Journal of the Practice of Cardiovascular Sciences

CURRICULUM IN CARDIOLOGY - JOURNAL CLUB
Year
: 2016  |  Volume : 2  |  Issue : 3  |  Page : 181--182

Role of Vitamin D in heart failure with reduced ejection fraction


Dinkar Bhasin 
 Department of Cardiology, All India Institute of Medical Sciences, New Delhi, India

Correspondence Address:
Dinkar Bhasin
Department of Cardiology, All India Institute of Medical Sciences, New Delhi
India




How to cite this article:
Bhasin D. Role of Vitamin D in heart failure with reduced ejection fraction.J Pract Cardiovasc Sci 2016;2:181-182


How to cite this URL:
Bhasin D. Role of Vitamin D in heart failure with reduced ejection fraction. J Pract Cardiovasc Sci [serial online] 2016 [cited 2020 Oct 31 ];2:181-182
Available from: https://www.j-pcs.org/text.asp?2016/2/3/181/201382


Full Text

 Citation



Witte KK, Byrom R, Gierula J, Paton MF, Jamil HA, Lowry JE, et al. Effects of Vitamin D on cardiac function in patients with chronic heart failure: The VINDICATE study. J Am Coll Cardiol 2016;67:2593-603.

 Introduction



The role of Vitamin D in heart failure remains debatable. There are several studies reporting possible effects of Vitamin D deficiency on the human heart. A few observational studies have reported a high prevalence of Vitamin D deficiency in the development of heart failure.[1] Low Vitamin D levels have also been associated with higher left ventricular (LV) volumes.[2] In addition, serum parathyroid hormone and Vitamin D levels were reported in a study to be independently associated with all-cause mortality and cardiovascular mortality.[3] However, some studies have questioned the protective role of Vitamin D in heart failure. A previous study reported that Vitamin D did not improve the 6-min walk test (6MWT), peak VO2 max (oxygen consumption) or muscle strength in heart failure patients.[4] Vitamin D also did not improve the quality of life in older patients with heart failure.[5] Boxer et al. reported that 6 months of Vitamin D supplementation significantly improves ejection fraction in elderly patients with heart failure and Vitamin D deficiency.[6]

The VINDICATE study by Witte et al. evaluated the role of supplemental Vitamin D3 on exercise function and cardiac parameters in patients with heart failure with reduced ejection fraction.[7]

Selection of patients

A total of 223 patients were recruited in the study if the symptom status was stable as New York Heart Association Class II/III and LV ejection fraction (LVEF) was <45% for more than 3 months. Only Vitamin D deficient patients (<20 ng/mL) were recruited. Patients taking calcium or Vitamin D supplements, those with other treatable causes of heart failure, and patients with significant renal dysfunction were excluded from this study.

 Methodology



The patients were randomized into two groups using block randomization to receive either Vitamin D supplementation (100 ug [4000 IU] of cholecalciferol) or placebo. The baseline parameters of the two groups were similar. Patients were followed up for 12 months with 6MWT, echocardiography and biochemical tests done at three monthly intervals. The study assessed the difference in change in 6MWT distance as the primary endpoint. Parameters of cardiac function such as LVEF, LV end-systolic and LV end-diastolic volumes and dimensions (LVEDV, LVESV, LVEDD, and LVESD) were the predefined secondary endpoints. The safety profile of Vitamin D was assessed using serum calcium, creatinine, and Vitamin D levels as additional secondary endpoints of the study.

 Results



The analysis was done in 163 patients (83 the in Vitamin D group and eighty in the placebo group) as remaining were lost to follow-up. The serum Vitamin D levels increased significantly in patients receiving Vitamin D supplementation. There was also a significant improvement in the secondary outcomes of the echocardiographic parameters of LVEF, LVEDD, LVEDV, LVESV, and LVESD. The difference in mean change in LVEF was 6.07% (3.20–8.94; P < 0.001). However, there was no significant difference in change in the 6MWT distance in the two groups. A dose-response relationship was seen between Vitamin D levels and LVEF (R = 0.05; P = 0.023) and Vitamin D levels and LVEDV (R = −0.02; P = 0.035). No drug-related adverse events were observed in the study. The significant improvement seen in the echocardiographic parameters suggests reverse remodeling and a dose-response relationship demonstrated between Vitamin D and LV echocardiographic parameters may suggest a causative and therapeutic role of Vitamin D in LV systolic dysfunction.

 Discussion



The strengths of the study were that it was a blinded and placebo-controlled trial with a sample size larger than the previous studies and a fairly long follow-up of 12 months. Over 90% of the patients were on optimal medical therapy in both groups (beta-blockers and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers). All patients enrolled in the study were deficient in Vitamin D, therefore, removing the possibility of heterogeneity in the study population. Endpoints for the study were practical and easily measurable echocardiographic parameters. There were a few limitations also of this study: the study was powered to study 6MWT distance only which has a high variability as an end-point measure. It was not powered to study the secondary end points of echocardiographic parameters. It did not study hard clinical end points such as total deaths or major adverse cardiac events. A very high proportion of patients had atrial fibrillation (nearly 50%) which is higher than that seen in contemporary studies. With such high rates of atrial fibrillation, estimation of EF by echocardiography may be unreliable. The rates of attrition in the study were high (>25%).

The study shows a beneficial effect of Vitamin D therapy on parameters of LV function in patients with heart failure and Vitamin D deficiency; however, this needs confirmation in adequately powered, larger studies that use objective measures of LV function such as cardiac magnetic resonance imaging. However, Vitamin D supplementation appears safe in this population and should be replenished in patients with Vitamin D deficiency as no harm was demonstrated in this study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1Zittermann A, Schleithoff SS, Tenderich G, Berthold HK, Körfer R, Stehle P. Low Vitamin D status: A contributing factor in the pathogenesis of congestive heart failure? J Am Coll Cardiol 2003;41:105-12.
2Ameri P, Ronco D, Casu M, Denegri A, Bovio M, Menoni S, et al. High prevalence of Vitamin D deficiency and its association with left ventricular dilation: An echocardiography study in elderly patients with chronic heart failure. Nutr Metab Cardiovasc Dis 2010;20:633-40.
3Schierbeck LL, Jensen TS, Bang U, Jensen G, Køber L, Jensen JE. Parathyroid hormone and Vitamin D – Markers for cardiovascular and all cause mortality in heart failure. Eur J Heart Fail 2011;13:626-32.
4Dalbeni A, Scaturro G, Degan M, Minuz P, Delva P. Effects of six months of Vitamin D supplementation in patients with heart failure: A randomized double-blind controlled trial. Nutr Metab Cardiovasc Dis 2014;24:861-8.
5Witham MD, Crighton LJ, Gillespie ND, Struthers AD, McMurdo ME. The effects of Vitamin D supplementation on physical function and quality of life in older patients with heart failure: A randomized controlled trial. Circ Heart Fail 2010;3:195-201.
6Boxer RS, Kenny AM, Schmotzer BJ, Vest M, Fiutem JJ, Piña IL. A randomized controlled trial of high dose Vitamin D3 in patients with heart failure. JACC Heart Fail 2013;1:84-90.
7Witte KK, Byrom R, Gierula J, Paton MF, Jamil HA, Lowry JE, et al. Effects of Vitamin D on cardiac function in patients with chronic HF: The VINDICATE study. J Am Coll Cardiol 2016;67:2593-603.