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ORIGINAL ARTICLE
Year : 2021  |  Volume : 69  |  Issue : 4  |  Page : 944-949

Prospective Analysis of Role of hsTnT and NT-proBNP in Prediction of Neurogenic Stress Cardiomyopathy in Patients with Aneurysmal Subarachnoid Haemorrhage


Department of Neurosurgery, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research (GIPMER), New Delhi, India

Date of Submission15-Apr-2020
Date of Decision07-Aug-2020
Date of Acceptance12-Feb-2021
Date of Web Publication14-Aug-2021

Correspondence Address:
Dr. Amit K Sharma
Department of Neurosurgery, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research (GIPMER), New Delhi - 110 002
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.323891

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 » Abstract 


Background: Neurogenic stress cardiomyopathy (NSC), also known as stress-induced cardiomyopathy (SIC), is a significant complication of aneurysmal subarachnoid hemorrhage and an important contributor to morbidity mortality.
Objective: This prospective observational study assessed whether the high sensitive troponin T (hsTnT) and N-terminal pro-B-type natriuretic peptide (NTproBNP) helps in the prediction of NSC after SAH.
Methods: The consecutive patients with aSAH without any cardiac history were included prospectively over 12 months. Neurological assessment for the grade of SAH (Hunt & Hess and WFNS grade), electrocardiogram, and echocardiography done at admission. The serial measurements of serum hsTnT and NTproBNP for consecutive 7 days done. The NSC is defined as transient hypokinesia of the ventricular wall on echocardiography.
Results: The study included 69 patients, and 7 (10.1%) were diagnosed with NSC. The NSC had a positive correlation with Hunt and Hess grade (P = 0.010), and the serum levels of hsTnT and NTproBNP were higher in patients with NSC in comparison to without NSC over all 7 days. The peak levels of hsTnT and NTproBNP were significantly higher in patients with cardiomyopathy (P = 0.000 and 0.032, respectively). The best cut-off level of peak hsTnT was 0.032 pg/dl to predict cardiomyopathy with sensitivity and specificity of 100% and 80%, respectively, and NTproBNP was 430.6 ng/dL with sensitivity and specificity of 86% and 73%, respectively.
Conclusion: The peak levels of hsTnT and NTproBNP with abnormal ECG and echocardiography at admission help identify NSC in the early phase of aSAH.


Keywords: hsTnT, neurogenic stress cardiomyopathy, NTproBNP
Key Message: The hsTnT, NTproBNP levels, ECG, and echocardiography must be done at admission for early diagnosis of NSC. The early detection and management of NSC could potentially improve outcome in patients with aneurysmal SAH.


How to cite this article:
Sharma AK, Singh D, Mahajan B, Tandon M, Singh H. Prospective Analysis of Role of hsTnT and NT-proBNP in Prediction of Neurogenic Stress Cardiomyopathy in Patients with Aneurysmal Subarachnoid Haemorrhage. Neurol India 2021;69:944-9

How to cite this URL:
Sharma AK, Singh D, Mahajan B, Tandon M, Singh H. Prospective Analysis of Role of hsTnT and NT-proBNP in Prediction of Neurogenic Stress Cardiomyopathy in Patients with Aneurysmal Subarachnoid Haemorrhage. Neurol India [serial online] 2021 [cited 2021 Oct 22];69:944-9. Available from: https://www.neurologyindia.com/text.asp?2021/69/4/944/323891




Acute myocardial dysfunction is a significant complication of aneurysmal SAH.[1] Several proposed mechanisms leading to myocardial injury have been described in the literature.[1],[2] However, over-sympathetic stimulation with catecholamine surge leading to cardiac myocyte injury due to hypercontraction. The resulting myocardial injury has been described in the literature as neurogenic stunned myocardium[3] and neurocardiogenic injury,[4] also known as neurogenic stress cardiomyopathy (NSC)/stress-induced cardiomyopathy.[1] Clinically, it may present as an electrocardiogram (ECG) changes like ST-segment/T wave changes and prolong-QT segment,[5] echocardiographic changes like decreased ejection fraction and regional wall motion dyskinesias,[6] and elevation of cardiac biomarkers like Cardiac hsTnT and NTproBNP.[4] Even though NSC is mostly reversible,[7],[8] there is a higher risk of associated poor neurological and functional outcomes and even death.[9],[10],[11] Hence, timely diagnosis and intervention of NSC in aSAH patients are essential to ensure adequate cerebral blood flow and improve functional outcomes. The study's primary aim was to assess the role of hsTnT and NTproBNP in the early detection of NSC in patients with aSAH.


 » Methods Top


The study was done at GIPMER for 1 year after obtaining valid informed consent and institutional ethical clearance. All patients with spontaneous, aneurysmal SAH without previous history of any cardiac disease included. After admission, the modified Hunt and Hess scale used to grade aSAH, and the quantitative measurement of hsTnT and NTproBNP were done daily for seven consecutive days. The hsTnT >0.014 ng/ml and NTproBNP >150 pg/mL were taken as elevated. At admission, 12-lead ECG was done and considered abnormal if ST-T wave changes, prolonged QT interval, or any rhythm abnormality was present. The echocardiography was also performed at admission and reported abnormal in case of regional wall motion abnormality or ejection fraction <50%.[12],[13] As per Gothenberg criteria,[2],[14] SIC/NSC labeled if

  1. transient wall motion abnormality like hypokinesia, akinesia, or dyskinesia of LVE segment,
  2. no evidence of ischemia or myocarditis explaining the left ventricular regional abnormality,
  3. moderate elevation of cardiac troponin.


Statistics

The analysis done using IBM SPSS version 23.0. All continuous variables checked for normality. The mean ± SD and median with interquartile range used to report normally and non-normally distributed data. The t-test and Mann–Whitney U test used to compare groups with normal and non-normal continuous variables. ROC/AUC curve used to define the cut-off values, sensitivity, and specificity to detect NSC/SIC.


 » Results Top


Demographic and clinical data

Sixty-nine patients included had mean age 49.3 years ± 13.47, and most were females (38; 55.1%). The patients with hypertension and diabetes were 47.8% and 14.5%, respectively. The mean arterial blood pressure was 102 mmHg. Twenty-five (36.2%) patients had poor Hunt and Hess grade (3-5), whereas 8 (11.6%) had WFNS grade 3-5. Our study's mean duration of symptoms was 7.42 ± 4.7 days, with five patients (46.3%) presenting within 5 days after onset of symptoms to our institute, and 23.1% of patients (16/69) presented in less than 3 days of onset of symptoms. Nine patients (13%) had mortality. The clinical profile of included patients described in [Table 1].
Table 1: Patient characteristics

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Cardiac clinical and biochemical parameters

Elevated peak hsTnT and NTproBNP

Thirty-eight (55.1%) of the patients demonstrated elevated peak levels of hsTnT. Fifty-eight percent of patients had the highest peak levels of hsTnT on the initial 3 days (58%) and then gradually declines over the next few days. Similarly, 42% of patients had peak levels NTproBNP on the initial 2 days (42%) [Figure 1]. A positive correlation observed between elevated peak hsTnT and poor Hunt & Hess grade (OR = 3.1; P = 0.033). Similarly, between the elevated peak NTproBNP and poor Hunt & Hess grade (OR = 3.9; P = 0.021), a positive correlation was observed.
Figure 1: Showing day of the peak level of hsTnT and NTproBNP

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ECG changes and low ejection fraction (<50%)

Thirty-three percent had abnormal ECG at admission, with 23% had ST-T wave changes, and 3% had QT prolongation. The ST-T wave changes positively correlated with elevated peak hsTnT (P = 0.030) and NTproBNP levels (P = 0.032). Factors like age, hypertension, and Fischer grade were not correlated with ST-T wave changes significantly. The echocardiography done in all 69 patients, and 13% (9/69) of patients had an EF of <50%. The mean ejection fraction of the patients with a low EF group was 46.1% ± 4.2 (mean ± S.D) [Table 2]. Of these nine patients, 7 (77.8%) had elevated peak levels of both hsTnT and NTproBNP. The ST-segment and T wave changes on ECG noted in five of such patients (55.6%) and found significant (P = 0.026) [Table 2].
Table 2: Clinical variables in patients with and without NSC

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Neurogenic stress cardiomyopathy

Echocardiography performed in all 69 patients. Stress cardiomyopathy, by definition, was labeled in 7 patients, who had a median EF of 45% in comparison to a median ejection fraction of 60% in patients without stress cardiomyopathy. Median LVEF for NSC patients and without NSC was statistically significantly different, U = 79.5, z= -3.89, P = 0.000. The poor SAH grade (Hunt and Hess grade >3) had a positive correlation with the NSC (OR = 10.9; P = 0.010). The abnormal ECG and incidence of NSC had a significant correlation (P = 0.002). The peak hsTnT levels (Median: 0.310 ng/ml) and NTproBNP levels (Median: 701.2 pg/mL) were significantly more in patients with NSC with P value <0.000 and 0.032 respectively [Figure 2]. The median levels of both hsTnT and NTproBNP levels were significantly higher in patients with NSC on all 7 days as compared to without NSC [Figure 3]. The peak day of levels of hsTnT for each seven patients with NSC and the serum levels of hsTnT for seven consecutive days of each patient as shown in [Figure 4]. The peak hsTnT with cut-off levels >0.032 pg/dl had a sensitivity of 100% and a specificity of 80%, whereas peak NTproBNP levels >430.6 ng/dL had a sensitivity of 86% and specificity of 73% to predict the NSC. Similarly, the best cut-off levels for hsTnT and NTproBNP on day 1, day 2, and day three after admission with respective P values presented in [Table 3] and [Figure 5]. The peak hsTnT and NTproBNP had the best diagnostic value in [Table 4]. Three patients (43%) with NSC had mortality; out of these three patients, two patients had infarction, and one patient developed hydrocephalus. A significant positive correlation observed between NSC and mortality (P = 0.042). The multivariate analysis was done to look for relationship between variables like age, gender, poor Hunt & Hess grade, hypertension, and cardiac biomarkers (hsTnT and NTproBNP). A significant association observed between hsTnT and NTproBNP levels at admission (P = 0.008 and 0.011 respectively).
Figure 2: Peak levels of hsTnT and NTproBNP in patients with and without NSC. NSC Neurogenic stress cardiomyopathy

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Figure 3: Levels of hsTnT and NTproBNP in patients with and without NSC. NSC Neurogenic stress cardiomyopathy

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Figure 4: Figure showing (a) hsTnT levels of each 7 patients with NSC over 7 days, and (b) peak day of hsTnT level. NSC Neurogenic stress cardiomyopathy

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Table 3: Best cut-offof variables

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Table 4: Sensitivity and Specificity of biomarkers to detect NSC

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Figure 5: ROC curves for hsTnT and NTproBNP for (a) Peak levels, (b) day-1, (c) day-2, and (d) day-3 after admission

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 » Discussion Top


Aneurysmal SAH is associated with significant poor neurological and functional outcomes, and even death has been reported in up to 50% cases.[15] The aSAH can induce sudden cardiac dysfunction for patients with no prior underlying cardiovascular disease. It may be suspected if elevated levels of cardiac biomarkers and ECG abnormalities with reduced EF is present.[16] The currently reported prevalence of NSC among aSAH patients range from 2.2% to 17%.[16],[17] The most acceptable current evidence-based theory of NSC heavily relies on catecholamine-induced myocardial injury.[1],[3] The study aimed to look for an association between cardiac biomarkers and NSC. The initial SAH[17] itself and subsequent vasospasm with delayed cerebral ischemia[18] are considered to be a significant cause of mortality, but NSC also described to be associated with a higher death rate.[19] A significant positive correlation observed between NSC and mortality (P = 0.042). As a result, early identification and treatment of NSC are important for improving patient outcome. The principle observation of this study was that stress cardiomyopathy was seen frequently after SAH and that at admission, poor Hunt & Hess SAH grade had a significant association with incidence of Stress cardiomyopathy. Previously available studies reported severe neurologic injury (Hunt and Hess grade > 3) as a major predictor for NSC.[4],[19],[20] Our study observed that the NSC correlated positively with the Hunt and Hess grade (OR = 10.1; P = 0.01). These findings add to the evidence that myocardial injury following aSAH is neurally mediated. It was observed that elevated peak levels of both cardiac markers were significantly higher in the NSC group, and the current assay for hsTnT allows for measurement of even very low levels of TnT and helps in early and timely detection of myocardial injury.[21] It was observed that the sensitivity and specificity of hsTnT and NTproBNP were high for the detection of stress cardiomyopathy especially if done during the acute phase of SAH. In multivariate analysis, hsTnT and NTproBNP were the only variables significantly associated with NSC when variables like age, gender, hypertension, poor Hunt & Hess grade were taken into account. It was observed that the peak levels of both hsTnT and NTproBNP was observed on the first 3 days followed by a daily decline, indicating early myocardial injury[21],[22] and the persistent high levels of cardiac biomarkers, hsTnT, point towards the possible continuing myocardial insult, which has varied presentation ranging from subclinical ECG abnormalities to cardiac failure.[5],[6] Hence, serial measurement of biomarkers is necessary as these might be the only evidence of underlying myocardial injury. It was also observed that 2 out of 7 patients with NSC had the highest level of hsTnT on day 7, indicating a persistent rise in hsTnT towards underlying myocardial injury. The new hsTnT assay is a 4th generation cTnT assay.[23] It allows the detection of very low levels of cTn and has emerged as a tool for the detection of any subclinical myocardial injury even in an asymptomatic patient.[24] Due to lower limit of detection and high precision, the current assay detects more subtle elevation indicating cardiac injury.[25] The hsTnT analyses are generally related to ischemia. The elevated levels of cTn may be seen in patients with acute coronary and non-coronary artery diseases like renal disease, pulmonary embolism, sepsis, stroke, hypertension, stress-cardiomyopathy, and acute heart failure, etc., and have been proposed as a useful prognostic factor for named diseases.[26] The important clinical dilemma is distinguishing between the cTn rise because of the acute coronary syndrome and those due to more chronic/non-cardiac or non-coronary pathology. Hence, a baseline level soon after admission helps future comparison, along with the ECG and ECHO, to look for any abnormalities. In aSAH, where there is a risk of the sympathetic storm-driven myocardial injury, with no history of any cardiac ailment, elevated hsTnT levels at admission, and features of cardiac dysfunction on ECG/ECHO point towards the neurally mediated cardiac dysfunction. Also, the levels of hsTnT and change in levels on serial measurement help differentiate acute myocardial injury and prompt intervention and prognostication. It was observed that the patients with stress cardiomyopathy had lower levels of mean arterial pressure at admission, indicating a component of myocardial injury already at admission. It may signify the importance of early measurement of cardiac markers at admission to identify stress cardiomyopathy. This study's limitation is its small sample size and inclusion criteria of patients to rule out cardiac disease based on history alone. The study's strength lies in its prospective design and consecutive 7 days measurement of serum levels of hsTnT and NTproBNP starting from the day of admission. It allowed a temporal profile of the levels in patients with and without NSC. In summary, we found that elevated levels of hsTnT and NTproBNP have a high sensitivity and specificity for the early identification of NSC, making hsTnT and NTproBNP an important marker for screening of possible NSC in patients of SAH.


 » Conclusion Top


We, therefore recommend hsTnT, NTproBNP levels, ECG, and echocardiography that must be done at admission for early diagnosis of NSC. The early detection and management of NSC could potentially improve outcome in patients with aneurysmal SAH.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 » References Top

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Dubin RF, Li Y, He J, Jaar BG, Kallem R, Lash JP, et al. Predictors of high sensitivity cardiac troponin T in chronic kidney disease patients: A cross-sectional study in the chronic renal insufficiency cohort (CRIC). BMC Nephrol 2013;14:229.  Back to cited text no. 24
    
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
 
 
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  [Table 1], [Table 2], [Table 3], [Table 4]



 

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