The risk predictive power of high-sensitive cardiac troponin T change in addition to the Revised Cardiac Risk Index could facilitate 1) detection of patients at highest risk for perioperative myocardial ischemia, 2) evaluation and development of cardioprotective therapeutic strategies, and 3) decisions for admission to and discharge from high-density care units.
Lidocaine exerts cardioprotective effects when administered before or after the ischemic insult. This effect is mediated through an antiapoptotic and not through an antiinflammatory pathway and may be therapeutically exploitable.
OBJECTIVES:
Extracorporeal membrane oxygenation (ECMO) is a potentially lifesaving procedure in acute respiratory distress syndrome (ARDS) due to COVID-19. Previous studies have shown a high prevalence of clinically silent cerebral microbleeds in patients with COVID-19. Based on this fact, together with the hemotrauma and the requirement of therapeutic anticoagulation on ECMO support, we hypothesized an increased risk of intracranial hemorrhages (ICHs). We analyzed ICH occurrence rate, circumstances and clinical outcome in patients that received ECMO support due to COVID-19–induced ARDS in comparison to viral non-COVID-19–induced ARDS intracerebral hemorrhage.
DESIGN:
Multicenter, retrospective analysis between January 2010 and May 2021.
SETTING:
Three tertiary care ECMO centers in Germany and Switzerland.
PATIENTS:
Two-hundred ten ARDS patients on ECMO support (COVID-19,
n
= 142 vs viral non-COVID,
n
= 68).
INTERVENTIONS:
None.
MEASUREMENTS AND MAIN RESULTS:
Evaluation of ICH occurrence rate, parameters of coagulation and anticoagulation strategies, inflammation, and ICU survival. COVID-19 and non-COVID-19 ARDS patients showed comparable disease severity regarding Sequential Organ Failure Assessment score, while the oxygenation index before ECMO cannulation was higher in the COVID group (82 vs 65 mm Hg). Overall, ICH of any severity occurred in 29 of 142 COVID-19 patients (20%) versus four of 68 patients in the control ECMO group (6%). Fifteen of those 29 ICH events in the COVID-19 group were classified as major (52%) including nine fatal cases (9/29, 31%). In the control group, there was only one major ICH event (1/4, 25%). The adjusted subhazard ratio for the occurrence of an ICH in the COVID-19 group was 5.82 (97.5% CI, 1.9–17.8;
p
= 0.002). The overall ICU mortality in the presence of ICH of any severity was 88%.
CONCLUSIONS:
This retrospective multicenter analysis showed a six-fold increased adjusted risk for ICH and a 3.5-fold increased incidence of ICH in COVID-19 patients on ECMO. Prospective studies are needed to confirm this observation and to determine whether the bleeding risk can be reduced by adjusting anticoagulation strategies.
Background
Preoperative risk prediction in patients at elevated cardiovascular risk shows limited accuracy. Platelet to lymphocyte ratio (PLR) and neutrophil to lymphocyte ratio (NLR) indicate systemic inflammation. Both have been investigated for outcome prediction in the field of oncology and cardiovascular medicine, as well as risk prediction of adverse cardiovascular events in non-surgical patients at increased cardiovascular risk.
Methods
For this post-hoc analysis, we included all 38 coronary heart disease patients from the Leukocytes and Cardiovascular Perioperative Events cohort-1 study scheduled for elective non-cardiac surgery. We evaluated preoperative differential blood counts for association with major adverse cardiovascular and cerebrovascular events (MACCE) defined as the composite endpoint of death, myocardial ischemia, myocardial infarction, myocardial injury after non-cardiac surgery, or embolic or thrombotic stroke within 30 days after surgery. We used Youden’s index to calculate cut-off values for PLR and NLR. Additive risk-predictive values were assessed using receiver operating characteristic curve and net reclassification (NRI) improvement analyses.
Results
Patients with the composite endpoint MACCE had higher PLR and NLR (309 [206; 380] vs. 160 [132; 203], p = 0.001; 4.9 [3.5; 8.1] vs. 2.6 [2.2; 3.4]), p = 0.001). Calculated cut-offs for PLR > 204.4 and NLR > 3.1 were associated with increased risk of 30-day MACCE (OR 7, 95% CI [1.2; 44.7], p = 0.034; OR 36, 95% CI [1.8; 686.6], p = 0.001). Furthermore, NLR improved risk prediction in coronary heart disease patients undergoing non-cardiac surgery when combined with hs-cTnT or NT-proBNP (NRI total = 0.23, p = 0.008, NRI total = 0.26, p = 0.005).
Conclusions
Both PLR and NLR were associated with perioperative cardiovascular adverse events in coronary heart disease patients. NLR proved to be of additional value for preoperative risk stratification. Both PLR and NLR could be used as inexpensive and broadly available tools for perioperative risk assessment.
Trial registration
NCT02874508, August 22, 2016.
These results suggest that cardiac-specific overexpression of a constitutively active form of I-2 is deleterious for cardiac function under conditions of pressure overload. Thus, the long-term inhibition of PP1 by I-2 is not a therapeutic option in the treatment of heart failure.
Immune cells drive atherosclerotic lesion progression and plaque destabilization. Coronary heart disease patients undergoing noncardiac surgery are at risk for perioperative major adverse cardiac and cerebrovascular events (MACCE). It is unclear whether differential leukocyte subpopulations contribute to perioperative MACCE and thereby could aid identification of patients prone to perioperative cardiovascular events. First, we performed a hypothesis-generating post hoc analysis of the LeukoCAPE-1 study (n = 38). We analyzed preoperative counts of 6 leukocyte subpopulations in coronary heart disease patients for association with MACCE (composite of cardiac death, myocardial infarction, myocardial ischemia, myocardial injury after noncardiac surgery, thromboembolic stroke) within 30 d after surgery. Regulatory T cells (Tregs) were the only leukocyte subgroup associated with MACCE. We found reduced Tregs in patients experiencing MACCE versus no-MACCE (0.02 [0.01; 0.03] vs. 0.04 [0.03; 0.05] Tregs nl −1 , P = 0.002). Using Youden index, we derived the optimal threshold value for association with MACCE to be 0.027Tregs nl −1 . Subsequently, we recruited 233 coronary heart disease patients for the prospective, observational LeukoCAPE-2 study and independently validated this Treg cutoff for prediction of MACCE within 30 d after noncardiac surgery. After multivariate logistic regression, Tregs < 0.027 cells nl −1 remained an independent predictor for MACCE (OR = 2.54 [1.22; 5.23], P = 0.012).Tregs improved risk discrimination of the revised cardiac risk index based on ΔAUC (area under the curve; ΔAUC = 0.09, P = 0.02), NRI (0.26), and IDI (0.06). Preoperative Treg levels below 0.027 cells nl −1 predicted perioperative MACCE and can be measured to increase accuracy of established preoperative cardiac risk stratification in coronary heart disease patients undergoing noncardiac surgery.
Noncardiac surgery was associated with an increase in atherogenic leukocyte subsets. In a post hoc analysis, elevated pre-OP presepsin was associated with MACCE and improved NT-proBNP-based risk assessment. After validation in an independent data set, a presepsin cutoff of 184 pg·mL might qualify to complement NT-proBNP-based risk prediction, thereby increasing the proportion of correctly identified high-risk patients.
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