One of the hallmarks of cardiac failure is that despite persistent and often elevated sympathetic stimulation reflecting the body’s effort to compensate for depressed systemic hemodynamics, the response by the heart is muted. This can be viewed as a protective mechanism, because unbridled sympathetic stimulation leads to myocardial damage, fibrosis, and arrhythmia. Alternatively, it can be thought of as a direct contributor to depressed function and reserve capacity worthy of therapeutic targeting. This paradox has at its core the complexities of beta-adrenergic signaling and the manner by which it is altered in the failing heart.
Kass, D. A. (2013). Et Tu PDE2?∗. Journal of the American College of Cardiology, 62(17), 1607–1609. https://doi.org/10.1016/j.jacc.2013.06.003