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Background: Hypereosinophilic syndrome can produce cardiac involvement and endomyocardial fibrosis, which have a poor prognosis. However, there is limited information regarding cardiac involvement among migrants from Latin America with eosinophilia related to helminthiasis. Methods: We conducted a pilot observational study where an echocardiography was performed on migrants from Latin America with both eosinophilia (>450 cells/μL) and a diagnosis of helminth infection, and on migrants from Latin America without eosinophilia or helminth infection. Microbiological techniques included a stool microscopic examination using the Ritchie's formalin-ether technique, and a specific serology to detect Strongyloides stercoralis antibodies. Results: 37 participants were included, 20 with eosinophilia and 17 without eosinophilia. Twenty (54.1%) were men with a mean age of 41.3 (SD 14.3) years. Helminthic infections diagnosed in the group with eosinophilia were: 17 cases of S. stercoralis infection, 1 case of hookworm infection, and 2 cases of S. stercoralis and hookworm coinfection. Among participants with eosinophilia, echocardiographic findings revealed a greater right ventricle thickness (p = 0.001) and left atrial area and volume index (p = 0.003 and p = 0.004, respectively), while showing a lower left atrial strain (p = 0.006) and E-wave deceleration time (p = 0.008). An increase was shown in both posterior and anterior mitral leaflet thickness (p = 0.0014 and p = 0.004, respectively) when compared with participants without eosinophilia. Conclusions: Migrants from Latin America with eosinophilia related to helminthic infections might present incipient echocardiographic alterations suggestive of early diastolic dysfunction, that could be related to eosinophilia-induced changes in the endomyocardium. Author summary: A recent study in migrants from Sub-Saharan Africa with eosinophilia related to helminth infection describes initial findings on cardiac ultrasound in the form of thickening of the posterior leaflet of the mitral valve, but with no clinical manifestations, representing the early stage of the endomyocardial fibrosis process. The aim of the present study is to evaluate the relationship between eosinophilia secondary to helminth infection and cardiac involvement in Latin American patients. In our cohort, eosinophilia in patients was mainly due to Strongyloides stercoralis infection. Among patients with eosinophilia, echocardiographic findings revealed a greater right ventricle thickness and left atrial area and volume index, while showing a lower left atrial strain and E-wave deceleration time when compared with patients without eosinophilia. These alterations are suggestive of early diastolic dysfunction that could be related to eosinophilia-induced changes in the endomyocardium. [ABSTRACT FROM AUTHOR]

A recent genome-wide association study (GWAS) identified a locus in chromosome 11 associated with the chronic cardiac form of Chagas disease. Here we aimed to elucidate the potential functional mechanism underlying this genetic association by analyzing the correlation among single nucleotide polymorphisms (SNPs) and DNA methylation (DNAm) levels as cis methylation quantitative trait loci (cis-mQTL) within this region. A total of 2,611 SNPs were tested against 2,647 DNAm sites, in a subset of 37 chronic Chagas cardiomyopathy patients and 20 asymptomatic individuals from the GWAS. We identified 6,958 significant cis-mQTLs (False Discovery Rate [FDR]<0.05) at 1 Mb each side of the GWAS leading variant, where six of them potentially modulate the expression of the SAC3D1 gene, the reported gene in the previous GWAS. In addition, a total of 268 cis-mQTLs showed differential methylation between chronic Chagas cardiomyopathy patients and asymptomatic individuals. The most significant cis-mQTLs mapped in the gene bodies of POLA2 (FDR = 1.04x10-11), PLAAT3 (FDR = 7.22x10-03), and CCDC88B (FDR = 1.89x10-02) that have been associated with cardiovascular and hematological traits in previous studies. One of the most relevant interactions correlated with hypermethylation of CCDC88B. This gene is involved in the inflammatory response, and its methylation and expression levels have been previously reported in Chagas cardiomyopathy. Our findings support the functional relevance of the previously associated genomic region, highlighting the regulation of novel genes that could play a role in the chronic cardiac form of the disease. Author summary: Genome-wide association studies (GWAS) have provided extensive information regarding the genetic component of complex traits, including parasitic diseases such as Chagas disease. However, these associations mapped in regulatory regions of the genome and assigning them a functional consequence have been cumbersome. In this study we aimed to evaluate the functional mechanism underlying the previously reported genomic association with chronic Chagas cardiomyopathy, by assessing the correlation between methylation changes and the underlying genetic variations within the region. These methylation quantitative trait loci (mQTLs) may be involved in gene expression regulation. We identified mQTLs in three genes that have been associated with cardiovascular diseases in previous studies. Interestingly, one of these genes was previously identified as differentially methylated and expressed in heart biopsies of chronic Chagas cardiomyopathy patients. Our results suggest novel genes that could play a role in the chronic Chagas cardiomyopathy, evidencing the functional relevance of the previously associated loci. [ABSTRACT FROM AUTHOR]