Graphical Abstract: Loss of a child and incident atrial fibrillation.
Bereavement following the loss of a child is among the most extreme sources of stress that a family can face. A major adverse life event of this kind, and the stress associated with it, has a profound impact on an individual, with direct measurable psychological and physiological effects. Loss of a child places the parents at risk of experiencing more chronic, prolonged stress, complicated grief, and mental health disorders, including depression.[2,3] Associations between bereavement and adverse health outcomes following the loss of a loved one have been documented for various outcomes, including death, acute myocardial infarction, and stroke, especially in the first week following the loss.[4–6] A more transient risk of incident atrial fibrillation has been previously documented as well, but most of this previous work has focused on spousal bereavement. Several studies have examined the association between sources of stress other than bereavement, and incidence of atrial fibrillation, but mixed findings have been noted. Loss of a child is an extreme stressor and a more rare experience, as compared with loss of a spouse or other major life event, and, as such, it is harder to study health effects in the absence of a large and comprehensive database.
Wei and colleagues, in their study published in this issue of the European Heart Journal, used such a large, national database—the Swedish Medical Birth Register—from which they were able to derive a cohort of parents with children born between 1973 and 2014. The completeness of the dataset and the linkage across birth registers and health claims data at the national level uniquely allowed the researchers to study the association between bereavement following child loss in parents and a future diagnosis of atrial fibrillation. A validated definition based on codes in the International Classification of Diseases 8th–10th revisions (ICD 8–10) was used to identify atrial fibrillation, demonstrating another strength of this study. A cohort as large as 3 924 237 individuals was identified, with medical events followed from the time of the child's birth. Within this cohort, 1.7% (n = 64 628) of the parents experienced loss of a child during the period of observation. Incident atrial fibrillation occurred in 95 188 of the parents during follow-up, with an ~15% increased risk of incident atrial fibrillation amongst parents who experienced child loss vs. those who did not. The highest risk was observed in the first week after the loss, consistent with previous literature on adverse health outcomes in the setting of bereavement. Also in line with previous work was the finding of greater adverse health risk among mothers vs. fathers. While the research team identified an increased risk for the association with loss of one child, no association was found for the association between having lost two or more children and atrial fibrillation risk. Loss of multiple children is a rare event and, as such, with fewer observations, quantifying effects on health outcomes for surviving parents in observational studies becomes much more challenging. Thus, other study designs, such as qualitative designs or case studies, may be more informative for capturing health consequences for survivors.
Large observational registers also have limitations for studying the heterogeneity in effects and outcomes of the kind reported in this paper; they lack information on variables that could moderate the effects of loss on health outcomes, such as coping mechanisms, cognitive appraisal, and psychological and environmental resources, including access to therapy or social support. As extreme as they may be, major life stressors can impact individuals in different ways, as individuals vary in the way they cognitively process the event, the different coping behaviours they adopt and how and when they use them, and their access to support resources. In the case of atrial fibrillation incidence, an underlying genetic vulnerability may also partially explain the association between death of offspring and incident atrial fibrillation in surviving parents. The researchers tested this hypothesis by stratifying the analyses by the child's cause of death. They found the association between child loss and incident atrial fibrillation to be strongest when the child's cause of death was attributed to cardiovascular disease, thus providing indirect support for genetic vulnerability among parents. Yet, even when children died of causes other than cardiovascular, the association between loss of a child and subsequent incident atrial fibrillation was observed. It should be noted that, in all claims data, attributing cause of death is challenging, often not completely documented, and risk of misclassification is real. It is also hard to discern whether the death was sudden or preceded by a long illness, and how this may have interacted with the observed association. Therefore, we are unable with certainty to rule out alternative factors that may explain the increased risk of atrial fibrillation associated with loss of a child in this cohort study or to understand the exact nature of stress exposure and its moderating or interacting factors for the association with incident atrial fibrillation.
Potential physiological pathways that may explain the link between the stress of child loss and incident atrial fibrillation, were, however, suggested by the authors. In general, stress reactions are linked with a cascade of responses, at the behavioural, autonomic, and hormonal level, all of which can be directly or indirectly linked with adverse health outcomes. For atrial fibrillation in particular, research on physiological mechanisms linking stress to incidence is not extensive, and, indeed, it was initially suggested that stress and emotional responses were a consequence of experiencing atrial fibrillation, rather than a trigger. Our current understanding, however, has evolved following the real-time demonstration that negative emotions precede symptomatic atrial fibrillation. As such, a 'triggering effect' through a pathway of stress-provoked sympathetic arousal precipitating alteration in atrial electrophysiology is a very likely pathway for the association between acute stress and atrial fibrillation, and fits with the reported observations that the effect of bereavement following child loss was seen particularly in the first week following the event. Long-term exposures to a stressful context may also increase the risk of atrial fibrillation over time through multidimensional pathways. These pathways can be behavioural (e.g. smoking or substance use), inflammatory, or autonomic, or mediated by the hypothalamic–pituitary–adrenal axis or the renin–angiotensin–aldosterone system, with either direct electrophysiological effects, or indirect effects through the promotion of atrial fibrosis, increased atrial pressure, and atrial stretching.[11,12]
The key question is whether these insights—the findings reported by Wei et al. and the work by others reported previously—provide evidence of an 'actionable target' for reducing the risk of adverse health outcomes, including atrial fibrillation, among parents and families who are confronted with the loss of a child. Currently, the World Health Organization advises against universal offering of structured psychological interventions or benzodiazepines following bereavement in adults who do not meet criteria for a mental disorder, but instead culturally appropriate mourning and encouragement to reactivate social networks is recommended. When considering psychotropic medications in scenarios where parents following the death of a child face a mental health crisis, considerations of drug-induced arrhythmia should also be weighed and be of special concern. Unfortunately, drug-induced arrhythmia as an alternative explanation for the observed link between stress and incident atrial fibrillation was not examined as part of the study of Wei et al.
In a minority of situations, complicated grief may occur, as well as bereavement-related major depressive disorder. For these scenarios, interpersonal therapy and complicated grief treatment have proven effective in reducing grief symptoms and symptoms of depression, with the latter treatment strategy showing a faster time to response. To our knowledge, no direct psychological interventions have been tested for reducing atrial fibrillation risk, and this would be an important opportunity for further investigation to understand whether atrial fibrillation risk associated with stress may indeed be modifiable. Randomized controlled trials testing interventions that are specifically tailored to support parents who have faced the loss of a child have been rare and may represent an important need to address in future work (Graphical abstract).
In conclusion, through a valuable comprehensive national data asset, a potential link between stress and incident atrial fibrillation was demonstrated for the first time in parents who had faced the devastating loss of a child. Assessment of the parents' needs and activating support sources are important priorities when faced with bereavement due to loss of a child, along with an understanding of how we can tailor interventions to individuals in need. The research of Wei and colleagues has highlighted the risk parents may face after losing a child, while also exposing evidence gaps that may be filled by mechanistic and efficacy research targeting pathways and interventions to mitigate the identified risk.
Eur Heart J. 2021;42(15):1496-1498. © 2021 Oxford University Press
Copyright 2007 European Society of Cardiology. Published by Oxford University Press. All rights reserved.