Abstract
The pathophysiology of stress cardiomyopathy (SCM), also known as takotsubo syndrome, is poorly understood. SCM usually occurs sporadically, often in association with a stressful event, but clusters of cases are reported after major natural disasters. There is some evidence that this is a familial condition. We have examined three possible models for an underlying genetic predisposition to SCM. Our primary study cohort consists of 28 women who suffered SCM as a result of two devastating earthquakes that struck the city of Christchurch, New Zealand, in 2010 and 2011. To seek possible underlying genetic factors we carried out exome analysis, genotyping array analysis, and array comparative genomic hybridization on these subjects. The most striking finding was the observation of a markedly elevated rate of rare, heterogeneous copy number variants (CNV) of uncertain clinical significance (in 12/28 subjects). Several of these CNVs impacted on genes of cardiac relevance including RBFOX1, GPC5, KCNRG, CHODL, and GPBP1L1. There is no physical overlap between the CNVs, and the genes they impact do not appear to be functionally related. The recognition that SCM predisposition may be associated with a high rate of rare CNVs offers a novel perspective on this enigmatic condition.
Highlights
Stress cardiomyopathy (SCM), known as “broken heart syndrome” or takotsubo syndrome[1,2], is a condition that captures widespread public interest
Several approaches to analysis of the identified variants were used, all of them hypothesising the involvement of gene variants with a low population minor allele frequency (MAF), that were over-represented in the earthquake-associated SCM (EqSCM) cohort
Beginning with a cohort of 28 stress cardiomyopathy (SCM) cases triggered by two major earthquakes that caused extensive death and damage in Christchurch (New Zealand), we carried out exploratory analyses of three models for genetic predisposition to this disorder
Summary
Stress cardiomyopathy (SCM), known as “broken heart syndrome” or takotsubo syndrome[1,2], is a condition that captures widespread public interest. For a major natural disaster, the tertiary hospital in Christchurch continued to function, allowing the collection of a relatively large homogenous cohort of cases which have been followed over several years[18,19,20,21,22,23]. Most research around this disorder has focused on sporadic SCM associated with heterogenous triggers[4,24,25]. Some retrospective case series have suggested that the incidence of SCM is increased in patients with anxiety conditions, but in our studies we did not find any correlation with psychiatric or anxiety disorders[19,23]
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