Supplemental thiamine for the treatment of acute heart failure syndrome: a randomized controlled trial

Howard A Smithline, Michael Donnino, Fidela S J Blank, Richard Barus, Ryan A Coute, Alexander B Knee, Paul Visintainer, Howard A Smithline, Michael Donnino, Fidela S J Blank, Richard Barus, Ryan A Coute, Alexander B Knee, Paul Visintainer

Abstract

Background: The purpose of this pilot study was to determine if a definitive clinical trial of thiamine supplementation was warranted in patients with acute heart failure. We hypothesized that thiamine, when added to standard of care, would improve dyspnea (primary outcome) in hospitalized patients with acute heart failure. Peak expiratory flow rate, type B natriuretic peptide, free fatty acids, glucose, hospital length of stay, as well as 30-day rehospitalization and mortality were pre-planned secondary outcome measures.

Methods: This was a blinded experimental study at two urban academic hospitals. Consecutive patients admitted from the Emergency Department with a primary diagnosis of acute heart failure were recruited over 2 years. Patients on a daily dietary supplement were excluded. Randomization was stratified by type B natriuretic peptide and diabetes medication categories. Subjects received study drug (100 mg thiamine or placebo) in the evening of their first and second day. Outcome measures were obtained 8 h after study drug infusion. Dyspnea was measured on a 100-mm visual analog scale sitting up on oxygen, sitting up off oxygen, and lying supine off oxygen with 0 indicating no dyspnea. Data were analyzed using mixed-models as well as linear, negative binomial and logistic regression models to assess the impact of group on outcome measures.

Results: Of 130 subjects randomized, 118 had evaluable data (55 in the control and 63 in the treatment groups), 89% in both groups were adjudicated to have primarily AHF. Thiamine values increased significantly in the treatment group and were unchanged in the control group. One patient had thiamine deficiency. Only dyspnea measured sitting upright on oxygen differed significantly by group over time. No change was found for the other measures of dyspnea and all of the secondary measures.

Conclusions: In mild-moderate acute heart failure patients without thiamine deficiency, a standard dosing regimen of thiamine did not improve dyspnea, biomarkers, or other clinical parameters.

Trial registration: ClinicalTrials.gov: NCT00680706 , May 20, 2008 (retrospectively registered).

Keywords: Acute heart failure; Dyspnea; Thiamine.

Conflict of interest statement

Ethics approval and consent to participate

The human ethics committee of both hospitals approved this study. Specifically, this study was approved by the Institutional Review Board of the Human Research Protection Program at Baystate Medical Center, and the Institutional Review Board of the Human Subjects Protection Office at Beth Israel Deaconess Medical Center. All subjects consented to be in this study and signed approved consent documents.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

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Fig. 1
Study Design
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Fig. 2
Flow Chart

References

    1. Gheorghiade M, Filippatos G, De Luca L, Burnett J. Congestion in acute heart failure syndromes: an essential target of evaluation and treatment. Am J Med. 2006;119:S3–S10. doi: 10.1016/j.amjmed.2006.09.011.
    1. Neely JR, Morgan HE. Relationship between carbohydrate and lipid metabolism and the energy balance of heart muscle. Annu Rev Physiol. 1974;36:413–459. doi: 10.1146/annurev.ph.36.030174.002213.
    1. Smith CS, Bottomley PA, Schulman SP, Gerstenblith G, Weiss RG. Altered creatine kinase adenosine triphosphate kinetics in failing hypertrophied human myocardium. Circulation. 2006;114:1151–1158. doi: 10.1161/CIRCULATIONAHA.106.613646.
    1. Weiss RG, Gerstenblith G, Bottomley PA. ATP flux through creatine kinase in the normal, stressed, and failing human heart. Proc Natl Acad Sci U S A. 2005;102:808–813. doi: 10.1073/pnas.0408962102.
    1. Fragasso G, et al. Effects of metabolic modulation by trimetazidine on left ventricular function and phosphocreatine/adenosine triphosphate ratio in patients with heart failure. Eur Heart J. 2006;27:942–948. doi: 10.1093/eurheartj/ehi816.
    1. Morrow DA, Givertz MM. Modulation of myocardial energetics: emerging evidence for a therapeutic target in cardiovascular disease. Circulation. 2005;112:3218–3221. doi: 10.1161/CIRCULATIONAHA.105.581819.
    1. Hanninen SA, Darling PB, Sole MJ, Barr A, Keith ME. The prevalence of thiamin deficiency in hospitalized patients with congestive heart failure. J Am Coll Cardiol. 2006;47:354–361. doi: 10.1016/j.jacc.2005.08.060.
    1. Strumilo S, Czerniecki J, Dobrzyn P. Regulatory effect of thiamin pyrophosphate on pig heart pyruvate dehydrogenase complex. Biochem Biophys Res Commun. 1999;256:341–345. doi: 10.1006/bbrc.1999.0321.
    1. Sutherland DJ, Jaussi AW, Gubler CJ. The effects of thiamine deprivation, and oxythiamine- and pyrithiamine-treatment on cardiac function and metabolism in the rat. J Nutr Sci Vitaminol (Tokyo) 1974;20:35–54. doi: 10.3177/jnsv.20.35.
    1. Januzzi JLJ, et al. The N-terminal pro-BNP investigation of dyspnea in the emergency department (PRIDE) study. Am J Cardiol. 2005;95:948–954. doi: 10.1016/j.amjcard.2004.12.032.
    1. Pang PS, et al. A proposal to standardize dyspnoea measurement in clinical trials of acute heart failure syndromes: the need for a uniform approach. Eur Heart J. 2008;29:816–824. doi: 10.1093/eurheartj/ehn048.
    1. StataCorp. Stata Statistical Software: Release 12. College Station, TX: StataCorp LP; 2011. .
    1. Ardehali H, et al. Targeting myocardial substrate metabolism in heart failure: potential for new therapies. Eur J Heart Fail. 2012;14:120–129. doi: 10.1093/eurjhf/hfr173.
    1. Gao D, Ning N, Niu X, Hao G, Meng Z. Trimetazidine: a meta-analysis of randomised controlled trials in heart failure. Heart. 2011;97:278–286. doi: 10.1136/hrt.2010.208751.
    1. Heo KS, Fujiwara K, Abe J. Glucagon-like peptide-1 and its cardiovascular effects. Curr Atheroscler Rep. 2012;14:422–428. doi: 10.1007/s11883-012-0265-9.
    1. Stanley WC, Dabkowski ER, Ribeiro RFJ, O’Connell KA. Dietary fat and heart failure: moving from lipotoxicity to lipoprotection. Circ Res. 2012;110:764–776. doi: 10.1161/CIRCRESAHA.111.253104.
    1. Bersin RM, et al. Improved hemodynamic function and mechanical efficiency in congestive heart failure with sodium dichloroacetate. J Am Coll Cardiol. 1994;23:1617–1624. doi: 10.1016/0735-1097(94)90665-3.
    1. Abozguia K, et al. Metabolic modulator perhexiline corrects energy deficiency and improves exercise capacity in symptomatic hypertrophic cardiomyopathy. Circulation. 2010;122:1562–1569. doi: 10.1161/CIRCULATIONAHA.109.934059.
    1. Fragasso G, et al. Effect of partial inhibition of fatty acid oxidation by trimetazidine on whole body energy metabolism in patients with chronic heart failure. Heart. 2011;97:1495–1500. doi: 10.1136/hrt.2011.226332.
    1. Halbirk M, et al. Cardiovascular and metabolic effects of 48-h glucagon-like peptide-1 infusion in compensated chronic patients with heart failure. Am J Physiol Heart Circ Physiol. 2010;298:H1096–H1102. doi: 10.1152/ajpheart.00930.2009.
    1. Halbirk M, et al. Suppression of circulating free fatty acids with acipimox in chronic heart failure patients changes whole body metabolism but does not affect cardiac function. Am J Physiol Heart Circ Physiol. 2010;299:H1220–H1225. doi: 10.1152/ajpheart.00475.2010.
    1. Rieck J, et al. Urinary loss of thiamine is increased by low doses of furosemide in healthy volunteers. J Lab Clin Med. 1999;134:238–243. doi: 10.1016/S0022-2143(99)90203-2.
    1. Lennie TA, Moser DK, Heo S, Chung ML, Zambroski CH. Factors influencing food intake in patients with heart failure: a comparison with healthy elders. J Cardiovasc Nurs. 2006;21:123–129. doi: 10.1097/00005082-200603000-00008.
    1. Seligmann H, Halkin H, Rauchfleisch S, et al. Thiamine deficiency in patients with congestive heart failure receiving long-term furosemide therapy: a pilot study. Am J Med. 1991;91:151–155. doi: 10.1016/0002-9343(91)90007-K.
    1. Pfitzenmeyer P, Guilland JC, d’Athis P, Petit-Marnier C, Gaudet M. Thiamine status of elderly patients with cardiac failure including the effects of supplementation. Int J Vitam Nutr Res. 1994;64:113–118.
    1. Shimon I, Almog S, Vered Z, et al. Improved left ventricular function after thiamine supplementation in patients with congestive heart failure receiving long-term furosemide therapy. Am J Med. 1995;98:485–490. doi: 10.1016/S0002-9343(99)80349-0.
    1. Smithline HA. Thiamine for the treatment of acute decompensated heart failure. Am J Emerg Med. 2007;25:124–126. doi: 10.1016/j.ajem.2006.05.008.
    1. Schoenenberger Andreas W., Schoenenberger-Berzins Renate, der Maur Christoph Auf, Suter Paolo M., Vergopoulos Athanasios, Erne Paul. Thiamine supplementation in symptomatic chronic heart failure: a randomized, double-blind, placebo-controlled, cross-over pilot study. Clinical Research in Cardiology. 2011;101(3):159–164. doi: 10.1007/s00392-011-0376-2.
    1. Donnino MW, et al. Randomized, double-blind, placebo-controlled trial of thiamine as a metabolic resuscitator in septic shock: a pilot study. Crit Care Med. 2016;44:360–367. doi: 10.1097/CCM.0000000000001572.
    1. Smithline HA, Donnino M, Greenblatt DJ. Pharmacokinetics of high-dose oral thiamine hydrochloride in healthy subjects. BMC Clin Pharmacol. 2012;12:4. doi: 10.1186/1472-6904-12-4.

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