UBC Centre for Heart Lung Innovation, Vancouver, BC, Canada.
UBC Department of Pathology and Laboratory Medicine, Vancouver, BC, Canada.
Lab Invest. 2022 Jan;102(1):14-24. doi: 10.1038/s41374-021-00669-4. Epub 2021 Oct 4.
The prevalence and contribution of cardiotropic viruses to various expressions of heart failure are increasing, yet primarily underappreciated and underreported due to variable clinical syndromes, a lack of consensus diagnostic standards and insufficient clinical laboratory tools. In this study, we developed an advanced methodology for identifying viruses across a spectrum of heart failure patients. We designed a custom tissue microarray from 78 patients with conditions commonly associated with virus-related heart failure, conditions where viral contribution is typically uncertain, or conditions for which the etiological agent remains suspect but elusive. Subsequently, we employed advanced, highly sensitive in situ hybridization to probe for common cardiotropic viruses: adenovirus 2, coxsackievirus B3, cytomegalovirus, Epstein-Barr virus, hepatitis C and E, influenza B and parvovirus B19. Viral RNA was detected in 46.4% (32/69) of heart failure patients, with 50% of virus-positive samples containing more than one virus. Adenovirus 2 was the most prevalent, detected in 27.5% (19/69) of heart failure patients, while in contrast to previous reports, parvovirus B19 was detected in only 4.3% (3/69). As anticipated, viruses were detected in 77.8% (7/9) of patients with viral myocarditis and 37.5% (6/16) with dilated cardiomyopathy. Additionally, viruses were detected in 50% of patients with coronary artery disease (3/6) and hypertrophic cardiomyopathy (2/4) and in 28.6% (2/7) of transplant rejection cases. We also report for the first time viral detection within a granulomatous lesion of cardiac sarcoidosis and in giant cell myocarditis, conditions for which etiological agents remain unknown. Our study has revealed a higher than anticipated prevalence of cardiotropic viruses within cardiac muscle tissue in a spectrum of heart failure conditions, including those not previously associated with a viral trigger or exacerbating role. Our work forges a path towards a deeper understanding of viruses in heart failure pathogenesis and opens possibilities for personalized patient therapeutic approaches.
心脏病毒在各种心力衰竭表现中的流行率和贡献正在增加，但由于临床表现多样、缺乏共识诊断标准以及临床实验室工具不足，这些病毒在很大程度上仍未被充分认识和报道。在这项研究中，我们开发了一种先进的方法来鉴定心力衰竭患者的各种病毒。我们从 78 名患有常见病毒相关性心力衰竭、病毒作用通常不确定或病因不明但可疑的疾病的患者中设计了一个定制的组织微阵列。随后，我们采用了先进的、高度敏感的原位杂交技术来探测常见的心脏病毒：腺病毒 2、柯萨奇病毒 B3、巨细胞病毒、EB 病毒、丙型和戊型肝炎病毒、乙型流感病毒和细小病毒 B19。在 69 例心力衰竭患者中，有 46.4%（32/69）检测到病毒 RNA，其中 50%的病毒阳性样本中含有一种以上的病毒。腺病毒 2 最为常见，在 27.5%（19/69）的心力衰竭患者中被检测到，而与之前的报道相反，细小病毒 B19 仅在 4.3%（3/69）的患者中被检测到。正如预期的那样，在 77.8%（7/9）的病毒性心肌炎患者和 37.5%（6/16）的扩张型心肌病患者中检测到了病毒。此外，在 50%的冠状动脉疾病（3/6）和肥厚型心肌病（2/4）患者以及 28.6%（2/7）的移植排斥反应患者中也检测到了病毒。我们还首次报告了在心脏结节病的肉芽肿病变和巨细胞心肌炎中检测到病毒，这两种疾病的病因仍不清楚。我们的研究揭示了在一系列心力衰竭疾病中，心肌组织中心脏病毒的流行率高于预期，包括那些以前与病毒触发或加重作用无关的疾病。我们的工作为深入了解心力衰竭发病机制中的病毒开辟了道路，并为个性化的患者治疗方法提供了可能。
