A study of sarcomere in hypertrophic cardiomyopathy using second-harmonic generation microscopy
K Fragkiadakis, M Kefalogianni, D Kavalieros, S Psilodimitrakopoulos, E Kampanieris, O Malikides, S Socratous, T Gaitanaki, T Pateromichelakis, M Tzardi, E Kranioti, E Simantirakis, E Stratakis, M MarketouAbstract
Introduction
Second Harmonic Generation (SHG) microscopy is a promising label-free imaging technique in cardiology that specifically visualizes myosin thick filaments within sarcomeres. Ultrastructural abnormalities affecting sarcomeres are common in heart muscle diseases, genetic or acquired, and their early recognition is crucial for diagnosis and management. Hypertrophic cardiomyopathy (HCM), a prototypical genetic myocardial disease caused by sarcomeric gene mutations, disrupts sarcomere structure and function. Understanding these pathological alterations through SHG microscopy could enhance future HCM management and reduce adverse outcomes, including heart failure and sudden cardiac death.
Purpose
To study the sarcomere length, myofibril undulation, and sinuosity in cardiac samples from HCM patients.
Materials/Methods: Postmortem myocardial samples from the left ventricle of patients with HCM were compared with those from age-matched individuals who had a morphologically normal heart. The samples were visualized under a non-linear laser microscope using SHG imaging.
Results
We identified that the sarcomere length was significantly longer in HCM compared with healthy hearts (1.796 ± 0.108 µm vs 1.710 ± 0.190 µm, p=0.027). Moreover, the degree of undulation in myosin fibers was significantly reduced in HCM (0.139 ± 0.237 vs. 0.319 ± 0.448, p=0.041). However, no significant difference in mean fibril sinuosity was present among both groups (p=0.135).
Conclusion
This multidimensional characterization of sarcomeric abnormalities enhances the mechanistic understanding of how genetic mutations reshape sarcomere structure and function in HCM. Our study advances the field by translating cutting-edge imaging techniques to human cardiomyopathy tissue, quantifying novel structural biomarkers, and paving avenues for diagnostic and treatment strategies tailored to sarcomere-level pathologies in HCM.Imaging of HCM myocardium with SHG microscopy