Drawing representing the functional consequences of myocardial disarray: Force as well as longitudinal and transmural conduction velocity vectors are represented in the absence (A) and in the presence (B) of myocardial disarray. 3D imaging in the murine myocardium (C and D): The challenge of producing large, transparent and fluorescently labelled volumes has been recently achieved applying a true tissue transformation approach: CLARITY. This method transforms an intact tissue into a nanoporous, hydrogel-hybridized, lipid-free form that, by removing membrane lipid bilayers, allows high transparency, immunolabelling, and structural and molecular preservation. This method in combination with advanced microscopy, allows 3D reconstruction of massive heart tissue at sub-cellular resolution. An image of whole left ventricle before (top) and after tissue clearing (bottom) is shown in (C). In (D), an example of 3D rendering of the sympathetic neurons network imaged upon whole-mount. Figure modified from Pianca et al.⁸⁸