Association between Troponin I Levels during Sepsis and Postsepsis Cardiovascular Complications

Garcia, Michael A.; Rucci, Justin M; Thai, Khanh K.; Lu, Yun; Kipnis, Patricia; Go, Alan S.; Desai, Manisha; Bosch, Nicholas A; Martínez, Adriana; Clancy, Heather; Devis, Ycar; Myers, Laura C.; Liu, Vincent X; Walkey, Allan J.

doi:10.1164/rccm.202103-0613oc

“…In our study, model discrimination was highest for the most common postsepsis complication of atrial fibrillation and lower for the less common ASCVD outcomes. Although prior studies demonstrated that elevated troponin during sepsis was a risk factor for postsepsis cardiovascular events when modeled from a causal inference perspective (29), our findings suggest that sepsis-associated clinical measures may not add substantial contributions beyond presepsis risk factors for prediction of postsepsis ASCVD events. Existing research also suggests that atrial fibrillation (30) and heart failure, including septic cardiomyopathy (31), should be formally recognized as organ dysfunction criteria that make up the definition of sepsis itself.…”

Section: Discussioncontrasting

confidence: 70%

Prognostic Accuracy of Presepsis and Intrasepsis Characteristics for Prediction of Cardiovascular Events After a Sepsis Hospitalization

Walkey

¹

,

Knox

²

,

Myers

³

et al. 2022

Critical Care Explorations

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OBJECTIVES: Sepsis survivors face increased risk for cardiovascular complications; however, the contribution of intrasepsis events to cardiovascular risk profiles is unclear. SETTING: Kaiser Permanente Northern California (KPNC) and Intermountain Healthcare (IH) integrated healthcare delivery systems. SUBJECTS: Sepsis survivors (2011–2017 [KPNC] and 2018–2020 [IH]) greater than or equal to 40 years old without prior cardiovascular disease. DESIGN: Data across KPNC and IH were harmonized and grouped into presepsis (demographics, atherosclerotic cardiovascular disease scores, comorbidities) or intrasepsis factors (e.g., laboratory values, vital signs, organ support, infection source) with random split for training/internal validation datasets (75%/25%) within KPNC and IH. Models were bidirectionally, externally validated between healthcare systems. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Changes to predictive accuracy (C-statistic) of cause-specific proportional hazards models predicting 1-year cardiovascular outcomes (atherosclerotic cardiovascular disease, heart failure, and atrial fibrillation events) were compared between models that did and did not contain intrasepsis factors. Among 39,590 KPNC and 16,388 IH sepsis survivors, 3,503 (8.8%) at Kaiser Permanente (KP) and 600 (3.7%) at IH experienced a cardiovascular event within 1-year after hospital discharge, including 996 (2.5%) at KP and 192 (1.2%) IH with an atherosclerotic event first, 564 (1.4%) at KP and 117 (0.7%) IH with a heart failure event, 2,310 (5.8%) at KP and 371 (2.3%) with an atrial fibrillation event. Death within 1 year after sepsis occurred for 7,948 (20%) KP and 2,085 (12.7%) IH patients. Combined models with presepsis and intrasepsis factors had better discrimination for cardiovascular events (KPNC C-statistic 0.783 [95% CI, 0.766–0.799]; IH 0.763 [0.726–0.801]) as compared with presepsis cardiovascular risk alone (KPNC: 0.666 [0.648–0.683], IH 0.660 [0.619–0.702]) during internal validation. External validation of models across healthcare systems showed similar performance (KPNC model within IH data C-statistic: 0.734 [0.725–0.744]; IH model within KPNC data: 0.787 [0.768–0.805]). CONCLUSIONS: Across two large healthcare systems, intrasepsis factors improved postsepsis cardiovascular risk prediction as compared with presepsis cardiovascular risk profiles. Further exploration of sepsis factors that contribute to postsepsis cardiovascular events is warranted for improved mechanistic and predictive models.

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“…These findings, associated with a trend to less myocardial injury as assessed by hs-cTrop release, may be related to an improvement in cardiovascular outcomes after sepsis [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Myocardial effects of angiotensin II compared to norepinephrine in an animal model of septic shock

Garcia

¹

,

Su

²

,

Dewachter

³

et al. 2022

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Background Angiotensin II is one of the vasopressors available for use in septic shock. However, its effects on the septic myocardium remain unclear. The aim of the study was to compare the effects of angiotensin II and norepinephrine on cardiac function and myocardial oxygen consumption, inflammation and injury in experimental septic shock. Methods This randomized, open-label, controlled study was performed in 20 anesthetized and mechanically ventilated pigs. Septic shock was induced by fecal peritonitis in 16 animals, and four pigs served as shams. Resuscitation with fluids, antimicrobial therapy and abdominal drainage was initiated one hour after the onset of septic shock. Septic pigs were randomly allocated to receive one of the two drugs to maintain mean arterial pressure between 65 and 75 mmHg for 8 h. Results There were no differences in MAP, cardiac output, heart rate, fluid balance or tissue perfusion indices in the two treatment groups but myocardial oxygen consumption was greater in the norepinephrine-treated animals. Myocardial mRNA expression of interleukin-6, interleukin-6 receptor, interleukin-1 alpha, and interleukin-1 beta was higher in the norepinephrine than in the angiotensin II group. Conclusions In septic shock, angiotensin II administration is associated with a similar level of cardiovascular resuscitation and less myocardial oxygen consumption, and inflammation compared to norepinephrine. Supplementary Information The online version contains supplementary material available at 10.1186/s13054-022-04161-3.

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“…David suggested the elevated levels of CK-MB and cTnI in patients with septic shock [ 30 ]. In recent years, it has been found that the increase of myocardial enzyme level not only reflects the injury of ischemic myocardial disease but also indicated myocardial injury and poor prognosis of noncardiogenic diseases such as sepsis [ 31 ]. Abnormal myocardial enzymes may suggest that myocardial injury “without early intervention” can rapidly develop into cardiac dysfunction and heart failure, thus inducing MODS.…”

Section: Discussionmentioning

confidence: 99%

Evaluation Value and Clinical Significance of Cardiac Troponin Level and Pediatric Sequential Organ Failure Score in the Definition of Sepsis 3.0 in Critically Ill Children

Wu

¹

,

Shen²,

Wang

³

et al. 2022

Computational and Mathematical Methods in Medicine

2

0

1

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Objective. A case-control study was conducted to explore the value and clinical significance of troponin level and pediatric sequential organ failure score in the evaluation of sepsis 3.0 definition in critically ill children. Methods. 180 children with sepsis who were admitted to the ICU from March 2019 to June 2021 were enrolled in our hospital as the research objects. In addition, 100 children with general infection did not meet the diagnostic criteria of systemic inflammatory response syndrome (SIRS) as controls. The creatine kinase MB (CK-MB) and cardiac troponin I (cTnI) data at the 1st and 24-72 h after admission to pediatric intensive care unit (PICU) were enrolled as the observation indexes of myocardial enzymology. In the meantime, the relevant literature was reviewed to obtain the indicators related to sepsis death. The data of the first examination in the medical history data were enrolled for analysis. According to the definition of sepsis 3.0 in critically ill children, they were assigned into sepsis and nonsepsis group. According to the survival outcome of discharge and 30 days after discharge, the patients were assigned into the death subgroup and survival subgroup and were assigned into the sequential organ failure assessment SOFA score ≥ 2 subgroup and< 2 subgroup according to SOFA score. COX proportional hazard regression was used to analyze the relationship between CK-MB, cTnI, and SOFA scores and prognosis. ROC curve was adopted to analyze the value of CK-MB, cTnI, and SOFA scores in the evaluation of critical sepsis in children. Results. Univariate analysis indicated that the prognosis of children with sepsis was correlated with abnormal levels of CK-MB and cTnI, SOFA score, oxygenation index < 200 , mean arterial pressure, and Glasgow coma scale (GCS), and the difference was statistically significant ( P < 0.05 ). The results of COX regression analysis indicated that the variables that were remarkably associated with death from sepsis in children were CK-MB, elevated cTnI levels, and SOFA score ≥ 2 , and serum cTnI and/or CK-MB levels and SOFA score were remarkably higher correlation ( r = 0.453 , P < 0.05 ). In terms of the myocardial enzyme levels in the sepsis group and the nonsepsis group, the levels of CK-MB and (or) cTnI augmented in 121/180 cases (67.22%) in the sepsis group and in 19/100 cases (19.00%) in the nonsepsis group. The levels of CK-MB and (or) cTnI were augmented, and the difference was statistically significant ( P < 0.05 ). The levels of CK-MB and cTnI in the sepsis group at admission to ICU and 24 to 72 hours after admission were remarkably higher compared to the nonsepsis group. The levels of CK-MB and cTnI at 24-72 h were higher compared to ICU. The myocardial enzyme levels of different SOFA scores and survival outcome subgroups in the sepsis group were compared. The subgroup with SFOA score ≥ 2 points had remarkably higher levels of CK-MB and (or) cTnI than the subgroup with <2 points. The survival subgroup of CK-MB and cTnI level was remarkably higher compared to the death subgroup, the CK-MB and cTnI levels in each subgroup at 224-72 hours were remarkably higher compared to the ICU, and the difference was statistically significant ( P < 0.05 ). Kaplan-Meier method and log-rank test indicated that the survival rates of groups 1 to 4 at 30 days were 33.23%, 78.71%, 40.03%, and 100.00%, respectively. The average survival time and their 95% CI were 12.82 d (10.52~ 16.26 d), 22.34 d (18.76~ 25.81 d), 14.65 d (11.62~ 16.38 d), and 30 d (30.00~ 30.00 d), respectively. Pairwise comparison indicated that the survival time of children in group 1 was the shortest, and that in group 4 was the longest. The results of ROC curve research showed that the CK-MB, cTnI, and SOFA scores and AUC for the combination test were 0.778 (95% CI 0.642–0.914), 0.736 (95% CI 0.602–0.890), 0.848 (95% CI 0.733–0.963), and 0.934 (95% CI 0.854–0.999), respectively. The AUC of combined diagnosis was remarkably higher compared to single factor prediction, and the difference was statistically significant ( P < 0.05 ). Predictive value showed the joint test > SOFA score > CK − MB > cTnI . Conclusion. Troponin level and pediatric SOFA score can be adopted as effective indicators to assess the severity and prognosis of patients with sepsis and can guide the formulation of a reasonable treatment plan.

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Association between Troponin I Levels during Sepsis and Postsepsis Cardiovascular Complications

Cited by 30 publications

References 27 publications

Prognostic Accuracy of Presepsis and Intrasepsis Characteristics for Prediction of Cardiovascular Events After a Sepsis Hospitalization

Prognostic Accuracy of Presepsis and Intrasepsis Characteristics for Prediction of Cardiovascular Events After a Sepsis Hospitalization

Myocardial effects of angiotensin II compared to norepinephrine in an animal model of septic shock

Evaluation Value and Clinical Significance of Cardiac Troponin Level and Pediatric Sequential Organ Failure Score in the Definition of Sepsis 3.0 in Critically Ill Children

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