Prognostic Value of Soluble Urokinase-Type Plasminogen Activator Receptor and High-Sensitivity C-Reactive Protein on Postoperative Mortality in Patients Undergoing Elective On-Pump Cardiac Surgery.

OBJECTIVES: Elevated soluble urokinase-type plasminogen activator receptor (suPAR) and high-sensitivity C-reactive protein (hsCRP) have been associated with increased mortality in patients with cardiovascular disease. The aim of the present study was to explore the relationship between suPAR and hsCRP values and associated mortality after elective cardiac surgery. A secondary aim was to assess whether a combined risk model of European System for Cardiac Operative Risk Evaluation (EuroSCORE II), suPAR, and/or hsCRP would improve the prognostic accuracy compared with EuroSCORE II alone. DESIGN: Retrospective observational study. SETTING: Single-center, university hospital. PARTICIPANTS: Adult patients admitted for elective on-pump cardiac surgery were included. Biobank blood samples were obtained from previous research projects at a tertiary heart center from 2012 to 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 931 patients were included. Kaplan-Meier and Cox proportional hazard analyses were used to explore a potential association between preoperative suPAR and hsCRP values and all-cause mortality up to one year after surgery. Thirty-day mortality was predicted from suPAR, hsCRP, and EuroSCORE II by logistic regression and compared using area under the receiver operating characteristics curve and Brier scores. After adjustment for known confounders, a doubling of suPAR and hsCRP corresponded to a hazard ratio for all-cause mortality of 2.27 (95% confidence interval 1.65-3.11; p < 0.001) and 1.26 (95% confidence interval 1.07-1.49; p = 0.005), respectively. However, adding the biomarkers to EuroSCORE II did not improve prediction/discrimination with respect to 30-day mortality. CONCLUSIONS: Elevated preoperative levels of suPAR and hsCRP were associated with all-cause mortality in elective cardiac surgery patients. However, inclusion of biomarkers did not improve the prognostic accuracy of EuroSCORE II.

Coronary artery bypass surgery plus medical therapy versus medical therapy alone for ischaemic heart disease: a protocol for a systematic review with meta-analysis and trial sequential analysis.

BACKGROUND: Despite increasing survival, cardiovascular disease remains the primary cause of death worldwide with an estimated 7.4 million annual deaths. The main symptom of ischaemic heart disease is chest pain (angina pectoris) most often caused by blockage of a coronary artery. The aim of coronary artery bypass surgery is revascularisation achieved by surgically grafting harvested arteries or veins distal to the coronary lesion restoring blood flow to the heart muscle. Older evidence suggested a clear survival benefit of coronary artery bypass graft surgery, but more recent trials yield less clear evidence. We want to assess the benefits and harms of coronary artery bypass surgery combined with different medical therapies versus medical therapy alone in patients with ischaemic heart disease. METHODS: This protocol for a systematic review follows the recommendations of Cochrane and the eight-step assessment procedure suggested by Jakobsen and colleagues. We plan to include all randomised clinical trials assessing coronary artery bypass surgery combined with different medical therapies versus medical therapy alone in patients with ischaemic heart disease. We plan to search the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, LILACS, Science Citation Index Expanded on Web of Science, and BIOSIS to identify relevant trials. Any eligible trial will be assessed as high risk or low risk of bias, and our conclusions will primarily be based on trials at low risk of bias. The analyses of the extracted data will be performed using Review Manager 5, STATA 16 and trial sequential analysis. For both our primary and secondary outcomes, we will create a 'Summary of Findings' table and use GRADE to assess the certainty of the evidence. DISCUSSION: Coronary artery bypass surgery is invasive and can cause death, which is why its use must be thoroughly studied to determine if it yields a large enough long-term benefit for the thousands of patients receiving it every year. SYSTEMATIC REVIEW REGISTRATION: PROSPERO ID 131924.

Pulmonary artery perfusion versus no pulmonary per-fusion during cardiopulmonary bypass.


During conventional cardiopulmonary bypass (CPB) there is no active perfusion of the pulmonary circulation and the mechanical ventilation is ceased leaving the lungs exposed to warm ischemia.
 
Pulmonary dysfunction is seen in varying degrees after major surgery, but more severe in cardiac surgery patients probably due to the effects of CPB. The evidence for effect and safety are limited, but active pulmonary artery perfusion during CPB could be beneficial for the patients' postoperative oxygenation.
Our aim was in a randomised clinical trial to assess primarily the effect of pulmonary artery perfusion during CPB on postoperative oxygenation in patients diagnosed with chronic obstructive pulmonary disease (COPD), secondarily to assess other possible benefits and harms. Furthermore, we wanted in a systematic review with meta-analyses of all randomised clinical trials to investigate the pooled effects of pulmonary artery perfusion during CPB. 
We planned and conducted a randomised, partly blinded, clinical trial assigning cardiac surgery patients diagnosed with COPD to receive pulmonary artery perfusion with oxygenated blood or histidine-tryptophan-ketoglutarate (HTK) solution compared to no pulmonary perfusion during CPB. The primary outcome was the oxygenation index measured during and after surgery. Secondary outcomes were intubation time, serious adverse events, days alive outside the intensive care unit and outside the hospital, 30- and 90-days mortality. 
Secondly, we conducted a systematic review of randomised clinical trials comparing benefits and harms of using pulmonary artery perfusion versus no pulmonary perfusion during CPB pooling results in meta-analyses and trial sequential analyses (TSA).
 
Of the 90 randomised patients 89 were included in analysis of the primary outcome, the inverse oxygenation index, measured at a single time point 21 hours after CPB start and longitudinally 1, 3, 5, 7, and 21 hours after CPB start. At 21 hours, patients randomised to pulmonary artery perfusion with oxygenated blood had a higher inverse oxygenation index compared to patients randomised to no pulmonary perfusion during CPB (mean difference (MD) 0.94; 95% confidence interval (CI), 0.05 to 1.83; P=0.04). The inverse oxygenation index was also significantly higher at 21 hours after CPB start (MD 0.99; CI, 0.29 to 1.69; P=0.007), and longitudinally (P=0.009), for patients receiving pulmonary artery perfusion with oxygenated blood compared to pulmonary artery perfusion with HTK solution. This corresponds to a PaO2 difference of 23 mmHg with a median FiO2 of 0.32. We found no additional significant differences for the remaining comparisons of the inverse oxygenation index neither for any of the secondary outcomes. 
The systematic review identified 4 trials with a total of 210 patients. In meta-analyses pulmonary artery perfusion with blood versus no pulmonary perfusion during CPB was not associated with relative risk of death (1.7; 95% CI, 0.4 to 6.9; 210 patients in three trials with high and one trial with low risk of bias), serious adverse events (1.2; 95% CI, 0.8 to 1.8; 180 patients in two trials with high and one trial with low risk of bias) or intubation time (-0.4 hours; 95% CI, -1.1 to 0.4; 176 patients in three trials with high and one trial with low risk of bias). TSA on mortality, serious adverse events, and PaO2/FiO2 ratio showed that required information sizes have not been reached, but pulmonary artery perfusion with blood was associated with a higher PaO2/FiO2 ratio (27.8 mmHg; 95% CI, 5.7 to 50.0 mmHg; 119 patients in two trials with high and one trial with low risk of bias). TSA on intubation time showed that the boundary for lack of superiority (futility) was crossed refuting a shorten intubation time of 1.5 hours or more. 
Our trial provided additional knowledge about the use of pulmonary artery perfusion during CPB in cardiac surgery patients with COPD, and improved oxygenation for patients receiving pulmonary artery perfusion with oxygenated blood. Pulmonary artery perfusion with HTK solution did not result in an improved oxygenation. In line with this, the systematic review including data from additional trials showed a possible association between pulmonary artery perfusion with blood and improved oxygenation, but no significant associations with mortality, serious adverse events or intubation time. However, all data are too sparse to be conclusive.