Demographic, clinical and pathological features of sudden deaths due to myocarditis: Results from a state-wide population-based autopsy study

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Highlights

  • Sudden deaths from myocarditis are studied over a 10-year period.

  • Demographic, clinical and pathological features are analyzed.

  • The incidence of fatal myocarditis is 0.70% of autopsied sudden deaths.

  • In 17.5% cases, no significant myocyte necrosis is identified.

  • Determination of myocarditis as cause of death remains a challenge to pathologist.

Abstract

Causes of sudden cardiac deaths have been widely reported with limited data focused specifically on myocarditis. A retrospective review of cases from the Office of the Chief Medical Examiner (OCME), State of Maryland yielded a total of 103 sudden unexpected deaths (SUDs) due to myocarditis (0.17% of all SUDs and 0.70% of autopsied SUDs) from 2005 through 2014. Most deaths occurred in patients <30 years of age with a male:female ratio 1.3:1. Of the 103 cases, 45 (43.7%) patients were witnessed collapsed. Four deaths occurred during exertion, such as exercising at the gym or performing heavy physical work, and 2 deaths were associated with emotional stress. The common cardiac macroscopic findings included ventricular dilatation (39.8%), mild coronary stenosis (17.5%), mottled myocardial appearance (15.5%), and myocardial fibrosis (10.7%). The histological classification of myocarditis was based on the predominant type of inflammatory cell infiltration. In our study group, lymphocytic myocarditis was most common, accounting for 56 cases (54.4%), followed by neutrophilic (32 cases, 31.7%), eosinophilic (13 cases, 12.6%) and giant cell type (2 cases, 1.9%). Microscopic examination revealed myocyte necrosis in 69 cases (67.0%) and interstitial or perivascular fibrosis in 48 cases (46.6%). The percentage of myocyte necrosis was 75.0% (42/58 cases) in lymphocytic, 65.6% (21/31 cases) in neutrophilic, 30.8% (4/13 cases) in eosinophilic, and 100% (2/2 cases) in giant cell myocarditis. Determination of myocarditis as cause of death continues to present a major challenge to forensic pathologists, because histopathologic findings can be subtle and the diagnosis of myocarditis remains difficult.

Introduction

Myocarditis is an inflammatory disease of the heart that can cause sudden and unexpected death in otherwise healthy individuals. A population-based study in reported that the death certificate-based incidence of fatal myocarditis was 0.46 per 100.000 person-years and that myocarditis was recorded to cause 0.47 of in all deaths was 0.47 of 1000 deaths in the general Finland population from 1970 to 1998 [1]. A review of all deaths from Tokyo from 1958 to 1984 reported that myocarditis was the cause of death in 0.15% of autopsy cases [2]. In a 1996 study from France, 0.8% of sudden deaths was caused by myocarditis [3], and another study in the Southern Ontario between 1969 and 1978 indicated that 2.7% of sudden deaths was caused by viral myocarditis [4]. It has been reported that the incidence of myocarditis in sudden cardiac death was much higher in younger age groups (less than 35 years), with 12% of sudden cardiac deaths attributed to myocarditis in young Australians [5] and 34.7% in a Chinese autopsy case study [6].

Myocarditis has been considered a common cause of dilated cardiomyopathy (DCM), which is defined by the presence of ventricular dilatation and ventricular systolic dysfunction [7], [8]; however, the mechanism of myocarditis progression to DCM remains to be elucidated. In the forensic autopsy, ventricular dilatation is common in deaths due to myocarditis, especially in subacute and chronic myocarditis [2]. Identification of the association between myocarditis and DCM could contribute to a better understanding of the pathophysiology of myocarditis and its progression to DCM.

Various degrees of certainty exist in defining the cause of a sudden death event [6]. Davies first introduced using probability in determining whether a pathologic finding might account for sudden death by describing coronary artery lesions in 1999 [9]. A grading method for the certainty of diagnosis in sudden cardiac deaths was suggested by a European guideline in 2008 [10] and modified by other researchers in 2014 [6]. In the grading methods, the degree of certainty of diagnosis is classified as certain, highly probable and uncertain, and in the setting of probable and uncertain categories, further consideration of other pathologic findings is needed.

Despite wide reports of the incidence of myocarditis and grading certainty in sudden unexpected death, no recent study has focused specifically on myocarditis. There are limited available data covering death scene investigation findings and certification of myocarditis as direct cause of death [11]. To our best knowledge, a systemic study of myocarditis as cause of death in forensic autopsy population has not been reported in the recent literature. This study aimed to provide updated statistical data of the incidence of myocarditis, to consider certainty of diagnosis of myocarditis as cause of death, and to better understand potential risk factors for progression of myocarditis to DCM in a state-wide medical examiner system in the United States.

Section snippets

Setting

The State of Maryland consists of 23 counties and a Baltimore city, with a population of 5,773,552 according to the 2014 U.S. Census. The Office of the Chief Medical Examiner (OCME) is a state-wide medical examiner system that is responsible for conducting death investigations and certifying the cause and manner of all non-natural deaths, including homicides, suicides, accidents, and deaths that are sudden unexpected in the State of Maryland. The autopsy procedures/protocols at the OCME have

Epidemiological profile

The Office of Medical Examiner (OCME) is responsible for medico-legal investigation of all sudden unexpected deaths (SUDs) in the State of Maryland. Between January 1, 2005 and December 31, 2014, a total of 62,130 SUDs were investigated by the OCME in Maryland. Of the 62,130 SUDs, 14,733 cases were autopsied (23.7%). The cause of death was certified as myocarditis in 103 cases, which was 0.17% of the total SUDs and 0.70% of the autopsied SUDs. Most of the cases were reported in 2005 (total 22

Discussion

Although myocarditis is usually a mild disease with a favorable outcome, it may sometimes cause sudden death. The incidence of death due to myocarditis has been previously reported in a range from 0.047 to 34.7%, with younger patients disproportionately represented among all the deaths [1], [2], [3], [4], [5]. In the USA, the incidence of myocarditis in forensic autopsy population was 0.6% in the State of Indiana from 1987 to 1991 [14]. In Wayne County, the State of Michigan, the incidence was

Acknowledgments

The authors want to thank Dr. Jennifer Bynum from Johns Hopkins Pathology Department for her assistance in manuscript preparation. This study was in part supported by the Key Projects of National Natural Science Foundation of China (No. 81430047) and the China Postdoctoral Science Foundation (No. 2016M601507). Dr. Liliang Li acknowledges the financial support from the State Scholarship Fund of China Scholarship Council (No.: 201306100058) for his visit to the University of Maryland School of

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