Laboratory for Molecular Cardiology, Department of Cardiology, Centre for Cardiac, Vascular, Pulmonary and Infectious Diseases, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark.
Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
Sci Rep. 2020 Jun 22;10(1):10039. doi: 10.1038/s41598-020-66671-w.
Atrial fibrillation (AF) has traditionally been considered an electrical heart disease. However, genetic studies have revealed that the structural architecture of the heart also play a significant role. We evaluated the functional and structural consequences of harboring a titin-truncating variant (TTNtv) in AF patients, using cardiac magnetic resonance (CMR). Seventeen early-onset AF cases carrying a TTNtv, were matched 1:1 with non-AF controls and a replication cohort of early-onset AF cases without TTNtv, and underwent CMR. Cardiac volumes and left atrial late gadolinium enhancement (LA LGE), as a fibrosis proxy, were measured by a blinded operator. Results: AF cases with TTNtv had significantly reduced left ventricular ejection fraction (LVEF) compared with controls (57 ± 4 vs 64 ± 5%, P < 0.001). We obtained similar findings in early-onset AF patients without TTNtv compared with controls (61 ± 4 vs 64 ± 5%, P = 0.02). We furthermore found a statistically significant increase in LA LGE when comparing early-onset AF TTNtv cases with controls. Using state-of-the-art CMR, we found that early-onset AF patients, irrespective of TTNtv carrier status, had reduced LVEF, indicating that early-onset AF might not be as benign as previously thought.
心房颤动（AF）传统上被认为是一种心脏电疾病。然而，遗传研究表明，心脏的结构架构也起着重要作用。我们使用心脏磁共振（CMR）评估了携带肌联蛋白截断变异（TTNtv）的 AF 患者的功能和结构后果。17 例携带 TTNtv 的早发性 AF 病例与 1:1 配对的非 AF 对照组和没有 TTNtv 的早发性 AF 病例复制队列进行了 CMR 检查。通过一位盲法操作员测量了心脏容积和左心房晚期钆增强（LA LGE），作为纤维化的替代指标。结果：与对照组相比，携带 TTNtv 的 AF 病例的左心室射血分数（LVEF）明显降低（57±4%比 64±5%，P<0.001）。我们在没有 TTNtv 的早发性 AF 患者中也获得了与对照组相似的发现（61±4%比 64±5%，P=0.02）。与对照组相比，我们还发现早发性 AF TTNtv 病例的 LA LGE 有统计学上的显著增加。使用最先进的 CMR，我们发现，无论是否携带 TTNtv，早发性 AF 患者的 LVEF 均降低，这表明早发性 AF 可能并不像以前认为的那样良性。
