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ORIGINAL ARTICLE
Year : 2022  |  Volume : 70  |  Issue : 4  |  Page : 1475-1480

Role of High-Sensitivity Troponin-T And N-Terminal Pro B-Type Natriuretic Peptide as an Early Predictor of Myocardial Dysfunction in Aneurysmal Subarachnoid Hemorrhage: A Prospective Observational Study


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

Date of Submission11-Apr-2020
Date of Decision25-Jul-2020
Date of Acceptance16-Jan-2021
Date of Web Publication30-Aug-2022

Correspondence Address:
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: 10.4103/0028-3886.355116

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 » Abstract 


Background: Acute cardiac complications are commonly seen in aneurysmal subarachnoid hemorrhage (aSAH) patients and may vary from subclinical electrocardiographic abnormalities, or reduced ejection fraction on echocardiography, elevated levels of cardiac markers (cardiac troponin and Brain natriuretic peptide) to heart failure.
Objective: This study was done to evaluate the role of cardiac markers (high-sensitive Troponin-T and N-terminal pro-B-type natriuretic peptide) in early identification of cardiac complications and hence dysfunction.
Methods: All consecutive patients with aSAH without any previous cardiac history were included. At admission, neurological evaluation using Hunt and Hess grading (H and H grade), with electrocardiography to look for any changes, echocardiography for ejection fraction, and any wall motion abnormalities was also done. The serial serum levels of high-sensitive Troponin-T (hsTnT) and N-terminal pro B-type natriuretic peptide (NT pro-BNP) for 7 consecutive days was measured with hsTnT >0.14 ng/ml and NT pro-BNP >150 pg/mL considered elevated.
Results: A total of 69 patients were included. The elevated peak level of hsTnT and NT pro-BNP was seen in 55.1% and 69.6% of patients. A positive correlation was seen between hsTnT (P = 0.033) and NT pro-BNP (P = 0.011) and poor SAH grade (H and H grade 3-5), similarly, abnormal ECG also significantly correlated with elevated peak hsTnT (P = 0.002) and NT proBNP (P = 0.000). Also, significant difference in peak hsTnT (P = 0.000) and NT-proBNP (P = 0.000) in patients with or without reduced ejection fraction (EF).
Conclusion: The elevated peak levels of hsTnT and NTproBNP along with ECG and echocardiography abnormalities may help in early identification of myocardial injury, hence cardiac dysfunction.


Keywords: HsTnT, NTproBNP, subarachnoid hemorrhage
Key Message: The hsTnT and NT-proBNP quantification, especially serial measurement, ECG, and echocardiography done as early as possible could potentially predict patients with or at risk of cardiac complications.


How to cite this article:
Sharma AK, Singh D, Mahajan B, Tandon M, Singh H. Role of High-Sensitivity Troponin-T And N-Terminal Pro B-Type Natriuretic Peptide as an Early Predictor of Myocardial Dysfunction in Aneurysmal Subarachnoid Hemorrhage: A Prospective Observational Study. Neurol India 2022;70:1475-80

How to cite this URL:
Sharma AK, Singh D, Mahajan B, Tandon M, Singh H. Role of High-Sensitivity Troponin-T And N-Terminal Pro B-Type Natriuretic Peptide as an Early Predictor of Myocardial Dysfunction in Aneurysmal Subarachnoid Hemorrhage: A Prospective Observational Study. Neurol India [serial online] 2022 [cited 2022 Oct 7];70:1475-80. Available from: https://www.neurologyindia.com/text.asp?2022/70/4/1475/355116




The acute cardiac complications are frequent in aSAH and may vary from subclinical electrocardiographic changes,[1] elevated cardiac markers,[2] to cardiac failure.[3],[4],[5],[6] There is an association between cardiac complications with a poor neurological course with an increased risk of morbidity and even mortality.[1],[2],[3],[4],[5],[6],[7],[8],[9],[10],[11] There are several mechanisms described responsible for cardiac dysfunction; though the catecholamine surge with oversympathetic stimulation leading to myocardial injury is the most probable pathogenesis, hence, described as neurogenic stress cardiomyopathy.[12],[13],[14],[15],[16],[17] There are increasing reports in the literature indicating that persistent cardiac marker leak and neurogenic cardiomyopathy are associated with adverse cardiac and overall outcome.[18],[19],[20] The hsTnT, which is a recent method of measurement of cardiac troponin level, may even detect very low levels, hence rapid identification of cardiac injury with higher sensitivity and specificity as compared to cardiac troponin I used earlier.[21] There is no prospective study available in Indian literature evaluating the role of hsTnT and NT pro-BNP in aSAH patients. Hence, this prospective study was done with the primary aim to evaluate the role of hsTnT and NT-proBNP as a marker for early identification of acute cardiac dysfunction.


 » Methods Top


The study was done at GIPMER over one year after obtaining valid informed consent, and institutional ethical clearance. All consecutive patients diagnosed as acute aSAH without any previous cardiac history of coronary artery disease or cardiac ailment were included. Following admission, the SAH severity was assessed with Hunt and Hess grade (H and H grade).[21] The serial quantitative measurements of hsTnT and NT pro-BNP was done for 7 consecutive days of all included patients. The level > 0.014 ng/ml for hsTnT and >150 pg/mL for NT pro-BNP was considered elevated. The 12-lead ECG was done at admission and considered abnormal if ST-T wave changes, QT prolongation or rhythm change was seen, similarly, echocardiography was also done and reported abnormal if EF <50% or any wall motion abnormalities seen.

Statistics

The analysis was done using IBM SPSS version 23.0. All continuous variables were checked for normal distribution. Normally distributed continuous variables were reported as mean ± S.D, and median with interquartile range was used for non-normal distributed variables. To compare groups the t-teat was used for normal and Mann–Whitney U test used for non-normal distributed continuous variables. For comparison of incidences between groups with binary variables, Fischer's exact test was used. A value of P < 0.05 was considered statistically significant.


 » Results Top


Demographic and clinical data

A total of 69 (mean age 49.3 years; 55.1% females) patients were included. The prevalence of hypertension (HTN) and type-2 diabetes (DM) was 47.8% and 14.5%, respectively. The mean of mean arterial pressure was 102 mm Hg. Twenty-five (36.2%) patients were grouped into poor H and H grade (3-5). The clinical profile is shown in [Table 1].
Table 1: Clinical characteristic

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Cardiac markers

The elevated peak hsTnT was seen in 55.1% and NT proBNP was seen in 69.6% of patients. The peak level of hsTnT was seen on the initial 3 days in 58% of patients, whereas, 60.8% of patients had peak levels of NT pro-BNP on the first 2 days of admission [Figure 1]. A positive correlation was seen between poor H and H grade (3-5) and elevated peak hsTnT (P = 0.033) and NT pro-BNP (P = 0.011) as seen in [Figure 2]. We also noted that the median serum levels of cardiac hsTnT (0.03 ng/ml; P = 0.009) and NT-proBNP (474.9 pg/mL P = 0.015) were more in the poor SAH grade as compared to good SAH grade [Figure 3].
Figure 1: Showing highest (peak) level of hsTnT and NTproBNP in relation to day of presentation

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Figure 2: Correlation between Hunt and Hess grade with elevated hsTnT and NT-proBNP

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Figure 3: Peak levels of hsTnT and NTproBNP in patients with Low and poor grade SAH. Electrocardiographic changes

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Thirty-three percent had abnormal ECG at admission with 23% had ST-T wave changes, and 3% had QT prolongation. The patients with abnormal ECG had significantly higher levels of cardiac markers over consecutive 7 days [Figure 4]. Patients with abnormal ECG had higher serum peak levels of hsTnT (median = 0.013 ng/ml; P = 0.002) and NT pro-BNP (median = 549.1 pg/mL; P = 0.000) as shown in [Figure 5]. The ST-T wave changes had a positive correlation with elevated peak hsTnT (P = 0.030) and NTproBNP levels (P = 0.032). The echocardiography was 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). Of these 9 patients, 7 (77.8%) had elevated peak hsTnT and 7 (77.8%) had elevated peak NTproBNP. ST-T wave changes on ECG were seen in 5 of these patients (55.6) which was statistically significant (P = 0.026).
Figure 4: Levels of hsTnT and NTproBNP in patients with normal and abnormal ECG over 7 days

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Figure 5: Peak levels of hsTnT and NTproBNP in patients with normal and abnormal ECG. Echocardiographic changes

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The echocardiography was done in all 69 patients and 13% (9/69) of patients had an EF of <50%. The patients with reduced EF had significantly higher levels of cardiac markers over consecutive 7 days [Figure 6]. The mean ejection fraction of the patients with a low EF group was 46.1% ±4.2 (mean ± S.D). Of these nine patients, 7 (77.8%) had elevated peak hsTnT (median = 0.057 ng/ml; P = 0.000) and 7 (77.8%) had elevated peak NTproBNP (median = 496 pg/mL; P = P = 0.000) as shown in [Figure 7]. ST-T wave changes on ECG were seen in 5 of these patients (55.6) which was statistically significant (P = 0.026).
Figure 6: Levels of hsTnT and NTproBNP in patients with normal and low LVEF over 7 days

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Figure 7: Peak levels of hsTnT and NTproBNP in patients with normal and low LVEF

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 » Discussion Top


The cardiac complications following SAH have been very well described in literature and incidence has been estimated by up to 50% of SAH patients. [2],[5],[7],[22] In our prospective study of 69 patients, we tried to evaluate the role of the cardiac biomarkers (hsTnT and NT-proBNP) in predicting cardiac complications like ECG abnormalities and reduced EF indicating cardiac dysfunction due to myocardial injury during the early phase of SAH after admission. The hsTnT, which is a recent method of measurement of cardiac troponin level, may even detect very low levels, hence rapid identification of cardiac injury, and has been reported having high sensitivity and specificity for myocardial injury as compared to previously used cardiac troponin-I.[21] There are only a few studies available in the literature evaluating the role hsTnT and none in Indian literature. Cardiac troponins in previous studies have been positively correlated with the severity of the SAH grade, ECG abnormalities, and wall motion abnormalities. [2],[12] As previously reported that the prevalence of elevated cardiac markers increases as SAH severity increases. [2],[15] Similarly, we noted that patients with poor neurological status at admission (H and H grade >3) had significantly elevated levels of hsTnT (P = 0.033) and NT-proBNP (P = 0.011). We also noted that the median serum levels of cardiac hsTnT (0.03 ng/ml; P = 0.009) and NT-proBNP (474.9 pg/mL P = 0.015) were more in the poor SAH grade as compared to good SAH grade, adds to the reports of high catecholamine surge during early phase causing neurocardiogenic injury.[16] We observed that the hsTnT had its peak during the first 72 hours of the hospital admission, suggesting that myocardial injury occurs early in the disease, in comparison to cardiac ischemic injury, which has shown peak levels at or after 2–3 days of coronary ischemic injury.[17],[23] this suggests the importance of early measurement of cardiac markers at admission for detection of the cardiac complications. The major findings were, peak levels of hsTnT (P = 0.002) and NT-proBNP (P = 0.000) were significantly higher in patients with cardiac complications. The clinical significance of this study is that we were able to demonstrate a positive correlation between poor SAH grade and elevated peak levels of hsTnT and NT-proBNP, and persistent higher levels in poor SAH patients over 7 consecutive days indicate continuing markers leak indicating underlying myocardial injury. Also, presence of elevated cardiac marker levels has implications regarding peri-operative anesthetic management, like, optimization of timing of anaesthesia and risk of cardiovascular deterioration. In aSAH induced cardiac injury the management is aimed at preventing and correction of neurological damage and supportive care to cardiac function. Patients with elevated markers (hsTnT and NTproBNP), especially during acute phase, an ECG and ECHO is must to rule out left ventricular dysfunction (LVD), and if there is evidence of LVD along with clinical evidence of shock an aggressive intensive care is must. If LVD without shock is present, patient must be monitored with repeat ECG and repeat ECHO after 1-2 weeks. [6],[24] The coexisting vasospasm poses a therapeutic challenge, as Triple-H therapy along with nimodipine may improve cerebral blood flow but increases the cardiac afterload and O2 consumption. [5],[24] Hence continuous hemodynamic monitoring with CVP measurements, judicious fluid balance, and inotropic support is required. A metanalysis by bilt et al.[7] reported an association of bradycardia with decreased death and Liang et al.[25] reported that in aSAH patients who are on beta-blockers pre-admission had a lower risk of cardiomyopathy, indicating a possible cardioprotective role of beta-blocker in early phase of SAH to counteract the excessive catecholamine surge. Further studies are required to determine the exact role of early administration of beta-blockers in patients of aSAH presenting with LVD. In presence of cardiogenic shock, inotropic support is required to maintain cerebral perfusion. Agents like norepinephrine, which stimulates beta-receptors should be avoided, in view of underlying excess catecholamine surge as possible reason for cardiomyopathy. Hence agents like dobutamine and milrinone may be used.[26] In bivariate logistic regression analysis, peak hsTnT and NTproBNP were both associated with poor functional outcome. The strength of our study is one prospective design with cardiac markers levels measurement for 7 consecutive days following the admission of all included patients. Limitation of the study was its small sample size and inclusion of patients based on cardiac history alone to rule any ischemic coronary artery disease. It is recommended that all aSAH patients at admission should have cardiac evaluation including a complete clinical history along with a baseline levels of hsTnT and NTproBNP levels with serial measurments, ECG, and ECHO to look for cardiac output for monitoring myocardial dysfunction or hemodynamic instability. If required Cardiac angiography and non-invasive cardiac MRI may be considered in patients to differentiate an acute coronary syndrome.


 » Conclusion Top


Cardiac biomarkers (hsTnT and NT-proBNP) quantification, especially serial measurement, ECG and echocardiography should be done as early as possible following admission after ictus for early identification of patients with or at risk of cardiac complications, as timely detection of cardiac dysfunction and its timely management could potentially help in improving the outcome of SAH.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 » References Top

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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]
 
 
    Tables

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