Altered function of the left ventricle and clinical significance of heart-type fatty acid-binding protein in cardiac dysfunction among patients with sepsis.

The present study aimed to determine the clinical significance of heart-type fatty acid-binding protein (H-FABP) in patients with sepsis-induced cardiac dysfunction. A total of 30 healthy subjects served as the control group and 80 patients with sepsis were recruited for the present single-center prospective observational study for the final analysis. Among these patients, 50 developed cardiac dysfunction, while no cardiac dysfunction was detected in the remaining 30 patients. Echocardiography was performed on days 1, 3, 7 and 10 of hospitalization. Routine blood biochemistry, serum H-FABP, N-terminal pro-brain natriuretic peptide (NT-proBNP) and troponin I were also analyzed. Alterations in cardiac biomarkers and echocardiography results were compared between patients with sepsis who did and who did not develop any cardiac dysfunction to determine the time of the occurrence of sepsis-induced cardiac dysfunction. Furthermore, the significance of H-FABP in the prediction of the 28-day mortality rate was evaluated using binary logistic regression analysis for sepsis and receiver operating characteristic (ROC) curve analysis. In addition, the specificity and sensitivity of H-FABP in the prediction of sepsis-induced cardiac dysfunction were verified using ROC curve analysis. For patients with cardiac dysfunction, the levels of cardiac output (CO), stroke volume (SV), mitral early diastolic peak velocity to mitral atrial systolic peak velocity ratio (E/A) and left ventricle ejection fraction (LVEF) were relatively decreased, while the levels of H-FABP and NT-proBNP were markedly increased compared with patients with sepsis and without cardiac dysfunction. CO and SV initially increased and subsequently decreased. EF was elevated, and E/A initially decreased and subsequently increased. Furthermore, H-FABP and NT-proBNP decreased in sepsis patients with cardiac dysfunction. The results of the ROC curve and binary logistic regression analyses suggest that H-FABP was associated with the 28-day prognosis for patients with sepsis. An H-FABP level of >35.7 ng/ml was able to predict the 28-day mortality for patients with sepsis, with an area under the curve (AUC) of 0.680. Furthermore, >30.3 ng/ml was the threshold for the prediction of sepsis-induced cardiac dysfunction, and the sensitivity and specificity were 76.27 and 61.76%, respectively, with an AUC of 0.673. In summary, patients with sepsis had an increased risk of cardiac insufficiency on days 7-10 of hospitalization. In addition, H-FABP may serve as an indicator to predict the prognosis of patients with sepsis in the short term, which has a certain significance in the diagnosis of sepsis-induced cardiac dysfunction.

[Diagnostic value of heart-type fatty acid-binding protein combined with echocardiography in sepsis with cardiac insufficiency].

OBJECTIVE: To observe the value of heart-type fatty acid-binding protein (H-FABP) and echocardiographic indexes in the diagnosis of cardiac insufficiency in sepsis. METHODS: A prospective observational study was conducted. Eighty patients with sepsis admitted to the department of critical care medicine of the First Affiliated Hospital of Medical College of Shihezi University from October 2016 to January 2018 were enrolled. General clinical data such as gender, age, acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA) score, hospitalization time and 28-day mortality were recorded. Echocardiographic indexes at 1, 3, 7, 10 days after diagnosis, and white blood cell (WBC), neutrophilic granulocyte percentage (N%), N-terminal pro-brain natriuretic peptide (NT-proBNP), serum H-FABP level were recorded. Sepsis patients were divided into normal cardiac function group (n = 30) and cardiac insufficiency group (n = 50) according to cardiac function, the differences of echocardiographic indexes and cardiac markers between the two groups at different time points were compared. Logistic regression was used to screen out cardiac ultrasound indexes and cardiac markers that affect the occurrence of cardiac dysfunction in sepsis patients, and then receiver operating characteristic (ROC) curve analysis was performed. RESULTS: Comparing the general data of the two groups, only the SOFA score of the cardiac insufficiency group was significantly higher than that of the normal cardiac function group (6.12±4.09 vs. 4.57±2.45, P < 0.05). N% and H-FABP in cardiac insufficiency group were higher than those in normal cardiac function group at the same time (N%: F = 6.973, P = 0.010; H-FABP: F = 17.303, P = 0.000). Without considering the time factor, there were significant differences in left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular ejection fraction (LVEF), stroke volume (SV), cardiac output (CO), left ventricular fractional shortening (LVFS), E-point of septal separation (EPSS), isovolumic relaxation time (IVRT), E peak deceleration time (EDT), A peak duration (Ad), left ventricular systolic pulmonary vein velocity (S), blood flow velocity of pulmonary vein in early left ventricular diastolic period (D), tricuspid orifice early diastolic blood flow velocity (E'), tricuspid orifice late diastolic blood flow velocity (A'), systolic velocities of the right ventricular free wall tricuspid annulus (Sm), and pulmonary valve annulus blood flow velocity (PVBV) between the two groups. ROC curve analysis of cardiac ultrasound indicators and cardiac markers screened by Logistic regression showed that the area under ROC curve (AUC) and the positive and negative predictive values were: LVEDV was 0.636, 77.30%, 56.03%; SV was 0.779, 88.82%, 71.19%; LVEF was 0.753, 92.12%, 55.21%; CO was 0.754, 88.82%, 77.19%; LVFS was 0.728, 81.25%, 66.99%; EPSS was 0.663, 96.99%, 51.56%; IVRT was 0.775, 86.97%, 73.55%; A' was 0.908, 96.58%, 89.60%; Sm was 0.738, 93.37%, 56.77%; H-FABP was 0.673, 80.26%, 57.25%, respectively. H-FABP was tested in parallel with LVEDV, SV, LVEF, CO, LVFS, EPSS, IVRT, A', Sm, and the positive predictive values were higher than the single diagnostic test (85.45%, 93.91%, 96.72%, 94.74%, 89.43%, 98.00%, 92.00%, 99.42%, 93.60%, respectively), the negative predictive values were lower than the single diagnostic test (50.89%, 57.93%, 49.15%, 58.18%, 57.05%, 45.74%, 57.92%, 64.13%, 47.78%, respectively). CONCLUSIONS: Cardiac ultrasound indicators LVEDV, SV, LVEF, CO, LVFS, EPSS, IVRT, A', and Sm combined with H-FABP are of certain value in the diagnosis of sepsis-associated heart dysfunction.

Long-term prognostic value of coronary computed tomography angiography for asymptomatic patients with CAD in type 2 diabetes mellitus.

The present study was performed to investigate the prognostic value of coronary computed tomography angiography (CTA) results for asymptomatic patients with coronary artery disease (CAD) in type 2 diabetes mellitus (T2DM). A total of 164 asymptomatic patients with T2DM were enrolled at Weifang Traditional Chinese Hospital (Weifang, China). Coronary plaques and stenosis severity were evaluated after CTA. Structures >1 mm2 adjacent to or within the coronary artery lumen that could be clearly separated from the vessel lumen, was scored as a coronary plaque. Stenosis of ≥50% was considered as being obstructive. CAD was defined as the presence of any coronary plaque or a coronary artery calcium (CAC) score of >0. A CAC score of 0 and no coronary plaques was considered to indicate the absence of CAD. A 5-year follow-up was performed to determine the impact of the CTA findings and various clinicopathological characteristics on the prognosis of all participants. The primary end-point was any cardiac event. Event-free survival curves were plotted using the Kaplan-Meier method and compared using the log-rank test. Based on the coronary CTA results, the patients were classified into 3 groups according to the extent of stenosis: Normal coronary arteries, obstructive CAD and non-obstructive CAD. Significant differences in 5-year event-free survival were identified among the groups with normal coronary arteries, non-obstructive CAD and obstructive CAD (P=0.026). Further analysis indicated that the event-free survival rate of patients with 1-vessel CAD was 94.11%, that of patients with 2-vessel CAD was 73.68% and that associated with 3-vessel CAD was 61.54%. Multivariate Cox regression analysis revealed that non-obstructive as well as obstructive CAD diagnosed by coronary CTA are prognostic indicators for asymptomatic T2DM patients [hazard ratio (HR)=11.132, 95% confidence interval (CI): 1.857-66.742, P=0.008; HR=7.792, 95% CI: 1.750-34.698, P=0.007, respectively]. In conclusion, the present study suggests that coronary CTA may predict the prognosis of asymptomatic patients with T2DM.

H2S attenuates sepsis-induced cardiac dysfunction via a PI3K/Akt-dependent mechanism.

The heart is the most vulnerable target organ in sepsis, and it has been previously reported that hydrogen sulfide (H2S) has a protective role in heart dysfunction caused by sepsis. Additionally, studies have demonstrated that the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway has a protective function during sepsis. However, the potential association between H2S and PI3K/Akt in sepsis-induced cardiac dysfunction is unclear. Therefore, the PI3K inhibitor LY294002 was used to investigate the role of PI3K/Akt signaling in the protective effects of H2S during sepsis-induced myocardial injury. A rat sepsis model was established using cecal ligation and puncture (CLP) surgery. Sodium hydrosulfide, a H2S donor, was administered intraperitoneally (8.9 µmol/kg), and serum myocardial enzyme levels, inflammatory cytokine levels, cardiac histology and cardiomyocyte apoptosis were assessed to determine the extent of myocardial damage. The results demonstrated that exogenous H2S reduced serum myocardial enzyme levels, decreased the levels of the inflammatory factors tumor necrosis factor (TNF)-α and interleukin (IL)-6, and increased the level of anti-inflammatory IL-10 following CLP. Staining of histological sections demonstrated that myocardial damage and cardiomyocyte apoptosis were alleviated by the administration of exogenous H2S. Western blot analysis was used to detect phosphorylated and total PI3K and Akt levels, as well as NF-κB, B-cell lymphoma-2, Bcl-2-associated X protein (Bax) and caspase levels, and the results demonstrated that H2S significantly increased PI3K and Akt phosphorylation. This indicated that the PI3K/Akt signaling pathway was activated by H2S. Additionally, H2S reduced Bax and caspase expression, indicating that apoptosis was inhibited, and decreased NF-κB levels, indicating that inflammation was reduced. Furthermore, the PI3K inhibitor LY294002 eliminated the protective effects of H2S. In conclusion, the results of the current study suggest that exogenous H2S activates PI3K/Akt signaling to attenuate myocardial damage in sepsis.

Significance of hydrogen sulfide in sepsis-induced myocardial injury in rats.

Sepsis-induced myocardial injury is a detrimental disorder for intensive care medicine due to its high rates of morbidity and mortality. Data suggest that nuclear factor (NF)-κB serves a critical role in the pathogenesis of myocardial injury. Hydrogen sulfide (H2S) serves an important role in the physiology and pathophysiology of regulatory mechanisms, particularly during an inflammatory reaction. However, the relationship between NF-κB and H2S in sepsis-induced myocardial injury is not well understood, and the underlying mechanisms remain unclear. In the present study, 60 male Sprague Dawley rats were randomly divided into the following six groups: A sham group, cecal ligation and puncture (CLP) group, sham + propargylglycine (PAG) group, CLP + PAG group, sham + sodium hydrosulfide (NaHS) group and CLP + NaHS group, with 10 rats in each group. The rats in all groups were sacrificed 12 h after surgery for sample collection. Compared with the sham group, it was observed that the concentrations of Creatine Kinase-MB (CK-MB) and cardiac troponin I (cTnI) in the serum, and pathological scores of myocardial tissue were significantly increased in the CLP, CLP + NaHS and CLP + PAG groups (P<0.05). The pathological scores and concentrations of CK-MB and cTnI were significantly higher in the CLP + PAG group (P<0.05) and significantly lower in the CLP + NaHS group (P<0.05) when compared with the CLP group. The expression of cystathionine-γ-lyase (CSE) mRNA and content of interleukin (IL)-10 were significantly higher in the CLP group compared with the CLP + PAG group (P<0.05), while the expression of myocardial NF-κB and content of tumor necrosis factor (TNF)-α in the CLP group were significantly lowered compared with the CLP + PAG group (P<0.05). The expression of NF-κB and content of TNF-α were significantly increased in the CLP group when compared with the CLP + NaHS group (P<0.05), while the content of myocardial IL-10 in the CLP group was significantly lower than in the CLP + NaHS group (P<0.05). In conclusion, H2S acted as an anti-inflammatory cytokine and biomarker in sepsis-induced myocardial injury. Furthermore, H2S may downregulate the NF-κB subunit p65 to mediate inflammatory responses. The present data suggest that myocardial injury in sepsis may be relieved through the regulation of H2S expression, and provide an experimental basis for the treatment of sepsis patients presenting with myocardial injury. In addition, myocardial injury in sepsis may be identified by monitoring changes in the expression of H2S.