Priyanka N. Prem

The vascular endothelium, once considered an inert barrier, is now recognized as a dynamic, multifunctional organ central to cardiovascular homeostasis. It regulates vascular tone, blood pressure, coagulation, inflammation, and angiogenesis through a repertoire of biochemical mediators and mechanosensitive responses. Endothelial dysfunction (ED), a state of impaired vasodilatory, anti-inflammatory, and anti-thrombotic capacity, is a critical early event in the pathogenesis of cardiovascular, metabolic, and inflammatory diseases. This chapter reviews the structural and molecular foundations of endothelial biology, its physiological integration into cardiovascular function, and the pathophysiological basis of ED. We critically evaluate biochemical, invasive, and non-invasive approaches for endothelial function quantification, highlighting methodological challenges and the urgent need for standardization. Finally, we present recent advances, including novel local pulse wave velocity-based endothelial reactivity assessment techniques, and discuss future prospects for clinical translation, precision medicine, and therapeutic monitoring.

Heart transplantation remains the definitive treatment for advanced heart failure. Despite over five decades of advancements in transplantation, the fundamental approach to organ preservation outside the body has remained largely unchanged. Traditionally, the field has relied on static cold storage (SCS) as the clinical standard for preserving hearts from donors after brainstem death. While effective, SCS presents practical limitations, particularly in mitigating ischemic damage, assessing the organ quality in storage and transport, and expanding the donor pool to include extended-criteria donors or donations after circulatory death (DCD). The emergence of ex-vivo machine perfusion, a transformative innovation, offers enhanced preservation by reducing the risk of ischemic damage alongside the ability to assess and optimize grafts from extended-criteria donors and those obtained through DCD. This chapter explores the pivotal role of cardiac biomarkers in graft evaluation within this emerging technology, categorized into functional markers, cell injury and cell death markers, inflammatory markers, omics-based markers, and hormone/pro-hormone markers. By enhancing precision in identifying transplantable hearts, these biomarkers play a crucial role in improving the safety and efficacy of marginal graft utilization, providing reassurance about the advancements in the field. The chapter also includes practical recommendations for integrating these biomarkers into clinical protocols and outlines future research directions to drive innovation in cardiac transplantation.