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

Henrike Janssen,Gregor Theilmeier,Laura Kummer,Omke E Teebken,Claudia Schrimpf,Jan Larmann,Markus A Weigand,Bianca Sahlmann,Saad Rustum,Ralf Lichtinghagen,Larissa Felgner,Hans-Jörg Gillmann

doi:10.3389/fcvm.2020.00013

Abstract

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.

Highlights

Patients at elevated risk for cardiovascular complications are prone to perioperative adverse cardiac events, such as myocardial injury after non-cardiac surgery (MINS) [1] and face higher perioperative mortality [1,2,3,4]
We demonstrate that surgery is associated with cardiac complications in subsequent surgical procedures, and we provide descriptive evidence for the hypothesis that enhanced plaque vulnerability might be related to MINS
In the subgroup of patients with other surgeries, one patient was diagnosed with MINS after the first procedure and four after the second (Figure 5C). In this post-hoc analysis we demonstrate that in our cohort of patients at elevated cardiovascular risk undergoing vascular surgery, reoperation was associated with an increased MINS incidence

Summary

Introduction

Patients at elevated risk for cardiovascular complications are prone to perioperative adverse cardiac events, such as myocardial injury after non-cardiac surgery (MINS) [1] and face higher perioperative mortality [1,2,3,4]. Atherosclerosis and its complications are driven by systemic inflammation [5], the mechanisms underlying perioperative cardiovascular complications are not fully understood [6, 7]. Released IL-6 might have an important role in human plaque fissuring [10]. Unstable atherosclerotic lesions are prone to the development of plaque fissures and rupture [11, 12]. Plaque fissures and ruptures are among the mechanisms underlying MINS [7]. About 25% of patients with perioperative acute coronary synrome show signs of coronary plaque rupture [13]

Methods

Results

Conclusion