Abstract 6: Vitamin D3 Repletion Improves Heart Failure Patient Quality of Life and Neurohormonal Indices

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Abstract

Background: Vitamin D deficiency has been associated with cardiovascular mortality and sudden cardiac death in heart failure patients. Vitamin D may influence parathyroid hormone, the renin-angiotensin axis, natriuretic peptide gene expression, cardiac contractility, and cardiopulmonary function. Heart Failure (HF) studies using vitamin D to date have typically not used adequate repletion doses.

Objectives: The primary objectives of this research were to determine if vitamin D repletion over a six month period in New York Heart Association (NYHA) Class II-III HF patients would result in a change in neurohormonal markers, cardiopulmonary exercise parameters, circulating 25- hydroxyvitamin D, and quality of life.

Methods: A randomized, double-blinded, placebo-controlled trial assessing adjunctive Vitamin D3 supplementation in the treatment of NYHA Class II-III HF patients was conducted. Patients received 10,000 International Units (IU) per day of vitamin D3 or placebo for 6 months. Inclusion Criteria: 1) 25-hydroxyvitamin D level ≤32 ng/ml 2) stable medical regimen for 3 months. Exclusion Criteria: 1) any clinically unstable medical disorder 2) supplementation of vitamin D3 or D2 of greater than or equal to 2,000 IU/day. Study endpoints were: 1) B-type Natriuretic Peptide (BNP), 2) cardiopulmonary exercise parameters using Shape HF, 3) 25-hydroxyvitamin D, 4) intact parathyroid hormone (PTH), and 5) quality of life with the Kansas City Cardiomyopathy Questionnaire (KCCQ). Statistical analysis included independent samples t-test and multivariate regression.

Results: A total of 34 patients completed the study. When adjusted for baseline 25-hydroxyvitamin D, the difference between groups for BNP was significant ([[Unable to Display Character: ∆]]540 ±1928 pg/ml placebo vs [[Unable to Display Character: ∆]] 35 pg/ml ±1054 pg/ml treatment p=0.009). 25-hydroxyvitamin D was [[Unable to Display Character: ∆]]48.9 ±32 ng/ml treatment vs [[Unable to Display Character: ∆]]3.6 ± 9.4 ng/ml placebo, p<0.001 (mean 68 ng/ml treatment vs 23 ng/ml placebo). No toxicity was observed with treatment. PTH and exercise chronotropic response index trended towards improvement in the treatment group vs placebo group, respectively (([[Unable to Display Character: ∆]]-20 ±20 pg/ml vs [[Unable to Display Character: ∆]]7 ±54pg/ml (p=0.06)) and ([[Unable to Display Character: ∆]]0.13±0.26 versus [[Unable to Display Character: ∆]]-0.03 ± 0.23, p=0.12)). KCCQ quality of life total symptom ([[Unable to Display Character: ∆]]16 ±16 treatment vs [[Unable to Display Character: ∆]]-12 ±15 placebo, p< 0.001) and individual scores significantly improved from baseline in the treatment group.

Conclusions: Preliminary results show that vitamin D3 treatment of 10,000 IU/day in heart failure patients is safe, results in adequate circulating 25-hydroxyvitamin D levels, and achieves improvement in surrogate endpoint markers of HF outcomes.

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