Copy number variants implicate cardiac function and development pathways in earthquake-induced stress cardiomyopathy

Lacey, Cameron; Doudney, Kit; Bridgman, Paul; George, Peter M.; Mulder, Roger; Zarifeh, Julie; Kimber, Bridget; Cadzow, Murray; Black, Michael A.; Merriman, Tony R.; Lehnert, Klaus; Bickley, Vivienne M.; Pearson, John; Cameron, Vicky A; Kennedy, Martin A.

doi:10.1101/144675

Cited by 5 publications

(4 citation statements)

References 141 publications

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“…Furthermore, protracted previous stress may contribute, and this is often undisclosed and underappreciated. Takotsubo syndrome can also be precipitated after major events resulting in community stress, such as earthquakes (New Zealand 2010, 2011, and 2016), 26 and more recently, anxiety related to the COVID-19 pandemic. 27…”

Section: Clinical Featuresmentioning

confidence: 99%

Takotsubo Syndrome: Pathophysiology, Emerging Concepts, and Clinical Implications

et al. 2022

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Takotsubo syndrome is a condition characterized by acute transient left ventricular systolic dysfunction, which at presentation can be challenging to distinguish from acute myocardial infarction. Although previously thought to be a benign, self-limiting condition, recent studies have confirmed that patients with takotsubo syndrome have persistent subtle ongoing cardiac dysfunction, and many continue to have limiting symptoms despite restoration of left ventricular ejection fraction. Moreover, these patients have a substantial burden of morbidity and mortality, as well, with high rates of subsequent major adverse cardiovascular events that approach those of patients with acute coronary syndrome. The mechanisms behind this condition remain elusive. Despite substantial research, the medical community continues to have an incomplete understanding of its underlying pathogenesis and pathophysiology. Catecholamine-induced myocardial injury is the most established and well-known theory, but this does not explain all the clinical features and presentations of the condition, and numerous other pathways and abnormalities are emerging. Because of the poor understanding of its underlying pathophysiology, there is a lack of evidence-based interventions to treat the acute episode, to avoid recurrences, and to prevent major adverse cardiovascular events. This highlights the need for further research to gain a better understanding of the underlying pathophysiology to inform appropriate randomized controlled trials of interventions targeting the causative pathways. Only then can evidence-based management strategies be established to improve clinical outcomes of this potentially lethal condition.

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Section: Clinical Featuresmentioning

confidence: 99%

Takotsubo Syndrome: Pathophysiology, Emerging Concepts, and Clinical Implications

et al. 2022

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“…The exome sequence of family member III:18 was determined as part of an independent study (Lacey et al, ), her membership of the present family at the time unknown. A total of 24 million 102 nucleotides‐long paired‐end reads were generated using the Illumina HiSeq system (Macrogen, Seoul, Republic of Korea).…”

Section: Methodsmentioning

confidence: 99%

Penetrance and expressivity of the R858H CACNA1C variant in a five‐generation pedigree segregating an arrhythmogenic channelopathy

Gardner

Crozier

Binfield

et al. 2018

Molec Gen & Gen Med

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Background Isolated cardiac arrhythmia due to a variant in CACNA1C is of recent knowledge. Most reports have been of singleton cases or of quite small families, and estimates of penetrance and expressivity have been difficult to obtain. We here describe a large pedigree, from which such estimates have been calculated. Methods We studied a five‐generation family, in which a CACNA1C variant c.2573G>A p.Arg858His co‐segregates with syncope and cardiac arrest, documenting electrocardiographic data and cardiac symptomatology. The reported patients/families from the literature with CACNA1C gene variants were reviewed, and genotype–phenotype correlations are drawn. Results The range of phenotype in the studied family is wide, from no apparent effect, through an asymptomatic QT interval prolongation on electrocardiography, to episodes of presyncope and syncope, ventricular fibrillation, and sudden death. QT prolongation showed inconsistent correlation with functional cardiology. Based upon analysis of 28 heterozygous family members, estimates of penetrance and expressivity are derived. Conclusions These estimates of penetrance and expressivity, for this specific variant, may be useful in clinical practice. Review of the literature indicates that individual CACNA1C variants have their own particular genotype–phenotype correlations. We suggest that, at least in respect of the particular variant reported here, “arrhythmogenic channelopathy” may be a more fitting nomenclature than long QT syndrome.

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“…Stress cardiomyopathy (CM) is a systemic syndrome and a variant disorder of the copy number, in which the haploinsufficiency of overlapping genes with deletions or overexpression of duplicated genes leads to a relatively subtle modification of cardiac or adrenergic physiology, in a way that these individuals are at increased risk of suffering from CM when exposed to specific environmental triggers [20], [21].…”

Section: Articlementioning

confidence: 99%

Takotsubo Syndrome and Its Genetic Relationship: Case Report and Narrative Literature Review

Ferrari

Santos²,

Alvarenga³

et al. 2022

CLINICMED

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Introduction: Takotsubo Syndrome (TTS) is presented as a temporary loss of systolic function, it is usually associated with emotional or physical stress. However, its pathophysiology is not well defined. Thus, this article seeks the relationship between the genetic factor and the development of Takotsubo Syndrome. Methodology: The study is about a narrative review and two case reports on TTS. Results: TTS is related to the excess of catecholamines, and its genetic linkage is strongly considered due to recent studies where occasionally it has been noticed its hereditary connections, such as: increased cardiac sensitivity to catecholamines and cardiac vulnerability to adrenergic stressors, impaired regulation of norepinephrine release, syndrome fragile X, and CD36 deficiency. Discussion: There is still no conclusion of the leading factors to TTS. However, being female, being in the postmenopausal period, and exposed to stressful conditions are some of the risk factors that can develop the disease, and which are better accepted by the scientific community. Conclusions: Although TTS is a disease of low prevalence, it is increasingly present in the routine of the cardiologist. The great difficulty lies in its diagnosis as it does not present a pathognomonic symptom and it is similar to other diseases, such as ACS. This causes it to pass absent-mindedly during the emergency primary investigation. Thus, there is a need to expand studies related to this disease and to investigate its genetic association.

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Copy number variants implicate cardiac function and development pathways in earthquake-induced stress cardiomyopathy

Cited by 5 publications

References 141 publications

Takotsubo Syndrome: Pathophysiology, Emerging Concepts, and Clinical Implications

Takotsubo Syndrome: Pathophysiology, Emerging Concepts, and Clinical Implications

Penetrance and expressivity of the R858H CACNA1C variant in a five‐generation pedigree segregating an arrhythmogenic channelopathy

Takotsubo Syndrome and Its Genetic Relationship: Case Report and Narrative Literature Review

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