Vitamin D and heart failure – case closed or still an issue?

Heart failure (HF) is associated with several metabolic disturbances, including deranged calcium (Ca) metabolism in cardiomyocytes. Since the vitamin D hormone calcitriol plays a pivotal role in Ca metabolism, including Ca metabolism in cardiomyocytes, this review summarizes the present knowledge regarding the calcitriol/parathyroid hormone (PTH)/fibroblast growth factor-23 (FGF23) axis and its regulation in HF. In addition, calcitriol-associated clinical outcomes are summarized. Available data demonstrate elevated PTH and markedly elevated FGF23 concentrations, particularly in end-stage HF, despite preserved kidney function and guideline-conform treatment. These derangements are associated with severely suppressed circulating calcitriol and elevated overall mortality risk. Presented results in end-stage HF are based on patients awaiting heart transplantation, patients with ventricular assist device implantation, and heart transplant recipients. Available evidence does, however, not support the use of vitamin D supplements to reduce the prognosis of HF or to reduce mortality in patients with HF. Although vitamin D supplementation has not been tested in patients with severely reduced circulating calcitriol, data indicate that elevated FGF23 rather than vitamin D deficiency is an important independent predictor of suppressed circulating calcitriol in these patients. The cause of the elevation in FGF23 is, however, largely unknown. Future research should therefore clarify the origin of severely elevated FGF23 in patients with end-stage HF and preserved kidney function. Moreover, therapeutic strategies targeting FGF23 suppression in HF and its effects on circulating calcitriol and clinical events should be investigated. Altogether, the causes, consequences, and treatment options of the deranged calcitriol metabolism in HF remain an open question.