 24–170 LVG: LV mcg/kg/min Echo after LV hypokinesia injury U/L) myocardial Dobutamine 7 days: EF sparing apex anteroseptal and Troponin I dysfunction 45–50 % inferior max = 1.13 ng/ mL (NR < 0.06 ng/ mL) Samol 1 Comatose Contusion 1 LV hypokinesia T negativity in V3– CK max = 480U/ CAG: normal Catecholamines Mortality: No a et al. tSAH V6 with QT L LVG: LV Echo after [15] prolongation Troponin I max = hypokinesia 2 days: EF 45 % 6.8 ng/mL (NR midventricular < 0.04 ng/mL) Cardiac MRI: severe LV hypokinesia (EF 25 %) Santoro 1 NA NA 1 EF 30 % NA Troponin max CAG: normal Levosimendan: 0.1 Mortality: No a et al. = 4.72 ng/mL mcg/kg/min Echo after [16] 3 days: EF 50 % Krpata 1 GCS 7 Cerebral 3 EF 10–15 % T wave inversion CK max = 541U/ NA Norepinephrine Mortality: No a et al. edema LV akinesia V3–V6 L Milrinone: No dosage Echo after [17] Troponin max given 7 days: EF 65 % 3.23 ng/mLa Bonacchi 4 NA Contusion 1 EF 14 % NA NA NA Dopamine/dobutamine/ Mortality: 2 et al. EDH epinephrine/ patients [18] norepinephrine/ tSAH Echo after isoproterenol/ 3 days: EF milnirone: ECLS 55–59 % in 2 survived patients 123 Neurocrit Care

due to regional wall abnormalities of the ventricular myocardium with associated new electrocardiography normal changes and elevation of myocardial biomarkers in the NR absence of culprit atherosclerotic or cardiac condition causing the temporary ventricular dys- function [23, 24]. Since its’ initial description in 1990, TC Echo after 1 day: Recovered cardiac event Functional outcome/ cardiac outcome maximum, was almost exclusively reported in patients with severe

Max SAH. Only a few reports were published in patients with intraventricular hemorrhage, severe TBI although pathophysiologic mechanisms of both IVH

Treatment (s) entities may have similar effects on the neuro-cardiac axis. Perhaps, many of the earlier suggested criteria to define TC that excluded the presence of TBI had compounded the

creatinine kinase, conundrum [25]. Underlying pathophysiologic mechanisms are still incom- CK pletely understood. Most investigations suggest an NA NA Mortality: NA investigation (s) subdural hematoma, interconnected cascade of neuronal injury causing sympathetic

SDH overstimulation and direct catecholamine toxicity to the heart

a [26]. Supra-physiologic levels of epinephrine bind to myocardial B2-receptors causing myocardial protein Gs-to-Gi 0.06 ng/mL)

134U/L coupling switch, mediated cyclic adenosine monophosphate < = (cAMP) calcium overload in myocytes, and contraction-band necrosis reducing cardiac contractility [27, 28]. magnetic resonance imaging, Our patient had full recovery of cardiac function 21 days Troponin maxmL 0.11 (NR ng/ CK max extradural hemorrhage,

MRI after trauma. Even though transient and reversible in nature, some reports suggest recovery even up to 12-week postin- EDH echo jury [23]. Hemodynamic support is critical in patients with severe TBI based on current treatment concepts that emphasize maintenance of an adequate CPP [29]. Improv- ing cardiac function in patients with TC may be achieved by elevation in all leads left ventriculogram, Diffuse ST segment using dobutamine and other pharmacological, or non- echocardiogram pharmacologic treatment including extracorporeal life LVG support. Our patient failed to improve by using dobutamine at a dose of 6.0 mcg/kg/min. After adding levosimendan, cardiac function and heart rate markedly improved. not available, hypokinesia

left ventricle, Recently, the use of levosimendan has been reported in NA Echocardiography ECG Laboratory Other traumatic subarachnoid hemorrhage,

LV patients with aneurysmal SAH where dobutamine was deemed ineffective [30]. Levosimendan is a non-cate- tSAH 12 Moderate LV onset day cholamine inodilator used in the treatment of acute heart failure with higher improvement rate in cardiac function compared to dobutamine [31]. It increases the sensitivity of myofilaments to calcium, leading to increased myocardial Imaging TC SDH IVH Contusion contraction without increasing intracellular cAMP or cal- cium concentrations [31]. Through the opening of an ATP- extracorporeal life support, Glasgow Coma Scale, coronary artery angiogram, dependent potassium channel, vasodilatory effects in sys-

ECLS temic, coronary, pulmonary, and venous blood vessels may GCS CAG be observed [31]. Unlike other vasopressors, it improves Admission level of consciousness, GCS myocardial contractility without increasing myocardial oxygen consumption, and more importantly its action is independent of interactions with adrenergic receptors [31]. 1 GCS 7 tSAH of patients

ejection fraction, Nonetheless, its utilization in patients with TC remains continued

EF scarce, bearing the rarity of the entity itself. In one of the electrocardiography, ] traumatic brain injury, largest case series, levosimendan was successfully used in 19 Adrenaline in local institution Local laboratory ranges not available Noradrenaline in local institution [ Hong et al. range, ECG TBI References Number Table 1 a b c 13 patients with TC [16]. 123 Neurocrit Care

Table 2 Description of 3 studies on myocardial dysfunction in patients with traumatic brain injury References Number Patients Pathology Abnormal Increased CK or Abnormal Patients with of patients severe TBI ECG (%) troponin level (%)a echocardiography myocardial (%) (%)b dysfunction (%)c

Bahloul 7 5/7 (85) EDH, SDH, cerebral 7/7 (100) 2/7 (28.5) 3/7 (42.8) 7/7 (100) et al. edema, contusion [20] Prathep 139 78/139 (56) SDH, tSAH NA 98/139 (30.6) 31/139 (22.3) 31/139 (22.3) et al. contusion [21] Hasanin 50 50/50 (100) SDH, tSAH, IVH, 31/50 (62) 27/50 (54) 21/50 (42) 25/50 (50) et al. DAI, contusion [22] TBI traumatic brain injury, tSAH traumatic subarachnoid hemorrhage, ECG electrocardiography, EDH extradural hemorrhage, SDH subdural hematoma, IVH intraventricular hemorrhage, DAI , CK creatinine kinase, NA not available a According to local laboratory ranges b Evidence for decreased EF or cardiac wall motion abnormality c Clinical presentation and/or echocardiogram evidence of cardiac dysfunction

Conclusions References

We highlight the presentation of a patient suffering from 1. Lee VH, Connolly HM, Fulgham JR, Manno EM, Brown RD Jr, TBI with takotsubo cardiomyopathy. Although transient in Wijdicks EFM. Tako-tsubo cardiomyopathy in aneurysmal sub- arachnoid hemorrhage: an under appreciated ventricular nature and commonly associated with a good overall dysfunction. J Neurosurg. 2006;105:264–70. prognosis, increasing evidence suggests it is a more serious 2. Kilbourn KJ, Levy S, Staff I, Kureshi I, McCullough L. Clinical acute cardiac disorder with a variety of complications characteristics and outcomes of neurogenic stress cardiomyopa- [23, 24]. Its hemodynamic effect may be deleterious in thy in aneurysmal subarachnoid hemorrhage. Clin Neurol Neurosurg. 2013;115:909–14. certain TBI patients if unrecognized. Levosimendan may 3. Banki N, Kopelnik A, Tung P, et al. Prospective analysis of be an effective therapeutic agent in severe cases. prevalence, distribution, and rate of recovery of left ventricular systolic dysfunction in patients with subarachnoid hemorrhage. Acknowledgments Paul Rhomberg, MD, Department of Neuroradiol- J Neurosurg. 2006;105:15–20. ogy, Medical University of Innsbruck Anichstrasse 35, 6020 Innsbruck, 4. Finsterer J, Wahbi K. CNS disease triggering Takotsubo stress Austria provided neuroimaging data. Open access funding provided by cardiomyopathy: review. Int J Cardiol. 2014;177:322–9. University of Innsbruck and Medical University of Innsbruck. 5. Ruiz-Baile´n M, Aguayo-de Hoyos E, Lo´pez Martinez A, et al. Reversible myocardial dysfunction, a possible complication in Authors Contribution Chun Fai Cheah contributed to concept, critically ill patients without heart disease. J Crit Care. design, writing, and editing; Mario Kofler helped with design, editing, 2003;18:245–52. and critical revision of manuscript for intellectual content; Alois 6. Park JH, Kang SJ, Song JK, Kim HK, Lim CM, Kang DH, Koh Schiefecker helped in editing and critical revision of manuscript for Y. Left ventricular apical ballooning due to severe physical stress intellectual content; Ronny Beer and Bettina Pfausler contributed to in patients admitted to the medical ICU. Chest. 2005;128: concept, design, and critical revision of manuscript for intellectual 296–302. content; Gert Klug helped with echocardiography, data interpretation, 7. Palac RT, Sumner G, Laird R, O’Rourke DJ. Reversible and critical revision; Raimund Helbok contributed to idea, writing, myocardial dysfunction after traumatic brain injury: mechanisms reviewing, editing, and critical revision. and implications for heart transplantation. Prog Transplant. 2003;13:42–6. 8. Krishnamoorthy V, Sharma D, Prathep S, Vavilala MS. Myocardial dysfunction in acute traumatic brain injury relieved Compliance with Ethical Standards by surgical decompression. Case Rep Anaesthesiol. 2013;2013: 1–4. Conflict of interest The authors declare that they have no conflict of 9. Divekar A, Shah S, Joshi C. Neurogenic stunned myocardium and interest. transient severe tricuspid regurgitation in a child following non- accidental head trauma. Pediatr Cardiol. 2006;27(3):376–7. Open Access This article is distributed under the terms of the Creative 10. Deleu D, Kettern MA, Hanssens Y, Kumar S, Salim K, Miyares Commons Attribution 4.0 International License (http://creative F. Neurogenic stunned myocardium following hemorrhagic commons.org/licenses/by/4.0/), which permits unrestricted use, dis- . Saudi Med J. 2007;28(2):283–5. tribution, and reproduction in any medium, provided you give 11. Wippermann J, Bennink G, Wittwer T, Madershahian N, Ort- appropriate credit to the original author(s) and the source, provide a link mann C, Wahlers T. Reversal of myocardial dysfunction due to to the Creative Commons license, and indicate if changes were made. brain injury. Asian Cardiovasc Thorac Ann. 2008;16(3):30–1.

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12. Mare´chaux S, Goldstein P, Girardie P, Ennezat PV. Contractile 23. Lyon AR, Bossone E, Schneider B, et al. Current state of pattern of inverted takotsubo cardiomyopathy: illustration by knowledge on Takotsubo syndrome: a position statement from two-dimensional strain. Eur J Echocardiogr. 2009;10(2):332–3. the taskforce on Takotsubo syndrome of the heart failure asso- 13. Vergez M, Pirracchio R, Mateo J, Payen D, Cholley B. Tako ciation of the European society of cardiology. Eur J Heart Fail. tsubo cardiomyopathy in a patient with multiple trauma. Resus- 2016;18(1):8–27. citation. 2009;80(9):1074–7. 24. Templin C, Ghadri JR, Diekmann J, et al. Clinical features and 14. Riera M, Llompart-Pou JA, Carillo A, Blanco C. Head injury outcomes of Takotsubo (stress) cardiomyopathy. N Engl J Med. and inverted takotsubo cardiomyopathy. J Trauma. 2010;68: 2015;373(10):929–38. 13–5. 25. Bybee KA, Kara T, Prasad A, et al. Systematic review: transient 15. Samol A, Grude M, Stypmann J, et al. Acute global cardiac left ventricular apical ballooning: a syndrome that mimics ST- decompensation due to inverted takotsubo cardiomyopathy after segment elevation . Ann Intern Med. skull-brain trauma- a case report. Injury Extra. 2011;42(5):54–7. 2004;141(11):858–65. 16. Santoro F, Ieva R, Ferraretti A, et al. Safety and feasibility of 26. Wittstein IS, Thiemann DR, Lima JA, et al. Neurohumoral fea- levosimendan administration in takotsubo cardiomyopathy: a tures of myocardial stunning due to sudden emotional stress. case series. Cardiovasc Ther. 2013;31(6):133–7. N Engl J Med. 2005;352(6):539–48. 17. Krpata DM, Barksdle EM Jr. Trauma induced left ventricular 27. Lyon AR, Rees PS, Prasad S, Poole-Wilson PA, Harding SE. apical ballooning syndrome in a 15 year-old: a rare case of tako- Stress (Takotsubo) cardiomyopathy—a novel pathophysiological tsubo cardiomyopathy. J Pediatr Surg. 2013;48:876–9. hypothesis to explain catecholamine-induced acute myocardial 18. Bonacchi M, Vannini A, Harmelin G, et al. Inverted-takotsubo stunning. Nat Clin Prac Cardiovasc Med. 2008;5:22–9. cardiomyopathy: severe refractory heart failure in poly-trauma 28. Paur H, Wright PT, Sikkel MB, et al. High levels of circulating patients saved by emergency extracorporeal life support. Interact epinephrine trigger apical cardiodepression in a ß2-adrenergic Cardiovasc Thorac Surg. 2015;20(3):365–71. receptor/Gi–dependent manner: a new model of Takotsubo car- 19. Hong J, Glater-Welt LB, Siegel LB. Takotsubo cardiomyopathy diomyopathy. Circulation. 2012;126(6):697–706. in a 23 months-old following traumatic brain injury. Ann Pediatr 29. Brain Trauma Foundation, American Association of Neurological Child Health. 2014;2(4):1029. Surgeons (AANS), Congress of Neurological Surgeons (CNS), 20. Bahloul M, Chaari AN, Kallel H, et al. Neurogenic pulmonary AANS/CNS Joint Section on Neurotrauma and Critical Care. edema due to traumatic brain injury: evidence of cardiac dys- Guidelines for the management of severe traumatic brain injury, function. Am J Crit Care. 2006;15(5):462–70. 3rd edition. J Neurotrauma. 2007;24(suppl 1):S1–S106. 21. Prathep S, Sharma D, Hallman M, et al. Preliminary report on 30. Taccone FS, Brasseur A, Vincent JL, De Backer D. Levosi- cardiac dysfunction after isolated traumatic brain injury. Crit mendan for the treatment of subarachnoid haemorrhage-related Care Med. 2014;42:142–7. cardiogenic shock. Intensive Care Med. 2013;39(8):1497–8. 22. Hasanin A, Kamal A, Amin S, et al. Incidence and outcome of 31. Parissis JT, Rafouli-Stergiou P, Paraskevaidis I, Mebazaa A. cardiac injury in patients with severe head trauma. Scand J Levosimendan: from basic science to clinical practice. Heart Fail Trauma, Resus Emerg Med. 2016;24:58. Rev. 2009;14(4):265–75.

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