Chronic Heart Failure improved with 4,000 IU daily for a year – RCT April 2016

High-dose vitamin D improves heart structure, function in chronic heart failure

By: JENNIE SMITH, Cardiology News Digital Network APR 4, 2016
FROM ACC16

 Download the Study PDF from Vitamin D Life

Key clinical point: Oral supplementation of high-dose vitamin D3 led to significantly improved left ventricular function and structure in a cohort of vitamin-deficient patients.
Major finding: Treated patients had significantly improved left ventricular ejection fraction of +6.07% vs. nontreated patients at 1 year, and significant reversal of left ventricular remodeling (left ventricular end diastolic diameter –2.49 mm and left ventricular end systolic diameter –2.09 mm).
Data source: A single-site randomized trial in which 229 patients with LV CHF received high-dose vitamin D or placebo for 12 months.
Disclosures: The U.K.’s National Institute for Health Research supported the study, and none of its authors declared conflicts of interest.

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 Dr. Klaus Witte of the University of Leeds (England), found that 6-minute walk distance – 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 chronic heart failure (CHF) due to left ventricular systolic dysfunction (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 April 4 in JACC (doi: 10.1016/j.jacc.2016.03.508).

Of these patients, 163 completed follow-up at 12 months, and 6-minute walk distance (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% (95% confidence interval 3.20, 8.95; P less than .0001); and a reversal of left ventricular remodeling (left ventricular end diastolic diameter –2.49 mm (95% CI –4.09, –0.90; P equal to .002) and left ventricular end systolic diameter –2.09 mm (95% CI –4.11; –0.06; P equal to .043).
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.”
The U.K.’s National Institute for Health Research supported the study, and none of its authors declared conflicts of interest.

http://content.onlinejacc.org/article.aspx?articleID=2507290#tab1Publisher wants for PDF

clips from Science Daily on the study

• The ejection fraction of a healthy person is usually between 60% and 70%. In heart failure patients, the ejection fraction is often significantly impaired — in the patients enrolled into the VINDICATE study the average ejection fraction was 26%.
• In the 80 patients who took Vitamin D3, the heart's pumping function improved from 26% to 34%. In the others, who took placebo, there was no change in cardiac function.
• This means that for some heart disease patients, taking vitamin D3 regularly may lessen the need for them to be fitted with an implantable cardioverter defibrillator (ICD), a device which detects dangerous irregular heart rhythms and can shock the heart to restore a normal rhythm.
• Heart failure affects about 900,000 people in the UK and more than 23 million worldwide.
• The condition can affect people of all ages, but it is more common in older people — more than half of all people globally with heart failure are over the age of 75.