Dataset Information

Sex- and age-based differences in the natural history and outcome of dilated cardiomyopathy.

ABSTRACT:

Aim

To evaluate the relationship between sex, age and outcome in dilated cardiomyopathy (DCM).

Methods and results

We used proportional hazard modelling to examine the association between sex, age and all-cause mortality in consecutive patients with DCM. Overall, 881 patients (290 women, median age 52 years) were followed for a median of 4.9 years. Women were more likely to present with heart failure (64.0% vs. 54.5%; P = 0.007) and had more severe symptoms (P < 0.0001) compared to men. Women had smaller left ventricular end-diastolic volume (125 mL/m² vs. 135 mL/m² ; P < 0.001), higher left ventricular ejection fraction (40.2% vs. 37.9%; P = 0.019) and were less likely to have mid-wall late gadolinium enhancement (23.0% vs. 38.9%; P < 0.0001). During follow-up, 149 (16.9%) patients died, including 41 (4.7%) who died suddenly. After adjustment, all-cause mortality [hazard ratio (HR) 0.61, 95% confidence interval (CI) 0.41-0.92; P = 0.018] was lower in women, with similar trends for cardiovascular (HR 0.60, 95% CI 0.35-1.05; P = 0.07), non-sudden (HR 0.63, 95% CI 0.39-1.02; P = 0.06) and sudden death (HR 0.70, 95% CI 0.30-1.63; P = 0.41). All-cause mortality (per 10 years: HR 1.36, 95% CI 1.20-1.55; P < 0.0001) and non-sudden death (per 10 years: HR 1.51, 95% CI 1.26-1.82; P < 0.00001) increased with age. Cumulative incidence curves confirmed favourable outcomes, particularly in women and those <60 years. Increased all-cause mortality in patients >60 years of age was driven by non-sudden death.

Conclusion

Women with DCM have better survival compared to men, which may partly be due to less severe left ventricular dysfunction and a smaller scar burden. There is increased mortality driven by non-sudden death in patients >60 years of age that is less marked in women. Outcomes with contemporary treatment were favourable, with a low incidence of sudden death.

SUBMITTER: Halliday BP

PROVIDER: S-EPMC6392171 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background: Immune targeted therapy has become an attractive therapeutic approach for patients with dilated cardiomyopathy (DCM) recently. Genetic predisposition and gender play a critical role in immune-related responses of DCM. This study aimed to perform a bioinformatics analysis of molecular differences between male and female samples and identify immune-related ceRNA network in DCM. Methods: The gene expression microarray and clinical features dataset of GSE19303 was downloaded from the GEO. The raw data were preprocessed, followed by identification of differentially expressed genes (DEGs) between male and female DCM samples. Crucial functions and pathway enrichment analysis of DEGs were investigated through GO analysis and KEGG pathway analysis, respectively. A lncRNA-miRNA-mRNA network was constructed and a central module was extracted from the ceRNA network. Results: Compared with the female group, the male group benefits more from IA/IgG immunotherapy. Male patients of DCM had a significant positive correlation with the abundance of inflammatory cells (B cells, memory B cells, CD8+ Tem cells, and NK cells). Sex difference DEGs had a widespread impact on the signaling transduction, transcriptional regulation, and metabolism in DCM. Subsequently, we constructed an immune-related ceRNA network based on sex differences in DCM, including five lncRNAs, six miRNAs, and 29 mRNAs. Furthermore, we extracted a central module from the ceRNA network, including two lncRNAs (XIST and LINC00632), three miRNAs (miR-1-3p, miR-17-5p, and miR-22-3p), and six mRNAs (CBL, CXCL12, ESR1, IGF1R, IL6ST, and STC1). Among these DEGs, CBL, CXCL12, and IL6ST expression was considered to be associated with inflammatory cell infiltration in DCM. Conclusions: The identified ceRNA network and their enriched pathways may provide genetic insights into the phenotypic diversity of female and male patients with DCM and may provide a basis for development of sex-related individualization of immunotherapy.

Project description:In the past decade there has been a growing interest in understanding sex and gender differences in myocarditis and dilated cardiomyopathy (DCM), and the purpose of this review is to provide an update on this topic including epidemiology, pathogenesis and clinical presentation, diagnosis and management. Recently, many clinical studies have been conducted examining sex differences in myocarditis. Studies consistently report that myocarditis occurs more often in men than women with a sex ratio ranging from 1:2-4 female to male. Studies reveal that DCM also has a sex ratio of around 1:3 women to men and this is also true for familial/genetic forms of DCM. Animal models have demonstrated that DCM develops after myocarditis in susceptible mouse strains and evidence exists for this progress clinically as well. A consistent finding is that myocarditis occurs primarily in men under 50 years of age, but in women after age 50 or post-menopause. In contrast, DCM typically occurs after age 50, although the age that post-myocarditis DCM occurs has not been investigated. In a small study, more men with myocarditis presented with symptoms of chest pain while women presented with dyspnea. Men with myocarditis have been found to have higher levels of heart failure biomarkers soluble ST2, creatine kinase, myoglobin and T helper 17-associated cytokines while women develop a better regulatory immune response. Studies of the pathogenesis of disease have found that Toll-like receptor (TLR)2 and TLR4 signaling pathways play a central role in increasing inflammation during myocarditis and in promoting remodeling and fibrosis that leads to DCM, and all of these pathways are elevated in males. Management of myocarditis follows heart failure guidelines and there are currently no disease-specific therapies. Research on standard heart failure medications reveal important sex differences. Overall, many advances in our understanding of the effect of biologic sex on myocarditis and DCM have occurred over the past decade, but many gaps in our understanding remain. A better understanding of sex and gender effects are needed to develop disease-targeted and individualized medicine approaches in the future.

Dataset Information

Sex- and age-based differences in the natural history and outcome of dilated cardiomyopathy.

Aim

Methods and results

Conclusion

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