High-Dose Vitamin D Improves Heart Structure, Function in Heart Failure

Abstract

High-dose oral vitamin D supplements taken for 1 year significantly improved cardiac structure and function in patients with chronic heart failure secondary to left ventricular systolic dysfunction, according to results from a new study. However, the same study, led by Klaus Witte, MD, of the University of Leeds in England, found that distance in the 6-minute walk test (6 MWT) — the study’s primary outcome measure — was not improved after a year’s supplementation with vitamin D. It is unclear why vitamin D deficiency co-occurs in a majority of people with CHF due to LVSD or to what degree reversing it can improve outcomes. However, vitamin D deficiency is thought to interfere with calcium transport in cardiac cells, and may contribute to cardiac fibrosis and inflammation, leading to faster progression to heart failure following damage to cardiac muscle. The new VINDICATE study randomized 223 patients with CHF due to LVSD and vitamin D deficiency to 1 year’s treatment with 4,000 IU of 25(OH) vitamin D3 daily, or placebo, Dr. Witte and associates concluded at the annual meeting of the American College of Cardiology. The results were published online in the Journal of the American College of Cardiology [doi: 10.1016/j.jacc.2016.03.508]. Of these 223 patients, 163 completed follow-up at 12 months, and 6 MWT and echocardiography findings were recorded at baseline and follow-up. Dr. Witte and colleagues found significant evidence of improved function in the vitamin D–treated patients as measured by left ventricular ejection fraction +6.07%; and a reversal of left ventricular remodeling (left ventricular end diastolic diameter –2.49 mm and left ventricular end systolic diameter –2.09 mm. The researchers also drew blood at 3-month intervals to check for serum calcium concentration, renal function, and vitamin D levels. Treatment was well tolerated, and no patients suffered hypervitaminosis or required a dose adjustment. “There was no effect of vitamin D supplementation on the primary endpoint of 6 MWT distance, but there were statistically significant and prognostically and clinically relevant improvements in the secondary outcomes of left ventricular ejection fraction, dimensions, and volumes, suggesting that vitamin D is leading to beneficial reverse remodeling,” the investigators wrote in their analysis. The study’s failure to meet its primary endpoint despite significant results from its secondary endpoints led Dr. Witte and colleagues to say that its design led to underpowering. “Variability in the walk distance measure at baseline was much greater than predicted from our pilot study such that our sample size only had 7% post hoc power to detect a difference between the groups,” meaning it was underpowered to detect a clinically relevant change in walk distance. The findings “have implications for future studies using 6-minute walk distance as an outcome measure,” they wrote. The investigators championed the addition of vitamin D3 to CHF treatment regimens. As new therapies for CHF are “often expensive, increasingly technical, and frequently fail to meet the rigorous demands of large phase III clinical trials,” Dr. Witte and colleagues wrote, vitamin D “might be a cheap and safe additional option for CHF patients and may have beneficial effects on multiple features of the syndrome.” Jennie Smith is a Frontline Medical News freelance writer based in San Antonio, TX.