Thromboembolic Events in the Perioperative Period

The first chapter provides an overview of cardiovascular risk identification and modification in the perioperative period. In this chapter the identification of patients at risk using various risk models and biomarkers is described. Noninvasive and invasive preoperative (stress) testing as well as preoperative coronary revascularization is discussed. Finally short- and long-term risk reduction strategies such as beta-blocker therapy, statins and aspirins are evaluated. Chapter 2 summarizes the findings on perioperative stroke in noncardiac surgery. This chapter describes the pathophysiology of perioperative stroke and focuses on important issues regarding the initiation of beta-blocker therapy preoperative. Chapter 3 and 4 evaluate the risk for perioperative stroke in patients on beta-blocker therapy. Risk factors for perioperative stroke are discussed. Perioperative stroke is evaluated in patients on chronic beta-blocker use as well as in patients where beta-blockers are initiated prior to surgery. Intraoperative cardiac arrests are discussed in chapter 5. In a case-control study of surgical patients at the Erasmus Medical Center, the relationship between preoperative cardiovascular risk factors and intraoperative cardiac events is analyzed. In chapter 6 a risk model for postoperative pulmonary embolism after noncardiac surgery is developed. This chapter highlights the importance of on time thromboprophylaxis in relation to adverse postoperative venous thromboembolic processes. Chapter 7 describes the value of statins in the (postoperative) intensive care period. Proper use of statins in the postoperative period after both cardiac and noncardiac surgery is discussed. The second part of the chapter focuses on potential indications for statin therapy in the near future. The indication of statins has expanded to other patient categories often admitted to an intensive care unit. Therefore statin therapy may be the next logical step in the search for adjuvant therapy in common intensive cares diseases. The final chapter, chapter 8, discusses the value of epidural analgesia in addition to general anesthesia in COPD patients undergoing major abdominal surgery. Epidural analgesia is associated with improved outcome in surgical patients. However, since epidural analgesia might worsen postoperative respiratory function, it is unclear whether COPD patients benefit from epidural analgesia. This study aimed to examine the effects of epidural analgesia in addition to general anesthesia in COPD patients scheduled for major abdominal surgery

The preoperative cardiology consultation: Indications and risk modification

Background The cardiologist is regularly consulted preop-eratively by anaesthesiologists. However, insights into the efficiency and usefulness of these consultations are unclear. Methods This is a retrospective study of 24,174 preoperatively screened patients ≥18 years scheduled for elective non-cardiac surgery, which resulted in 273 (1%) referrals to the cardiologist for further preoperative evaluation. Medical charts were reviewed for patient characteristics, main reason for referring, requested diagnostic tests, interventions, adjustment in medical therapy, 30-day mortality and major adverse cardiac events. Results The most common reason for consultation was the evaluation of a cardiac murmur (95 patients, 35%). In 167 (61%) patients, no change in therapy was initiated by the cardiologist. Six consultations (2%) led to invasive interventions (electrical cardioversion, percutaneous coronary intervention or coronary artery bypass surgery). On average, consultation delayed clearance for surgery by two weeks. Conclusion In most patients referred to the cardiologist after being screened at an outpatient anaesthesiology clinic, echocardiography is performed for ruling out specific conditions and to be sure that no further improvement can be made in the patient’s health. In the majority, no change in therapy was initiated by the cardiologist. A more careful consideration about the potential benefits of consulting must be made for every patient

Immediate postoperative high-sensitivity troponin T concentrations and long-term patient-reported

BACKGROUND: Myocardial injury after noncardiac surgery is associated with mortality and major adverse postoperative cardiovascular events. The effect of postoperative troponin concentrations on patient-reported health-related quality of life (HRQoL) is unknown. OBJECTIVE: The study examined the association between immediate postoperative troponin concentrations and self-reported HRQoL 1 year after surgery. DESIGN: Prospective cohort study. SETTING: Single-centre tertiary care hospital in the Netherlands between July 2012 and 2015. PATIENTS: Patients aged at least 60 years undergoing moderate and major noncardiac surgery.None. MAIN OUTCOME MEASURES: HRQoL total score was assessed with the EuroQol five-dimensional questionnaire. Tobit regression analysis was used to determine the association between postoperative troponin concentrations and 1-year HRQoL. Peak high-sensitivity troponin T values were divided into four categories: less than 14, 14 to 49, 50 to 149 and at least 150 ng l. RESULTS: A total of 3085 patients with troponin measurements were included. 2634 (85.4%) patients were alive at 1-year follow-up of whom 1297 (49.2%) returned a completed questionnaire. The median score for HRQoL was 0.82 (0.85, 0.81, 0.77 and 0.71 per increasing troponin category). Multivariable analysis revealed betas of -0.06 [95% confidence interval (CI) -0.09 to -0.02], -0.11 (95% CI -0.18 to -0.04) and -0.18 (95% CI -0.29 to -0.07) for troponin levels of 14 to 49, 50 to 149 and at least 150 ng l when compared with values less than 14 ng l. Other independent predictors for lower HRQoL were chronic obstructive pulmonary disease, female sex, peripheral arterial disease and increasing age. CONCLUSION: Higher levels of postoperative troponin measured immediately after surgery were independently associated with lower self-reported HRQoL total score at 1-year follow-up

Postoperative troponin release is associated with major adverse cardiovascular events in the first year after noncardiac surgery

_Introduction:_ Troponin elevations after intermediate-to-high risk noncardiac surgery are common and can predict mortality. However, the prognostic value for early and late major adverse cardiovascular events (MACE) is less well investigated. The authors evaluated the relationship between postoperative troponin release and MACE in the first year after noncardiac surgery. _Methods:_ This observational cohort registry comprised data of patients aged ≥60 years undergoing intermediateto-high risk noncardiac surgery between July 2012 and 2015, at the Erasmus University Medical Center, Rotter

Type D Personality and Health-Related Quality of Life in Vascular Surgery Patients

Background: This study evaluated the association of type D personality and health-related quality of life (HRQoL) and assessed the stability of type D personality in vascular surgery patients during the year after surgery. Method: In a prospective cohort study between 2008 and 2014, 294 patients were assessed with validated questionnaires preoperatively and at 1, 6, and 12 months after surgery. Associations between type D personality, depression, and HRQoL were analyzed by generalized estimating equation models. Type D personality was analyzed in its standard dichotomous form as well as continuous (z) scores of its two components, negative affectivity (NA) and social inhibition (SI), and their interaction term. Results: Prevalence of type D personality varied between 18% and 25%. However, only 9% of the complete responders were classified as type D personality at all four assessments, whereas one third changed between type D classifications. Continuous scores showed greater stability over time. Dichotomized type D personality measured over time was significantly associated with impaired HRQoL, but this was not the case if measured once at baseline, like in general use. The continuous NA score and depression were also significantly associated with impaired HRQoL over time. Conclusion: Type D personality was not a stable trait over time. Preoperative assessment of type D personality did not predict improvement in HRQoL after vascular surgery. However, the study revealed associations between the NA component of type D personality, depression, and lower HRQoL. This indicates that measures of overall negative affect should be taken into account when assessing HRQoL patient-reported outcomes in vascular surgery patients

Circulating biomarkers of cardiovascular disease are related to aneurysm volume in abdominal aortic aneurysm

Background: Surveillance programs in abdominal aortic aneurysms (AAA) are mainly based on imaging and leave room for improvement to timely identify patients at risk for AAA growth. Many biomarkers are dysregulated in patients with AAA, which fuels interest in biomarkers as indicators of disease progression. We examined associations of 92 cardiovascular disease (CVD)-related circulating biomarkers with AAA and sac volume. Methods: In a cross-sectional analysis, we separately investigated (1) 110 watchful waiting (WW) patients (undergoing periodic surveillance imaging without planned intervention) and (2) 203 patients after endovascular aneurysm repair (EVAR). The Cardiovascular Panel III (Olink Proteomics AB, Sweden) was used to measure 92 CVD-related circulating biomarkers. We used cluster analyses to investigate protein-based subphenotypes, and linear regression to examine associations of biomarkers with AAA and sac volume on CT scans. Results: Cluster analyses revealed two biomarker-based subgroups in both WW and EVAR patients, with higher levels of 76 and 74 proteins, respectively, in one subgroup versus the other. In WW patients, uPA showed a borderline significant association with AAA volume. Adjusting for clinical characteristics, there was a difference of −0.092 (−0.148, −0.036) loge mL in AAA volume per SD uPA. In EVAR patients, after multivariable adjustment, four biomarkers remained significantly associated with sac volume. The mean effects on sac volume per SD difference were: LDLR: −0.128 (−0.212, −0.044), TFPI: 0.139 (0.049, 0.229), TIMP4: 0.110 (0.023, 0.197), IGFBP-2: 0.103 (0.012, 0.194). Conclusion: LDLR, TFPI, TIMP4, and IGFBP-2 were independently associated with sac volume after EVAR. Subgroups of patients with high levels of the majority of CVD-related biomarkers emphasize the intertwined relationship between AAA and CVD. ClinicalTrials.gov Identifier: NCT03703947.</p

Targeted proteomics and metabolomics for biomarker discovery in abdominal aortic aneurysm and post-EVAR sac volume

BACKGROUND AND AIMS: Abdominal aortic aneurysm (AAA) patients undergo uniform surveillance programs both leading up to, and following surgery. Circulating biomarkers could play a pivotal role in individualizing surveillance. We applied a multi-omics approach to identify relevant biomarkers and gain pathophysiological insights. MATERIALS AND METHODS: In this cross-sectional study, 108 AAA patients and 200 post-endovascular aneurysm repair (post-EVAR) patients were separately investigated. We performed partial least squares regression and ingenuity pathway analysis on circulating concentrations of 96 proteins (92 Olink Cardiovascular-III panel, 4 ELISA-assays) and 199 metabolites (measured by LC-TQMS), and their associations with CT-based AAA/sac volume. RESULTS: The median (25th-75th percentile) maximal diameter was 50.0 mm (46.0, 53.0) in the AAA group, and 55.4 mm (45.0, 64.2) in the post-EVAR group. Correcting for clinical characteristics in AAA patients, the aneurysm volume Z-score differed 0.068 (95 %CI: (0.042, 0.093)), 0.066 (0.047, 0.085) and -0.051 (-0.064, -0.038) per Z-score valine, leucine and uPA, respectively. After correcting for clinical characteristics and orthogonalization in the post-EVAR group, the sac volume Z-score differed 0.049 (0.034, 0.063) per Z-score TIMP-4, -0.050 (-0.064, -0.037) per Z-score LDL-receptor, -0.051 (-0.062, -0.040) per Z-score 1-OG/2-OG and -0.056 (-0.066, -0.045) per Z-score 1-LG/2-LG. CONCLUSIONS: The branched-chain amino acids and uPA were related to AAA volume. For post-EVAR patients, LDL-receptor, monoacylglycerols and TIMP-4 are potential biomarkers for sac volume. Additionally, distinct markers for sac change were identified.</p

Driving pressure during general anesthesia for open abdominal surgery (DESIGNATION) : study protocol of a randomized clinical trial

Background Intraoperative driving pressure (Delta P) is associated with development of postoperative pulmonary complications (PPC). When tidal volume (V-T) is kept constant, Delta P may change according to positive end-expiratory pressure (PEEP)-induced changes in lung aeration. Delta P may decrease if PEEP leads to a recruitment of collapsed lung tissue but will increase if PEEP mainly causes pulmonary overdistension. This study tests the hypothesis that individualized high PEEP, when compared to fixed low PEEP, protects against PPC in patients undergoing open abdominal surgery. Methods The "Driving prESsure durIng GeNeral AnesThesIa for Open abdomiNal surgery trial" (DESIGNATION) is an international, multicenter, two-group, double-blind randomized clinical superiority trial. A total of 1468 patients will be randomly assigned to one of the two intraoperative ventilation strategies. Investigators screen patients aged >= 18 years and with a body mass index <= 40 kg/m(2), scheduled for open abdominal surgery and at risk for PPC. Patients either receive an intraoperative ventilation strategy with individualized high PEEP with recruitment maneuvers (RM) ("individualized high PEEP") or one in which PEEP of 5 cm H2O without RM is used ("low PEEP"). In the "individualized high PEEP" group, PEEP is set at the level at which Delta P is lowest. In both groups of the trial, V-T is kept at 8 mL/kg predicted body weight. The primary endpoint is the occurrence of PPC, recorded as a collapsed composite of adverse pulmonary events. Discussion DESIGNATION will be the first randomized clinical trial that is adequately powered to compare the effects of individualized high PEEP with RM versus fixed low PEEP without RM on the occurrence of PPC after open abdominal surgery. The results of DESIGNATION will support anesthesiologists in their decisions regarding PEEP settings during open abdominal surgery

Targeted proteomics and metabolomics for biomarker discovery in abdominal aortic aneurysm and post-EVAR sac volume

BACKGROUND AND AIMS: Abdominal aortic aneurysm (AAA) patients undergo uniform surveillance programs both leading up to, and following surgery. Circulating biomarkers could play a pivotal role in individualizing surveillance. We applied a multi-omics approach to identify relevant biomarkers and gain pathophysiological insights. MATERIALS AND METHODS: In this cross-sectional study, 108 AAA patients and 200 post-endovascular aneurysm repair (post-EVAR) patients were separately investigated. We performed partial least squares regression and ingenuity pathway analysis on circulating concentrations of 96 proteins (92 Olink Cardiovascular-III panel, 4 ELISA-assays) and 199 metabolites (measured by LC-TQMS), and their associations with CT-based AAA/sac volume. RESULTS: The median (25th-75th percentile) maximal diameter was 50.0 mm (46.0, 53.0) in the AAA group, and 55.4 mm (45.0, 64.2) in the post-EVAR group. Correcting for clinical characteristics in AAA patients, the aneurysm volume Z-score differed 0.068 (95 %CI: (0.042, 0.093)), 0.066 (0.047, 0.085) and -0.051 (-0.064, -0.038) per Z-score valine, leucine and uPA, respectively. After correcting for clinical characteristics and orthogonalization in the post-EVAR group, the sac volume Z-score differed 0.049 (0.034, 0.063) per Z-score TIMP-4, -0.050 (-0.064, -0.037) per Z-score LDL-receptor, -0.051 (-0.062, -0.040) per Z-score 1-OG/2-OG and -0.056 (-0.066, -0.045) per Z-score 1-LG/2-LG. CONCLUSIONS: The branched-chain amino acids and uPA were related to AAA volume. For post-EVAR patients, LDL-receptor, monoacylglycerols and TIMP-4 are potential biomarkers for sac volume. Additionally, distinct markers for sac change were identified.</p

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)