Abstract
Introduction: Sudden cardiac death (SCD) is a major public health issue that has a tremendous impact on families and communities around the globe. SCD is currently a leading cause of mortality worldwide, estimated to be responsible for approximately 4.25 million deaths every year and cause approximately 60% of deaths due to cardiovascular disease.
Aim: To identify known pathophysiologic mechanisms of sudden cardiac death related to genetic variants causing mitochondrial dysfunction.
Methodology: An integrative review process informed by Whittemore and Knafl (2005) methodology was conducted. OVID Medline and Embase, Scopus, and Web of Science were searched for studies published between the 1st of January 2010 to the 31st of March 2023. Data was extracted manually and analysed using a constant comparative analysis.
Results and Discussion: A total of 78 articles were identified through the systematic search, with 17 included for data extraction. Genetic variants associated with SCD were identified in the genes PPA2, MT-RNR2, MT-TL1, and C1QBP, as well as multiple genetic components coinciding with Long QT Syndrome and Sengers Syndrome. These genetic variants reduced protein activity to induce varying degrees of mitochondrial dysfunction, presenting with reduced ATP synthesis, mitochondrial membrane potential, and oxygen consumption. Physical manifestations included hypertrophic and/or dilated cardiomyopathy, focal fibrosis, myocyte loss, and the presence of inflammatory infiltrates. No clear correlation was apparent between the specific genetic variants and degree of mitochondrial dysfunction or particular cardiac symptoms. However, several cases of SCD were precipitated by viral infections or the ingestion of insignificant amounts of alcohol. Genetic variants impaired oxidative phosphorylation, which led to reduced ATP synthesis and increased glycolysis within cardiac cells. ATP depletion suggestively disrupts ionic homeostasis, predisposing the development of fatal arrhythmias and mitochondrial swelling leading to cardiomyocyte death.
Conclusion: Gaining an understanding of the genetic variants will allow nurses to perform person-centred care and undertake accurate risk assessments in order to educate and prevent SCD events. Further research is necessary to further elicit the pathophysiological mechanism by which these identified genetic variants underpinning mitochondrial dysfunction induce SCD.