Author + information
- Klaus K. Witte, MDa,∗ (, )
- Rowena Byrom, RNa,
- John Gierula, BSca,
- Maria F. Paton, BSca,
- Haqeel A. Jamil, PhDa,
- Judith E. Lowry, MSca,
- Richard G. Gillott, MScb,
- Sally A. Barnes, MScb,
- Hemant Chumun, RNa,
- Lorraine C. Kearney, RNa,
- John P. Greenwood, PhDa,
- Sven Plein, PhDa,
- Graham R. Law, PhDa,
- Sue Pavitt, PhDc,
- Julian H. Barth, PhDd,
- Richard M. Cubbon, PhDa and
- Mark T. Kearney, MDa
- aLeeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, United Kingdom
- bLeeds Teaching Hospitals NHS Trust, Department of Cardiology, Leeds, United Kingdom
- cSchool of Dentistry, University of Leeds, Leeds, United Kingdom
- dLeeds Teaching Hospitals NHS Trust, Department of Clinical Biochemistry, Leeds, United Kingdom
- ↵∗Reprint requests and correspondence:
Dr. Klaus K. Witte, Division of Cardiovascular and Diabetes Research, Multidisciplinary Cardiovascular Research Centre (MCRC), Leeds Institute of Cardiovascular and Metabolic Medicine, LIGHT Building, University of Leeds, Clarendon Way, Leeds LS2 9JT, United Kingdom.
Background Patients with chronic heart failure (HF) secondary to left ventricular systolic dysfunction (LVSD) are frequently deficient in vitamin D. Low vitamin D levels are associated with a worse prognosis.
Objectives The VINDICATE (VitamIN D treatIng patients with Chronic heArT failurE) study was undertaken to establish safety and efficacy of high-dose 25 (OH) vitamin D3 (cholecalciferol) supplementation in patients with chronic HF due to LVSD.
Methods We enrolled 229 patients (179 men) with chronic HF due to LVSD and vitamin D deficiency (cholecalciferol <50 nmol/l [<20 ng/ml]). Participants were allocated to 1 year of vitamin D3 supplementation (4,000 IU [100 μg] daily) or matching non−calcium-based placebo. The primary endpoint was change in 6-minute walk distance between baseline and 12 months. Secondary endpoints included change in LV ejection fraction at 1 year, and safety measures of renal function and serum calcium concentration assessed every 3 months.
Results One year of high-dose vitamin D3 supplementation did not improve 6-min walk distance at 1 year, but was associated with a significant improvement in cardiac function (LV ejection fraction +6.07% [95% confidence interval (CI): 3.20 to 8.95; p < 0.0001]); and a reversal of LV remodeling (LV end diastolic diameter -2.49 mm [95% CI: -4.09 to -0.90; p = 0.002] and LV end systolic diameter -2.09 mm [95% CI: -4.11 to -0.06 p = 0.043]).
Conclusions One year of 100 μg daily vitamin D3 supplementation does not improve 6-min walk distance but has beneficial effects on LV structure and function in patients on contemporary optimal medical therapy. Further studies are necessary to determine whether these translate to improvements in outcomes. (VitamIN D Treating patIents With Chronic heArT failurE [VINDICATE]; NCT01619891)
VINDICATE was approved by the regional ethics committee [12/YH/0206], funded by the Medical Research Council-UK. Dr. Witte has received unrestricted research funding from Medtronik UK; and holds an NIHR Clinician Scientist Fellowship. Dr. Gierula holds an NIHR-HCS Doctoral Fellowship. Dr. M. T. Kearney is a British Heart Foundation Professor; and has received research funding from Medtronic UK. Dr. Paton is funded by a Leeds Charitable Foundation Fellowship. Dr. Cubbon holds an Intermediate Fellowship from the British Heart Foundation. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received March 17, 2016.
- Accepted March 21, 2016.
- The Authors