Computing indices of diastolic stiffness has been counterproductive

Most quantitative studies of the diastolic heart have been motivated by the desire to compute an index that reflects the left ventricle's resistance to filling and relates to the mechanical properties of the muscle comprising the heart. Despite considerable effort, no consensus has developed concerning how best to describe the diastolic left ventricle. These difficulties follow from the fact that most of the indices have been ad hoc empirical descriptions of data with little or no theoretical base in the mechanics of the heart. The indices that arise from more accurate theoretical analyses are rarely tested experimentally to validate the assertion that the parameters in the theoretical models actually reflect what they claim to reflect (e.g., the elasticity of the myocardium) before applying them to clinical data. These difficulties are compounded by the fact that in a clinical setting one can only observe a short segment of the diastolic pressure-volume curve that does not provide enough information to reliably compute any of the indices of stiffness that have been proposed to date. Meanwhile, new clinical observations and animal studies have shown that the diastolic pressure-volume curve shifts following administration of drugs that appear not to alter muscle's mechanical properties. These developments suggest that future work should focus on developing theoretical models capable of explaining these phenomena, validating these theories experimentally, and discovering their physiological significance, rather than attempting to relate chamber stiffness to disease.