Takotsubo Cardiomyopathy in Traumatic Brain Injury
Takotsubo cardiomyopathy (TC) is a well-known complication after aneurysmal subarachnoid hemorrhage and has been rarely described in patients with traumatic brain injury (TBI).
Case report and review of literature.
Here, we report a 73-year-old woman with mild traumatic brain injury (TBI) presenting in cardiogenic shock. Takotsubo cardiomyopathy (TC) was diagnosed by repeated echocardiography. Cardiovascular support by inotropic agents led to hemodynamic stabilization after initiation of levosimendan. Cardiac function fully recovered within 21 days. We performed an in-depth literature review and identified 16 reported patients with TBI and TC. Clinical course and characteristics are discussed in the context of our patient.
Takotsubo cardiomyopathy is under-recognized after TBI and may negatively impact outcome if left untreated.
KeywordsTraumatic brain injury Myocardial dysfunction Takotsubo cardiomyopathy Monitoring Echocardiography
Takotsubo cardiomyopathy (TC) is known to occur in patients with severe brain insult. It has been widely described after subarachnoid hemorrhage (SAH, 1.2–28 %) [1, 2, 3]; however, it rarely occurs in patients with intracerebral hemorrhage, ischemic stroke, and traumatic brain injury (TBI) . In medical ICU patients, the incidence ranges between 5.7 and 28 % [5, 6]. Here, we report a case of mild TBI with secondary hematoma progression presenting with severe TC and provide a comprehensive review of all reported TBI cases [7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19].
At this time, the electrocardiography showed sinus tachycardia at a rate of 130 beats per minute (bpm) with non-specific repolarization abnormalities with no correspondence to a distinct coronary artery territory. Laboratory myocardial biomarkers exceeded pathologic thresholds: Troponin T levels peaked at 0.54 ng/mL (normal range, <0.014 ng/mL) and NT-proBNP was 4690 ng/L (normal range 0–303 ng/L). Creatinine kinase (CK) was within normal range. Bedside transthoracic echocardiography demonstrated severe left ventricular (LV) myocardial dysfunction (ejection fraction 35 %), marked hypokinesia of the apical and midventricular portions of the left ventricle suggestive of takotsubo cardiomyopathy (TC). Only mild mitral regurgitation was detected. Invasive coronary angiography was not performed because of typical findings on echocardiogram and the limited therapeutic possibility due to intracranial bleeding.
As dobutamine was not improving the severe myocardial dysfunction, levosimendan was added (initial dose 0.03 mcg/kg/min, gradually increased to 0.12 mcg/kg/min) and maintained for 28 h. After initiation, no increased dosage of norepinephrine was needed. The heart rate decreased to less than 100 bpm, dobutamine and phenylephrine could be withdrawn, and norepinephrine was slowly decreased over the following days without significant drops in blood pressure. Repeated transthoracic echocardiography demonstrated improvement in LV myocardial function on day 8 (ejection fraction 40 %) (Fig. 1, Panel B) and further recovery on day 21 (Fig. 1, Panel C, ejection fraction 49.9 %, normal 54–74 %). Coronary angiography was not performed as coronary artery disease deemed unlikely due to recovery in cardiac function in repeated echocardiography suggestive for TC as underlying pathology. The patient was successfully weaned on day 11 and discharged for neurorehabilitation 21 days after trauma. At this time, she was fully awake with a GCS score of 15, mildly disabled with a grade 4 brachio-facial left-sided hemiparesis and dysphagia.
Review of Literature
We performed a comprehensive literature search using the search terms ‘Takotsubo cardiomyopathy,’ ‘Tako-tsubo cardiomyopathy,’ ‘stress cardiomyopathy,’ ‘stunned myocardium,’ ‘transient-left-ventricular ballooning syndrome,’ ‘apical ballooning syndrome,’ ‘myocardial dysfunction’ or ‘heart failure’ together with ‘traumatic brain injury,’ ‘head injury,’ and ‘polytrauma.’ Only articles in English language were included.
Reported cases of takotsubo cardiomyopathy with traumatic brain injury in the literature
Number of patients
Admission level of consciousness, GCS
TC onset day
Other investigation (s)
Functional outcome/cardiac outcome
Palac et al. 
EF 45 %
LV hypokinesia sparing apex
CK max = 1244 U/La
Troponin max = 1.4 ng/mL (NR < 0.5 ng/mL)
Dopamine, Norepinephrine, Vasopressin
Echo the same day: EF = 60 %
Krishnamoorthy et al. 
EF 35 %
Phenylephrine: 300 mcg
Ephedrine: 20 mg
Echo the same day: EF = 55 %
Divekar et al. 
EF 45 %.
T wave inversion in I, aVL, and V4–V6 with QT prolongation
CK max = 853 U/La
Troponin T max = 0.6 ng/mLa
Echo after 3 days: normal
Deleu et al. 
EF 18 %, Diffuse LV akinesia
Sinus tachycardia, diffuse, symmetric T wave inversion
CK max = 311 U/L (NR 39–238 U/L)
Troponin max = 0.08 ng/mL (NR < 0.03 ng/mL)
Epinephrineb: up to 3 mcg/min
Echo after 12 days: EF = 50 %
Wippermann et al. 
EF < 10 %
Anterior myocardial ischemia
Troponin I max = 2.3 ng/mLa
Echo after 2 days: EF = 50 %
Maréchaux et al. 
EF 20 %
LV akinesia sparing apex
Diffuse T wave inversion with QT prolongation
Troponin max = 1.6 ng/mL (NR < 0.1 ng/mL)
Vergez et al. 
Marked ST elevation (≥2 mm) negative T waves left precordium
Troponin I max = 3.2 ng/mL (NR < 0.02 ng/mL)
Norepinephrinec: 0.–0.83 mcg/kg/min
Dobutamine: 15 mcg/kg/min
Echo after 17 days: Improvement in apical LV contractility
Riera et al. 
Moderate to severe
LV hypokinesia sparing apex
Sinus tachycardia, subendocardial injury anteroseptal and inferior
CK max = 242U/L (NR 24–170 U/L)
Troponin I max = 1.13 ng/mL (NR < 0.06 ng/mL)
LVG: LV myocardial dysfunction
Norepinephrine: 0.8–1 mcg/kg/min
Echo after 7 days: EF 45–50 %
Samol et al. 
T negativity in V3–V6 with QT prolongation
CK max = 480U/La
Troponin I max = 6.8 ng/mL (NR < 0.04 ng/mL)
LVG: LV hypokinesia midventricular
Cardiac MRI: severe LV hypokinesia (EF 25 %)
Echo after 2 days: EF 45 %
Santoro et al. 
EF 30 %
Troponin max = 4.72 ng/mLa
Levosimendan: 0.1 mcg/kg/min
Echo after 3 days: EF 50 %
Krpata et al. 
EF 10–15 %
T wave inversion V3–V6
CK max = 541U/La
Troponin max = 3.23 ng/mLa
Milrinone: No dosage given
Echo after 7 days: EF 65 %
Bonacchi et al. 
EF 14 %
Mortality: 2 patients
Echo after 3 days: EF 55–59 % in 2 survived patients
Hong et al. 
Moderate LV hypokinesia
Diffuse ST segment elevation in all leads
CK max = 134U/La
Troponin max = 0.11 ng/mL (NR < 0.06 ng/mL)
Echo after 1 day: Recovered cardiac event
In summary, (1) brain injury pattern in TBI patients presenting with TC is heterogeneous and therefore unspecific, (2) in the majority of patients inotropic support using dobutamine leads to improved cardiac function, (3) patients presenting in severe refractory cardiovascular shock may necessitate extracorporeal life support, and (4) with adequate management of TC long-term prognosis is more dependent on the severity of brain injury.
Description of 3 studies on myocardial dysfunction in patients with traumatic brain injury
Number of patients
Patients severe TBI (%)
Abnormal ECG (%)
Increased CK or troponin level (%)a
Abnormal echocardiography (%)b
Patients with myocardial dysfunction (%)c
Bahloul et al. 
EDH, SDH, cerebral edema, contusion
Prathep et al. 
Hasanin et al. 
SDH, tSAH, IVH, DAI, contusion
Underlying pathophysiologic mechanisms are still incompletely understood. Most investigations suggest an interconnected cascade of neuronal injury causing sympathetic overstimulation and direct catecholamine toxicity to the heart . Supra-physiologic levels of epinephrine bind to myocardial B2-receptors causing myocardial protein Gs-to-Gi coupling switch, mediated cyclic adenosine monophosphate (cAMP) calcium overload in myocytes, and contraction-band necrosis reducing cardiac contractility [27, 28].
Our patient had full recovery of cardiac function 21 days after trauma. Even though transient and reversible in nature, some reports suggest recovery even up to 12-week postinjury . Hemodynamic support is critical in patients with severe TBI based on current treatment concepts that emphasize maintenance of an adequate CPP . Improving cardiac function in patients with TC may be achieved by using dobutamine and other pharmacological, or non-pharmacologic treatment including extracorporeal life 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.
Recently, the use of levosimendan has been reported in patients with aneurysmal SAH where dobutamine was deemed ineffective . Levosimendan is a non-catecholamine inodilator used in the treatment of acute heart failure with higher improvement rate in cardiac function compared to dobutamine . It increases the sensitivity of myofilaments to calcium, leading to increased myocardial contraction without increasing intracellular cAMP or calcium concentrations . Through the opening of an ATP-dependent potassium channel, vasodilatory effects in systemic, coronary, pulmonary, and venous blood vessels may be observed . Unlike other vasopressors, it improves myocardial contractility without increasing myocardial oxygen consumption, and more importantly its action is independent of interactions with adrenergic receptors . Nonetheless, its utilization in patients with TC remains scarce, bearing the rarity of the entity itself. In one of the largest case series, levosimendan was successfully used in 13 patients with TC .
We highlight the presentation of a patient suffering from TBI with takotsubo cardiomyopathy. Although transient in nature and commonly associated with a good overall prognosis, increasing evidence suggests it is a more serious acute cardiac disorder with a variety of complications [23, 24]. Its hemodynamic effect may be deleterious in certain TBI patients if unrecognized. Levosimendan may be an effective therapeutic agent in severe cases.
Paul Rhomberg, MD, Department of Neuroradiology, Medical University of Innsbruck Anichstrasse 35, 6020 Innsbruck, Austria provided neuroimaging data. Open access funding provided by University of Innsbruck and Medical University of Innsbruck.
Chun Fai Cheah contributed to concept, design, writing, and editing; Mario Kofler helped with design, editing, and critical revision of manuscript for intellectual content; Alois Schiefecker helped in editing and critical revision of manuscript for intellectual content; Ronny Beer and Bettina Pfausler contributed to concept, design, and critical revision of manuscript for intellectual content; Gert Klug helped with echocardiography, data interpretation, and critical revision; Raimund Helbok contributed to idea, writing, reviewing, editing, and critical revision.
Compliance with Ethical Standards
Conflict of interest
The authors declare that they have no conflict of interest.
Supplementary material 1 (AVI 3633 kb)
Supplementary material 2 (AVI 3492 kb)
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