Patient- and procedure-related factors in the pathophysiology of perioperative myocardial infarction/injury

https://doi.org/10.1016/j.ijcard.2022.01.015Get rights and content

Highlights

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    Perioperative myocardial infarction/injury (PMI) detected by cardiac troponin is a frequent complication of noncardiac surgery.

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    Procedural factors are more strongly associated with occurrence of PMI than patient factors in contrast to spontaneous AMI.

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    Repeated PMI increased 1-year mortality considerably. Mortality was particularly high in the first weeks after surgery.

Abstract

Background

Perioperative myocardial infarction/injury (PMI) is a frequent, often missed and incompletely understood complication of noncardiac surgery. The aim of this study was to evaluate whether patient- or procedure-related factors are more strongly associated to the development of PMI in patients undergoing repeated noncardiac surgery.

Methods

In this prospective observational study, patient- and procedure-related factors were evaluated for contribution to PMI using: 1) logistic regression modelling with PMI as primary endpoint, 2) evaluation of concordance of PMI occurrence in the first and the second noncardiac surgery (surgery 1 and 2). and 3) the correlation of the extent of cardiomyocyte injury quantified by high-sensitivity cardiac troponin T between surgery 1 and 2. The secondary endpoint was all-cause mortality associated with PMI reoccurrence in surgery 2.

Results

Among 784 patients undergoing repeated noncardiac surgery (in total 1′923 surgical procedures), 116 patients (14.8%) experienced PMI during surgery 1. Among these, PMI occurred again in surgery 2 in 35/116 (30.2%) patients. However, the vast majority of patients developing PMI during surgery 2 (96/131, 73.3%) had not developed PMI during surgery 1 (phi-coefficient 0.150, p < 0.001). The correlation between the extent of cardiomyocyte injury occurring during surgery 1 and 2 was 0.153. All-cause mortality following a second PMI in surgery 2 was dependent on time since surgery (adjusted hazard ratio 5.6 within 30 days and 2.4 within 360 days).

Conclusions

In high-risk patients, procedural factors are more strongly associated with occurrence of PMI than patient factors, but patient factors are also contributors to the occurrence of PMI.

Introduction

More than 300 million surgeries are performed worldwide every year [1]. Despite improvements in surgical techniques and anesthesia, the rate of in-hospital and 30-day mortality following noncardiac surgery remains much higher than anticipated by patients and physicians [2], [3], [4], [5]. Perioperative myocardial infarction/injury (PMI) has recently been identified as a contributor to a substantial number of these deaths [2], [3], [4], [5]. As ~90% of patients with PMI do not experience typical symptoms, mainly due to anesthesia and analgesia, these critical events are commonly missed in routine clinical practice without systematic PMI-screening [2], [6], [7]. Accordingly, little is known about the predominant pathophysiology underlying PMI [8], [9], [10]. Both patient-related factors including cardiovascular comorbidities, e.g. coronary artery disease (CAD), and procedure-related factors including the length of the operation or perioperative hypotension seem to play a role [11], [12]. However, the relative importance of patient-related and procedure-related factors has not been previously investigated. Knowledge of this would be of utmost importance to prioritize measures for PMI prevention.

In order to address this major unmet clinical need, we used patients undergoing repeated surgeries as an in-vivo model to test the hypothesis that patient-related factors (cardiovascular comorbidities) - and not procedure-related factors - are more strongly associated with the development of PMI among high-risk patients undergoing noncardiac surgery. If patient-related factors were dominant, most patients developing PMI during the first surgery (surgery 1) should more likely develop PMI during the second surgery (surgery 2), while most patients not developing PMI during surgery 1 should also not develop PMI during surgery 2 (high concordance). Similarly, using the perioperative cardiac troponin (cTn) increase as a measure for the extent of cardiomyocyte injury, the cTn increase in surgery 1 should correlate with the cTn increase in surgery 2 [13]. Further, multivariable modelling shall compare the factors within one model.

Section snippets

Study design and patients

This post-hoc analysis is based on the BASEL-PMI study, an ongoing prospective observational study implementing PMI screening into routine clinical practice in high-risk patients undergoing noncardiac surgery at the University Hospital Basel and the Cantonal Hospital Aarau, Switzerland [2], [14], [15]. The protocol was approved by the local ethics committee (EKNZ 2015/301) and registered (https://www.clinicaltrials.gov/NCT02573532). This report is in accordance with the STROBE guidelines for

Results

Overall, 784 patients undergoing a total of 1′923 surgeries were eligible for this analysis (Flow chart, Supplement Fig. 1).

Discussion

In order to advance the understanding of the pathophysiology of PMI, we used high-risk patients undergoing repeated noncardiac surgery in a prospective multicenter PMI screening study to test whether patient-related factors, especially cardiovascular comorbidities or procedure-related factors were more strongly associated with the perioperative development of PMI. To the best of our knowledge, this is the first study addressing this major uncertainty. We report four major findings.

First, in

Conclusion

In high-risk patients undergoing inpatient non-cardiac surgery, procedural factors are more strongly associated with occurrence of PMI than patient factors, but patient factors are also contributors to the occurrence of PMI. Recurrent PMI substantially increased mortality, particularly in the first weeks after surgery 2.

Contributors

Dr. Gueckel, Dr. Puelacher and Prof. Mueller contributed to design and conduct of the study, analyzed and interpreted the data, wrote the manuscript, and had final responsibility in the decision to submit for publication. Dr. Gueckel and Dr. Puelacher performed literature review and created the figures. Dr. Gueckel, Dr. Puelacher and Prof. Mueller had full access to the data. All authors contributed to data collection, provided critical feedback at various stages of the manuscript, approved the

Funding

This study was funded by the University Basel, the University Hospital Basel, the Swiss Heart Foundation, the Swiss National Science Foundation, Roche Diagnostics, Abbott, Astra Zeneca, the PhD Educational Platform for Health Sciences, the “Forschungsfond Kantonsspital Aarau”, and the Cardiovascular Research Foundation Basel.

The funders had no role in the design, data collection, statistical analysis, writing of this manuscript, or decision to publish.

Disclaimer

The study funders had no role in the study design, collection, analysis, and interpretation of data or report writing. The first authors, corresponding author and last author had full access to the data and the final responsibility to submit for publication.

Ethics approval

This study was approved by the local ethics committee (EKNZ 2015/301) and registered (https://www.clinicaltrials.gov/NCT02573532).

Declaration of Competing Interest

Dr. Puelacher reports grants from the Swiss Heart Foundation, Roche Diagnostics and the University Hospital Basel during the conduct of the study.

Dr. Gualandro reports grants for FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo, Brasil) and consulting fees from Servier and Roche, outside the submitted work.

Dr. Zimmermann reports a research grant from the Freiwillige Akademische Gesellschaft Basel outside of this work.

Dr. Arslani has received a research grant from the Swiss Academy

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