Abstract
AIMS: Inflammation has been implicated in the pathogenesis of desmoplakin (DSP) cardiomyopathy, and retrospective studies have described abnormal myocardial fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) findings in symptomatic patients eventually diagnosed with DSP cardiomyopathy. We aimed to prospectively investigate if ambulatory patients with DSP cardiomyopathy had myocardial FDG uptake PET/CT imaging indicative of myocardial inflammation and if they had circulating biomarker evidence of inflammation. METHODS: We prospectively recruited participants with DSP cardiomyopathy and participants with titin cardiomyopathy as a comparator group. Blood samples for clinical labs and proteomic profiling, myocardial perfusion single-photon emission computed tomography (SPECT) and myocardial FDG PET/CT were obtained for all participants. RESULTS: Ten participants with DSP cardiomyopathy (median age 36.5 years (28, 60); 80% female; 100% White and non-Hispanic) and four participants with titin cardiomyopathy (median age 55.5 years [38.5, 64]; 50% female; 100% White and non-Hispanic) were recruited. There were no significant differences between the groups in white blood cell count, ESR, hsCRP or hsTn. Three participants with DSP cardiomyopathy and two participants with titin cardiomyopathy had non-specific myocardial FDG uptake on PET/CT. All other participants had no myocardial FDG uptake. Integration of miRNA differential expression and their predicted targets from the differential expression proteomics data identified a total of 11 inverse miRNA-mRNA pairs potentially involved in the regulation of top 20 significantly enriched pathways, including pathways involved in metabolism, inflammasome/inflammatory signalling and cell death/pyroptosis. CONCLUSIONS: In a group of ambulatory patients with DSP and titin cardiomyopathy, we found no differences in FDG PET/CT findings or clinical circulating biomarkers of inflammation. However, miRNA-seq/proteomics analyses identified several enriched pathways and unique miRNA-protein pairs between DSP and titin cardiomyopathy, including pathways involved in inflammasome/inflammatory signalling. Future work will centre on evaluation during myocarditis-like episodes.