Leukocytes and Cardiovascular Perioperative Events-2 (LeukoCAPE-2)

Assoziationen Von Leukozyten-Sub-Populationen im Blut kardiovaskulärer Risikopatienten Mit Der Inzidenz Perioperativer kardiovaskulärer Ereignisse

The potential use of regulatory T cells as preoperative risk stratification tool is evaluated in order to improve clinical risk stratification and reduce perioperative morbidity and mortality.

Study Overview

• Status: Completed
• Conditions: Elective Non-cardiac Surgery

Detailed Description

Annually, there are more than 200 million surgeries worldwide. The POISE study revealed 5% of patients undergoing a non-cardiac surgery suffer perioperative myocardial infarcts going along with a perioperative mortality rate of about 11,6%. Possibilities to preoperatively identify patients at risk are limited and prophylactic interventions are not yet established or controversial.

Selected leukocyte subpopulations have been demonstrated to be associated with higher risk for cardiovascular events.

The aim of this study is to evaluate the potential use of regulatory T cells as preoperative risk stratification tool in order to improve clinical risk stratification and reduce perioperative morbidity and mortality. Therefore, high-risk cardiovascular patients scheduled for major non-cardiac surgery will be recruited. Blood will be drawn at predefined time points before surgery and up to three days postoperatively. Leukocytes will be analyzed by flow cytometry. During 30 day follow up adverse cardiovascular events will be recorded. ECGs will be recorded preoperatively and on post-OP day 3. High-sensitive cardiac Troponin T will be measured prior to the operation and on post-OP day one to three. The patient chart will be screened for cardiovascular events up to day 30. A telephone interview will be performed to detect cardiovascular events after discharge until post-OP day 30.

• Study Type: Observational
• Enrollment (Actual): 233

Contacts and Locations

Study Locations

• Germany
  • Baden-Württemberg
    • Heidelberg, Baden-Württemberg, Germany, 69120
      • Department of Anaesthesiology, University Hospital Heidelberg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients admitted to University Hospital Heidelberg suffering coronary heart disease and scheduled for major non-cardiac surgery

Description

Inclusion Criteria:

• 18 years or older
• Coronary heart disease
• Non-cardiac surgery
• Inpatient treatment
• Informed consent

Exclusion Criteria:

• 17 years of age or younger
• Known pregnancy or breastfeeding
• Missing informed consent
• Ambulatory or day-case surgery
• Emergency surgery
• Acute or chronic leukemia
• Current aplasia or leukopenia
• Current GM-CSF treatment
• Carotid artery surgery
• History of splenectomy
• Current intravenous or oral Cortisone treatment
• History of organ transplantation
• Current immunosuppressive medication
• Chemotherapy completed less than 14 days ago
• Entity which is part of the composite endpoint diagnosed within past 28 days

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiovascular Events	Number of participants with Cardiovascular Events defined as occurrence of Cardiac Death and/or Myocardial Ischemia and/or Myocardial Infarction and/or Myocardial Injury After Non-cardiac Surgery (MINS) and/or Embolic Stroke and/or Thrombotic Stroke recorded until postoperative day 30. Definitions according to European Perioperative Clinical Outcome-(EPCO) definitions detected at postoperative visits, documented in patient chart or detected during telephone interview after 30 postoperative days	30 days postoperative

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peripheral vascular occlusion	Diagnosed by a radiologist based on the results of duplex ultrasonography, angiography or CT-angiography.	30 days postoperative
New onset atrial fibrillation	Number of participants with new electrocardiographic detection of atrial fibrillation in postoperative ECG and/or documented in patient charts	30 days postoperative
Acute kidney injury	Number of participants with acute kidney injury according to KDIGO guidelines	30 days postoperative
Congestive heart failure	Number of participants with congestive heart failure according to European Perioperative Clinical Outcome (EPCO) definitions	30 days postoperative
Cardiac death	Number of participants with cardiac Death defined as death because of new myocardial infarction or ischemia, or atrial or ventricular arrhythmias, or cardiogenic pulmonary edema, or pulmonary embolism detected at postoperative visits, documented in patient chart or detected during telephone interview after 30 postoperative days	30 days postoperative
Myocardial Ischemia	Number of participants with myocardial ischemia defined as new electrocardiographic detection of myocardial ischemia in ECG and/or documented in patient charts which will be screened up to 30 postoperative days and/or detected during telephone interview after 30 postoperative days	30 days postoperative
Myocardial Infarction	Number of participants with Myocardial Infarction defined as an increase in serum cardiac biomarker values in combination with symptoms of ischemia or new/presumed new significant ST segment or T wave ECG changes or new left bundle branch block or development of pathological Q waves on ECG. Definition according to European Perioperative Clinical Outcome-(EPCO) definitions detected at postoperative visits, postoperative blood analyses, documented in patient chart or detected during telephone interview after 30 postoperative days	30 days postoperative
Myocardial Injury after Non-cardiac Surgery (MINS)	Number of participants with MINS defined as raise in postoperative hs-cTNT (high sensitivity cardiac troponin T) jugded due to myocardial ischemia detected at postoperative visits, documented in patient chart or detected during telephone interview after 30 postoperative days	30 days postoperative
Stroke	Number of participants with embolic or thrombotic stroke defined cerebral event with persistent residual motor, sensory or cognitive dysfunction detected at postoperative visits, documented in patient chart or detected during telephone interview after 30 postoperative days	30 days postoperative

Collaborators and Investigators

• Sponsor: University Hospital Heidelberg

Publications and helpful links

General Publications

• Rogacev KS, Cremers B, Zawada AM, Seiler S, Binder N, Ege P, Grosse-Dunker G, Heisel I, Hornof F, Jeken J, Rebling NM, Ulrich C, Scheller B, Bohm M, Fliser D, Heine GH. CD14++CD16+ monocytes independently predict cardiovascular events: a cohort study of 951 patients referred for elective coronary angiography. J Am Coll Cardiol. 2012 Oct 16;60(16):1512-20. doi: 10.1016/j.jacc.2012.07.019. Epub 2012 Sep 19.
• Berg KE, Ljungcrantz I, Andersson L, Bryngelsson C, Hedblad B, Fredrikson GN, Nilsson J, Bjorkbacka H. Elevated CD14++CD16- monocytes predict cardiovascular events. Circ Cardiovasc Genet. 2012 Feb 1;5(1):122-31. doi: 10.1161/CIRCGENETICS.111.960385. Epub 2012 Jan 11.
• Devereaux PJ, Xavier D, Pogue J, Guyatt G, Sigamani A, Garutti I, Leslie K, Rao-Melacini P, Chrolavicius S, Yang H, Macdonald C, Avezum A, Lanthier L, Hu W, Yusuf S; POISE (PeriOperative ISchemic Evaluation) Investigators. Characteristics and short-term prognosis of perioperative myocardial infarction in patients undergoing noncardiac surgery: a cohort study. Ann Intern Med. 2011 Apr 19;154(8):523-8. doi: 10.7326/0003-4819-154-8-201104190-00003.
• Devereaux PJ, Sessler DI. Cardiac Complications in Patients Undergoing Major Noncardiac Surgery. N Engl J Med. 2015 Dec 3;373(23):2258-69. doi: 10.1056/NEJMra1502824. No abstract available.
• Engelbertsen D, Andersson L, Ljungcrantz I, Wigren M, Hedblad B, Nilsson J, Bjorkbacka H. T-helper 2 immunity is associated with reduced risk of myocardial infarction and stroke. Arterioscler Thromb Vasc Biol. 2013 Mar;33(3):637-44. doi: 10.1161/ATVBAHA.112.300871. Epub 2013 Jan 10.
• Gillmann HJ, Meinders A, Grohennig A, Larmann J, Bunte C, Calmer S, Sahlmann B, Rustum S, Aper T, Lichtinghagen R, Koch A, Teebken OE, Theilmeier G. Perioperative levels and changes of high-sensitivity troponin T are associated with cardiovascular events in vascular surgery patients. Crit Care Med. 2014 Jun;42(6):1498-506. doi: 10.1097/CCM.0000000000000249.
• Kotfis K, Biernawska J, Zegan-Baranska M, Zukowski M. Peripheral Blood Lymphocyte Subsets (CD4+, CD8+ T Cells, NK Cells) in Patients with Cardiovascular and Neurological Complications after Carotid Endarterectomy. Int J Mol Sci. 2015 May 4;16(5):10077-94. doi: 10.3390/ijms160510077.
• Rogacev KS, Seiler S, Zawada AM, Reichart B, Herath E, Roth D, Ulrich C, Fliser D, Heine GH. CD14++CD16+ monocytes and cardiovascular outcome in patients with chronic kidney disease. Eur Heart J. 2011 Jan;32(1):84-92. doi: 10.1093/eurheartj/ehq371. Epub 2010 Oct 12.
• Weiser TG, Regenbogen SE, Thompson KD, Haynes AB, Lipsitz SR, Berry WR, Gawande AA. An estimation of the global volume of surgery: a modelling strategy based on available data. Lancet. 2008 Jul 12;372(9633):139-144. doi: 10.1016/S0140-6736(08)60878-8. Epub 2008 Jun 24.
• Weiser TG, Haynes AB, Molina G, Lipsitz SR, Esquivel MM, Uribe-Leitz T, Fu R, Azad T, Chao TE, Berry WR, Gawande AA. Size and distribution of the global volume of surgery in 2012. Bull World Health Organ. 2016 Mar 1;94(3):201-209F. doi: 10.2471/BLT.15.159293.
• Handke J, Scholz AS, Dehne S, Krisam J, Gillmann HJ, Janssen H, Arens C, Espeter F, Uhle F, Motsch J, Weigand MA, Larmann J. Presepsin for pre-operative prediction of major adverse cardiovascular events in coronary heart disease patients undergoing noncardiac surgery: Post hoc analysis of the Leukocytes and Cardiovascular Peri-operative Events-2 (LeukoCAPE-2) Study. Eur J Anaesthesiol. 2020 Oct;37(10):908-919. doi: 10.1097/EJA.0000000000001243.

Study record dates

Study Major Dates

• Study Start (Actual): April 10, 2017
• Primary Completion (Actual): January 5, 2018
• Study Completion (Actual): January 5, 2018

Study Registration Dates

• First Submitted: March 8, 2017
• First Submitted That Met QC Criteria: April 3, 2017
• First Posted (Actual): April 10, 2017

Study Record Updates

• Last Update Posted (Actual): January 30, 2018
• Last Update Submitted That Met QC Criteria: January 29, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Other Study ID Numbers: LeukoCAPE02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No