Elsevier

Resuscitation

Volume 175, June 2022, Pages 6-12
Resuscitation

Clinical paper
Cardiac arrest with successful cardiopulmonary resuscitation and survival induce histologic changes that correlate with survival time and lead to misdiagnosis in sudden arrhythmic death syndrome

https://doi.org/10.1016/j.resuscitation.2022.04.002Get rights and content

Abstract

Background

Sudden arrhythmic death syndrome (SADS), defined as sudden cardiac death (SCD) with a morphologically normal heart, is an important cause of sudden death. Hypoperfusion due to cardiac arrest followed by successful cardiopulmonary resuscitation (CPR) may induce histologic changes that mimic pathologic conditions. Detailed characterisation of such features and whether they could confound SADS diagnosis are not described.

Methods

Retrospective observational study analysing all consecutive cases of sudden death prospectively referred to a UK national cardiac pathology centre between 2017 and 2021. Cases showing hypoperfusion features were identified after review of clinical information and examination by expert cardiac pathologists.

Results

Out of 2,568 SCD cases, 126 (4.9%) were identified with hypoperfusion changes. Macroscopically, the commonest finding was left ventricular focal or diffuse subendocardial haemorrhage (13.5%). Microscopically, haemorrhage and contraction band necrosis (n = 50, 37.7%), subendocardial acute infarction (n = 44, 34.1%), interstitial mixed inflammatory cell infiltrates (n = 31, 24.9%), healing granulation tissue (n = 9, 7.1%) and subendocardial fibrosis (n = 1, 0.7%) were observed. These changes correlated to duration of survival following resuscitation. In a subcohort of 41 cases, autopsy pathologists misinterpreted such changes as ischaemic myocardial infarction (n = 7; 17%), myocarditis (n = 5; 12.1%), or other pathologies (n = 2; 4.8%) in 14 SADS cases.

Conclusion

We provide a comprehensive characterisation of hypoperfusion-related changes in the heart following successful CPR with survival, which are time related. These features can lead to diagnostic confusion among pathologists but knowledge of history of resuscitation with survival should help with general and expert pathology assessment and improve SADS diagnostic yield, prompting genetic screening of decedents’ relatives.

Introduction

Sudden arrhythmic death syndrome (SADS) has emerged as an important cause of sudden cardiac death (SCD), especially among the young, with a prevalence of up to 40% in this setting.[1], [2] SADS is defined as sudden cardiac death with a morphologically normal heart and negative toxicological results.3 Post-mortem examination, including histologic assessment of the heart, is essential to exclude non-cardiac causes of death and to ascertain the absence of pathologic features in the heart, prompting a diagnosis of SADS in the correct clinical context. Importantly, post-mortem diagnosis of SADS subsequently guides clinical decisions pertaining to genetic testing of decedents’ relatives, given that genetic electrical abnormalities that can cause fatal cardiac arrythmias are found in 22% to 53% of asymptomatic family members.[4], [5]

Post-mortem examination of the heart can be challenging for autopsy pathologists. Notably, morphologic findings associated with cardiac arrest and cardiopulmonary resuscitation (CPR) may introduce diagnostic uncertainty in the assessment of cardiac tissue.6 For instance, subendocardial haemorrhage, subendocardial infarction, and contraction band necrosis, previously described in the context of CPR, can mimic histologic features of ischaemic myocardial infarction or other cardiac pathologies.[7], [8] Therefore, failure to recognise such histologic patterns as consequences of cardiac arrest with hypoperfusion followed by successful CPR with survival could undermine the diagnosis of SADS by pathologists.

Although histologic changes have been previously described in the heart following cardiac arrest and survival after resuscitation, such observations were derived from animal studies or small clinical cohorts dating back from the 1960′s to the 1980s.[7], [8], [9], [10] It is unknown how current CPR interventions, recently introduced automated chest compression devices, and longer survival due to more effective CPR affect macroscopic and histologic appearances of the heart.[11], [12] Finally, there are no studies that have investigated whether CPR-related histologic features could confound the diagnosis of SADS in large cohorts of sudden death patients.

This study aimed to (i) describe morphologic patterns of cardiac arrest with successful CPR in the heart; (ii) explore a potential temporal relationship between distinct histologic findings and time from cardiac arrest with CPR to death; and (iii) assess whether such changes could confound the diagnosis of SADS in a large, contemporary cohort of presumed SCD referred to a national cardiac pathology centre.

Section snippets

Study setting

All cases of unexpected death in the United Kingdom are referred to the coroner, who establishes the need for a post-mortem examination. The Cardiac Risk in the Young (CRY) Centre based at St George’s University, London, provides a national expert cardiac pathology service for cases voluntarily referred by coroner’s pathologists when there is unexplained, presumed sudden cardiac death. All referred cases undergo a complete post-mortem examination at the referring centre. Cases are referred

Results

A total of 2,568 consecutive cases referred by more than 100 centres across the UK over the 5-year period were reviewed to identify those with macroscopic and/or microscopic features of hypoperfusion and reperfusion injury following CPR. Such findings were described in a subset of 126 (4.9%) cases among the initial cohort. Cardiac specimens with these changes were referred either as whole hearts (n = 84; 66.6%) or as H&E-stained heart tissue sections (n = 42; 33.4%). The mean age at death was

Discussion

In this study including a large contemporary cohort of sudden death cases, we describe various morphologic changes associated with cardiac arrest and CPR with survival at post-mortem examination of the heart and their relationship to survival time following successful resuscitation. In addition, we show that such features, more often observed in morphologically normal hearts, misled referring pathologists to suspect common cardiac pathologies such as ischaemic heart disease and myocarditis in

CRediT authorship contribution statement

Jose Coelho-Lima: Conceptualization, Data curation, Formal analysis, Methodology, Writing - original draft. Joseph Westaby: Data curation, Methodology, Supervision, Writing - review & editing. Mary N. Sheppard: Conceptualization, Methodology, Funding acquisition, Supervision, Writing - review & editing.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgments

We wish to thank the charity Cardiac Risk in The Young CRY (UK) for funding the Cardiovascular Pathology Department.

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