Heart Mind

: 2018  |  Volume : 2  |  Issue : 1  |  Page : 12--15

“Broken heart syndrome” Cardiovascular manifestations of traumatic brain injury

Huber S Padilla-Zambrano1, Ezequiel Garcia-Ballestas1, Alexis Narvaez Rojas2, Luis Rafael Moscote-Salazar3, Amrita Ghosh4, Ranabir Pal5, Amit Agrawal6,  
1 Centro De Investigaciones Biomédicas (CIB), Faculty of Medicine, University of Cartagena, Cartagena de Indias, Colombia
2 Department of Medicine, Faculty of Medicine, University of Cartagena, Cartagena de Indias, Bolívar, Colombia
3 Department of Neurosurgery, University of Cartagena, Cartagena, Colombia
4 Department of Biochemistry, Medical College, Kolkata, India
5 Department of Community Medicine, MGM Medical College and LSK Hospital, Kishanganj, India
6 Department of Neurosurgery, Narayna Medical College Hospital, Nellore, Andhra Pradesh, India

Correspondence Address:
Dr. Amit Agrawal
Department of Neurosurgery, Narayana Medical College Hospital, Chinthareddypalem, Nellore - 524 003, Andhra Pradesh


Cardiovascular dysfunction frequently complicates outcomes of traumatic brain injury (TBI), resulting in higher morbidity and mortality. TBI results in dysfunctions of the autonomic nervous system (mediated by catecholamines), altered systemic circulation homeostasis medicated by neurogenic stimuli, electrocardiographic, echocardiographic abnormities, and change in serum cardiac enzyme levels (not attributed to primary cardiac pathology). The present review attempts to find cardiovascular alterations following TBI, management to these patients, and their outcome.

How to cite this article:
Padilla-Zambrano HS, Garcia-Ballestas E, Rojas AN, Moscote-Salazar LR, Ghosh A, Pal R, Agrawal A. “Broken heart syndrome” Cardiovascular manifestations of traumatic brain injury.Heart Mind 2018;2:12-15

How to cite this URL:
Padilla-Zambrano HS, Garcia-Ballestas E, Rojas AN, Moscote-Salazar LR, Ghosh A, Pal R, Agrawal A. “Broken heart syndrome” Cardiovascular manifestations of traumatic brain injury. Heart Mind [serial online] 2018 [cited 2022 Sep 25 ];2:12-15
Available from: http://www.heartmindjournal.org/text.asp?2018/2/1/12/251481

Full Text


Traumatic brain injury (TBI) affects approximately 1.8 million people worldwide,[1] and it is also one of the main causes of brain death in intensive care units.[2] TBI is a disease with a complex physiopathological process caused by mechanical forces that produce physical, cognitive, vision, emotional, and sleep disorders, among others.[3] TBI is also associated with cardiac dysfunction,[1] leading to an increase in morbidity and mortality in patients[4] given that brain function plays an important role in cardiac functioning through neuronal and hormonal mechanisms.[5] The present article review describes the relation between the heart and the brain and the cardiovascular alterations that occur in TBI.

 Central Regulation of the Autonomic System

The autonomic nervous system (ANS) which constitutes a complex network in the central nervous system that involves structures such as insular and medial prefrontal region of the cerebral cortex, cerebral amygdala, terminal stria, hypothalamus, periaqueductal gray matter, parabrachial bridge, nucleus of the solitary tract, and medial reticular zone of the medulla[3],[6] has been denominated as a whole as “central autonomic network (CAN).”[7] The ANS, through its sympathetic division, exerts cardiac control and in the peripheral vasculature. In addition, it is important to understand that postganglionic sympathetic white fibers supply atria, ventricles, and coronary arteries via the cervical ganglia (superior, middle, and inferior cardiac nerves) or from the thoracic ganglia at the TI–T4 level, which generate an increase of heart rate, myocardial contractility, and coronary vasodilation.[3] The cardiovascular system is subjected to an autonomic control that has been called “neuro-autonomic cardiovascular regulation (NCR).”[8] Heart rate variation (HRV) has been suggested to evaluate the autonomic alteration, which reflects the activity of the sympathetic and parasympathetic nervous system,[8] being a very useful predictor in patients with TBI.[9] HRV is a noninvasive electrocardiographic marker that reflects the activity of the ANS divisions in the sinus node of the heart, showing the total number of fluctuations in the instantaneous heart rate and interbeat (RR) intervals.[3],[7] In addition, this marker shows the imbalance of the afferent and efferent fibers of the ANS, which causes ventricular tachyarrhythmias and sudden cardiac death, and the neural control.[5]

 Catecholaminergic Effects

The hypothalamic–pituitary–adrenal axis constitutes some fundamental hormonal regulator endocrine signals that integrate stress, physical activity, and metabolism. At the hypothalamic level, the suprachiasmatic nucleus releases the corticotropin-releasing hormone that stimulates the adrenal gland to release cortisol.[4],[10] An increase in the sympathetic tone causes a wave of catecholamines during the TBI that leads to cardiac damage due to hypertrophy and myocardial ischemia;[4],[5],[10],[11] in addition, in the long term, it can generate edema, transient fibrosis, inflammation, and contraction band necrosis.[4],[10] However, an alteration in the hypothalamus and the insular cortex alters the CAN, causing adverse effects at the cardiac level.[4] Injuries in this region increase the risk of cardiac complications and can cause fluctuations in blood pressure, cardiac arrhythmias, and myocyte death.[10]

 Systemic Circulatory Effects

The medium TBI (mTBI) produces alterations in the coupling between the ANS and the cardiovascular system NCR.[11] The degree of decoupling is proportional to the severity of the injury.[1],[12] The catecholaminergic storm characteristics of LCTM:[1],[4],[5],[8],[10],[13],[14] A subsequent systemic vasoconstriction increases afterload, cardiac output, and oxygen demand[14],[15] and also vasoconstriction (which reaches the coronary circulation) can lead to myocardial ischemia.[14] Systemic hypertension also leads to intense pulmonary hypertension, increase in hydrostatic pressure and induces a transudate that combined with left ventricular dysfunction can lead to produce an acute lung injury and neurogenic pulmonary edema seconds. A common complication of these pulmonary events is pneumonia, whose most frequent etiologic agent in these cases is Staphylococcus aureus.[4],[10],[14]

 Pulse Rate and Blood Pressure

When the surge of catecholamines increases, it causes hypertension,[5],[16] tachycardia, and increased oxygen demand that can lead to subendocardial ischemia causing a deterioration of ventricular function. However, marked sinus bradycardia occurs due to the baroreceptor reflex (triad of Cushing).[5],[11] The assessment of the RCN by measuring the heart rate and its fluctuations has been widely accepted.[8] The result of the spectral analysis of heart rate power decreases inversely proportional to the severity of the injury and reaches zero during brain death.[12]

 Electrocardiography Changes

Left ventricular systolic dysfunction (LVSD) is a common and reversible finding, and it is characterized by sinus rhythms and electrocardiographic alterations such as prolongation of the QT interval, ST-segment elevation, flat or inverted T-waves, U-waves, pointed or inverted T-waves, and widened QRS complex,[14],[17] which are associated with a worse prognosis.[10] These changes are influenced by variables in the natural evolution of the disease, geographical changes of the lesion, and the presence of edema or partial recovery of the myocardium.[18] These findings and their clinical correlation in the context of the patient can determine that it is a MAN, a TTS, or an acute myocardial infarction (AMI) product of a coronary disease.[15]

 Echocardiography Changes

Takotsubo syndrome (TTS) is characterized by dyskinesia, hypokinesia, or transient akinesia of segments of the left ventricle with or without apical involvement. There are very convincing reports that the ejection fraction is decreased, although there are those who maintain that despite apical ventricular akinesia, this remains.[19] In contrast, the MAN expresses electrocardiographic changes in an isolated form which disagree with the findings of echocardiography. Another way to differentiate a MAN is its reversible nature, which unlike coronary disease has an early resolution.[15],[20] Unlike TTS (regional abnormality of the ventricular wall), the MAN presents a transient global abnormality in the ventricular wall, and the elevation of enzymes is lower than in the AMI, but they maintain significant similarity.[5],[10],[13],[17]

 Myocardial Enzymes

When the TBI is produced accompanied by an increase in intracranial pressure, it can be prompted a stimulation of the A1 and A5, nuclei of the solitary tract, and postrema area within the medulla and hypothalamus, which leads to an excess of catecholamines, dysfunction autonomic and systemic inflammatory response.[14] It has been suggested that patients over 65 years of age with an increase in cardiac enzymes and abbreviated head injury scale of 4–6, we need to suspect trauma induced cardiac dysfunctions.[5] Myocardial biopsies of patients who were diagnosed with brain death have been observed, pathological characteristics that are associated with an increase in catecholamines, which are highly similar to the microscopic characteristics of stress cardiomyopathies.[1]

 Neurogenic Stunned Myocardium Syndrome

The neurogenic stunned myocardium is a reversible neurogenic myocardial lesion consisting of cardiac complications in the context of a neurological event due to an alteration in the RCN.[12] Initially, the transient LVSD phenomenon was described in the context of a coronary disease, but the eventual knowledge of the neurocardiac axis and its pathophysiological implication in different neurological lesions (subarachnoid hemorrhage [SAH], ischemic cerebrovascular disease [CVD], Guillain–Barre syndrome, status epilepticus, acute hydrocephalus, infarction acute spinal cord, and emotional stress) is demonstrative evidence to be taken into account when approaching a patient with a specific neurological condition.[21] It is understood that 50% of patients with a brain trauma have a cardiac lesion.[9] In particular, this condition is very similar to myocardial infarction, due to the fact that it also presents with electrocardiographic changes, decreased cardiac function, troponin increase, creatine kinase-MB increase and brain natriuretic peptide, and abnormalities of the ventricular wall.[1],[5],[11],[12],[14],[17] This condition is more frequently involved in the eventuality of a SAH or in ischemic CVD but is shared with TBI because it overlaps the pathophysiology of catecholaminergic toxicity and got very suggestive evidence.[1],[5],[9] MAN is a picture similar to AMI due to coronary disease, although the difference lies in the very absence of stenosis or coronary vasospasm by means of coronary angiography.[15] The diagnosis of MAN is essentially exclusive.

 Cardiac Dysfunction in Subarachnoid Hemorrhage

As mentioned in a previous section, cardiac dysfunction in the context of a SAH is a fairly incident condition in the clinic and constitutes a challenge for its diagnosis. About 10% of patients with SAH develop a LVSD in figures probably underestimated.[22] The SAH of aneurysmal etiology is the one that has a more evident relationship with this pathological process.[17],[23] The MAN is characterized by the aforementioned paraclinical findings; in addition, the coexistence of TTS should be discarded,[17] because, despite being a rare event, it is associated with higher mortality.[15] It is necessary to clarify that the electrocardiogram altered by itself is not a diagnosis of stress cardiomyopathy, since it occurs in most (or all) of the patients with SAH.[22]

 Takotsubo Syndrome

TTS was first described in 1990 and also called “broken heart syndrome;” it is a transient cardiomyopathy very similar to AMI that occurs before a physical or emotional trigger.[20],[24] Recently, the fact that TTS is not a cardiomyopathy has been conceptualized, although it meets the requirements to be classified as cardiomyopathy postulated by the American Heart Association and the European Society of Cardiology. The still precarious knowledge of pathophysiology has generated that sometimes it is classified as unclassifiable within the large group of cardiomyopathies, coupled with histological differences with this group. Therefore, toxic shock syndrome (TSS) has been considered to be a syndrome within the spectrum of ischemic heart disease.[25] It has been hypothesized that the transient decrease in contractility is part of a protective response to organic perfusion in the face of exorbitant adrenergic dynamism, as this condition is associated with the risk of ventricular fibrillation due to electrophysiological instability.[19] This entity is more common in people over 50 years of age with a female predominance (except in Japan), and it is an unattended problem worldwide, although the trend is an increase in cases due to the reduction of its neglect.[22],[24] There are many variants of TTS described, but we have been able to differentiate four common subtypes according to their morphology to echocardiography: mainly the apical englobamiento of the left ventricle, and succeeding in frequency, the medioventricular, the basal, and focal movement patterns of the wall.[24]


Coronary angiography with ventriculography is considered the gold standard for diagnosing TTS,[24] although echocardiography has great diagnostic utility and the cardinal diagnostic criterion of TTS is the apical englobamiento of the left ventricle,[23] owing to this deformity its nomenclature (octopus trap).[24] Cardiac enzymes and electrocardiographic findings support the diagnosis of TTS.[5],[17] The symptoms are not diagnostic criteria because they can be an asymptomatic incidental finding, although these symptoms are precordial pain, dyspnea, or syncope, and in the context of a neurological disease, the asthenic or complaining feature of the patient can be weakened or underestimated by the decrease in the state of consciousness.[5],[20],[24] It is necessary to clarify that the TTS has been reported at different severities and it is possible that the subjective component biases the defining character to diagnose this entity; this explains that there are numerous criteria to diagnose.[20] The Mayo Clinic criteria, since its appearance in 2004 by a dedicated group of cardiologists, have undergone certain modifications to date, as indicated below. The aforementioned echocardiographic findings and the discarding of stenosis, obstruction or coronary thrombosis, or of the concomitance of some other etiologies of catecholaminergic storm, such as pheochromocytoma, are the diagnostic criteria of TTS.[5],[10],[17],[20],[26] In addition to these, the InterTAK criteria, which are the result of a global consensus, include the possible knowledge of the physical or emotional trigger, the quality of a postmenopausal woman, and the discarding of an infectious myocarditis. In addition, these latter criteria do not exclude coronary stenosis but may be a coexisting feature. Comorbidities that complicate the application of these criteria are pheochromocytoma and coronary heart disease.[20],[24] Very similar to these criteria are the Segovia Cubero criteria that divide these conditioning factors into mandatory criteria, major criteria, and minor criteria. There are other criteria such as the Japanese guidelines for the diagnosis of TTS that enclose that TTS in the context of a cerebrovascular event within entities that simulate a TSS (CVD with myocardial dysfunction similar to takotsubo); these criteria contain numerous items that startle the exclusive nature of the diagnosis.[20]


First of all, the exclusion of AMI or suspension of its treatment (antiaggregants, ß-blockers, and oxygen) is mandatory. The self-limited and transitory nature of the TTS does not require a specific or optimal management, which does not mean that the treatment is null, but tends to be very conservative, abiding by that bioethical principle PRIMUM NIL NOCERE (first, not doing harm), with the exception of cases with substantial risk of death.[19] However, treatment is determined by the occurrence of complications during the acute phase, so that, in the face of LVSD and in the context of established risk factors, it is necessary to stratify the risk of TTS to determine a treatment. Those at high risk should remain in an intensive care unit and in the presence of signs of shock, fluid infusion, inotropic agents or the use of an intra-aortic balloon pump are measures of circulatory support indicated.[5],[20] Those therapeutic agents supported by the discarded diagnosis (AMI), very commonly the aspirin, because it has not shown benefits in the TSS management. If heart failure coexists, treatment with diuretics or nitroglycerin has shown effectiveness in the management of TSS. Those hemodynamically stable patients are treated with diuretics, angiotensin-converting enzyme inhibitors, and β-blockers (mainly carvedilol). The low contractility of the apical segment can lead to thromboembolism, and therefore, the prophylactic treatment consists of anticoagulation until there is recovery of the mobility of this segment.[19],[20] β-blockers have been shown to be of great utility in cases with dynamic obstruction of the left ventricular outflow tract obstruction, prevention of malignant arrhythmias, prevention of TTS, and reduction of the risk of cardiac rupture.[19]


In this review, we investigated the possible pathophysiological pathways of cardiovascular complications of TBI. The literature suggest that clinicians need to keep in mind the probability of cardiovascular changes in patients with TBI. However, there is a need to conduct further translational studies that are required to supplement these observations with changes in the levels of cardiac enzymes or associated abnormalities and their correlation with overall outcomes of TBI.

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Conflicts of interest

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1Prathep S, Sharma D, Hallman M, Joffe A, Krishnamoorthy V, Mackensen GB, et al. Preliminary report on cardiac dysfunction after isolated traumatic brain injury. Crit Care Med 2014;42:142-7.
2Rzheutskaya RE. Characteristics of hemodynamic disorders in patients with severe traumatic brain injury. Crit Care Res Pract 2012;2012:606179.
3Esterov D, Greenwald BD. Autonomic dysfunction after mild traumatic brain injury. Brain Sci 2017;7. pii: E100.
4Gregory T, Smith M. Cardiovascular complications of brain injury. Contin Educ Anaesth Crit Care Pain 2012;12:67-71.
5Manikandan S. Heart in the brain injured. J Neuroanaesthesiol Crit Care 2016;3:12-5.
6McCorry LK. Physiology of the autonomic nervous system. Am J Pharm Educ 2007;71:78.
7Riganello F, Dolce G, Sannita WG. Heart rate variability and the central autonomic network in the severe disorder of consciousness. J Rehabil Med 2012;44:495-501.
8Len TK, Neary JP. Cerebrovascular pathophysiology following mild traumatic brain injury. Clin Physiol Funct Imaging 2011;31:85-93.
9Hasanin A, Kamal A, Amin S, Zakaria D, El Sayed R, Mahmoud K, et al. Incidence and outcome of cardiac injury in patients with severe head trauma. Scand J Trauma Resusc Emerg Med 2016;24:58.
10Chen Z, Venkat P, Seyfried D, Chopp M, Yan T, Chen J, et al. Brain-heart interaction: Cardiac complications after stroke. Circ Res 2017;121:451-68.
11Lim HB, Smith M. Systemic complications after head injury: A clinical review. Anaesthesia 2007;62:474-82.
12Biso S, Wongrakpanich S, Agrawal A, Yadlapati S, Kishlyansky M, Figueredo V, et al. Areview of neurogenic stunned myocardium. Cardiovasc Psychiatry Neurol 2017;2017:5842182.
13Watanabe M, Izumo M, Akashi YJ. Novel understanding of Takotsubo syndrome. Int Heart J 2018;59:250-5.
14Wijayatilake DS, Sherren PB, Jigajinni SV. Systemic complications of traumatic brain injury. Curr Opin Anaesthesiol 2015;28:525-31.
15Hilz MJ, Wang R, Markus J, Ammon F, Hösl KM, Flanagan SR, et al. Severity of traumatic brain injury correlates with long-term cardiovascular autonomic dysfunction. J Neurol 2017;264:1956-67.
16Bhandarkar P, Munivenkatappa A, Roy N, Kumar V, Samudrala VD, Kamble J, et al. On-admission blood pressure and pulse rate in trauma patients and their correlation with mortality: Cushing's phenomenon revisited. Int J Crit Illn Inj Sci 2017;7:14-7.
17Pinnamaneni S, Dutta T, Melcer J, Aronow WS. Neurogenic stress cardiomyopathy associated with subarachnoid hemorrhage. Future Cardiol 2015;11:77-87.
18Samudrala VD, Kumar A, Agrawal A. Electrocardiographic changes in patients with isolated traumatic brain injury and their correlation with outcome. Indian J Neurotrauma 2016;13:70-4.
19Templin C, Ghadri JR, Diekmann J, Napp LC, Bataiosu DR, Jaguszewski M, et al. Clinical features and outcomes of Takotsubo (Stress) cardiomyopathy. N Engl J Med 2015;373:929-38.
20Rengachary SS, Watanabe I. Ultrastructure and pathogenesis of intracranial arachnoid cysts. J Neuropathol Exp Neurol 1981;40:61-83.
21Kerro A, Woods T, Chang JJ. Neurogenic stunned myocardium in subarachnoid hemorrhage. J Crit Care 2017;38:27-34.
22Ghadri JR, Wittstein IS, Prasad A, Sharkey S, Dote K, Akashi YJ, et al. International expert consensus document on Takotsubo syndrome (Part I): Clinical characteristics, diagnostic criteria, and pathophysiology. Eur Heart J 2018;39:2032-46.
23Pelliccia F, Sinagra G, Elliott P, Parodi G, Basso C, Camici PG, et al. Takotsubo is not a cardiomyopathy. Int J Cardiol 2018;254:250-3.
24Omerovic E. Takotsubo syndrome-scientific basis for current treatment strategies. Heart Fail Clin 2016;12:577-86.
25Ranieri M, Finsterer J, Bedini G, Parati EA, Bersano A. Takotsubo syndrome: Clinical features, pathogenesis, treatment, and relationship with cerebrovascular diseases. Curr Neurol Neurosci Rep 2018;18:20.
26Ono R, Falcão LM. Takotsubo cardiomyopathy systematic review: Pathophysiologic process, clinical presentation and diagnostic approach to Takotsubo cardiomyopathy. Int J Cardiol 2016;209:196-205.