Divakaran Sanjay, Randhawa Vinay, Tahir Usman A, Robertson Matthew, Waheed Anam A, Perillo Anna, Barrett Leanne, Blankstein Ron, Feinberg Mark W, Di Carli Marcelo F, Lakdawala Neal K
Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Harvard Medical School, Boston, Massachusetts, USA.
ESC Heart Fail. 2025 Apr;12(2):1485-1489. doi: 10.1002/ehf2.15154. Epub 2024 Dec 4.
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.
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.
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.
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.
炎症被认为与桥粒斑蛋白（DSP）心肌病的发病机制有关，回顾性研究描述了最终被诊断为DSP心肌病的有症状患者心肌氟脱氧葡萄糖（FDG）正电子发射断层扫描/计算机断层扫描（PET/CT）的异常表现。我们旨在前瞻性地研究患有DSP心肌病的非卧床患者是否有提示心肌炎症的心肌FDG摄取PET/CT成像，以及他们是否有循环炎症生物标志物的证据。
我们前瞻性招募了患有DSP心肌病的参与者以及作为对照的患有肌联蛋白心肌病的参与者。为所有参与者采集了用于临床实验室检查和蛋白质组分析的血样、心肌灌注单光子发射计算机断层扫描（SPECT）和心肌FDG PET/CT。
招募了10名患有DSP心肌病的参与者（中位年龄36.5岁[28,60]；80%为女性；100%为非西班牙裔白人）和4名患有肌联蛋白心肌病的参与者（中位年龄55.5岁[38.5,64]；50%为女性；100%为非西班牙裔白人）。两组在白细胞计数、红细胞沉降率（ESR）、高敏C反应蛋白（hsCRP）或高敏肌钙蛋白方面无显著差异。3名患有DSP心肌病的参与者和2名患有肌联蛋白心肌病的参与者在PET/CT上有非特异性心肌FDG摄取。所有其他参与者均无心肌FDG摄取。整合来自差异表达蛋白质组学数据的微小RNA（miRNA）差异表达及其预测靶点，共鉴定出11对反向miRNA-信使核糖核酸（mRNA）对，可能参与了前20条显著富集通路的调控，包括参与代谢、炎性小体/炎症信号传导和细胞死亡/焦亡的通路。
在一组患有DSP和肌联蛋白心肌病的非卧床患者中，我们发现FDG PET/CT表现或临床循环炎症生物标志物方面无差异。然而，miRNA测序/蛋白质组学分析确定了DSP和肌联蛋白心肌病之间的几个富集通路和独特的miRNA-蛋白质对，包括参与炎性小体/炎症信号传导的通路。未来的工作将集中在心肌炎样发作期间的评估。
