Prognostic Significance of Estimated Plasma Volume Status in Patients with Heart Failure: A Systematic Review and Meta-Analysis.

AimsThe utility of growth differentiation factor‐15 (GDF‐15) in predicting long‐term adverse outcomes in heart failure (HF) patients is not well established. This study explored the relationship between GDF‐15 levels and adverse outcomes in HF patients across various ejection fraction (EF) phenotypes associated with coronary heart disease (CHD) and evaluated the added prognostic value of incorporating GDF‐15 into the Meta‐Analysis Global Group in Chronic Heart Failure (MAGGIC) risk score‐based model.Methods and resultsThis single‐centre cohort study included 823 HF patients, categorized into 230 (27.9%) reduced EF (HFrEF), 271 (32.9%) mid‐range EF (HFmrEF), and 322 (39.1%) preserved EF (HFpEF) groups. The median age was 68.0 years (range: 56.0–77.0), and 245 (29.8%) were females. Compared with the HFrEF and HFmrEF groups, the HFpEF group had a higher GDF‐15 concentration (P = 0.002) and a higher MAGGIC risk score (P < 0.001). We examined the associations between GDF‐15 levels and the risks of all‐cause mortality and HF rehospitalization using Cox regression models. The C‐index, integrated discrimination improvement (IDI), and net reclassification improvement (NRI) metrics were employed to assess the incremental prognostic value. During the 9.4 year follow‐up period, 425 patients died, and 484 were rehospitalized due to HF. Multivariate Cox regression analysis revealed that elevated GDF‐15 levels were significantly associated with an increased risk of all‐cause mortality [hazard ratio (HR) = 1.36, 95% confidence interval (CI): 1.20–1.54; P < 0.001] and HF rehospitalization (HR = 1.75, 95% CI: 1.57–1.95; P < 0.001) across all HF phenotypes. This association remained significant when GDF‐15 was treated as a categorical variable (high GDF‐15 group: all‐cause death: HR = 1.73, 95% CI: 1.40–2.14; P < 0.001; HF rehospitalization: HR = 3.37, 95% CI: 2.73–4.15; P < 0.001). Inclusion of GDF‐15 in the MAGGIC risk score‐based model provided additional prognostic value for all HF patients (Δ C‐index = 0.021, 95% CI: 0.002–0.041; IDI = 0.011, 95% CI: 0.001–0.025; continuous NRI = 0.489, 95% CI: 0.174–0.629) and HF rehospitalization (Δ C‐index = 0.034, 95% CI: 0.005–0.063; IDI = 0.021, 95% CI: 0.007–0.032; continuous NRI = 0.307, 95% CI: 0.147–0.548), particularly in the HFpEF subgroup.ConclusionsGDF‐15 is identified as an independent risk factor for adverse outcomes in HF patients across the entire EF spectrum in the context of CHD. Integrating GDF‐15 into the MAGGIC risk score‐based model enhances its prognostic capability for adverse outcomes in the general HF population. This incremental prognostic effect was observed specifically in the HFpEF subgroup and not in other subgroups.

Cystatin C (CysC)'s predictive utility for long-term adverse outcomes in heart failure (HF) patients with normal to mild renal insufficiency remains unclear. This study investigates the relationship between CysC and adverse outcomes in HF patients across the whole ejection fraction (EF) spectrum with normal to mild renal insufficiency. In this single-center cohort study, 637 HF patients with normal to mild renal insufficiency were categorized into reduced EF (HFrEF), mid-range EF (HFmrEF), and preserved EF (HFpEF) groups. Associations between natural log unit (CysC) and risks of all-cause mortality and HF rehospitalization were examined using Cox regression models. C-index, IDI, and NRI assessed the incremental prognostic value. Over a follow-up of 9.4 years, 271 patients died, and 330 were rehospitalized for HF. Multivariate Cox regression analysis indicated significant associations between elevated CysC levels and increased risks of all-cause mortality (HR = 1.99, 95% CI: 1.57-2.54) and HF rehospitalization (HR = 1.95, 95% CI: 1.57-2.42) across all patients. HR's for all-cause mortality observed for HFmrEF (HR 4.73, 95% CI: 2.08-10.74) and HFrEF (HR 15.11, 95% CI: 6.24-36.60) were higher compared to those for HFpEF patients (HR = 1.48, 95% CI 0.98-2.23), and CysC showed less prognostic impact on all-cause mortality in HFpEF patients. Including CysC in the MAGGIC risk score-based model provided additional prognostic value for all subjects, even with N-terminal pro-brain natriuretic peptide (NT-proBNP) levels added. CysC is an independent risk factor for adverse outcomes in HF patients across EF spectrum with normal to mild renal insufficiency. Integrating CysC into the MAGGIC risk score-based model enhances its prognostic capability for predicting adverse outcomes in the general HF population. Its prognostic effect on all-cause mortality is limited in HFpEF patients.

453-P: Association between Triglyceride, Glucose, and Body Mass Index and Long-Term Adverse Outcomes in Heart Failure Patients with Coronary Heart Disease

BackgroundThe triglyceride glucose-body mass index (TyG-BMI) is recognized as a reliable surrogate for evaluating insulin resistance and an effective predictor of cardiovascular disease. However, the link between TyG-BMI index and adverse outcomes in heart failure (HF) patients remains unclear. This study examines the correlation of the TyG-BMI index with long-term adverse outcomes in HF patients with coronary heart disease (CHD).MethodsThis single-center, prospective cohort study included 823 HF patients with CHD. The TyG-BMI index was calculated as follows: ln [fasting triglyceride (mg/dL) × fasting blood glucose (mg/dL)/2] × BMI. To explore the association between the TyG-BMI index and the occurrences of all-cause mortality and HF rehospitalization, we utilized multivariate Cox regression models and restricted cubic splines with threshold analysis.ResultsOver a follow-up period of 9.4 years, 425 patients died, and 484 were rehospitalized due to HF. Threshold analysis revealed a significant reverse “J”-shaped relationship between the TyG-BMI index and all-cause mortality, indicating a decreased risk of all-cause mortality with higher TyG-BMI index values below 240.0 (adjusted model: HR 0.90, 95% CI 0.86–0.93; Log-likelihood ratio p = 0.003). A distinct “U”-shaped nonlinear relationship was observed with HF rehospitalization, with the inflection point at 228.56 (adjusted model: below: HR 0.95, 95% CI 0.91–0.98; above: HR 1.08, 95% CI 1.03–1.13; Log-likelihood ratio p < 0.001).ConclusionsThis study reveals a nonlinear association between the TyG-BMI index and both all-cause mortality and HF rehospitalization in HF patients with CHD, positioning the TyG-BMI index as a significant prognostic marker in this population.

Functional mitral regurgitation at discharge and outcomes in patients hospitalized for acute decompensated heart failure with a preserved or reduced ejection fraction.

Background and aimsNon-alcoholic fatty liver disease (NAFLD) is associated with a higher risk of heart failure (HF) than those without NAFLD. However, the prognostic impact of NAFLD in HF is still controversial. This meta-analysis aimed to explore the association between NAFLD and the risk of adverse outcomes in patients with HF.MethodsWe searched multiple electronic databases (Embase, PubMed, and Google Scholar) for potentially related studies up to June 30, 2022. Cohort studies reported multivariable adjusted relative risks and 95% confidence intervals (CIs) of adverse outcomes in HF patients with NAFLD comparing those without NAFLD were included for analysis.ResultsA total of six studies involving 12,374 patients with HF were included for analysis, with a median follow-up duration of 2.5 years. The pooled analysis showed that HF patients with NAFLD were associated with a significantly increased risk of major composite adverse outcomes (HR 1.61, 95% CI 1.25-2.07), all-cause mortality (HR 1.66, 95% CI 1.39-1.98), and HF hospitalization or re-hospitalization (HR 1.71, 95% CI 1.03-2.86).ConclusionNAFLD is associated with a worse prognosis in patients with HF. Effective screening and treatment strategies are needed to improve the prognosis in HF patients with NAFLD.

Serum Brain-Derived Neurotropic Factor Level Predicts Adverse Clinical Outcomes in Patients With Heart Failure

Heart failure and co-morbidity revisited; the elephant in the room.

Uric acid and risk of heart failure: a systematic review and meta-analysis.

Systematic vitamin D supplementation and monitoring: improving outcomes in heart failure?

This systematic review and meta-analysis aimed to investigate the association between serum uric acid (SUA) levels and the incidence rate and prognosis of heart failure (HF), as well as the impact of uric acid-lowering treatment on HF patients. PubMed and Embase were searched for original articles reporting on the association between SUA and HF incidence, adverse outcomes, and the effect of uric acid-lowering treatment in HF patients. Data were pooled using random effects or fixed effects models. Univariable meta-regression analysis assessed the influence of study characteristics on research outcomes. Statistical analyses were conducted using RevMan software and STATA software version 15.0. Eleven studies on HF incidence and 24 studies on adverse outcomes in HF patients were included. Higher SUA levels were associated with an increased risk of HF (RR: 1.81, 95% CI: 1.53-2.16), all-cause mortality (RR: 1.44, 95% CI: 1.25-1.66), cardiac death (RR: 1.56, 95% CI: 1.32-1.84), and HF rehospitalization (RR: 2.07, 95% CI: 1.37-3.13) in HF patients. Uric acid-lowering treatment was found to increase all-cause mortality in HF patients (RR: 1.15, 95% CI: 1.05-1.25). Uric acid is an independent predictor of heart failure occurrence and adverse prognosis. Targeting uric acid lowering as a therapeutic intervention does not improve the prognosis of patients with heart failure. It may not be advisable to use traditional urate-lowering drugs in young patients with heart failure, and elderly patients should exercise caution when using them.

Background: Perturbation of energy metabolism exacerbates cardiac dysfunction, serving as a potential therapeutic target in congestive heart failure. Although circulating free fatty acids (FFAs) are linked to insulin resistance and risk of coronary heart disease, it still remains unclear whether circulating FFAs are associated with the prognosis of patients with acute heart failure (AHF).Methods: This single-center, observational cohort study enrolled 183 AHF patients (de novo heart failure or decompensated chronic heart failure) in the Second Affiliated Hospital, Zhejiang University School of Medicine. All-cause mortality and heart failure (HF) rehospitalization within 1 year after discharge were investigated. Serum FFAs were modeled as quartiles as well as a continuous variable (per SD of FFAs). The restricted cubic splines and cox proportional hazards models were applied to evaluate the association between the serum FFAs level and all-cause mortality or HF rehospitalization.Results: During a 1-year follow-up, a total of 71 (38.8%) patients had all-cause mortality or HF rehospitalization. The levels of serum FFAs positively contributed to the risk of death or HF rehospitalization, which was not associated with the status of insulin resistance. When modeled with restricted cubic splines, the serum FFAs increased linearly for the incidence of death or HF rehospitalization. In a multivariable analysis adjusting for sex, age, body-mass index, coronary artery disease, diabetes mellitus, hypertension, left ventricular ejection fraction and N-terminal pro-brain natriuretic peptid, each SD (303.07 μmol/L) higher FFAs were associated with 26% higher risk of death or HF rehospitalization (95% confidence interval, 2–55%). Each increasing quartile of FFAs was associated with differentially elevated hazard ratios for death or HF rehospitalization of 1 (reference), 1.71 (95% confidence interval, [0.81, 3.62]), 1.41 (95% confidence interval, [0.64, 3.09]), and 3.18 (95% confidence interval, [1.53, 6.63]), respectively.Conclusion: Serum FFA levels at admission among patients with AHF were associated with an increased risk of adverse outcomes. Additional studies are needed to determine the causal-effect relationship between FFAs and acute cardiac dysfunction and whether FFAs could be a potential target for AHF management.

HbA1c variability is associated with adverse outcomes in heart failure patients with and without diabetes

The neutrophil-to-lymphocyte ratio (NLR) is an emerging biomarker reflecting systemic inflammation, playing a critical role in heart failure (HF) prognosis. Elevated NLR, indicative of neutrophilia and lymphocytopenia, correlates with worsened outcomes, including higher mortality and adverse cardiac events. Studies highlight its utility as a robust indicator for risk stratification and management in both acute and chronic HF conditions. This study aims to analyze the correlation of NLR as a predictor of mortality in acute heart failure patients. This systematic review and meta-analysis explored the relationship between the neutrophil-to-lymphocyte ratio (NLR) and clinical outcomes in heart failure (HF) patients, including mortality, rehospitalization, disease progression, and functional capacity. A comprehensive search of PubMed, Scopus, Embase, and Web of Science identified 38 studies meeting the inclusion criteria. Quality and bias were assessed using established tools, and statistical analyses evaluated pooled effect sizes, heterogeneity, and optimal NLR cutoffs, evaluating their prognostic accuracy for HF outcomes. The findings highlight that heart failure (HF) patients who survived had significantly lower neutrophil-to-lymphocyte ratio (NLR) values compared to those who died (pooled standardized mean difference {SMD} = -0.48; 95% confidence interval {CI}: -0.54, -0.43; p < 0.05). Elevated NLR is significantly associated with increased mortality in heart failure patients, with most studies showing strong inverse associations and odds ratios (ORs) below 1. Odds ratios further supported this, with higher NLR linked to increased mortality risk (e.g., OR = 0.38). The area under the curve (AUC) of 0.834 indicates strong predictive accuracy for mortality, with optimal NLR cutoffs of 5.91 and 6.18 balancing sensitivity (84.6%) and specificity (84.6%). High heterogeneity (I² = 90%) shows the variability among studies. The study has concluded that an elevated neutrophil-to-lymphocyte ratio (NLR) is consistently associated with increased mortality in patients with heart failure (HF). Thus, the neutrophil-to-lymphocyte ratio (NLR) can be used as a reliable prognostic marker in patients with heart failure.

PurposeThis study sought to develop models with good identification for adverse outcomes in patients with heart failure (HF) and find strong factors that affect prognosis.Patients and MethodsA total of 5004 qualifying cases were selected, among which 498 cases had adverse outcomes and 4506 cases were discharged after improvement. The study subjects were hospitalized patients diagnosed with HF from a regional cardiovascular hospital and the cardiology department of a medical university hospital in Shanxi Province of China between January 2014 and June 2019. Synthesizing minority oversampling technology combined with edited nearest neighbors (SMOTE+ENN) was used to pre-process unbalanced data. Traditional logistic regression (LR), k-nearest neighbor (KNN), support vector machine (SVM), random forest (RF), and extreme gradient boosting (XGBoost) were used to build risk identification models, and each model was repeated 100 times. Model discrimination and calibration were estimated using F1-score, the area under the receiver-operating characteristic curve (AUROC), and Brier score. The best performing of the five models was used to identify the risk of adverse outcomes and evaluate the influencing factors.ResultsThe SME-XGBoost was the best performing model with means of F1-score (0.3673, 95% confidence interval [CI]: 0.3633–0.3712), AUC (0.8010, CI: 0.7974–0.8046), and Brier score (0.1769, CI: 0.1748–0.1789). Age, N-terminal pronatriuretic peptide, pulmonary disease, etc. were the most significant factors of adverse outcomes in patients with HF.ConclusionThe combination of SMOTE+ENN and advanced machine learning methods effectively improved the discrimination efficacy of adverse outcomes in HF patients, accurately stratified patients at risk of adverse outcomes, and found the top factors of adverse outcomes. These models and factors emphasize the importance of health status data in determining adverse outcomes in patients with HF.