Vitamin D deficiency and secondary hyperparathyroidism in adult Fontan patients

Abstract

Background: The prevalence of vitamin D deficiency and secondary hyperparathyroidism (sHPT) in adult Fontan patients remains unstudied, and the role of vitamin D and parathyroid hormone (PTH) levels in assessing heart and circulatory failure in these patients is unclear.

Methods: We compared vitamin D deficiency and sHPT prevalence in adult Fontan patients (n = 35; mean age 33 ± 7.5 years) to adults with mild congenital heart disease (ACHD, n = 14). We analyzed associations between laboratory measurements, patient characteristics, and clinical events.

Findings: Vitamin D deficiency was highly prevalent in both Fontan patients and ACHD controls (76.5 % vs. 71.4 %, p = 0.726). sHPT was exclusively present in Fontan patients (31.4 %). PTH levels correlated with NYHA class (r = 0.412), O2 saturation (r = -0.39), systemic ventricular function (r = 0.465), and NT-proBNP levels (r = 0.742). 25-hydroxyvitamin D showed an inverse correlation with NYHA class and systemic ventricular function (both r ≤ -0.38). Fontan patients with sHPT had a higher incidence of prior hospitalization for worsening heart failure and atrial arrhythmias compared to Fontan patients without HPT or ACHD controls. (Hospitalization: Fontan with HPT vs. Fontan without HPT: OR 5.46 [95 % CI 1.25-23.86], p = 0.021; arrhythmia: Fontan with HPT vs. Fontan without HPT: OR 1.96 [95 % CI 1.13-3.4], p = 0.035; ACHD: OR 11.45 [95 % CI 1.7-77.28], p=<0.001). PTH showed significant correlation with inflammatory markers, particularly with GDF-15 (r = 0.8).

Conclusion: Our study is the first to demonstrate a high prevalence of vitamin D deficiency and sHPT in adult Fontan patients. As PTH strongly correlates with heart failure severity, it seems to be a promising biomarker in Fontan patients.

Keywords: 25-Hydroxyvitamin D; Fontan; Heart failure; Parathyroid hormone; Protein losing enteropathy; Secondary hyperparathyroidism; Vitamin D deficiency.

Fig. 1

Differences in parameters of systemic inflammation between Fontan patients with sHPT, Fontan patients without sHPT, and the mild ACHD group. A: GDF-15 (ng/l). B: CRP (mg/l). C: neutrophil to lymphocyte ratio. D: IL-6 (ng/l). Levels of significance depicted as follows: *p < 0.05, **p < 0.01, ***p < 0.001. ACHD: adult congenital heart disease; CRP: C reactive protein; GDF-15: growth differentiation factor 15; sHPT: secondary hyperparathyroidism; IL-6: interleukin-6.

Fig. 2

A: Percentage of patients hospitalized due to worsening heart failure: 5 out of 11 (45.5 %) Fontan patients with sHPT were hospitalized, whereas only 2 out of 24 (8.3 %) Fontan patients without sHPT and none of the mild ACHD group were hospitalized. B: Percentage of patients with atrial arrhythmia: Atrial arrhythmia was present in 9 out of 11 (81.8 %) Fontan patients with sHPT, in 10 out of 24 (41.7 %) Fontan patients without sHPT, and in 1 out of 14 (7.1 %) mild ACHD controls. C: Fontan patients with sHPT showed significantly higher levels of NT-proBNP. D: PTH levels in the three patient groups. Secondary sHPT was defined as PTH> 65 ng/l, Levels of significance depicted as follows: *p < 0.05, **p < 0.01, ***p < 0.001. ACHD: adult congenital heart disease; NT-proBNP: N-terminal pro-B-type natriuretic peptide; PTH: parathyroid hormone.