Emergence of Laplace Therapeutics
A large number of chronic heart failure patients escape from the benefits of neurohormonal blockade only to transit into a discouragingly miserable state of what the physician often refers to as "end-stage heart failure." Conceptually, the designation of "end-stage" as a description of a clinical scenario implies pessimism concerning recourse to a therapeutic avenue. A variety of surgical therapeutic techniques that take advantage of the law of Laplace, designed to effectively restore the cardiac shape from a spherical, mechanically inefficient pump to a more elliptical, structurally sound organ are now being employed. Additionally, the field of mechanical device implantation is surging ahead at a rapid pace. The weight of evidence regarding mechanical unloading using assist devices suggests that hemodynamic restoration is accompanied by regression of cellular hypertrophy, normalization of the neuroendocrine axis, improved expression of contractile proteins, enhanced cellular respiratory control, and decreases in markers of apoptosis and cellular stress. Thus, these lines of data point toward discarding the notion of "end-stage" heart failure. We are at a new crossroad in our quest to tackle chronic heart failure. It is our contention that the use of antiremodeling strategies, including device approaches, will soon signal the end of "end-stage" heart failure.

Insight into the pathophysiology of chronic heart failure has advanced rapidly in the past decade with a shift in therapy toward a multidimensional approach that focuses on the neurohormonal component of this disorder. This has largely evolved from a series of "modular shifts," including the application of the cardio-renal model (diuretics), hemodynamic model (inotropic therapy), and cardio-peripheral model (vasodilators), to the more recent advancement of the neurohormonal model. Whereas the earlier conceptual models all fulfilled the basic clinical needs of symptomatic relief and cardio-resurrection, only the neurohormonal model has provided an effective target to address symptom relief in concert with survival benefits. Yet a large number of chronic heart failure patients escape from the benefits of neurohormonal blockade only to transit into a discouragingly miserable state that the physician often refers to as "end-stage heart failure."