Myocardial function at the early phase of traumatic brain injury: a prospective controlled study

Myocardial dysfunction has been described after brain injuries, leading to the concept of brain-heart interaction [1]. A paroxysmal sympathetic hyperactivity with higher plasma-level of endogenous norepinephrine has been observed after subarachnoid hemorrhage (SAH) and stroke, resulting in a cardiac dysfunction [2‐4]. Transmural myocardial lesions were also reported after brain death in a series of post mortem examination [5]. Experimentally, the extreme elevation of intra-cranial pressure by inflating a subdural balloon induced acute cardiac failure related to an increased sympathetic activity, electrocardiographic abnormalities and myocardial damage [6, 7]. After traumatic brain injury (TBI), neurogenic pulmonary edema has been also reported [8] and high troponin concentrations were associated with an unfavorable neurologic outcome and mortality [9]. Recently, in a retrospective cohort of 139 patients with severe TBI, 12 % of the patients had a cardiac dysfunction with a reduced left ventricular ejection fraction (LVEF) and regional wall motion abnormalities [10]. These clinical findings were corroborated by experimental data which reported significant echocardiographic myocardial injury [11], while other authors reported no cardiac dysfunction within the first 24 h in a rat model of diffuse TBI [12]. Hence, the myocardial function after TBI remains unclear and its exploration relies upon experimental models and uncontrolled retrospective clinical studies. Possible confounding factors like associated multiple trauma, hemorrhagic shock, cardio-vascular co-morbidities or lung-heart interaction might also hinder the interpretation of the association between cardiac failure and severe TBI.

Assessment of cardiac function in clinical practice is based upon standard two dimensional (2D) echocardiography [13], that provides validated systolic and diastolic indices [14]. Since myocardial functionality results from a complex interplay between deformation (longitudinal, radial and circumferential) and twist/untwist mechanics, conventional echocardiography only partially described cardiac function. Conversely, Speckle Tracking Echocardiography (STE) offers a comprehensive and sensitive evaluation of regional myocardial function. For instance, in pathological conditions like sepsis or heart failure, conventional 2D-echocardiography demonstrated no LVEF impairment whereas speckle tracking echocardiography (STE) detected changes in myocardial function [15, 16].

The present study aimed at evaluating myocardial function at the early phase of TBI using conventional 2D echocardiography and complementary STE analysis. A matched cohort of non-TBI patients undergoing general anesthesia for a peripheral surgery served as control group. Our main hypothesis was a systematic 10 % decrease in the left ventricle ejection fraction in the TBI group compared to the control group.

From November 2014 to November 2015, we conducted a prospective case-control single blinded study in a Level-I trauma center (Grenoble University Hospital, France). The regional ethics committee (number: 14-CHUG-34) and the national agency for drugs safety (Number: 2014-A01370-47) approved the study design. This trial was registered on ClinicalTrials.gov, number: NCT02380482. Written informed consent was obtained from the patient or patients’ next of kin.

In this prospective controlled study, we did not find a systematic major myocardial dysfunction at the early phase of TBI with severe lesions on cerebral CT scan. These findings were obtained from conventional cardiac ultrasonography and speckle tracking analysis. Despite no major change in cardiac function, several STE changes suggested correct adaptation of the left systolic function and a slight impairment of the left diastolic function.

We reported the absence of alteration of the systolic function after a TBI since the LVEF was similar between the TBI and the control groups. More interestingly, none of the TBI patients had a decreased systolic function and the minimum LVEF was 56 % using the Simpson’s method. Speckle tracking analyses further confirmed these findings through similar systolic indices. Only the circumferential strain peak at the apical level and the rotation at the basal level were higher in the TBI cohort. These findings were in line with a trend toward a global increase of all systolic indices in STE. Taken together, these results rather suggested a slight increase in the systolic function after TBI since STE was able to detect early LV functional changes in the setting of systemic diseases with a cardiac issue [19]. Accordingly, a systemic adrenergic or sympathetic hyperactivity was described after TBI [20, 21]. We, thus, assume that these sympathetic and neuro-endocrine adaptations could be more responsible for an activation of systolic myocardial function rather than a global myocardial depression.

Another major result of the present study was the slightly impaired diastolic function. We only reported a significant higher IVRT in the TBI cohort. All STE-derived parameters tended to be lower in TBI patients without reaching a statistical significance. Taken together, we cannot conclude to any significant diastolic myocardial dysfunction at the early phase of TBI. However, the increase in the IVRT may be interpreted as a starting diastolic modification in the TBI cohort. A trend in lower diastolic STE indexes further confirmed this hypothesis. Similarly, diastolic dysfunction was previously described in patients with SAH and a concomitant pulmonary edema [22]. In a small series of seven patients with TBI, echocardiographic diastolic dysfunction was also reported in patients with a neurogenic pulmonary edema [8]. Taken together, these findings further corroborated the TBI-induced modifications in left diastolic parameters observed in our cohort. Exposition to vasopressor in the TBI cohort to maintain cerebral perfusion pressure may induce these modifications in our study. Even if our study was not designed to assess the effect of vasopressor on myocardial function, the use of vasopressor in the TBI cohort might account for an increase in left ventricle afterload with potential effects on systolic and diastolic parameters.

Our study is inconsistent with several experimental and clinical studies dealing with the brain-heart interaction. Several explanations may account for these controversial results. First, we investigated the myocardial function at the early phase of TBI, within the first 24 h. This time point was chosen according to the existing literature that described early myocardial dysfunction [23]. Accordingly, in a recent retrospective study, conventional cardiac ultrasonography was mostly performed on day one, revealing an acute myocardial depression after TBI [10]. Nevertheless, we cannot exclude a delayed myocardial dysfunction occurring within the first post-traumatic days [24]. In our study, slight systolic and diastolic STE changes might be undermined by the early ultrasound assessment and might be significant in later examinations. Second, we do not deny the concept of acute cardiac failure following brain injuries and the hemodynamic evaluation is part of the global assessment of severity in critically ill patients [25]. Nevertheless, the concept of neurogenic cardiac failure was mainly based on different experimental models [11] such as SAH [26] or brain death. In the clinical setting, echocardiography modifications [23] and electrocardiographic abnormalities [27] were also described in SAH patients, epileptic patients [28], stroke patients [24], or brain death patients [29]. Myocardial dysfunction after TBI has been extended from these conditions but only few studies showed an acute cardiac failure after TBI [10], mainly case report [30] and retrospective study [10]. Hence, there is no prospective controlled study comprehensively assessing cardiac function after TBI and possible confounding factors like multiple trauma, associated co-morbidities and hemorrhagic shock might induce a cardiac failure independently of the cerebral injury. To our knowledge, we conducted the first prospective controlled trial regarding cardiac dysfunction matching a TBI cohort with a control cohort according to age and gender. The potential sympathetic tonus due to emergency context and traumatic pathology was controlled since both cohorts were trauma patients admitted for an emergency treatment. Lung-heart interactions were also controlled since in both cohorts, patients were under mechanical ventilation and general anesthesia. We, thus, believe that our study adds to the existing literature to explore rigorously cardiac consequences of TBI.

We acknowledge several limits of our study. First, only two third of the TBI patients had a severe TBI according to the GCS definition. However, all TBI patients had severe injuries on cerebral CT scan. Six patients had a GCS between 9 and 13. Among them, three patients underwent an immediate neurosurgery, two patients had cerebral injuries classified TCDB VI and the last one had a compromised cerebral blood flow on the transcranial Doppler (Diastolic velocity = 26 cm/s and Pulsatility Index = 1,89). Despite relatively high GCS, these patients should be considered as severe from the clinical standpoint and did not explain the lack of difference between the TBI and the control groups. Moreover, the median length of stay in the ICU was 21 days with 13 days of mechanical ventilation attesting a global severity of the included patients. Second, we only tested the hypothesis of a systematic global decrease of the cardiac performance after TBI. We cannot conclude that a myocardial depression is not possible after TBI. We acknowledge that a neurogenic cardiac failure may occur in this context supporting the use of the conventional cardiac ultrasonography for hemodynamic management. Since TBI could be associated with preexisting comorbidities or a multiple trauma, we even strongly recommend the use of conventional ultrasonography at the bedside to optimize the cardiac output of these patients.

Controlling confounding factors for non-cerebral acute cardiac failure, we did not find a systematic acute myocardial depression after TBI. STE analysis rather suggested an adequate adaptation of the left systolic function, while the diastolic function slightly decreased. The observed changes were not clinically relevant and our study further suggested no systematic cardiac consequences of severe traumatic cerebral injuries. These findings did not challenge the usefulness of cardiac ultrasonography for the management of TBI patients.