Sudden cardiac death with stress and restraint: The association with sudden adult death syndrome,cardiomyopathy and coronary artery disease

Introduction

It is well established that there is an association between psychological stress and sudden cardiac death (SCD). Both chronic and acute psychological influences have been found to play a role in rhythmic disturbances. ¹ Sudden death rates increase during a natural disaster, for example an earthquake, a personal tragedy such as the death/funeral of a family member, and during physical restraint, assault/fighting, verbal arguments and being aggressively chased.^2–4

The main substrate for SCD in the older population is coronary artery disease, and the death can be linked to acute psychological stress.^5,6 However, SCD in the young is becoming increasingly recognised and mainly occurs in the absence of coronary artery disease. Genetic cardiac diseases, including channelopathies and cardiomyopathies, are more prevalent in this younger patient population.^7,8 There is also increased risk of sudden death in psychiatric patients and in association with psychotrophic drugs.^9,10 This study sought to establish the associations and causes of SCD under psychological stress in this younger population. One hundred and ten SCD cases occurring under acute psychological stress are presented.

Methods and materials

Results

Discussion

Cardiovascular events are a major cause of morbidity and mortality in the developed world and are mainly due to coronary artery disease. One hundred and ten cases of cardiac causes of SCD associated with psychological stress in a predominantly young cohort are reported. In more than half of cases, SCD presented as a primary event without any previous relevant medical history. It is interesting that the majority of subjects referred were male (87.5%) and young. It has been reported in the literature that males suffer from SDC after a stressful event more frequently than females. ¹³ Similar to other studies, the main emotional stressors precipitating SCD were found to be restraint and altercation.^2–5,14 A recent review of 145,425 custodial deaths over a 65-year period show a significant rise in the number of sudden unexplained deaths associated with the use of restraints. ¹⁵ Restraint, especially in the face-down position, leads to significant reduction in lung function ¹⁶ and can also lead to death with sickle-cell crisis, as reported in one of our cases. ¹⁷ Determining the cause of death when a restrained person suddenly dies is a problem for death investigators. Common elements in this syndrome include prone restraint with pressure on the upper torso; handcuffing, leg restraint or hogtying; acute psychosis and agitation, often stimulant drug induced; or physical exertion, struggle and obesity. Establishing a temporal association between the restraint and the sudden death is critical. ¹⁸

The majority of our cases had a morphologically normal heart, indicating sudden adult death syndrome (SADS) with the likelihood of death being precipitated by an electrical disturbance as in the channelopathies. ¹⁹ Increased activity of the hypothalamic-pituitary-adrenal axis is thought to lead to catecholamine hypersecretion and intense activation of the adrenergic receptors throughout the cardiovascular system which may provoke malignant ventricular arrhythmias and SCD in people with normal hearts, with a higher risk if there is a predisposing susceptibility to ventricular arrhythmias e.g. the genetic ion channelopathies and/or acquired drug-induced QT prolongation. It is plausible that the genetic channelopathies, including Brugada syndrome, short QT syndrome, long QT syndrome, catecholaminergic polymorphic ventricular tachycardia (CPVT) syndromes, or acquired long QT for example with use of antipsychotic drugs, may predispose individuals with structurally normal hearts to SCD in the setting of emotional stress^20,21 and to stress (Takotsubo) cardiomyopathy. ²² It is estimated that at least 20% of episodes of ventricular arrhythmias of SCD are precipitated by emotional stress.^5,23,24 Twenty per cent of cases in the current study had a psychiatric history and were on psychotropic drugs, and it is well established that such patients have a higher incidence of sudden death. ¹⁰ A proportion of cases also had a positive non-fatal toxicology or a history of taking antipsychotic medication and alcohol use. The pro-arrhythmic effects of alcohol and antipsychotic medication are well described.^25,26 Psychiatric patients have been reported to be five times as likely to experience sudden unexpected death as individuals from the general population, and recent reports indicate that exposure to antipsychotic drugs further exacerbate this risk even at low doses. ²⁷ The cardiac side effects include prolongation of the QT interval, causing ventricular arrhythmias or torsades de pointes, both often leading to SCD. ²⁸ Furthermore, as the neurobiological basis of many psychiatric conditions becomes elucidated, the potential for protein mutations to predispose to both neurological disease and cardiac arrhythmia becomes increasingly plausible, with some evidence emerging in animal models. ²⁹

The connection between the heart and the brain has long been recognised. Cardiac arrhythmias, especially ventricular arrhythmias, can be incited by psychological effects. In a setting of personal danger, or when there is a perceived threat of injury, high adrenaline surges are a physiological response, and an individual can be ‘scared to death’ or ‘die of fright’. ¹⁴ It is possible that SCD resulting from either stress or through exertion in sport share common pathophysiology, and insights from the catecholaminergic polymorphic ventricular tachycardia (CPVT) syndrome demonstrate the importance of catecholamines in potentially triggering ventricular tachycardia and ventricular fibrillation in patients with a vulnerable substrate resulting from ryanodine receptor mutations. ¹⁷

Stress cardiomyopathy (SCM), also known as Takotsubo cardiomyopathy, has been proposed as an underlying aetiology of SCD with stress.^18,19 SCM is characterised by transient apical ballooning and acute heart failure in the absence of coronary artery disease, and it is believed to be a form of acute catecholamine-induced myocardial stunning.^20,21 SCM is more common in females, and full recovery occurs in most cases, but sudden death can occur, with an in-hospital mortality rate during the acute phase of 2% with malignant ventricular arrhythmias. ²² Several mechanisms have been proposed: catecholamine myocardial damage, microvascular spasm or neural mediated myocardial stunning. ³⁰ There was one case in this study of idiopathic acute infarction causing sudden death in the presence of normal coronary arteries which may be due to coronary spasm and can be part of the lethal spectrum of stress cardiomyopathy. ³¹

The present study also links SCD with stress to structural cardiomyopathy, particularly LVH which is a similar finding to SCD during exercise/exertion. ³² It is plausible that marked LVH predisposes to stress-related fatal ventricular arrhythmias. SCD with exertion/sport may share a common pathological mechanism to SCD secondary to sympathetic nerve activation and catecholamine surges.^33–35

A number of epidemiological studies have suggested that ‘stress may be an etiological factor in the development of coronary artery disease and myocardial infarction’. ³⁶ Acute episodes of psychological stress raise blood pressure and increase platelet aggregation.^11,12 Sympatho-adrenal activation elevates myocardial work demand, which results in ischemia. ³⁶ These changes have the potential to rupture vulnerable plaque and precipitate intraluminal thrombosis, resulting in infarction. Myocardial bridging of the LAD was identified in two subjects who were also assaulted with blows to the chest, raising the possibility of commotio cordis. ⁶ There is also a high risk of sudden death as a complication of anomalous coronary artery during or immediately after exertion. ³⁷ Aortic dissection, of which there was one case in the present study, is also linked to stress. ³⁸

Medico-legal autopsies are essential for the recognition and correct investigation of SCD under stress, particularly when the causes are suspected to be of cardiac genetic origin, that is, channelopathies and cardiomyopathies. An early diagnosis through clinical screening and genetic testing would be especially important to help affected first-degree relatives who may also be at risk of SCD. ⁸

Case law holds that if the sudden psychological stress is caused by criminal conduct, the resulting death of a victim of the criminal conduct can be prosecuted as homicide. Pathologists, psychiatrists and cardiologists are often called to testify in such circumstances, ¹⁴ especially those involving the police or mental-health workers. It is important to raise awareness in law-enforcement agencies and mental-health facilities as well as the public in general of the greater susceptibility for SCD in individuals harbouring cardiac disease (inherited or acquired) and where restraint, significant exertion and mental distress can contribute to their death. Several studies, including the current one, postulate that the mechanism of sudden death under stress may be multifactorial, resulting from a cascade of predisposing risk factors, including underlying cardiac disease, obesity, mental health, alcohol and/or drug use as well as physical exertion. ³⁹

A thorough autopsy with toxicology is therefore critical to establish the correct cause of death and, when applicable, the acquittal of police or medical/psychiatric staff from any wrongdoing. In the UK, SCD in such scenarios has led to controversial outcomes, ⁴⁰ and the use of expert cardiac pathology in these high-profile cases is increasing. ⁴¹