Improved left ventricular function after thiamine supplementation in patients with congestive heart failure receiving long-term furosemide therapy

doi:10.1016/S0002-9343(99)80349-0

The American Journal of Medicine

Volume 98, Issue 5, May 1995, Pages 485-490

https://doi.org/10.1016/S0002-9343(99)80349-0 Get rights and content

Purpose

We have previously found thiamine (vitamin B₁) deficiency in patients with congestive heart failure (CHF) who had received long-term furosemide therapy. In the present study, we assessed the effect of thiamine repletion on thiamine status, functional capacity, and left ventricular ejection fraction (LVEF) in patients with moderate to severe CHF who had received furosemide in closes of 80 mg/d or more for at least 3 months.

Patients and methods

Thirty patients were randomized to 1 week of double-blind inpatient therapy with either IV thiamine 200 mg/d or placebo (n = 15 each). All previous drugs were continued. Following discharge, all 30 patients received oral thiamine 200 mg/d as outpatients for 6 weeks. Thiamine status was determined by the erythrocyte thiamine-pyrophosphate effect (TPPE). LVEF was determined by echocardiography.

Results

TPPE, diuresis, and LVEF were unchanged with IV placebo. After IV thiamine, TPPE decreased (11.7% ± 6.5% to 5.4% ± 3.2%; P <0.01). LVEF increased (0.28 ± 0.11 to 0.32 ± 0.09; P <0.05), as did diuresis (1,731 ± 800 mL/d to 2,389 ± 752 mL/d; P <0.02), and sodium excretion (84 ± 52 mEq/d to 116 ± 83 mEq/d, P <0.05). In the 27 patients completing the full 7-week intervention, LVEF rose by 22% (0.27 ± 0.10 to 0.33 ± 0.11, P <0.01).

Conclusions

Thiamine repletion can improve left ventricular function and biochemical evidence of thiamine deficiency in some patients with moderate-to-severe CHF who are receiving long-term furosemide therapy.

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Cited by (173)

Does thiamine supplementation affect heart failure? A systematic review and meta-analysis of randomized control trials
2023, Heart and Lung
Heart failure is a pathophysiological condition where decreased cardiac output is observed subsequent to any structural deformity or cessation of normal function. Thiamine deficiency is one of the risk factors responsible for causing HF; other risk factors include hypertension, smoking, and obesity.
We conducted a systemic review and meta-analysis of RCTs to scrutinize whether the heart failure patients would benefit from thiamine supplementation or not when compared to placebo.
We selected only those double-arm randomized controlled trials (RCTs) which included participants presenting with symptomatic heart failure. We excluded all the articles published in languages other than English Language. Furthermore, all the studies other than RCTs were also omitted. Articles yielded from the electronic search were exported to EndNote Reference Library software to remove any duplicates. Analyses were done using the Review manager 5.4 tool. Mean values and standard deviations were retrieved for the continuous outcomes given as raw data.
The 6 RCTs selected for the statistical analysis consisted of 298 participants (158 in the intervention group, 140 in the placebo group). The outcomes resulted to be non-significant with LVEF p-value= 0.08, NT-pro BNP p-value= 0.94, LVEDV p-value= 0.53, 6MWT p-value=0.59, mortality p-value= 0.61, hospitalization p-value= 0.53 and dyspnea p-value= 0.77. Heart rate is the only significant outcome with a p-value=0.04.
To conclude, except for heart rate, thiamine supplementation had no effect on the outcomes of heart failure patients.
The effects of thiamine supplementation on patients with heart failure: A systematic review and meta-analysis of randomized controlled trials
2022, Complementary Therapies in Medicine
Citation Excerpt :
One study19 had two high-risk bias domains and the other studies were assessed as having unclear risk of bias in at least one domain. Four studies18,20,21,23 were conducted under low risk of bias in random sequence generation and the remaining four17,19,22,24 did not address this domain. Allocation concealment, Blinding, Incomplete outcome data, and Selective reporting were under low risk in over half of these studies, though Pfitzenmeyer et al.19 did not perform blindly in both participants and outcome assessment.
Micronutrients can benefit patients with heart failure (HF). Thiamine is a critical vitamin, while the impact of thiamine supplementation on patients with HF remains unclear. Systematic review and meta-analysis were conducted to evaluate the effects of thiamine supplementation on clinical outcomes in patients with HF.
Databases including Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, Scopus, and CNKI were searched from inception to June 29th 2022. Randomized controlled trials (RCTs) comparing thiamine supplementation with placebo were included. Meta-analysis was conducted with the software Review Manager 5.4. The quality assessment was performed according to Cochrane Risk of Bias Tool 2.0.
Eight studies including 384 patients were included in this review. The results of overall systematic review showed no benefit of thiamine supplementation in HF patients. Compared with the control group, the experimental group had no statistically significant improvements in LVEF (Mean Difference, − 0.19; 95 % CI, − 2.78 to 0.96; I² = 49 %; P = 0.10) in patients with chronic heart failure (CHF). Other outcomes including NYHA class, BNP or NT-proBNP, thiamine status, symptom changes, and quality of life were not improved by thiamine supplementation in CHF patients. Similarly, no improvements in clinical outcomes were found in patients with acute heart failure (AHF) in the studies included.
This systematic review and meta-analysis found no evidence to support the effects of thiamine supplementation in patients with HF, though thiamine supplementation is promising in improving cardiac functions, thiamine status and relieving HF-related symptoms. More well-designed RCTs with large sample sizes are required.
High-Dose Thiamine Supplementation in Older Patients With Heart Failure: A Pilot Randomized Controlled Crossover Trial (THIAMINE-HF)
2022, CJC Open
Citation Excerpt :
In this pilot trial of thiamine supplementation in older adults with HFrEF, we were unable to recruit the target number of patients within 11 months, but our other feasibility targets were reached, including retention, refusal, and adherence rates. Similar to a recent parallel group thiamine trial,8 our study did not identify statistically significant benefits of thiamine supplementation, despite using a higher daily dose (500 mg) than previous trials (100-300 mg).7,8,18-20 The use of sensitive markers, such as peak GLS on echocardiography and NT-proBNP level, reveal nonsignificant improvement with supplementation over 3 months.
Thiamine supplementation may improve cardiac function in older adults with heart failure (HF). Our objectives were to determine the following: (i) the feasibility of conducting a large trial of thiamine supplementation in HF; and (ii) the effects of thiamine on clinical outcomes.
We conducted a double-blinded randomized placebo-controlled 2-period crossover feasibility study from June 2018 to April 2021. Adults aged ≥ 60 years with symptomatic HF and reduced ejection fraction (≤ 45%) were included. Participants were randomized to thiamine mononitrate 500 mg, or placebo, for 90 days and were switched to the opposite treatment for 90 days after a 6-week washout period. The primary feasibility outcome was recruitment of 24 participants in 11 months.
We screened 330 patients over 21 months to recruit 24 patients. Participants’ mean age was 73.4 years. The targets for refusal rate, retention rate, and adherence rate were met. Nonsignificant improvements occurred in left ventricular ejection fraction and N-terminal pro-brain natriuretic peptide (NT-proBNP) level with thiamine. A total of 13 serious adverse events occurred in 7 patients; none were related to the study drug.
Although we did not reach our recruitment target, we found high-dose thiamine supplementation to be well tolerated, with potential improvements in biomarker outcomes. A larger trial of thiamine supplementation is warranted.
La supplémentation en thiamine peut améliorer la fonction cardiaque chez les personnes âgées atteintes d’insuffisance cardiaque (IC). Nos objectifs visaient à déterminer : (i) la faisabilité d’un essai de grande envergure sur la supplémentation en thiamine lors d’IC ; (ii) les effets de la thiamine sur les résultats cliniques.
Nous avons réalisé une étude de faisabilité croisée à double insu et à répartition aléatoire contre placebo sur deux périodes de juin 2018 à avril 2021. Nous avons retenu les adultes de ≥ 60 ans qui avaient une IC symptomatique et une fraction d’éjection réduite (≤ 45 %). Nous avons réparti les participants de façon aléatoire pour recevoir 500 mg de mononitrate de thiamine ou le placebo durant 90 jours, et avons inversé le traitement durant 90 jours après une période de lavage de 6 semaines. Le principal critère de faisabilité était le recrutement de 24 participants en 11 mois.
Nous avons recruté 24 patients sur les 330 patients sélectionnés durant 21 mois. L’âge moyen des participants était de 73,4 ans. Les cibles des taux de refus, des taux de rétention et des taux d’adhésion ont été atteintes. Avec la thiamine, nous avons observé des améliorations non significatives de la fraction d’éjection ventriculaire gauche et de la concentration de propeptide natriurétique de type B N-terminal (NT-proBNP). Parmi les 13 événements indésirables sérieux qu’ont subis sept patients, aucun n’a été associé au médicament étudié.
Bien que nous n’ayons pas atteint notre cible de recrutement, nous avons observé que la supplémentation en thiamine à dose élevée était bien tolérée et qu’il y avait des améliorations potentielles des résultats des biomarqueurs. Un essai de plus grande envergure sur la supplémentation en thiamine est justifié.
Gut microbiome in people living with HIV is associated with impaired thiamine and folate syntheses
2021, Microbial Pathogenesis
People living with HIV have a high incidence of cardiovascular and neurological diseases as comorbid disorders that are commonly linked to inflammation. While microbial translocation can augment inflammation during HIV infection, functional microbiome shifts that may increase pro-inflammatory responses have not been fully characterized. In addition, defining HIV-induced microbiome changes has been complicated by high variability among individuals. Here we conducted functional annotation of previously-published 16S ribosomal RNA gene sequences of 305 HIV positive and 249 negative individuals, with adjustment for geographic region, sex, sexual behavior, and age. Metagenome profiles were inferred from these individuals' 16S data. HIV infection was associated with impaired microbial vitamin B synthesis; around half of the gene families in thiamine and folate biosynthesis pathways were significantly less abundant in the HIV positive group than the negative control. These results are consistent with the high prevalence of thiamine and folate deficiencies in HIV infections. These HIV-induced microbiota shifts have the potential to influence cardiovascular and neurocognitive diseases, given the documented associations between B-vitamin deficiencies, inflammation, and these diseases. We also observed that most essential amino acid biosynthesis pathways were downregulated in the microbiome of HIV-infected individuals. Microbial vitamin B and amino acid synthesis pathways were not significantly recovered by antiretroviral treatment when we compared 262 ART positive and 184 ART negative individuals. Our meta-analysis provides a new outlook for understanding vitamin B and amino acid deficiencies in HIV patients, suggesting that interventions for reversing HIV-induced microbiome shifts may aid in lessening the burdens of HIV comorbidities.
Relevance of nutritional assessment and treatment to counteract cardiac cachexia and sarcopenia in chronic heart failure
2021, Clinical Nutrition
Chronic heart failure (CHF) is frequently associated with the involuntary loss of body weight and muscle wasting, which can determine the course of the disease and its prognosis. While there is no gold standard malnutrition screening tool for their detection in the CHF population, several bioelectrical and imaging methods have been used to assess body composition in these patients (such as Dual Energy X-Ray Absorptiometry and muscle ultrasound, among other techniques). In addition, numerous nutritional biomarkers have been found to be useful in the determination of the nutritional status. Nutritional considerations include the slow and progressive supply of nutrients, avoiding high volumes, which could ultimately lead to refeeding syndrome and worsen the clinical picture. If oral feeding is insufficient, hypercaloric and hyperproteic supplementation should be considered. β-Hydroxy-β-methylbutyrate and omega-3 polyunsaturated fatty acid administration prove to be beneficial in certain patients with CHF, and several interventional studies with micronutrient supplementation have also described their possible role in these subjects. Taking into account that CHF is sometimes associated with gastrointestinal dysfunction, parenteral nutritional support may be required in selected cases. In addition, potential therapeutic options regarding nutritional state and muscle wasting have also been tested in clinical studies. This review summarises the scientific evidence that demonstrates the necessity to carry out a careful nutritional evaluation and nutritional treatment to prevent or improve cardiac cachexia and sarcopenia in CHF, as well as improve its course.
Vitamin B<inf>12</inf> deficiency in heart failure: another “brick in the wall”
2020, Hellenic Journal of Cardiology

View all citing articles on Scopus

^**: Affiliated to the Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.

^***: Supported by the USA-Israel Binational Science Foundation (BSF), grant 88-00007(ZV).

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Clinical studyImproved left ventricular function after thiamine supplementation in patients with congestive heart failure receiving long-term furosemide therapy**,***

Purpose

Patients and methods

Results

Conclusions

Am J Med.

Am J Clin Nutr.

Am J Med.

J Am Coll Cardiol.

Am J Clin Nutr.

Life Sci.

Am J Clin Nutr.

Ann Thorac Surg.

Ann Emerg Med.

Cardiovascular beriberi.

Lancet

Cardiac beriberi: two modes of presentation

BMJ

The haemodynamic, histopathological and hormonal features of alcoholic cardiac beriberi

Q J Med.

Furosemide-induced thiamine deficiency

Jpn Circ J Shi.

Clinical study
Improved left ventricular function after thiamine supplementation in patients with congestive heart failure receiving long-term furosemide therapy,*