Elevated plasma histone H4 levels are an important risk factor for the development of septic cardiomyopathy

Abstract

Background: Myocardial impairment is a major complication and an important prognostic predictor of sepsis. Therefore, early and accurate diagnosis as well as timely management of septic cardiomyopathy is critical to achieve favorable outcomes. Aims: To investigate the risk factors of septic cardiomyopathy. Study Design: Cross-sectional study Methods: This study performed between May 2016 and June 2018 recruited 93 septic patients from the intensive care unit. All patients received standardized treatments. Septic patients were divided into two groups: non cardiomyopathy (n=45) and septic cardiomyopathy group (n=48). Blood samples were collected and transthoracic echocardiography was performed within 24 hours of intensive care unit admission. Septic patients with one ultrasound abnormality but no history of heart disease were diagnosed as having septic cardiomyopathy. Plasma histones, cardiac troponin I, and N-terminal pro-brain natriuretic peptide were measured using ELISA. Sequential Organ Failure Assessment scores, vasopressor use, and the outcomes of intensive care unit stay were analyzed. Spearman rank analysis was used to determine the correlation between plasma histone H4 and other parameters. Binary logistic regression and receiver operating characteristic curve analysis were used to determine the risk factors for septic cardiomyopathy. Results: Compared with the non-cardiomyopathy group, the septic cardiomyopathy group had significantly higher plasma H4 and cardiac troponin I levels, a higher Sequential Organ Failure Assessment score, more frequent vasopressor use, and a higher mortality rate (p<0.05). Plasma histone H4 levels positively correlated with cardiac troponin I (r=0.577, p<0.001), N-terminal pro-brain natriuretic peptide (r=0.349, p=0.001), and Sequential Organ Failure Assessment scores (r=0.469, p<0.001). Binary logistic regression and receiver operating characteristic curve analyses revealed that elevated plasma histone H4 levels and vasopressor use were important risk factors for septic cardiomyopathy (p<0.05). Conclusion: Elevated plasma histone H4 levels could be used to predict septic cardiomyopathy in patients with sepsis.

Plasma Histone H4 and Its Implications in the Setting of Sepsis-related Myocardial Dysfunction

“…However, since there exists no significant myocardial injury in patients with TTC, plasma histone H4 levels might be expected to be much lower in TTC patients in comparison to patients with S-CMP, even if this S-CMP is of a fully reversible nature. Accordingly, comparison of S-CMP cases with global and segmental wall motion abnormalities with regard to admission rates, as well as plasma histone H4 levels, might have been an interesting subgroup analysis in the study (1). Within this context, patients with segmental wall motion abnormalities on TTE, together with relatively lower histone H4 levels, might strongly suggest an existing TTC rather than S-CMP.…”

“…In clinical practice, septic cardiomyopathy (S-CMP) has been regarded as a poorly understood phenomenon with a variety of underlying mechanisms-including detrimental impacts of cytokines and nitric oxide on the myocardium-and generally presents with emerging systolic and/or diastolic dysfunction on transthoracic echocardiogram (TTE) in septic patients (1)(2)(3). Within this context, the association of inflammation markers, in particular, with left ventricular systolic dysfunction might also be substantiated by previous reports in diverse clinical scenarios other than sepsis (4).…”

“…Interestingly, S-CMP, though renowned for its reversible nature (1), might not fully recover in certain settings, potentially suggesting some degree of permanent myocardial injury (3). In their recently published elegant article (1), Lu et al (1) suggested plasma histone H4 as an important predictor of S-CMP evolution, along with vasopressor use, in a mixed population of sepsis and septic shock patients. Of note, the authors particularly focused on histone H4 both as a consequence and trigger of myocardial injury/dysfunction in the setting of S-CMP.…”

Plasma Histone H4 and Its Further Implications in the Setting of Sepsis-related Myocardial Dysfunctıon

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In clinical practice, septic cardiomyopathy (S-CMP) has been regarded as a poorly understood phenomenon with a variety of underlying mechanisms-including detrimental impacts of cytokines and nitric oxide on the myocardium-and generally presents with emerging systolic and/or diastolic dysfunction on transthoracic echocardiogram (TTE) in septic patients (1)(2)(3). Within this context, the association of inflammation markers, in particular, with left ventricular systolic dysfunction might also be substantiated by previous reports in diverse clinical scenarios other than sepsis (4).

…”

“…Interestingly, S-CMP, though renowned for its reversible nature (1), might not fully recover in certain settings, potentially suggesting some degree of permanent myocardial injury (3). In their recently published elegant article (1), Lu et al (1) suggested plasma histone H4 as an important predictor of S-CMP evolution, along with vasopressor use, in a mixed population of sepsis and septic shock patients. Of note, the authors particularly focused on histone H4 both as a consequence and trigger of myocardial injury/dysfunction in the setting of S-CMP.…”