Natriuretic peptide testing strategies in heart failure: A 2023 update.

Natriuretic peptides (NPs), including B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP), have been recommended as standard biomarkers for diagnosing heart failure (HF), and one of the strongest risk predictors for mortality and HF hospitalization regardless of ejection fraction (EF) and etiology of HF. BNP is an active neurohormone opposing renin-angiotensin-aldosterone and sympathetic nervous system overactivated in HF, whereas NT-proBNP is an inactive prohormone released from cardiomyocytes in response to wall stress. Despite substantial advances in the development of guideline-directed medical therapy (GDMT) for HF with reduced EF, studies demonstrating direct benefits of NP-guided chronic HF therapy on mortality, HF hospitalization, and GDMT optimization have yielded conflicting results. However, accumulating evidence shows that achieving prespecified BNP or NT-proBNP target over time is significantly associated with favorable outcomes, suggesting that benefits of serially measured NPs may be limited to particular groups of HF patients, such as those with extreme levels of baseline BNP or NT-proBNP, which could represent severe phenotypes of HF associated with natriuretic peptide resistance or cardiorenal syndrome. Over the past decade, clinical utilization of BNP and NT-proBNP has been expanded, especially using serial NP measurements for guiding HF therapy, optimizing GDMT and identifying at-risk patients with HF phenotypes who may be minimally symptomatic or asymptomatic.

Prognostic Value of Hemodynamic Gain Index in Patients With Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Assessment of functional capacity in patients with heart failure with reduced ejection fraction (HFrEF) is essential for risk stratification, and it traditionally relied on cardiopulmonary exercise testing (CPET)-derived peak oxygen consumption (peak Vo2). OBJECTIVES: This study sought to investigate the prognostic value of alternative nonmetabolic exercise testing parameters in a contemporary cohort with HFrEF. METHODS: Medical records of 1,067 consecutive patients with chronic HFrEF who underwent CPET from December 2012 to September 2020 were reviewed for a primary outcome that was a composite of all-cause mortality, left ventricular assist device implantation, and/or heart transplantation. Multivariable Cox regression and log-rank testing were used to determine prognostic values of various exercise testing variables. RESULTS: The primary outcome was identified in 331 of 954 patients (34.7%) of the HFrEF cohort (median follow-up time, 946 days). After adjustment for demographics, cardiac parameters, and comorbidities, higher hemodynamic gain index (HGI) and peak rate-pressure product (RPP) were associated with greater event-free survival (adjusted HR per doubling: 0.76 and 0.36; 95% CI: 0.67-0.87 and 0.28-0.47; all P < 0.001, respectively). Moreover, HGI (area under the curve [AUC]: 0.69; 95% CI: 0.65-0.72) and peak RPP (AUC: 0.71; 95% CI: 0.68-0.74) were comparable to the standard peak Vo2 (AUC: 0.70; 95% CI: 0.66-0.73; P for comparison = 0.607 and 0.393, respectively) for primary outcome discrimination. CONCLUSIONS: HGI and peak RPP show good correlation with peak Vo2 in terms of prognostication and outcome discrimination in patients with HFrEF and may serve as suitable alternatives to CPET-derived prognostic variables.

Prognostic Value of Natriuretic Peptide Levels for Adverse Renal Outcomes in Patients With Moderate to Severe Acute Kidney Injury With or Without Heart Failure.

Background Natriuretic peptides have been recommended as biomarkers for the diagnosis and prognosis of patients with heart failure and are often elevated in the setting of acute kidney injury. We sought to demonstrate the associations between increased baseline NT-proBNP (N-terminal pro-B-type natriuretic peptide) and adverse renal outcomes in patients with moderate-to-severe acute kidney injury. Methods and Results We reviewed electronic medical records of consecutive patients with acute kidney injury stage 2 and 3 admitted to the Cleveland Clinic between September 2011 and December 2021. Patients with NT-proBNP levels collected before renal consultation or dialysis initiation were included. Adverse renal outcomes included dialysis requirement and dialysis dependence defined as patients undergoing dialysis within 72 hours before hospital discharge or in-hospital mortality. In our study cohort (n=3811), 2521 (66%) patients underwent dialysis, 1619 (42%) patients became dialysis dependent, and 1325 (35%) patients had in-hospital mortality. After adjusting for cardiorenal risk factors, compared with the lowest quartile, the highest quartile of NT-proBNP (≥18 215 pg/mL) was associated with increased likelihood of dialysis requirement (adjusted odds ratio [OR], 2.36 [95% CI, 1.87-2.99]), dialysis dependence (adjusted OR, 1.89 [95% CI, 2.53-1.34]), and in-hospital mortality (adjusted OR, 1.34 [95% CI, 1.01-1.34]). Conclusions Increased NT-proBNP was associated with an increased risk of dialysis requirement, becoming dialysis dependent, and in-hospital mortality in patients with moderate-to-severe acute kidney injury.

Hidradenitis Suppurativa and Risk of Coronary Artery Disease: A Systematic Review and Meta-Analysis.

Background: Patients with hidradenitis suppurativa (HS) may have a higher risk of coronary artery disease (CAD) due to the excessive inflammatory burden. However, data on this association is still relatively limited. Aims: To investigate the association between HS and risk of prevalent and incident CAD by combining result from all available studies using systematic review and meta-analysis technique. Materials and Methods: Potentially eligible studies were identified from Medline and EMBASE databases from inception to November 2021 using search strategy that comprised of terms for 'hidradenitis suppurativa' (HS) and 'coronary artery disease' (CAD). Eligible study must be cohort study that consisted of one cohort of patients with HS and another cohort of individuals without HS. The study must report incidence or prevalence of CAD in both groups. The retrieved point estimates with standard errors from each study were summarized into pooled result using random-effect model and generic inverse variance method. Meta-analyses of the prevalent and incident CAD were conducted separately. Results: A total of 876 articles were identified. After two rounds of independent review by three investigators, seven cohort studies (four incident studies and three prevalent studies) met the eligibility criteria and were analysed in the meta-analyses. The meta-analysis found a significantly elevated risk of both incident and prevalent CAD in patients with HS compared to individuals without psoriasis with the pooled risk ratio of 1.38 (95% CI, 1.21-1.58; I2 83%) and 1.70 (95% CI, 1.13-2.57; I2 89%), respectively. Limitations: Limited accuracy of diagnosis of HS and CSD as most included studies relied on diagnostic codes and high between-study statistical heterogeneity. Conclusions: The current systematic review and meta-analysis found a significantly increased risk of both prevalent and incident CAD among patients with HS.

Substance Use-Associated Mortality among Heart Donors after the COVID-19 National Emergency Increased but Did Not Affect Peri-Transplant Outcomes.

INTRODUCTION: The COVID-19 pandemic and consequent social isolation prompted a surge in mental health disorders and substance use in the general population and, therefore, in potential organ donors. We aimed to evaluate if this led to a change in donor characteristics, including the mechanism and circumstance of death, and how this may have affected clinical outcomes following heart transplantation. METHODS: We identified all heart donors from the SRTR database between 18 October 2018 and 31 December 2021, excluding those who donated immediately after the US national emergency declaration. Donors were stratified into pre-COVID-19 (Pre-Cov; through 12 March 2020) and post-COVID-19 national emergency declaration cohorts (Post-Cov; 1 August 2020 through 31 December 2021) based on the heart procurement date. Relevant demographics, cause of death, and substance use history were collected in addition to graft cold ischemic time, the incidence of primary graft dysfunction (PGD), and recipient survival at 30 days post-transplant. RESULTS: A total of 10,314 heart donors were identified; 4941 were stratified into the Pre-Cov and 5373 into the Post-Cov cohorts. There was no difference in demographics, but illicit drug use was significantly higher in the Post-Cov group, leading to an increased incidence of death from drug intoxication. Fatal gunshot wounds were also more common. Despite these changes, the incidence of PGD remained similar (p = 0.371), and there was no difference in 30 days recipient survival (p = 0.545). CONCLUSION: Our findings confirm that COVID-19 had a major impact on mental health and psychosocial life with an associated increase in illicit substance use and fatal intoxication rates in heart transplant donors. These changes did not alter peri-operative mortality following heart transplantation. Future studies are needed to ensure that long-term outcomes remain unaffected.

Hemodynamic Gain Index and Exercise Capacity in Heart Failure With Preserved Ejection Fraction.

Decreased exercise capacity portends a poor prognosis in heart failure with preserved ejection fraction (HFpEF). The hemodynamic gain index (HGI) is an integrated marker of hemodynamic reserve measured during exercise stress testing and is associated with survival. The goal of this study was to establish the association of HGI with exercise capacity, serum biomarkers, and echocardiography features in subjects with HFpEF. In 209 subjects with HFpEF enrolled in the RELAX (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Diastolic Heart Failure) trial who underwent cardiopulmonary exercise testing, we calculated the HGI ([peak heart rate [HR] × peak systolic blood pressure [SBP]-[HR at rest × SBP at rest])/(HR at rest × SBP at rest) and tested associations with outcomes of interest. The median (interquartile range) HGI was 0.94 (0.5 to 1.3) beats per min/mm Hg. In multivariable-adjusted linear regression, higher HGI was associated with greater peak oxygen consumption (VO2), VO2 at anaerobic threshold, peak minute ventilation, and 6-minute walk distance (all p <0.001). Higher HGI was associated with lower serum high-sensitivity troponin I, pro-collagen III, N-terminal pro-B-type natriuretic peptide, and creatinine (all p <0.05) and with longer deceleration time, lower E/A ratio, and lower left atrial volume index by echocardiography (all p <0.05). In conclusion, higher HGI in stable HFpEF was associated with greater exercise capacity, a biomarker profile indicating less myocardial injury and fibrosis and less kidney dysfunction, and with less severe diastolic dysfunction. These results suggest that HGI, an easily calculated metric from routine exercise testing, is a marker of functional capacity and disease severity in HFpEF and may serve as a surrogate for VO2 parameters for use in treadmill testing without gas exchange capability.

Retinal Microvasculature: A Potential Window Into Heart Failure Prevention.

Endothelial dysfunction and microvascular disease have been shown to play an important role in the development and progression of heart failure (HF). Retinal imaging provides a unique opportunity to noninvasively assess vascular structure and function, vessel features, and microcirculation within the retina. Accumulating evidence suggests that retinal vessel caliber, microvascular features, and vascular characteristics extracted from various imaging modalities are associated with alterations in left ventricular structure and function in stage B HF, as well as incident development of symptomatic HF in the general population. Moreover, dynamic retinal vessel analysis has been shown to differentiate HF patients based on their phenotypes. Given the increasing availability of rapid image acquisition devices (eg, nonmydriatic widefield systems and smartphone-based retinal cameras) and the integration of artificial intelligence-based interrogation/assessment techniques, retinal imaging is a promising noninvasive tool, in conjunction with cardiac imaging and biomarkers, to prevent HF and risk stratify those at risk of developing HF. This review focuses on the current evidence on retinal microvasculature changes, and potential clinical relevance and promising utility of retinal imaging in HF.

Validation of prognostic value of the hemodynamic gain index in different groups of patients undergoing exercise stress testing.

Background: Recently, the hemodynamic gain index (HGI) has shown to be a strong independent predictor of all-cause mortality and associated with metabolic equivalents (METs) in a cohort of male patients. However, the prognostic implications of the HGI have never been externally validated with subgroup analyses based on gender, body mass index (BMI) of 35 kg/m2, history of heart failure (HF), coronary artery disease (CAD) and beta-blocker use. Methods: We identified 126,356 consecutive patients undergoing treadmill exercise testing between January 1st, 1991 and February 27th, 2015. HGI was calculated using the formula: [(SBPpeak × HRpeak) - (SBPrest × HRrest)] / (SBPrest × HRrest). Cox regression models were used to determine the associations between HGI quartiles and all-cause mortality with adjustment for cardiovascular risk factors and exercise testing parameters. Results: Mean age was 53.5 ± 12.6 years. There were 74,724 (59.1 %) male, 5940 (4.7 %) HF, 21,123 (16.7 %) CAD, and 30,568 (24.2 %) beta-blocker-using patients. During the median follow up of 7.1 years, 9929 (7.9 %) died. Median HGI was 1.93 (interquartile range [IQR] 1.40-2.54) bpm/mmHg. After adjustment for the covariates, lower HGI was independently associated with all-cause mortality in the entire cohort (quartile 1 vs 4, adjusted hazard ratio [95 % confidence interval] 1.33 [IQR 1.21-1.45], p < 0.001), and subgroups of men, women, patients with body mass index <35 kg/m2, with and without HF, CAD, and beta-blocker use. The HGI also correlates well with METs in every subgroup. Conclusions: The HGI is a strong predictor of long-term mortality independently of traditional cardiovascular risk factors, and exercise performance across patient subgroups.

Relation of Statin Use to Gut Microbial Trimethylamine N-Oxide and Cardiovascular Risk.

Accumulating evidence suggests that statins can influence the microbiota. We investigated the effects of statin therapy on circulating levels of atherogenic gut microbial metabolite, trimethylamine N-oxide (TMAO), and subsequent clinical outcomes. We examined the effects of statin use on plasma TMAO in patients who are statin-naive with dyslipidemia previously enrolled in 2 intervention studies, International Medical Innovations (n = 79) and Advances in Atorvastatin Research Group (n = 27) in a post hoc analysis. A propensity score matching model stratified by statin use was used to validate the associations between statin use, plasma TMAO, and major adverse cardiovascular events across 4,007 patients who underwent elective coronary angiography. In the International Medical Innovations cohort, at 4 weeks, statin use was associated with decreased plasma TMAO (p = 0.03) and a return to baseline after statin discontinuation. In both intervention cohorts, patients with higher baseline TMAO (predefined cutoff 6.18 µM) showed significant reductions in TMAO (all p <0.05). Propensity score matching on statin use (1,196 patient-pairs) revealed lower plasma TMAO (p = 0.002) with statin use. An adjusted cox regression model including statin use, TMAO, and cholesterol showed preserved association of statin use and TMAO but not cholesterol with major adverse cardiovascular events (p = 0.005, p <0.001, p = 0.24, respectively). A likelihood ratio test showed improved model fit (p <0.001) with the addition of TMAO. In conclusion, our findings demonstrate that statin therapy significantly decreases plasma TMAO levels, suggesting the potential contribution of a statin-mediated reduction of TMAO production in cardiovascular benefits in addition to improved lipid profile and attenuated inflammation.

Usefulness of Serum Biomarkers of Endothelial Glycocalyx Damage in Prognosis of Decompensated Patients with Heart Failure with Reduced Ejection Fraction.

The surface layer of endothelium contains the endothelial glycocalyx (eGC), consisting of proteoglycan polymers. Syndecan-1, heparan sulfate, and hyaluronic acid are major constituents of eGC, and their increasing detection in serum represents active degradation of eGC. Serum was obtained from patients with no heart failure (non-HF) and with HF with reduced ejection fraction (HFrEF) of <40%, either stable chronic HF (CHF) or acute decompensated HF (ADHF). Syndecan-1, heparan sulfate, and hyaluronic acid were measured for comparisons in the groups, adjusting for clinical and laboratory values. In our study cohort, 51 non-HF, 66 ADHF, and 72 patients with CHF were enrolled. Between ADHF and CHF, left ventricular (LV) mass index, LV ejection fraction, and pulmonary capillary wedge pressure did not differ. Patients with ADHF had significantly higher levels of eGC constituents compared with CHF and non-HF. During follow-up, 21 patients with HF died, and the mortality rate was higher in patients with higher serum syndecan-1 or heparan sulfate (log-rank p = 0.007 and 0.016, respectively). In multivariate analysis, a doubling of serum heparan sulfate concentration amounted to a 31.5% increase in all-cause mortality (hazard ratio = 1.315, confidence interval = 1.012-1.709, p = 0.040). In conclusion, serum biomarkers of eGC were elevated in ADHF (but not in CHF) in patients with HFrEF, suggesting the potential roles of eGC degradation and endothelial dysfunction in HF decompensation. Only elevated heparin sulfate was associated with higher all-cause mortality after adjusting for traditional risk variables in patients with HFrEF.

Body mass index and risk of clostridioides difficile infection: a systematic review and meta-analysis.

OBJECTIVE: To comprehensively investigate the association between obesity/high body mass index (BMI) and risk of Clostridioides difficile infection (CDI) using systematic review and meta-analysis. METHODS: Potentially eligible studies were identified from Medline and EMBASE databases from inception to February 2021 using search strategy consisting of terms for "Body Mass Index" and "Clostridioides Difficile". We only included studies that consist of a group of individuals with CDI and another group without CDI. Then, the studies must report their BMI or history of obesity. Odds ratio (OR) and 95% CIs of the association between BMI status and CDI were retrieved from each study and combined using the generic inverse variance method. Funnel plot was used to assess publication bias. RESULTS: A total of 4609 articles were identified. After two rounds of systematic review, 17 studies met the eligibility criteria and were included into the meta-analysis. Pooled analysis showed that individuals with high BMI had a significantly decreased odds of CDI with the pooled OR of 0.88 (95% CI 0.80-0.97). This meta-analysis had high statistical heterogeneity with I2 of 74%. Funnel plot was symmetric, which was not suggestive of presence of publication bias. CONCLUSION: This meta-analysis revealed a significant negative association between BMI and CDI.

Intestinal barrier dysfunction is associated with elevated right atrial pressure in patients with advanced decompensated heart failure.

We prospectively performed serial differential sugar absorption test in 29 consecutively consented patients with advanced decompensated heart failure admitted to the heart failure intensive care unit for hemodynamically-guided therapy. We observed that intestinal barrier function was significantly impaired in our study cohort, and increased intestinal permeability was associated with elevated right atrial pressure and poorer prognosis yet without any association with systemic levels of the gut microbial metabolite, trimethylamine N-oxide (TMAO) or intestinal fatty acid binding protein that were thought to be indicative of intestinal abnormalities.

Statins and the risk of polyneuropathy: A systematic review and two meta-analyses.

INTRODUCTION/AIMS: Previous studies have shown inconsistent data on the relationship between statin use and polyneuropathy (PN). The current systematic review and meta-analyses were conducted to comprehensively investigate the risk of incident PN among statin-users compared with non-users by identifying all available studies and summarizing their results. METHODS: A systematic review was conducted from MEDLINE and EMBASE databases from inception to October 31, 2020. We included cohort and case-control studies that compared the risk of incident PN between statin-users and non-users. Point estimates and standard errors from eligible studies were pooled together using the generic inverse variance method. RESULTS: Of 4968 retrieved articles, 6 studies in non-diabetic populations and 2 studies in diabetic populations fulfilled the inclusion criteria. Two meta-analyses were performed. The pooled analyses did not find a statistically significant association between the use of statins and risk of incident PN with the pooled odds ratio of 1.24 (95% confidence interval [CI], 0.88-1.76; I2 74%) and 0.82 (95% CI, 0.56-1.21; I2 80%) in non-diabetic and diabetic groups respectively. DISCUSSION: No significant association between the use of statins and the risk of PN was observed in this systematic review and these two meta-analyses. However, there was a high degree of heterogeneity of the meta-analyses.

Myxedema Psychosis after Levothyroxine Withdrawal in Radioactive Iodine Treatment of Differentiated Thyroid Cancer: A Case Report.

Neuropsychiatric symptoms, especially acute psychosis (often referred to as myxedema madness or psychosis), are rare but possible clinical presentations of patients with hypothyroidism. A 42-year-old woman with papillary thyroid carcinoma and recent total thyroidectomy had developed flat affect, paranoid delusion, and visual and auditory hallucination during inpatient admission for elective radioactive iodine treatment. On admission, her history and physical exam did not reveal symptoms and signs of significant hypothyroidism. Other medical causes of acute psychosis were excluded, and the patient was immediately treated with thyroid hormone replacement therapy. Subsequently, her thyroid function normalized, and her psychotic symptoms gradually improved. Although there is a lack of classic signs and symptoms of hypothyroidism, myxedema madness should be recognized as one of the potentially treatable causes of acute psychosis.

The Association Between Asthma and Risk of Myasthenia Gravis: A Systematic Review and Meta-analysis.

PURPOSE: This study aimed to investigate the association between asthma and risk of myasthenia gravis (MG) using the method of systematic review and meta-analysis. METHODS: Potentially eligible studies were identified from Medline and EMBASE databases from inception to July 2020 using search strategy that comprised terms for "Asthma" and "Myasthenia Gravis". Eligible cohort study must consist of one cohort of individuals with asthma and another cohort of individuals without asthma. Then, the study must report relative risk (RR) with 95% confidence intervals (95% CIs) of incident MG between the groups. Eligible case-control studies must include cases with MG and controls without MG. Then, the study must explore their history of asthma. Odds ratio (OR) with 95% CIs of the association between asthma status and MG must be reported. Point estimates with standard errors were retrieved from each study and were combined together using the generic inverse variance method. RESULTS: A total of 6,835 articles were identified. After two rounds of independent review by five investigators, two cohort studies and three case-control studies met the eligibility criteria and were included into the meta-analysis. Pooled analysis showed that asthma was significantly associated with risk of MG with the pooled risk ratio of 1.38 (95% CI 1.02-1.86). Funnel plot was symmetric, which was not suggestive of publication bias. CONCLUSION: The current study found a significant association between asthma and increased risk of MG.

Gut Microbiome and Precision Nutrition in Heart Failure: Hype or Hope?

PURPOSE OF REVIEW: Over the past decade, the gut microbiome has been shown to play an important role in the pathogenesis of heart failure (HF) and serves as a mediator that links host genomes and environmental exposure (especially dietary intake) to the development and progression of HF. Given that alterations in gut microbial composition and metabolism are commonly seen in patients with HF, the use of gut microbial metabolites as diagnostic and prognostic biomarkers, as well as novel therapeutic targets for HF, is promising. RECENT FINDINGS: Alterations in gut microbial composition and function have bidirectional relationships with HF. Gut microbial metabolites, including short-chain fatty acids, bile acids, trimethylamine N-oxide (TMAO), and amino acid metabolites, have been shown to play a significant role in HF. For example, TMAO has been consistently demonstrated as an independent predictor of worse prognosis in patients with HF, and a potential therapeutic target for cardiac remodeling and HF. However, clinical studies on dietary interventions targeting gut microbial metabolites have demonstrated inconsistent findings, which could be from variations in the study population, gut microbial communities, and study designs. Measurement of gut microbial metabolites can improve risk stratification and potentially identify HF patients who are more likely to respond to personalized pharmacologic or dietary interventions targeting specific pathways associated with the gut microbiome.

Interleukin-6 and Outcomes in Acute Heart Failure: An ASCEND-HF Substudy.

BACKGROUND: The inflammatory cytokine IL-6 has been previously implicated in the pathophysiology of acute decompensated heart failure (HF). Prior observations in acute HF patients have suggested that IL-6 may be associated with outcomes and modulated by nesiritide. We aimed to evaluate the associations between serial IL-6 measurements, mortality and rehospitalization in acute HF. METHODS AND RESULTS: We analyzed the associations between IL-6 in acute HF, readmission, and mortality (30 and 180 days) using a cohort of 883 hospitalized patients from the ASCEND-HF trial (nesiritide vs placebo). Plasma IL-6 was measured at randomization (baseline), 48-72 hours, and 30 days. The median IL-6 was highest at baseline (14.1 pg/mL) and decreased at subsequent time points (7.6 pg/mL at 30 days). In a univariable Cox regression analysis, the baseline IL-6 was associated with 30- and 180-day mortality (hazard ratio per log 1.74, 95% confidence interval 1.09-2.78, P = .021; hazard ratio 3.23, confidence interval 1.18-8.86, P = .022, respectively). However, there was no association after multivariable adjustment. IL-6 at 48-72 hours was found to be independently associated with 30-day mortality (hazard ratio 8.2, confidence interval 1.2-57.5, P= .03), but not 180-day mortality in multivariable analysis that included the ASCEND-HF risk model and amino terminal pro-B-type natriuretic peptide as covariates. In comparison with placebo, nesiritide therapy was not associated with differences in serial IL-6 levels. CONCLUSIONS: Although elevated IL-6 levels were associated with higher all-cause mortality in acute HF, no independent association with this outcome was identified at baseline or 30-day measurements. In contrast with prior reports, we did not observe any impact of nesiritide over placebo on serial IL-6 levels.

Gut microbiome - A potential mediator of pathogenesis in heart failure and its comorbidities: State-of-the-art review.

Gut microbiome (GMB) has been increasingly recognized as a contributor to development and progression of heart failure (HF), immune-mediated subtypes of cardiomyopathy (myocarditis and anthracycline-induced cardiotoxicity), response to certain cardiovascular drugs, and HF-related comorbidities, such as chronic kidney disease, cardiorenal syndrome, insulin resistance, malnutrition, and cardiac cachexia. Gut microbiome is also responsible for the "gut hypothesis" of HF, which explains the adverse effects of gut barrier dysfunction and translocation of GMB on the progression of HF. Furthermore, accumulating evidence has suggested that gut microbial metabolites, including short chain fatty acids, trimethylamine N-oxide (TMAO), amino acid metabolites, and bile acids, are mechanistically linked to pathogenesis of HF, and could, therefore, serve as potential therapeutic targets for HF. Even though there are a variety of proposed therapeutic approaches, such as dietary modifications, prebiotics, probiotics, TMAO synthesis inhibitors, and fecal microbial transplant, targeting GMB in HF is still in its infancy and, indeed, requires further preclinical and clinical evidence. In this review, we aim to highlight the role gut microbiome plays in HF pathophysiology and its potential as a novel therapeutic target in HF.