Pathophysiological and Pedigree Analysis of Left Ventricular Noncompaction in Japanese Macaques (Macaca fuscata)

Left ventricular noncompaction (LVNC) involving genetic mutation is categorized as an unclassified cardiomyopathy, and its diagnostic criteria have not been standardized. This could be because precise animal models of LVNC have not been created in any laboratory animal species. This study aimed to analyze the pathophysiology and familial tendency of LVNC in Japanese macaques. Two Japanese macaques with LVNC, and their parents who were suspected of having cardiac disease, were examined. One macaque with LVNC was examined using chest radiography, echocardiography, cardiac biomarkers, cardiac MRI, and pathologic examination, and the other macaque was examined using chest radiography, echocardiography, and cardiac biomarkers. Their common father and the mother of one of the macaques with LVNC were tested for chest radiography and cardiac biomarkers. Echocardiography revealed a meshwork with trabeculation and deep intertrabecular recesses in all their left ventricular walls. The 2 macaques with LVNC demonstrated a layered appearance of the myocardium, consisting of noncompacted myocardium on the endocardial side and compacted myocardium on the epicardial side, with a noncompacted/compacted ratio of 6.0 and 5.8, respectively. One of the 2 macaques with LVNC (case 1) had elevated levels of troponin I, troponin T, atrial natriuretic peptide, and brain natriuretic peptide. The second macaque with LVNC (case 2) showed blood flow in the intertrabecular recesses on echocardiography. The common father (case 3) of the 2 macaques with LVNC and the mother (case 4) of one of the macaques with LVNC had elevated levels of troponin I and troponin T. In case 1, histopathologic examination revealed fibrous thickening of the endocardium, fibrosis of the myocardial interstitium, myocardial disarray, vacuolar degeneration, anisonucleosis, and necrosis of myocardial cells. This suggests that Japanese macaques could serve as a reliable animal model of human LVNC.