Introduction to the Biophysics of the Failing Heart
Heart failure is a primary, progressive disorder of cardiac muscle that leads to remodeling of the ventricles. While there has been much focus on the end-stage ventricular phenotype from the clinical standpoint, a better understanding of the molecular mechanisms provides significant insight regarding pathways involved in the preclinical states (the so-called Class I-II HF) where novel interventions may be targeted. Thus chapters in this book emphasize many of the biophysical components of the ventricle and working cardiac myocytes that contribute to molecular mechanisms determining its structure and function. While topics covered in each of the chapters may provide insights into the primary causes of ventricular remodeling, it is important to take into account that many of these processes (metabolic, cytoskeletal, sarcomere, and channel remodeling) are set in motion as a response to a primary stimulus and thus can be compensatory in the primary preclinical stages of disease. As illuminated in the book, it is common that the primary stimulus is biophysical in nature involving altered mechanics and stress–strain properties, for example. The transition from compensatory to pathogenic (or unregulated response) is likely to drive a significant component of the loss of function that defines the later stages of heart failure. Many of these components of cardiovascular structure and function work in concert. Yet in the early stages only subsets of the molecular framework are activated with end-stage disease representing the so-called common endpoint where all compensatory mechanisms have been exhausted. Understanding the relative role and contribution of each of these components/pathways (coupled to their specific pathogenic stimuli) in the early preclinical stages of ventricular remodeling provides both novel biomarkers and indicates new specific avenues of therapeutic intervention with a goal of altering the natural history of the disease process. As described in this book, many of the approaches and basic tools are in-hand to accomplish this understanding.