Role of Extracellular Calcium Control, Calcium Sensing, and Regulation of Calcium Regulating Hormones in Heart Failure

Calcium plays a pivotal role in excitation-contraction coupling of cardiomyocytes and many other cellular responses observed in cardiovascular cells. Thus maintaining a healthy status requires very strict regulation of cytoplasmatic but also plasma ionized calcium concentration. Plasma ionized calcium is regulated by calcium sensing and the regulation of calcium uptake and secretion. Under conditions of heart failure, however, electrolyte deregulation occurs due to an activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system because both systems are coupled calcium regulation and thereby also to the regulation of hormones controlling calcium homeostasis such as parathyroid hormone, parathyroid hormone-related protein, and vitamin D that are activated in a calcium-dependent way. Of note, these hormones and receptors have also direct cardiac effects that modulate cardiac and renal function. Therefore, they play not only a role in end-stage heart failure but also in essential hypertension and reno-cardiovascular complications. In this review we summarize our current understanding about the role of calcium deregulation in heart failure and discuss the consequences from these observations. In conclusion, controlling plasma ionized calcium, plasma parathyroid hormone, and vitamin D status are pivotal in successful pharmacotreatment of patients with heart failure.