Sequential Surgical Procedures in Vascular Surgery Patients Are Associated With Perioperative Adverse Cardiac Events

Patients at elevated cardiovascular risk are prone to perioperative cardiovascular complications, like myocardial injury after non-cardiac surgery (MINS). We have demonstrated in a mouse model of atherosclerosis that perioperative stress leads to an increase in plaque volume and higher plaque vulnerability. Regulatory T cells (Tregs) play a pivotal role in development and destabilization of atherosclerotic plaques. For this exploratory post-hoc analysis we identified 40 patients recruited into a prospective perioperative biomarker study, who within the inclusion period underwent sequential open vascular surgery. On the basis of protein markers measured in the biomarker study, we evaluated the perioperative inflammatory response in patients' plasma before and after index surgery as well as before and after a second surgical procedure. We also analyzed available immunohistochemistry samples to describe plaque vulnerability in patients who underwent bilateral carotid endarterectomy (CEA) in two subsequent surgical procedures. Finally, we assessed if MINS was associated with sequential surgery. The inflammatory response of both surgeries was characterized by postoperative increases of interleukin-6,−10, Pentraxin 3 and C-reactive protein with no clear-cut difference between the two time points of surgery. Plaques from CEA extracted during the second surgery contained less Tregs, as measured by Foxp3 staining, than plaques from the first intervention. The 2nd surgical procedure was associated with MINS. In conclusion, we provide descriptive evidence that sequential surgical procedures involve repeat inflammation, and we hypothesize that elevated rates of cardiovascular complications after the second procedure could be related to reduced levels of intraplaque Tregs, a finding that deserves confirmatory testing and mechanistic exploration in future populations

Risk factors for perioperative complications in inguinal hernia repair – a systematic review

The current literature suggests that perioperative complications occur in 8%–10% of all inguinal hernia repairs. However, the clinical relevance of these complications is currently unknown. In our review, based on 571,445 hernia repairs reported in 39 publications, we identified the following potential risk factors: patient age, ASA score, diabetes, smoking, mode of admission (emergency vs. elective surgery), surgery in low resource settings, type of anesthesia, and (in men) bilateral and sliding hernias. The most commonly reported complications are bleeding (0.9%), wound infection (0.5%), and pulmonary and cardiovascular complications (0.2%). In 3.9% of the included publications, a reliable grading of the reported complications according to Clavien-Dindo classification was possible. Using this classification retrospectively, we could show that, in patients with complications, these are clinically relevant for about 22% of these patients (Clavien-Dindo grade ≥IIIa). About 78% of all patients suffered from complications needing only minor (meaning mostly medical) intervention (Clavien-Dindo grade <III). Especially with regard to the low incidence of complications in inguinal hernia repair, future studies should use the Clavien-Dindo classification to achieve better comparability between studies, thus enabling better correlation with potential risk factors

Prospective evaluation of preoperative lung ultrasound for prediction of perioperative outcome and myocardial injury in adult patients undergoing vascular surgery (LUPPO study)

BACKGROUND Myocardial injury after non-cardiac surgery (MINS) is a frequent perioperative event in vascular surgery, associated both with worse outcome and subsequent cardiovascular events. Current guidelines advocate troponin (hs-cTnT) and NT-proBNP measurements in selected patients before surgery, but accurate preoperative identification of patients at risk for MINS is an unmet clinical need. Focused lung ultrasound (LUS) might help to select patients at increased risk for MINS, because it can visualize B-line artifacts correlating to cardiopulmonary disease. Therefore, we investigated whether quantification of B-line artifacts improves perioperative risk predictive accuracy for MINS. METHODS In this prospective single-center observational study, 136 consecutive open vascular surgery patients underwent conventional preoperative assessment expanded by lung ultrasound. Lung ultrasound B-lines were counted in each of 28 bilateral scan fields of the anterior and lateral chest. Improvement of risk predictive accuracy was quantified with area under receiver operating characteristic (ROC) curve analysis and net reclassification improvement (NRI). RESULTS We included 118 patients into the final analysis. Twenty-three (19%) patients fulfilled the criteria for the primary endpoint MINS. Three or more bilateral positive B-line fields were calculated as the best ROC-derived cutoff associated with an increased incidence of MINS (odds ratio: 4.4; 95% confidence interval [CI]: 1.5 to 12.7; P=0.007). Adding LUS to hs-cTnT measurements improved risk predictive accuracy for MINS (NRI: 0.36, P=0.043). CONCLUSIONS Lung ultrasound in combination with hs-cTnT showed a better test accuracy than hs-cTnT alone and might guide clinicians to identify vascular patients at increased risk for MINS

Renal function interferes with copeptin in prediction of major adverse cardiac events in patients undergoing vascular surgery.

OBJECTIVE:Precise perioperative risk stratification is important in vascular surgery patients who are at high risk for major adverse cardiovascular events (MACE) peri- and postoperatively. In clinical practice, the patient's perioperative risk is predicted by various indicators, e.g. revised cardiac index (RCRI) or modifications thereof. Patients suffering from chronic kidney disease (CKD) are stratified into a higher risk category. We hypothesized that Copeptin as a novel biomarker for hemodynamic stress could help to improve the prediction of perioperative cardiovascular events in patients undergoing vascular surgery including patients with chronic kidney disease. METHODS:477 consecutive patients undergoing abdominal aortic, peripheral arterial or carotid surgery from June 2007 to October 2012 were prospectively enrolled. Primary endpoint was 30-day postoperative major adverse cardiovascular events (MACE). RESULTS:41 patients reached the primary endpoint, including 63.4% aortic, 26.8% carotid, and 9.8% peripheral surgeries. Linear regression analysis showed that RCRI (P< .001), pre- (P< .001), postoperative Copeptin (P< .001) and Copeptin level change (P= .001) were associated with perioperative MACE, but CKD remained independently associated with MACE and Copeptin levels. Multivariate regression showed that increased Copeptin levels added risk predictive information to the RCRI (P= .003). Especially in the intermediate RCRI categories was Copeptin significantly associated with the occurrence of MACE. (P< .05 Kruskal Wallis test). Subdivision of the study cohort into CKD stages revealed that preoperative Copeptin was significantly associated with CKD stages (P< .0001) and preoperative Copeptin measurements could not predict MACE in patients with more severe CKD stages. CONCLUSION:Preoperative Copeptin loses its risk predictive potential for perioperative MACE in patients with chronic kidney disease undergoing vascular surgery

Demographical data of study population subdivided into surgical procedures.

<p>P depicts P value of univariate linear regression calculated for each variable and type of surgery. The number of patients (n) for each group as well as percentage (%) is depicted. Other variables are shown as median with 25–75 percentile. Abbreviations are used as follows: coronary artery disease (CAD), revised cardiac risk index (RCRI), glomerular filtration rate (GFR), preoperative values for Copeptin (preop Copeptin), postoperative values for Copeptin (postop Copeptin), change of Copeptin levels between pre- and postoperative sample (Copeptin delta absolute), Major adverse cardiovascular events (MACE).</p><p>Demographical data of study population subdivided into surgical procedures.</p

Copeptin is elevated in patients sustaining Major Adverse Cardiovascular Events (MACE) throughout the perioperative phase.

<p>Boxplots of pre- (A) and postoperative (B) Copeptin levels as well as perioperative Copeptin change (C) (pmol/L). Groups were analyzed by Mann-Whitney U test (A) P = .0001, (B) P = .0002, (C) P = .014.</p

ROC analysis comparing the RCRI alone or combined with Copeptin-derived parameters.

<p>Only preoperative Copeptin (blue dotted line) improved risk predictive accuracy of the RCRI (P = .0371, AUC .752). The RCRI-ROC Curve (black line) (AUC .714) indicates prediction of the occurrence of major adverse cardiovascular events (MACE). The combination of RCRI and postoperative Copeptin (red dashed line) (P = .0620, AUC .751) and RCRI and Copeptin changes (P = .1525, AUC .710) during the perioperative course (green dashed and dotted line) do not reach significantly larger AUCs. * marks significant values.</p

Analysis of Copeptin levels.

<p>Linear regression analysis of pre-, postoperative Copeptin levels and Copeptin change (pmol/L) and existing comorbidities as well as RCRI category and surgical procedure,</p><p>*marks significant confounders, abbreviations are used as follows: BMI (Body mass index), TIA (transitory ischemic attack), COPD (chronic obstructive pulmonary disease), CAD (coronary artery disease), RCRI (Revised cardiac index), surgical procedure (type of surgery performed subdivided into aortic, carotid and peripheral surgeries). Significance reveals results of linear regression analysis; significant results were additionally used in multivariate regression (significance multivariate) results are shown with P values.</p><p>Analysis of Copeptin levels.</p

Copeptin interferes with kidney injury in prediction of MACE.

<p>Preoperative Copeptin levels (pmol/L) are significantly (P<.0001) elevated in patients with chronic kidney disease increasing with severity of kidney injury (A). Preoperative Copeptin is not associated with MACE in patients with CKD 1&2 (B) (P = .3787) or CKD 4&5 (D) (P = .2264) but shows significant association with MACE in CKD 3 (C) (P = .0163). Data were analyzed using Mann Whitney U test for comparing two groups and Kruskal Wallis test followed by Dunns test for multiple comparisons. Blots are depicted as 5–95 percentile.</p

Linear regression analysis of MACE and existing comorbidities.

<p>*marks significant confounders.</p><p>Abbreviations are used as follows: BMI (Body mass index), TIA (transitory ischemic attack) COPD (chronic obstructive pulmonary disease), CAD (coronary artery disease), RCRI (Revised cardiac index), Surgical procedure (type of surgery performed subdivided into aortic, carotid and peripheral arterial procedures). Copeptin preoperative, postoperative and Copeptin change; significant results were additionally used in multivariate regression (significance multivariate) results are shown with p values. Comorbidities and putative risk predictors were analyzed in separate univariate and multivariate analysis.</p><p>Linear regression analysis of MACE and existing comorbidities.</p