Effects of Vitamin D on Cardiac Function in Patients With Chronic HF: The VINDICATE Study

Klaus K Witte, Rowena Byrom, John Gierula, Maria F Paton, Haqeel A Jamil, Judith E Lowry, Richard G Gillott, Sally A Barnes, Hemant Chumun, Lorraine C Kearney, John P Greenwood, Sven Plein, Graham R Law, Sue Pavitt, Julian H Barth, Richard M Cubbon, Mark T Kearney, Klaus K Witte, Rowena Byrom, John Gierula, Maria F Paton, Haqeel A Jamil, Judith E Lowry, Richard G Gillott, Sally A Barnes, Hemant Chumun, Lorraine C Kearney, John P Greenwood, Sven Plein, Graham R Law, Sue Pavitt, Julian H Barth, Richard M Cubbon, Mark T Kearney

Abstract

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).

Keywords: heart failure; left ventricular function; remodeling; vitamin D.

Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1
Figure 1
Consort Diagram Demonstrating Patient Enrollment and Disposition for VINDICATE VINDICATE = VitamIN D treatIng patients with Chronic heArT failurE.
Figure 2
Figure 2
Median and Interquartile Ranges for Vitamin D, Creatinine, Calcium, and Parathyroid Concentrations at 3 Monthly Time Points in VINDICATE by Treatment Allocation Vitamin D concentrations are described in relation to deficiency (green line), sufficiency (orange line), and the accepted upper limit for hypervitaminosis D (red line). Serum calcium levels are described in relation to upper limit of normal range (red line), and serum parathyroid hormone concentrations in relation to the normal range (between red lines). Conversion factors: vitamin D nmol/l · 0.4 = ng/ml; creatinine mmol/l · 0.11 = mg/dl; calcium mmol/l · 4 = mg/dl; parathyroid hormone pmol/l · 9.4 = pg/ml. VINDICATE = VitamIN D treatIng patients with Chronic heArT failurE.
Figure 3
Figure 3
Median and Interquartile Ranges for 6-Minute Walk Test Distance, and LVEF, LVEDD, and LVEDV Measured by Echocardiography at Baseline and Final Visit in VINDICATE by Treatment Allocation LVEDD = left ventricular end-diastolic dimension; LVEDV = left ventricular end-diastolic volume; LVEF = left ventricular ejection fraction; VINDICATE = VitamIN D treatIng patients with Chronic heArT failurE.
Central Illustration
Central Illustration
Vitamin D in Chronic Heart Failure: Impact on Left Ventricular Structure and Function Vitamin D improves left ventricular ejection fractions and reduces left ventricular dimensions and volumes.

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