An autopsy case of sudden unexpected death of a young adult with progressive intraventricular conduction delay

ElsevierVolume 240, December 2022, 154226Pathology - Research and PracticeAuthor links open overlay panelAbstract

Herein, we describe an autopsy case of the sudden unexpected death of a 23-year-old man. Retrospective analysis of electrocardiograms revealed progressive widening of the QRS interval. Autopsy showed mild mitral valve prolapse and hypertrabeculation of the left ventricle. Microscopic examination revealed very scarce but considerable minimal myocardial necrotic foci in the left ventricle, and a marked reduction in conduction fibers in the left branch. These findings may be associated with intraventricular conduction delay. Genetic investigation revealed four rare possibly pathogenic variants, including the Emery-Dreifuss muscular dystrophy-associated genetic variant SYNE2_p.A6155 V that is evaluated as pathogenic by most in silico predictive tools. The other possibly pathogenic variants detected were PLEC_p.P973L, TTN_p.I22171T, and p.A12216T. Although these variants are reported to have uncertain significance in the guidelines of the American College of Medical Genetics and Genomics, progressive conduction delay may have been associated with vulnerability of myocytes due to Emery-Dreifuss muscular dystrophy-associated genetic variants in the present case. Younger individuals with progressive conduction delay may require medical work-up and genetic investigation, even if they have no other clinical signs and no or mild structural heart disease.

Introduction

A prolonged or wide QRS interval, defined as ≥ 120 ms on a 12-lead electrocardiogram (ECG), is a manifestation of intraventricular conduction delay or block [1]. Increased QRS duration has been associated with arrhythmogenic death in ischemic heart disease [2], cardiomyopathy [1], and Brugada syndrome [3]. Recent investigations have also showed that prolonged QRS duration is associated with an increased risk of sudden cardiac death in the general population without significant cardiac disease [4], [5]. The duration of the QRS complex reflects impulse propagation and myocardial activation. Therefore, changes in the QRS interval may be associated with cardiac structural abnormalities or functional electrophysiological abnormalities. However, the pathological substrate of the heart that is associated with a prolonged QRS interval has not been fully clarified [4], [5].

Herein, we described the pathological and genetic findings of a young adult who died suddenly and had progressive intraventricular conduction delay found on retrospective temporal investigation of 12-lead ECGs. Written consent was obtained from the next of kin. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Section snippetsCase

A 23-year-old man was found dead in the bedroom. Resuscitation was not successful. He had no history of heart or other disease; however, he had visited a hospital for chest pain, a small amount of brady sputum and respiratory discomfort 2 years before his death. He was admitted and underwent a careful whole-body examination, but no pathological condition requiring therapy was found.

Pathological findings

At autopsy, no traumatic injury was found, and toxicological investigation was negative. The heart weighed 350 g.

Discussion

Tikkanen et al. showed that a prolonged QRS duration is significantly related to the risk of sudden cardiac death [4]. Furthermore, a study of 9511 middle-aged individuals without known cardiac disease showed that a QRS duration ≥ 110 ms on ECG is a significant independent risk marker [5]. Therefore, younger individuals with intraventricular conduction delay may require careful examination, even if they do not have clinical symptoms or evidence of significant structural heart disease. This is

CRediT authorship contribution statement

Yukiko Hata: Conceptualization, Funding acquisition, Investigation, Data calculation, Writing – original draft. Ryotaro Hachiwaka: Data curation, Validation. Shojiro Ichomata: Data curation, Investigation, Validation, Visualization. Yoshiaki Yamaguchi: Data curation, Investigation, Validation, Visualization. Naoki Nishida: Conceptualization, Data curation, Investigation, Methodology, Visualization, Writing – review & editing.

Declarations of interest

None.

Acknowledgments

This work was supported in part by the JSPS KAKENHI (grant number JP21H03211 to Y.H.). The authors thank Syuko Matsumori, Miyuki Maekawa, Misa Kusaba, and Osamu Yamamoto for their technical assistance. We thank Kelly Zammit, BVSc, from Edanz (https://jp.edanz.com/ac) for editing a draft of this manuscript.

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