Myoarchitectural disarray of hypertrophic cardiomyopathy begins pre‐birth. Issue 5 (26th July 2019)

• Record Type: Journal Article
• Authors: Garcia‐Canadilla, Patricia; Cook, Andrew C.; Mohun, Timothy J.; Oji, Onyedikachi; Schlossarek, Saskia; Carrier, Lucie; McKenna, William J.; Moon, James C.; Captur, Gabriella
• Is Part Of: Journal of anatomy. Volume 235:Issue 5(2019)
• Page Start: 962
• Page End: 976
• Publication Date: 2019-07-26
• Subjects: cardiac embryology -- developmental biology -- hypertrophic cardiomyopathy -- myocardial disarray; Anatomy -- Periodicals; 571.3
• DOI: 10.1111/joa.13058
• Languages: English
• ISSNs: 0021-8782

Abstract

Abstract: Myoarchitectural disarray – the multiscalar disorganisation of myocytes, is a recognised histopathological hallmark of adult human hypertrophic cardiomyopathy (HCM). It occurs before the establishment of left ventricular hypertrophy (LVH) but its early origins and evolution around the time of birth are unknown. Our aim is to investigate whether myoarchitectural abnormalities in HCM are present in the fetal heart. We used wild‐type, heterozygous and homozygous hearts ( n = 56) from a Mybpc3 ‐targeted knock‐out HCM mouse model and imaged the 3D micro‐structure by high‐resolution episcopic microscopy. We developed a novel structure tensor approach to extract, display and quantify myocyte orientation and its local angular uniformity by helical angle, angle of intrusion and myoarchitectural disarray index, respectively, immediately before and after birth. In wild‐type, we demonstrate uniformity of orientation of cardiomyocytes with smooth transitions of helical angle transmurally both before and after birth but with traces of disarray at the septal insertion points of the right ventricle. In comparison, heterozygous mice free of LVH, and homozygous mice showed not only loss of the normal linear helical angulation transmural profiles observed in wild‐type but also fewer circumferentially arranged myocytes at birth. Heterozygous and homozygous showed more disarray with a wider distribution than in wild‐type before birth. In heterozygous mice, disarray was seen in the anterior, septal and inferior walls irrespective of stage, whereas in homozygous mice it extended to the whole LV circumference including the lateral wall. In conclusion, myoarchitectural disarray is detectable in the fetal heart of an HCM mouse model before the development of LVH. Abstract : Myoarchitectural disarray is a recognised histopathological hallmark of adult human hypertrophic cardiomyopathy. Our aim is to investigate whether myoarchitectural abnormalities in a Mybpc3‐targeted knock‐out HCM mouse model are present before birth using high‐resolution episcopic microscopy. We demonstrated that heterozygous and homozygous showed more disarray with a wider distribution than in wildtype before birth.