Congenital heart disease (CHD) is a diverse group of structural heart malformations that develop during embryogenesis. These anomalies represent the most prevalent type of cardiac abnormality, affecting approximately 1% of live births on an annual basis. The Caspase Recruitment Domain Family Member (CARD8) gene, which plays a regulatory role in the process of inflammation and the modulation of the inflammasome pathway, has been the focus of investigation due to its potential involvement in the development of cardiovascular disease.

The objective of this study is to describe the evidence of CARD8 polymorphisms that influence inflammatory and hematologic responses associated with the development of congenital heart disease.

This narrative review study was conducted through searches in PubMed and SciELO platforms, using terms such as "card8 gene," "inflammasome," "anemia," "hematologic markers," and "congenital heart disease," without a specific time period. A comprehensive search was conducted to identify all articles that indicated the presence of CARD8 polymorphisms associated with congenital heart disease.

Initially, 598 scientific articles were selected, of which 52 were included based on the search hypothesis: CARD8 mRNA hyperexpression has been demonstrated to activate cytokine regulation in endothelial cells, hematopoiesis, and atherosclerotic lesions. The single- nucleotide variants (SNVs) rs2043211, rs2043211, and rs35829419 have been identified as significant contributors to cardiovascular events, particularly in the context of the risk of inflammatory and hematologic diseases, including chronic anemia due to inflammation. Notably, research findings indicate that interactions between these specific SNVs do not appear to be associated with disease predisposition or cardiovascular events. Recent research indicates that alternative splicing can result in the production of several isoforms of the CARD8 protein. Some of these isoforms have been associated with an increased risk of cardiac anomalies, while others have been shown to offer protection against different conditions. Despite the limited understanding of the functional properties of the isoforms, there is evidence that each plays a distinct role. Elucidation of the functions of these isoforms, in conjunction with their specific expression in cells and diseases, may prove pivotal to a more profound comprehension of the multifaceted roles of CARD8 in inflammation and inflammatory conditions. However, the extent of knowledge concerning the genetic alterations in the function of the card8 gene and the regulation of inflammatory markers in patients with CHD remains limited. The study of single-nucleotide polymorphisms (SNPs) in the context of congenital heart disease is imperative for elucidating the potential molecular mechanisms that contribute to pathogenesis. Furthermore, this research facilitates the identification of genetic biomarkers that can assist in the prevention, early diagnosis, and genetic counseling of at-risk families. Consequently, the investigation of the relationship between polymorphisms in the card8 gene and the incidence of congenital heart disease can provide significant contributions to the advancement of scientific understanding of the genetic factors underlying these conditions. Moreover, this investigation can facilitate the development of personalized therapeutic strategies.