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ORIGINAL RESEARCH
Year : 2021  |  Volume : 5  |  Issue : 2  |  Page : 134-138

Vitamin D Correlation with Echocardiographic Function in Patients of Congestive Heart Failure


Department of Medicine, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India

Date of Submission26-Aug-2020
Date of Decision18-Oct-2020
Date of Web Publication24-Mar-2021

Correspondence Address:
Dr. Vivek Mohanty
Room No – 225, Building No – 84, Department of Medicine, All India Institute of Medical Sciences, Rishikesh - 249 203, Uttarakhand
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jiae.jiae_55_20

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  Abstract 

Background: The association between vitamin D and heart failure, especially left ventricular (LV) function, is still not clear. Objectives: We aimed to study the correlation between 25-hydroxy vitamin D levels and parameters of cardiac systolic and diastolic functions in patients with LV systolic heart failure. Materials and Methods: Ninety patients of heart failure coming to our hospital with systolic heart failure (LV ejection fraction <40%) were included. Venous sample were taken for measurement of 25-hyrdoxy vitamin D levels. Transthoracic echocardiography was done for all patients, and parameters of LV systolic and diastolic functions were taken. Results: Compared to patients having vitamin D <20 ng/ml, patients having vitamin D levels ≥20 ng/ml had higher early diastolic mitral annular velocity (e'), significantly lower ratio of early diastolic mitral inflow velocity (E) to e' (E/e'), significantly shorter isovolumetric relaxation time (IVRT) suggestive of better diastolic function. Furthermore, patients having vitamin D <20 ng/ml had higher LV end-systolic volume, LV end-systolic diameter, larger LV end-diastolic diameter, higher interventricular septum thickness, higher LV wall thickness, and higher LV mass. Conclusion: Reduced vitamin D (<20 ng/ml) was associated with worse systolic function in terms of systolic volume and diameter, diastolic function in terms of lower e′, higher E/e′, and longer IVRT.

Keywords: Heart failure, ventricular function, Vitamin D


How to cite this article:
Mohanty V, Pathania M, Bhasi A. Vitamin D Correlation with Echocardiographic Function in Patients of Congestive Heart Failure. J Indian Acad Echocardiogr Cardiovasc Imaging 2021;5:134-8

How to cite this URL:
Mohanty V, Pathania M, Bhasi A. Vitamin D Correlation with Echocardiographic Function in Patients of Congestive Heart Failure. J Indian Acad Echocardiogr Cardiovasc Imaging [serial online] 2021 [cited 2021 Nov 29];5:134-8. Available from: https://www.jiaecho.org/text.asp?2021/5/2/134/311858


  Introduction Top


Heart failure is a condition characterized by contractile dysfunction of cardiac myocyte. Cardiac myocytes, to maintain their contractile function, require a continuous supply of high-energy substrates including micronutrients. Most of the cross-sectional studies have demonstrated that heart failure is associated with deficiency of essential micronutrients. Thus, correction of these deficiencies may play an important role in limiting or even possibly reversing the progressive myocyte dysfunction/necrosis or apoptosis which characterize heart failure.[1] Vitamin D deficiency is common in heart failure patients because poor work capacity results in sun avoidance in these patients. Vitamin D receptor has been found to have a cardioprotective role through its anti-inflammatory, anti-fibrotic, and anti-apoptotic effect on cardiac myocytes.[2] Cardiac muscle possesses vitamin D receptor and a calcitriol-dependent calcium-binding protein. Furthermore, a voltage-dependent calcium channel which gets activated by calcitriol coexists in these muscles. Experimental studies have found that vitamin D receptor suppresses T2-helper cell-mediated inflammation of the heart.[3] Vitamin D receptor activation via calcitriol and paricalcitol causes improvement in capillary deficit and could potentially limit the degree of fibrosis of the heart, thus playing a key role in reducing left ventricular (LV) hypertrophy.[4] Vitamin D deficiency causes secondary hyperparathyroidism and increased circulating levels of parathyroid hormone (PTH). PTH has been found to activate protein kinase C (PKC) of cardiac myocytes. Activation of this PKC leads to activation of fetal protein in cardiac myocytes and other hypertrophic growth factors which leads to LV hypertrophy. Furthermore, PTH-related peptide which is expressed in cardiovascular cells (smooth muscles and endothelial cells) plays a key role in the mechanism in vasorelaxation.[5] Low level of circulating vitamin D has thus been found to be directly contributing to the pathogenesis and symptomatology of heart failure.[6] Thus, the possible mechanisms by which vitamin D supplementation can reduce disease progression and symptoms severity include-

  1. Negative regulation of activity of the renin -angiotensin -aldosterone system which has a key role in the pathogenesis of remodeling of the left ventricle following heart failure
  2. Vitamin D causes suppression of i-PTH which in multiple studies have been found to be independent risk factor for heart failure[7]
  3. Inflammatory mediators tumor necrosis factor-alpha and interleukin-6 are downregulated. Vitamin D affects the transcription of cyclo-oxygenase and nuclear factor-kappa B and activates signal cascades like mitogen-activated protein kinase which are important in inflammation pathway
  4. It directly promotes cardiac myocyte growth and differentiation by means of vitamin D receptor
  5. In the endothelium, it regulates the activity of nitric oxide/peroxynitrite and helps in normal functioning of the cardiac myocytes.


Aim of the study

We aimed to study the correlation between serum 25-hydroxy vitamin D levels and echocardiographic parameters of cardiac systolic and diastolic functions in patients with LV systolic heart failure.


  Materials and Methods Top


Study procedure

The study included ninety patients of systolic heart failure coming to our hospital with LV ejection fraction <40%. All the patients fulfilling the inclusion criteria were informed about the methodology of this study. Informed and written consent was taken in English, Hindi/local language as per patient convenience. Detailed history, physical examination, and blood pressure measurement were done. Serum vitamin D measured was determined by electrochemiluminescence immunoassay, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) was measured using Nano-Check™ NT-proBNP test which was an immunochromatography assay. Low Vitamin D level was defined as <20 ng/ml as per the National Health and Nutritional Examination surveys (1988–1994 and 2000–2004).[8] Transthoracic echocardiography was performed in all patients with Philips Epiq 7C echocardiography machine.

With 2.5-MHz multifrequency phased array transducer, standard grayscale two-dimensional (2D) and tissue Doppler cine loops from three consecutive beats were obtained at end-expiratory apnea from standard apical views at depths of 12 cm–20 cm. Gain settings were adjusted for routine grayscale 2D imaging to optimize endocardial definition. Routine digital grayscale 2D and tissue Doppler cine loops were obtained, including mid-LV short-axis views at the level of the papillary muscle and standard apical views (four-chamber, two-chamber, and long-axis). Sector width was optimized to allow for complete myocardial visualization while maximizing the frame rate. LV end-diastolic volume (EDV), end-systolic volume (ESV), and ejection fraction (EF) were obtained with the modified biplane Simpson's method from the apical two- and four-chamber images. Left atrial volume (LAV) was calculated using the prolate ellipse method. All measurements were made in >3 consecutive cardiac cycles and in >5 cycles if the patient's rhythm was AF and average values were used for the final analyses.

The pulsed-wave Doppler-derived transmitral flow profile, pulmonary venous flow profile, and color tissue Doppler-derived mitral annular velocity were obtained from the apical four-chamber view. The mitral flow early diastolic wave velocity (E), late diastolic atrial contraction wave velocity (A), and the E-wave deceleration time (E-DcT) were measured; the pulsed-wave Doppler-derived pulmonary venous systolic wave velocity (PV-S), early diastolic wave velocity (PV-D), atrial contraction reverse wave velocity (PV-Ar), and the D-wave DcT (PV D-DcT) were also measured. Spectral pulsed-wave tissue Doppler-derived mitral annular peak systolic velocity (s′), early diastolic velocity (e′), late diastolic velocity (a′), and the E/e′ ratio were calculated to estimate the LV filling pressure for all patients.

Statistical analysis

All analyses were conducted using the Statistical Package for the Social Sciences software, version 21 (SPSS Inc., Chicago, IL, USA). Categorical data were expressed as numbers. Continuous data were expressed as mean ± standard deviation and were compared using Student's t-test. Correlations were checked for echocardiographic parameters against vitamin D level using Pearson's correlation coefficient.


  Results Top


Patient characteristics

Basic demographic characteristics

In our study, 51.5% of the participants were male and 48.5% of the participants were female [Table 1]. The mean age (years) was 53.77 ± 13.02 and ranged from 21 to 81. The most common cause for heart failure in our study was found to be coronary artery disease which accounted for 56.6% of the cases, followed by dilated cardiomyopathy which accounted for 28.8% of the cases. The most common comorbidity was found to be hypertension which was present in 51.1%, followed by chronic obstructive pulmonary disease (COPD) which was found in 35.1% of the patients and diabetes in 37.7%. The demographics of the cohort involved in the study are given in [Table 1].
Table 1: Demographics of the study population (n=90)

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Vitamin D and N-terminal pro-B-type natriuretic peptide levels in the study group

Overall, the mean vitamin D level was 20.68 ± 14.10 ng/ml. Fifty-two (57.8%) patients had their vitamin D levels below 20 ng/ml (considered deficient) and 38 (42.2%) had vitamin D levels ≥20 ng/ml (considered within normal range).

The mean NT-proBNP level in our study was 4785.61 ± 2695.88 pg/ml. There was no significant difference between NT-proBNP levels in patients with vitamin D < 20 ng/ml versus patients with vitamin D ≥20 ng/ml (5320.84 ± 2885.4 vs. 4071.95 ± 2593.81, P = 0.179) [Table 2].
Table 2: Vitamin D and NT-proBNP levels between the two groups

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Echocardiographic measurements

[Table 3] shows the mean values of all echocardiographic LV diastolic and systolic function parameters. Tissue Doppler imaging-derived values were measured from septal and lateral mitral annular positions and averaged. The average e′ velocity was 6.02 ± 1.61 cm/s, the average a′ velocity was 7.2 ± 2.3 cm/s, and the average s′ velocity was 5.1 ± 1.5 cm/s. Mitral flow E wave velocity was 81.7 ± 24 cm/s, and A wave velocity was 62 ± 27 cm/s. LAV was 76.5 ± 22.3 ml, LV EDV was 175 ± 52.4 ml, LV ESV was 115.2 ± 40.1 ml, and LV EF was 32.8 ± 5.9%. Isovolumic relaxation time (IVRT) was 104.2 ± 20.9 ms. The interventricular septal (IVS) thickness was 11.5 ± 3.4 mm, LV posterior wall (PW) thickness was 11.9 ± 3.1 mm, and mean LV wall thickness was 11.5 ± 3.05 mm. In addition, the mean LV mass was 333.2 ± 169 g. The ratios E/A, E/e′, and e′/a′ were 1.61 ± 1.02, 14.5 ± 6.9, and 0.98 ± 0.35, respectively [Table 3].
Table 3: Echocardiographic measurements among the study population

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Correlations between echocardiographic determinants of left ventricular diastolic and systolic function and vitamin D and N-terminal pro-B-type natriuretic peptide levels

Regarding the diastolic function, it was found that there was a significant positive correlation between vitamin D and average e′ velocity (r = 0.524, P < 0.001) and a significant negative correlation between vitamin D and both IVRT (r = 0.58, P < 0.001) and E/e′ (r = 0.632 P < 0.001). The ratio e′/a′ only showed a trend toward a weak negative correlation (r = 0.242, P = 0.06), while other parameters of diastolic function did not show any correlation with vitamin D levels [Table 4].
Table 4: Correlations between echocardiographic determinants of LV diastolic and systolic functions versus vitamin D and NT-proBNP levels

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Comparisons between echocardiographic determinants of left ventricular diastolic and systolic functions according to vitamin D levels

It was found that, compared to patients with vitamin D <20 ng/ml, patients with vitamin D level ≥ 20 ng/ml had significantly higher average e′ (6.2 ± 1.7 vs. 5.4 ± 1.7, P = 0.029), significantly shorter IVRT (100.5 ± 22.1 vs. 116.7 ± 23.5 ms, P = 0.014), and significantly lower E/e′ (12.2 ± 4.28 vs. 18.5 ± 8.2, P = 0.002). This is suggestive of a better diastolic function. There was no significant difference between both the groups regarding average a′, E wave velocity, A wave velocity, E-DcT, LAV, E/A, and e′/a′.

It was found that, compared to patients with vitamin D ≥ 20 ng/ml, patients with vitamin D level <20 ng/ml had higher LV ESV (95 ± 21.2 vs. 119.6 ± 48.2 ml, P = 0.048), larger end-systolic diameter (45.1 ± 4.7 vs. 48.5 ± 7.5 mm, P = 0.059), higher IVS thickness (9.3 ± 1.7 vs. 12.1 ± 3.6 mm, P < 0.001), higher PW thickness (9.1 ± 1.7 vs. 13.5 ± 3.8 mm, P < 0.001), higher mean LV wall thickness (9.3 ± 1.5 vs. 13.1 ± 29 mm, P < 0.001), and higher LV mass (268 ± 78 vs. 372 ± 194 g, P = 0.041), while average s′, EDV, and EF were not different [Table 5].
Table 5: Comparisons between echocardiographic determinants of left ventricular diastolic and systolic functions according to vitamin D level

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  Discussion Top


The study showed that in patients with heart failure, vitamin D deficiency was associated with worse LV systolic function and LV diastolic function.

Vitamin D effect on systolic and diastolic functions

In this study, serum vitamin D levels negatively correlated with ESV, EDV, and average s′. Furthermore, a negative correlation was found between vitamin D levels and LV thickness and LV mass. Thus, vitamin D deficiency may result in myocardial fibrosis, fiber thickening, and anti-apoptosis resulting in LV dilatation. Similarly, vitamin D deficiency was associated with lower average e', higher E/e′ ratio, and longer IVRT, indirectly suggesting higher LV filling pressure.

Vitamin D, N-terminal pro-B-type natriuretic peptide, and cardiac function

In our study, all patients had higher NT-proBNP levels. The mean value for those who had vitamin D <20 ng/ml or >20 ng/ml was comparable.

Possible mechanisms

Vitamin D deficiency directly causes myocyte hypertrophy, extracellular matrix proliferation, and deposition in the myocardial tissue. Thus, it plays an important role in ventricular remodeling following heart failure including LV dilatation.[7] Furthermore, it plays an important role in vascular compliance and myocardial and arterial wall stiffness, thus determining diastolic functioning.

Comparison with previous studies

Our study findings are consistent with findings from other studies, which showed that vitamin D deficiency was associated with worse LV function.[9],[10] Furthermore, lower serum vitamin D levels were found to be associated with larger ventricular diameters and reduced fractional shortening.[11] Similar to other studies,[12],[13] our study found that lower vitamin D levels were associated with higher LV wall thickness. However, other studies have shown no correlation between vitamin D and LV dimensions.[14],[15] Our study showed a significant association between vitamin D levels and diastolic dysfunction which is in contrast to previous studies.[16],[17] Nevertheless, such controversy remains in this regard and warrants further research.

Limitations

The study was a single-center experience with a relatively small sample size. Furthermore, it did not include patients of heart failure with preserved EF. LV parameters with healthy controls were also not compared. Thus, further studies with large sample size addressing these issues need to be carried out.


  Conclusion Top


Our study showed that vitamin D levels significantly correlated with both LV systolic and diastolic functions. Low serum levels of vitamin D (<20 ng/ml) were associated with increased LV thickness, mass, ESV, and diameter. Similarly, it was associated with worse LV diastolic function in terms of lower e′, higher E/e′, and longer IVRT.

Recommendations

Vitamin D levels should be determined in all patients with heart failure with reduced EF followed by supplementation which may be beneficial in terms of improvement in LV wall thickness and systolic and diastolic functions.

Acknowledgment

We would like to thank the Department of Medicine and Cardiology, AIIMS, Rishikesh.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Soukoulis V, Dihu JB, Sole M, Anker SD, Cleland J, Fonarow GC, et al. Micronutrient deficiencies an unmet need in heart failure. J Am Coll Cardiol 2009;54:1660-73.  Back to cited text no. 1
    
2.
Bae S, Singh SS, Yu H, Lee JY, Cho BR, Kang PM. Vitamin D signaling pathway plays an important role in the development of heart failure after myocardial infarction. J Appl Physiol (1985) 2013;114:979-87.  Back to cited text no. 2
    
3.
Song J, Chen X, Cheng L, Rao M, Chen K, Zhang N, et al. Vitamin D receptor restricts T helper 2-biased inflammation in the heart. Cardiovasc Res 2018;114:870-9.  Back to cited text no. 3
    
4.
Koleganova N, Piecha G, Ritz E, Gross ML. Calcitriol ameliorates capillary deficit and fibrosis of the heart in subtotally nephrectomized rats. Nephrol Dial Transplant 2009;24:778-87.  Back to cited text no. 4
    
5.
Schlüter KD, Piper HM. Cardiovascular actions of parathyroid hormone and parathyroid hormone-related peptide. Cardiovasc Res 1998;37:34-41.  Back to cited text no. 5
    
6.
Zittermann 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.  Back to cited text no. 6
    
7.
Zhao JD, Jia JJ, Dong PS, Zhao D, Yang XM, Li DL, et al. Effect of Vitamin D on ventricular remodelling in heart failure: A meta-analysis of randomised controlled trials. BMJ Open 2018;8:e020545.  Back to cited text no. 7
    
8.
Kendrick J, Targher G, Smits G, Chonchol M. 25-Hydroxyvitamin D deficiency is independently associated with cardiovascular disease in the third national health and nutrition examination survey. Atherosclerosis 2009;205:255-60. Shane E, Mancini D, Aaronson K, Silverberg SJ, Seibel MJ, Addesso V, et al. Bone mass, Vitamin D deficiency, and hyperparathyroidism in congestive heart failure. Am J Med 1997;103:197-207.  Back to cited text no. 8
    
9.
Matias PJ, Ferreira C, Jorge C, Borges M, Aires I, Amaral T, et al. 25-Hydroxyvitamin D3, arterial calcifications and cardiovascular risk markers in haemodialysis patients. Nephrol Dial Transplant 2009;24:611-8.  Back to cited text no. 9
    
10.
Jegger D, da Silva RF, Lartaud I, Gaillard V, Jeanrenaud X, Nasratullah M, et al. Effects of an aging vascular model on healthy and diseased hearts. Am J Physiol Heart Circ Physiol 2007;293:H1334-43.  Back to cited text no. 10
    
11.
Briese S, Wiesner S, Will JC, Lembcke A, Opgen-Rhein B, Nissel R, et al. Arterial and cardiac disease in young adults with childhood-onset end-stage renal disease–impact of calcium and Vitamin D therapy. Nephrol Dial Transplat 2006;21:1906-14.  Back to cited text no. 11
    
12.
Bucharles S, Barberato SH, Stinghen AE, Gruber B, Meister H, Mehl A, et al. Hypovitaminosis D is associated with systemic inflammation and concentric myocardial geometric pattern in hemodialysis patients with low iPTH levels. Nephron Clin Pract 2011;118:c384-91.  Back to cited text no. 12
    
13.
Pilz S, Henry RM, Snijder MB, van Dam RM, Nijpels G, Stehouwer CD, et al. Vitamin D deficiency and myocardial structure and function in older men and women: The Hoorn study. J Endocrinol Invest 2010;33:612-7.  Back to cited text no. 13
    
14.
van Ballegooijen AJ, Snijder MB, Visser M, van den Hurk K, Kamp O, Dekker JM, et al. Vitamin D in relation to myocardial structure and function after eight years of follow-up: The Hoorn study. Ann Nutr Metab 2012;60:69-77.  Back to cited text no. 14
    
15.
Pilz S, Henry RM, Snijder MB, van Dam RM, Nijpels G, Stehouwer CD, et al. Vitamin D deficiency and myocardial structure and function in older men and women: The Hoorn study. J Endocrinol Invest 2010;33:612-7.  Back to cited text no. 15
    
16.
Pilz S, Henry RM, Snijder MB, van Dam RM, Nijpels G, Stehouwer CD, et al. Vitamin D deficiency and myocardial structure and function in older men and women: The Hoorn study. J Endocrinol Invest 2010;33:612-7.  Back to cited text no. 16
    
17.
Pilz S, Henry RM, Snijder MB, van Dam RM, Nijpels G, Stehouwer CD, et al. Vitamin D deficiency and myocardial structure and function in older men and women: The Hoorn study. J Endocrinol Invest 2010;33:612-7.  Back to cited text no. 17
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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