Vitamin D Supplementation for Treatment of Heart Failure (DELIGHTFUL)

The central objective of this proposal is to establish that vitamin D supplementation in heart failure patients with low vitamin D levels will have improved outcomes compared to placebo. In addition the investigators will also evaluate the role of genetics in regard to vitamin D and heart failure. The investigators will be evaluating what is currently a novel approach of identifying patients with low vitamin D and treating this low vitamin D level. The investigators will be able to evaluate the importance of vitamin D supplementation in these patients and the role of genetics on our defined outcomes.

Primary Objective To determine how rapid vitamin D supplementation affects biomarkers and submaximal exercise capacity in systolic HF patients with low vitamin D status. Working Hypothesis 1: HF patients when supplemented with vitamin D for 6 months will have lower measures of inflammation and extracellular-matrix remodeling compared with placebo. Working Hypothesis 2: HF patients when supplemented with vitamin D for 6 months will have longer 6-minute walk length compared with placebo. Secondary Objectives To establish a relationship between the CYP2R1 variant and surrogate markers in systolic HF patients. Working Hypothesis 3: HF patients with the CYP2R1 G allele will have higher measures of inflammation and extracellular-matrix remodeling compared to AA subjects. This relationship will also be seen in subjects with the CYP2R1 TagSNP variants. Working Hypothesis 4: HF patients with CYP2R1 variant alleles will have shorter 6-minute walk length compared to subjects without these variants. To genotype HF subjects for the VDR variants and additional tag SNPs, to ascertain the relationship between VDR genetic variation and surrogate markers in systolic HF patients. Working Hypothesis 5: HF patients with VDR variants will have greater measures of inflammation and extracellular-matrix remodeling compared to subjects without VDR variants. Working Hypothesis 6: HF patients with VDR variants will have a shorter 6-minute walk length compared to subjects without these variants.

Vitamin D supplementation will be an oral load of 100,000 IU then 2000 IU by mouth daily of vitamin D3 (cholecalciferol)for 6 months

Vitamin D supplementation will be an oral load of 100,000 IU then 2000 IU by mouth daily of vitamin D3 (cholecalciferol)for 6 months

Biomarkers - C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-a (TNF-a), propeptide procollagen type I, plasma procollagen III, matrix metalloproteinase 2 (MMP-2), MMP-9 and tissue inhibitor of matrix metalloproteinases-1 (TIMP-1).

Kansas City Cardiomyopathy Questionnaire for quality of life is measured on a scale of 0 - 100, with 100 being best.

Genotyped for the restricted fragment length polymorphism at the BsmI site. In addition CYP2R1, CYP27B1, CYP24 will also be genotyped.

Inclusion Criteria: HF patients with LV systolic dysfunction of ischemic or non-ischemic origin and an LVEF <40% using nuclear ventriculography or echocardiography within the last 6 months. Attempts should have been made at optimizing medical therapy and the participant should be stable on these medications for at least 3 months. Patients with a 25(OH)D level between 10-25 ng/ml Exclusion Criteria: Inability to give informed consent Patients with sarcoidosis or other granulomatous disease that can alter vitamin D metabolism Patients with primary valvular HF, hypertrophic cardiomyopathy, and drug-induced HF Renal dysfunction defined as serum creatinine > 2.5 mg/dl Pregnant women Patients <18 years of age Patients on vitamin D supplementation