Omega-3 supplementation and outcomes of heart failure: A systematic review of clinical trials.

BACKGROUNDS: Omega-3 supplements are endorsed for heart failure (HF) patients to reduce hospitalizations and mortality, offering anti-inflammatory and cardioprotective benefits. METHODS: A comprehensive search was conducted in various databases until November 2022. Eligible studies included clinical trials on patients with HF. Data extraction covered study details, omega-3 specifics, outcomes, and limitations. The JADAD scale was used to assess the risk of bias in randomized controlled trials. RESULTS: The review process involved 572 records from database searches, resulting in 19 studies after eliminating duplicates and screening. These studies assessed the impact of omega-3 on various clinical outcomes, such as mortality, hospitalization, cardiac function, and quality of life. Studied duration varied from weeks to years. Omega-3 supplementation demonstrated potential benefits such as improved heart function, reduced inflammation, and decreased risk of cardiovascular events. CONCLUSION: Omega-3 supplementation could benefit heart disease treatment, potentially reducing therapy duration and improving outcomes. Starting omega-3 supplementation for HF patients seems favorable.

Prescription, Compliance, and Burden Associated with Salt-Restricted Diets in Heart Failure Patients: Results from the French National OFICSel Observatory.

(1) Background: There is much debate about the use of salt-restricted diet for managing heart failure (HF). Dietary guidelines are inconsistent and lack evidence. (2) Method: The OFICSel observatory collected data about adults hospitalised for HF. The data, collected using study-specific surveys, were used to describe HF management, including diets, from the cardiologists' and patients' perspectives. Cardiologists provided the patients' clinical, biological, echocardiography, and treatment data, while the patients provided dietary, medical history, sociodemographic, morphometric, quality of life, and burden data (burden scale in restricted diets (BIRD) questionnaire). The differences between the diet recommended by the cardiologist, understood by the patient, and the estimated salt intake (by the patient) and diet burden were assessed. (3) Results: Between March and June 2017, 300 cardiologists enrolled 2822 patients. Most patients (90%) were recommended diets with <6 g of salt/day. Mean daily salt consumption was 4.7 g (standard deviation (SD): 2.4). Only 33% of patients complied with their recommended diet, 34% over-complied, and 19% under-complied (14% unknown). Dietary restrictions in HF patients were associated with increased burden (mean BIRD score of 8.1/48 [SD: 8.8]). (4) Conclusion: Healthcare professionals do not always follow dietary recommendations, and their patients do not always understand and comply with diets recommended. Restrictive diets in HF patients are associated with increased burden. An evidence-based approach to developing and recommending HF-specific diets is required.

Promising Nutritional Fruits Against Cardiovascular Diseases: An Overview of Experimental Evidence and Understanding Their Mechanisms of Action.

Cardiovascular diseases (CVDs) are one of the leading causes of morbidity and mortality in both developed and developing countries, affecting millions of individuals each year. Despite the fact that successful therapeutic drugs for the management and treatment of CVDs are available on the market, nutritional fruits appear to offer the greatest benefits to the heart and have been proved to alleviate CVDs. Experimental studies have also demonstrated that nutritional fruits have potential protective effects against CVDs. The aim of the review was to provide a comprehensive summary of scientific evidence on the effect of 10 of the most commonly available nutritional fruits reported against CVDs and describe the associated mechanisms of action. Relevant literatures were searched and collected from several scientific databases including PubMed, ScienceDirect, Google Scholar and Scopus. In the context of CVDs, 10 commonly consumed nutritious fruits including apple, avocado, grapes, mango, orange, kiwi, pomegranate, papaya, pineapple, and watermelon were analysed and addressed. The cardioprotective mechanisms of the 10 nutritional fruits were also compiled and highlighted. Overall, the present review found that the nutritious fruits and their constituents have significant benefits for the management and treatment of CVDs such as myocardial infarction, hypertension, peripheral artery disease, coronary artery disease, cardiomyopathies, dyslipidemias, ischemic stroke, aortic aneurysm, atherosclerosis, cardiac hypertrophy and heart failure, diabetic cardiovascular complications, drug-induced cardiotoxicity and cardiomyopathy. Among the 10 nutritional fruits, pomegranate and grapes have been well explored, and the mechanisms of action are well documented against CVDs. All of the nutritional fruits mentioned are edible and readily accessible on the market. Consuming these fruits, which may contain varying amounts of active constituents depending on the food source and season, the development of nutritious fruits-based health supplements would be more realistic for consistent CVD protection.

Dietary Management of Heart Failure: DASH Diet and Precision Nutrition Perspectives.

Heart failure (HF) is a major health care burden increasing in prevalence over time. Effective, evidence-based interventions for HF prevention and management are needed to improve patient longevity, symptom control, and quality of life. Dietary Approaches to Stop Hypertension (DASH) diet interventions can have a positive impact for HF patients. However, the absence of a consensus for comprehensive dietary guidelines and for pragmatic evidence limits the ability of health care providers to implement clinical recommendations. The refinement of medical nutrition therapy through precision nutrition approaches has the potential to reduce the burden of HF, improve clinical care, and meet the needs of diverse patients. The aim of this review is to summarize current evidence related to HF dietary recommendations including DASH diet nutritional interventions and to develop initial recommendations for DASH diet implementation in outpatient HF management. Articles involving human studies were obtained using the following search terms: Dietary Approaches to Stop Hypertension (DASH diet), diet pattern, diet, metabolism, and heart failure. Only full-text articles written in English were included in this review. As DASH nutritional interventions have been proposed, limitations of these studies are the small sample size and non-randomization of interventions, leading to less reliable evidence. Randomized controlled interventions are needed to offer definitive evidence related to the use of the DASH diet in HF management.

Vitamin D status and predictors of 25-hydroxyvitamin D levels in patients with heart failure living in a sunny region / Estado de la vitamina D y predictores de los niveles de 25-hidroxivitamina D en pacientes con insuficiencia cardíaca residentes en una región soleada

AIMS: hypovitaminosis D has frequently been identified in patients with heart failure (HF). However, few studies have been conducted in regions with high solar incidence. Therefore, this study aimed to evaluate vitamin D status and predictors of 25-hydroxyvitamin D (25(OH)D) levels in patients with HF living in a sunny region (5 °- 6 °S). METHODS: this cross-sectional study enrolled 70 patients with HF. Biodemographic, clinical, biochemical, dietary, and sun exposure data were collected, and 25(OH)D levels were measured. RESULTS: the mean 25(OH)D level was 40.1 (12.4) ng/mL, and 24.3 % (95 % CI: 14.2-33.8) of patients with HF had hypovitaminosis D (25(OH) D < 30 ng/mL). Female patients (p = 0.001), those with ischemic etiology (p = 0.03) and those with high parathyroid hormone levels (> 67 pg/mL) (p = 0.034) were more likely to present hypovitaminosis D. Higher 25(OH)D levels were observed in men than in women (β = 7.78, p = 0.005) and in patients with HF in New York Heart Association (NHYA) functional class I when compared to those in class III/IV (β = 8.23, p = 0.032). CONCLUSIONS: the majority of patients with HF had sufficient 25(OH)D levels. Sex and functional classification were identified as independent predictors of 25(OH)D levels. These results highlight the need for increased monitoring of vitamin D status among female patients with heart failure and those with more severe symptoms

OBJETIVOS: la hipovitaminosis D se ha identificado con frecuencia en pacientes con insuficiencia cardíaca (IC). Sin embargo, pocos estudios se han realizado en regiones con una alta exposición solar. Por lo tanto, este estudio tuvo como objetivo evaluar el estado de la vitamina D y los predictores de los niveles de 25-hidroxivitamina D (25(OH)D) en pacientes con IC que viven en una región soleada (5 °-6 °S). MÉTODOS: este estudio transversal incluyó a 70 pacientes con IC. Se recopilaron datos biodemográficos, clínicos, bioquímicos, dietéticos y de exposición solar, y se midieron los niveles de 25(OH)D. RESULTADOS: el nivel medio de 25(OH)D fue de 40,1 (12,4) ng/mL y el 24,3 % (IC 95 %: 14,2-33,8) de los pacientes con IC tenían hipovitaminosis D (25(OH)D < 30 ng/mL. Las pacientes mujeres (p = 0,001), aquellos con IC de etiología isquémica (p = 0,03) y aquellos otros pacientes con niveles altos de hormona paratiroidea (> 67 pg/mL) (p = 0,034) tenían más probabilidades de presentar hipovitaminosis D. Se observaron niveles más altos de 25(OH)D en los hombres que en las mujeres (β = 7,78, p = 0,005), y en los pacientes con IC de clase funcional I de la New York Heart Association (NHYA) que en los de clase III/IV (β = 8,23, p = 0,032). CONCLUSIONES: la mayoría de los pacientes con IC tenían niveles suficientes de 25(OH)D. El sexo y la clasificación funcional se identificaron como predictores independientes de los niveles de 25(OH)D. Estos resultados destacan la necesidad de un mayor control del estado de la vitamina D entre las mujeres con insuficiencia cardíaca y los pacientes con síntomas más graves

Caloric restriction reduces sympathetic activity similar to beta-blockers but conveys additional mitochondrio-protective effects in aged myocardium.

Increased activation of sympathetic nervous system contributes to congestive heart failure (CHF) progression, and inhibition of sympathetic overactivation by beta-blockers is successful in CHF patients. Similarly, caloric restriction (CR) reduces sympathetic activity but mediates additional effects. Here, we compared the cardiac effects of CR (- 40% kcal, 3 months) with beta-blocker therapy (BB), diuretic medication (DF) or control diet in 18-months-old Wistar rats. We continuously recorded blood pressure, heart rate, body temperature and activity with telemetric devices and analysed cardiac function, activated signalling cascades and markers of apoptosis and mitochondrial biogenesis. During our study, left ventricular (LV) systolic function improved markedly (CR), mildly (BB) or even deteriorated (DF; control). Diastolic function was preserved by CR and BB but impaired by DF. CR reduced blood pressure identical to DF and BB and heart rate identical to BB. Plasma noradrenaline was decreased by CR and BB but increased by DF. Only CR reduced LV oxidative damage and apoptosis, induced AMPK and Akt phosphorylation and increased mitochondrial biogenesis. Thus, additive to the reduction of sympathetic activity, CR achieves protective effects on mitochondria and improves LV function and ROS damage in aged hearts. CR mechanisms may provide additional therapeutic targets compared to traditional CHF therapy.

Simultaneous Pharmacokinetic Analysis of Nitrate and its Reduced Metabolite, Nitrite, Following Ingestion of Inorganic Nitrate in a Mixed Patient Population.

PURPOSE: The pharmacokinetic properties of plasma NO3- and its reduced metabolite, NO2-, have been separately described, but there has been no reported attempt to simultaneously model their pharmacokinetics following NO3- ingestion. This report describes development of such a model from retrospective analyses of concentrations largely obtained from primary endpoint efficacy trials. METHODS: Linear and non-linear mixed effects analyses were used to statistically define concentration dependency on time, dose, as well as patient and study variables, and to integrate NO3- and NO2- concentrations from studies conducted at different times, locations, patient groups, and several studies in which sample range was limited to a few hours. Published pharmacokinetic studies for both substances were used to supplement model development. RESULTS: A population pharmacokinetic model relating NO3- and NO2- concentrations was developed. The model incorporated endogenous levels of the two entities, and determined these were not influenced by exogenous NO3- delivery. Covariate analysis revealed intersubject variability in NO3- exposure was partially described by body weight differences influencing volume of distribution. The model was applied to visualize exposure versus response (muscle contraction performance) in individual patients. CONCLUSIONS: Extension of the present first-generation model, to ultimately optimize NO3- dose versus pharmacological effects, is warranted.

Comparison of probiotic yogurt and ordinary yogurt consumption on serum Pentraxin3, NT-proBNP, oxLDL, and ApoB100 in patients with chronic heart failure: a randomized, triple-blind, controlled trial.

BACKGROUND AND AIMS: Nowadays, the potential beneficial effects of probiotic yogurt as a functional food has raised much interest. Thus, the aim of this study was to compare the probiotic yogurt and ordinary yogurt consumption on some indices in patients with chronic heart failure (CHF). METHODS AND RESULTS: In this randomized, triple-blind clinical trial, 90 patients with CHF were randomly allocated into two groups to take either probiotic yogurt or ordinary yogurt for 10 weeks. The serum levels of pentraxin3 (PTX3), N-terminal pro-brain natriuretic peptide (NT-proBNP), oxidized low density lipoprotein (oxLDL), and apolipoprotein B100 (ApoB100) were measured at the baseline and at the end of week 10. P-Value <0.05 was defined as statistically significant. Final analyses were performed on 78 patients. The levels of PTX3 and oxLDL in both the groups decreased significantly after 10 weeks, and these reductions were greater in the probiotic group, where the difference between the groups was statistically significant for oxLDL (P-value: 0.051, adjusted P-value: 0.010) but not significant for PTX3 (P-value: 0.956, adjusted P-value: 0.236). The changes in the serum NT-proBNP levels were not statistically significant between the groups (P-value: 0.948, adjusted P-value: 0.306). ApoB100 significantly decreased in the control group compared to the probiotic group and the difference between the groups was significant at first but was not significant after adjusting for the confounders (P-value: 0.004, adjusted P-value: 0.280). CONCLUSION: The serum oxLDL significantly reduced due to probiotic yogurt consumption after 10 weeks compared to ordinary yogurt; thus, it may be useful for improving the oxidative status of CHF patients. The clinical trial registry number is IRCT20091114002709N48 (https://www.irct.ir/IRCT20091114002709N48, registered 12 March 2018).

The role of diet and nutrition in heart failure: A state-of-the-art narrative review.

Heart Failure (HF) incidence is increasing steadily worldwide, while prognosis remains poor. Though nutrition is a lifestyle factor implicated in prevention of HF, little is known about the effects of macro- and micronutrients as well as dietary patterns on the progression and treatment of HF. This is reflected in a lack of nutrition recommendations in all major HF scientific guidelines. In this state-of-the-art review, we examine and discuss the implications of evidence contained in existing randomized control trials as well as observational studies covering the topics of sodium restriction, dietary patterns and caloric restriction as well as supplementation of dietary fats and fatty acids, protein and amino acids and micronutrients in the setting of pre-existing HF. Finally, we explore future directions and discuss knowledge gaps regarding nutrition therapies for the treatment of HF.

Dietary Sodium Restriction for Heart Failure: A Systematic Review of Intervention Outcomes and Behavioral Determinants.

The 1500 mg/d dietary sodium restriction commonly recommended for patients with heart failure has recently been questioned. Poor adherence to sodium-restricted diets makes assessing the efficacy of sodium restriction challenging. Therefore, successful behavioral interventions are needed. We reviewed sodium restriction trials and descriptive studies of sodium restriction to: 1) determine if sodium restriction was achieved in interventions among heart failure patients; and 2) characterize predictors of successful dietary sodium restriction. Among 638 identified studies, 10 intervention trials, and 25 descriptive studies met inclusion criteria. We used content analysis to extract information about sodium restriction and behavioral determinants of sodium restriction. Dietary sodium was reduced in 7 trials; none achieved 1500 mg/d (range 1938-4564 mg/d). The interventions implemented in the interventional trials emphasized knowledge, skills, and self-regulation strategies, but few addressed the determinants correlated with successful sodium restriction in the descriptive studies (eg, social/cultural norms, social support, taste preferences, food access, self-efficacy). Findings suggest that incorporating determinants predictive of successful dietary sodium restriction may improve the success of interventional trials. Without effective interventions to deploy in trials, the safety and efficacy of sodium restriction remains unknown.

Evidence related to sodium restriction in patients with heart failure.

OBJECTIVES: to analyze the scientific production about sodium restriction in patients with heart failure. METHODS: integrative literature review from articles published from 2007 to 2017, located in the CINAHL and Scopus databases. RESULTS: thirteen studies were analyzed. Sodium intake restriction was associated with lower unfavorable clinical outcomes in patients with marked symptomatology. The 24-hour urine sodium dosage was the main tool to assess adherence to the low sodium diet. CONCLUSIONS: based on the studies included in this review, in symptomatic patients, dietary sodium restriction should be encouraged in clinical practice as a protective measure for health. However, in asymptomatic patients, it should be well studied.

Implications of Altered Ketone Metabolism and Therapeutic Ketosis in Heart Failure.

Despite existing therapy, patients with heart failure (HF) experience substantial morbidity and mortality, highlighting the urgent need to identify novel pathophysiological mechanisms and therapies, as well. Traditional models for pharmacological intervention have targeted neurohormonal axes and hemodynamic disturbances in HF. However, several studies have now highlighted the potential for ketone metabolic modulation as a promising treatment paradigm. During the pathophysiological progression of HF, the failing heart reduces fatty acid and glucose oxidation, with associated increases in ketone metabolism. Recent studies indicate that enhanced myocardial ketone use is adaptive in HF, and limited data demonstrate beneficial effects of exogenous ketone therapy in studies of animal models and humans with HF. This review will summarize current evidence supporting a salutary role for ketones in HF including (1) normal myocardial ketone use, (2) alterations in ketone metabolism in the failing heart, (3) effects of therapeutic ketosis in animals and humans with HF, and (4) the potential significance of ketosis associated with sodium-glucose cotransporter 2 inhibitors. Although a number of important questions remain regarding the use of therapeutic ketosis and mechanism of action in HF, current evidence suggests potential benefit, in particular, in HF with reduced ejection fraction, with theoretical rationale for its use in HF with preserved ejection fraction. Although it is early in its study and development, therapeutic ketosis across the spectrum of HF holds significant promise.

Effect of a double nutritional intervention on the nutritional status, functional capacity, and quality of life of patients with chronic heart failure: 12-month results from a randomized clinical trial / Efecto de una intervención nutricional doble sobre el estado nutricional, la capacidad funcional y la calidad de vida de pacientes con insuficiencia cardiaca crónica: resultados a los 12 meses de un ensayo clínico aleatorizado

INTRODUCTION: malnutrition is commonly associated with, and worsens the prognosis of heart failure. The management of chronic heart failure and its complications based only on the application of pharmacologic guidelines is incomplete. The benefits of interventions to improve nutritional status may be limited by the multifactorial nature of malnutrition. The objective of the present study was to determine whether nutritional advice and nutritional supplementation can improve the nutritional status of patients with chronic heart failure. METHODS: we performed a randomized clinical trial on an intention-to-treat basis with blinded observers. We divided a sample of 76 patients into 2 groups: one that received structured advice combined with nutritional supplements for 12 weeks (test group), and one that received treatment as usual (control group). The outcome measure was nutritional status as evaluated using the Subjective Global Assessment and the Mini Nutritional Assessment tools. After 12 weeks of treatment the test group received a leaflet that served as a reminder. No further interventions were applied in either group. Patients were followed for 1 year. RESULTS AND CONCLUSION: at 3 months of follow-up nutritional status improved 4-fold in the test group, whereas no change was observed in the control group. At 9 months nutritional status in the intervention group had improved 2-fold with respect to the baseline visit, whereas no differences were recorded in the control group. Differences in mortality and length of stay at 1 year did not reach statistical significance

INTRODUCCIÓN: la desnutrición se asocia comúnmente con la insuficiencia cardíaca y empeora su pronóstico. El tratamiento de la insuficiencia cardíaca crónica basado exclusivamente en la aplicación de las guías clínicas farmacológicas resulta insuficiente. Los beneficios de las intervenciones para mejorar el estado nutricional pueden quedar enmascarados por el carácter multifactorial de la desnutrición. El objetivo del estudio fue determinar si el asesoramiento nutricional más suplementos nutricionales puede mejorar el estado nutricional de los pacientes con insuficiencia cardiaca. MÉTODO: ensayo clínico aleatorizado basado en la intención de tratar con evaluadores sometidos a enmascaramiento. Una muestra de 76 pacientes en 2 grupos: uno que recibió asesoramiento estructurado más suplementos nutricionales durante 12 semanas (grupo de intervención) y otro que siguió el tratamiento habitual (grupo de control). El parámetro del resultado fue el estado nutricional evaluado utilizando como herramientas la Valoración Global Subjetiva y el Mini Nutritional Assesment. Después de 12 semanas de tratamiento, el grupo de intervención recibió a modo de recuerdo un folleto informativo. No se aplicaron más intervenciones en ninguno de los grupos. Se siguió a los pacientes durante 1 año. RESULTADOS Y CONCLUSIÓN: a los 3 meses de seguimiento, el estado nutricional mejoró cuatro veces en el grupo de intervención, mientras que no se observó ningún cambio en el grupo de control. A los 9 meses, el estado nutricional en el grupo de intervención había mejorado 2 veces con respecto a la visita inicial, mientras que no se registraron diferencias en el grupo de control. Las diferencias de mortalidad y estancia hospitalaria al cabo de 1 año no alcanzaron la significación estadística

Effect of Prebiotic Complex on Gut Microbiota and Endotoxemia in Female Rats with Modeled Heart Failure.

We studied the levels endotoxin and microbial markers in the blood of female rats with experimental heart failure and the effects of preliminary treatment with a prebiotic complex based on fermented wheat bran and inactivated Saccharomyces cerevisiae culture on these parameters. The concentrations of endotoxin, markers of lactobacilli, and opportunistic microorganisms were found to increase in rats with experimental heart failure and significantly decreased against the background of treatment with prebiotic complex. The dynamics of markers of bifidobacteria, eubacteria, and propionibacteria were reciprocal. The observed effect of the prebiotic complex effect on gut microbiota in rats with experimental heart failure suggests that this complex can be used for the correction of intestinal dysbiosis and endotoxemia in this clinical condition.

Why a d-ß-hydroxybutyrate monoester?

Much of the world's prominent and burdensome chronic diseases, such as diabetes, Alzheimer's, and heart disease, are caused by impaired metabolism. By acting as both an efficient fuel and a powerful signalling molecule, the natural ketone body, d-ß-hydroxybutyrate (ßHB), may help circumvent the metabolic malfunctions that aggravate some diseases. Historically, dietary interventions that elevate ßHB production by the liver, such as high-fat diets and partial starvation, have been used to treat chronic disease with varying degrees of success, owing to the potential downsides of such diets. The recent development of an ingestible ßHB monoester provides a new tool to quickly and accurately raise blood ketone concentration, opening a myriad of potential health applications. The ßHB monoester is a salt-free ßHB precursor that yields only the biologically active d-isoform of the metabolite, the pharmacokinetics of which have been studied, as has safety for human consumption in athletes and healthy volunteers. This review describes fundamental concepts of endogenous and exogenous ketone body metabolism, the differences between the ßHB monoester and other exogenous ketones and summarises the disease-specific biochemical and physiological rationales behind its clinical use in diabetes, neurodegenerative diseases, heart failure, sepsis related muscle atrophy, migraine, and epilepsy. We also address the limitations of using the ßHB monoester as an adjunctive nutritional therapy and areas of uncertainty that could guide future research.

Safety and efficacy of salt substitution with a low sodium-potassium enriched dietary salt in patients with heart failure with reduced ejection fraction: A pilot study.

BACKGROUND AND AIMS: Increased sodium intake is associated with increased risk of decompensation in patients with heart failure. This non-randomized, open-label, controlled study aimed to examine the feasibility, preliminary safety and efficacy of a low sodium-potassium enriched salt substitute compared to regular table salt in patients with heart failure with reduced ejection fraction (HFREF). METHODS: Fifty patients (68% male, NYHA I/II/III 6%/68%/26%, mean age 70 ± 9 years, LVEF 31 ± 5%, median BNP 112 pg/ml) were included. Of these, 30 patients received the salt substitute (maximum consumption of 2 g daily), who were prospectively compared to a control group of 20 age/sex/NYHA class-matched HFREF patients who consumed regular salt (maximum consumption of 2 g daily). Consumption of regular salt was prohibited in the salt substitution group. All patients were followed for 12 weeks. RESULTS: Patient groups did not differ by sex, age, LVEF, NYHA class, 6MWD, and BNP at baseline. In primary safety analysis, no significant differences were detected between groups regarding SBP (p = 0.052), DBP (p = 0.159), HR (p = 0.246), serum potassium (p = 0.579), serum sodium (p = 0.125), and eGFR (p = 0.710) throughout the 12 weeks. Secondary efficacy analysis revealed a statistically significant difference in 6MWD at 12 weeks between the salt substitute and regular salt groups after adjustment for baseline 6MWD (mean difference±SEM, 4.7 ± 2.1 m, F = 4.92, p = 0.031). CONCLUSIONS: In this pilot study, a low sodium-potassium enriched salt substitute was found to be safe compared to regular salt in HFREF patients, while it resulted in a small albeit significant improvement in exercise capacity, possibly justifying further investigation with randomized clinical studies.

Zinc Deficiency and Heart Failure: A Systematic Review of the Current Literature.

Zinc is an essential micronutrient that impacts the cardiovascular system through modulation of oxidative stress. It is unknown whether zinc levels are affected in heart failure (HF), and whether the association, if present, is causal. A systematic search for publications that report coexisting zinc deficiency in patients with HF was performed to provide an overview of the pathophysiological and epidemiological aspects of this association (last search April 2019). Review of the literature suggests multiple potential pathophysiologic causes for zinc deficiency in HF as a result of impaired micronutrient consumption, hyper-inflammatory state, upregulation of the renin-angiotensin-aldosterone axis, diminished absorption, and hyperzincuria from HF medications. In a longitudinal study of patients with HF in the setting of intestinal malabsorption, there was partial cardiomyocyte and left ventricular ejection fraction recovery with intravenous selenium and zinc supplementation. Two randomized double-blind control trials evaluating micronutrient and macronutrient supplementation including zinc in patients with HF found improvement in echocardiographic findings compared with placebo. Two recently completed studies evaluated the role for zinc supplementation in 2 different HF populations: a trial of zinc supplementation in patients with non-ischemic HF, and a trial of micronutrient supplementation (including B vitamins, vitamin D, and zinc) in veterans with systolic dysfunction; the results of which are still pending. Several pathobiological pathways to link zinc deficiency with the development and deterioration of HF are presented. Preliminary clinical data are supportive of such an association and future studies should further investigate the effects of zinc supplementation on outcomes in patients with HF.