Clinical Outcomes In Heart Failure Research Articles

The effects of angiotensin receptor-neprilysin inhibitors on clinical outcomes in heart failure with mildly reduced or preserved ejection fraction: real-world evidence from the CCA Database-HF Center

Abstract Background Recent clinical trials have demonstrated the potential efficacy and safety of angiotensin receptor-neprilysin inhibitors (ARNI) in patients with heart failure (HF) with mildly reduced or preserved ejection fraction. Nevertheless, the generalizability of these findings in real-world clinical settings remains to be determined. We aimed to compare the real-world effectiveness of ARNI versus angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB)on clinical outcomes in HF patients with mildly reduced or preserved ejection fraction. Methods Patient-level data was derived from the China Cardiovascular Association Database-HF Center Registry. We included exclusively a subpopulation of HF patients with left ventricular ejection fraction (LVEF) >40% and comorbid with hypertension. Patients prescripted with ARNI at discharge and sustaining to ARNI therapy during follow-up were categorized as the ARNI group, while those maintaining the usage of ACEI/ARB after discharge were designated as the ACEI/ARB group. In complete cases, the primary endpoint of all-cause mortality at one year was assessed by the 1:1 propensity score matching (PSM) method. Results In all HF patients with LVEF >40% comorbid with hypertension, the usage of ARNI has increased from 0.9% in 2017 to 37.2% in 2021. A total of 3348 patients in the ARNI group and 7688 patients in the ACEI/ARB group were identified for comparative effectiveness. After 1:1 PSM, 5482 patients were included in the primary analysis, with 2741 patients in each treatment arm. The proportion of patients receiving higher dosages of ARNI (200mg/d and 400mg/d) was 20.9%, 26.6%, 29.2%, and 30.3% at discharge, 1-month, 3-month, and 1-year, respectively. Over the 1-year follow-up, ARNI was associated with a 20% relative reduction in all-cause death compared to the ACEI/ARB therapy (10.5% vs. 12.9%, adjusted hazard ratio [HR], 0.80 [95% CI, 0.69-0.94], P=0.005). The absolute risk difference in all-cause death between ARNI and ACEI/ARB arms was 2.88 per 100 patient-years (incidence rate difference, -2.88 [95% CI, -4.86 to -0.9]). Cardiovascular death also tended to decrease in the ARNI group but with missed statistical significance (4.5% vs. 4.9%, adjusted HR, 0.89 [95% CI, 0.70-1.14], P=0.373). Treatment benefits were more significant in those with LVEF between 40-50% (adjusted HR, 0.62 [95% CI, 0.48-0.79]), 50-60% (adjusted HR, 0.85 [95% CI, 0.68-1.06]), but not observed in HF patients with LVEF>60% (adjusted HR, 1.80 [95% CI, 1.08-2.98]; Pinteraction<0.001). Conclusion In real-world clinical settings, treatment with ARNI was associated with a significant relative risk reduction in all-cause mortality compared with ACEI/ARB in HF patients with mildly reduced or preserved LVEF. The cardiovascular benefit was concentrated in patients with LVEF ≤60%.

Natriuretic peptides, kidney function and clinical outcomes in heart failure with mildly reduced or preserved ejection fraction: pooled data from the I-PRESERVE, TOPCAT, PARAGON and DELIVER trials

Abstract Background The prognostic utility of N-terminal pro-B-type (NT-proBNP) in patients with heart failure and chronic kidney disease (CKD) is incompletely understood since elevations in NT-proBNP could be related either to decreased clearance by the kidney or to increased severity of structural heart disease. Purpose We sought to assess the association of NT-proBNP with cardiovascular and mortality outcomes in patients with heart failure and mildly reduced or preserved ejection fraction, stratified by baseline kidney function. Methods We conducted a pooled analysis of individual participants with NT-proBNP and estimated glomerular filtration rate (eGFR) measured at baseline in the I-PRESERVE, TOPCAT (Americas region), PARAGON and DELIVER trials. We evaluated the relationship between NT-proBNP and kidney function using piecewise linear regression. Using multivariable Cox and Poisson regression models, we assessed the association of NT-proBNP with clinical outcomes across different levels of eGFR (≥60, 45-<60 and <45 mL/min/1.73m2). The primary outcome was hospitalisation for heart failure or cardiovascular death. Results Among 14,831 participants (mean age 72.1 years, 50.3% female, mean eGFR 63.3 mL/min/1.73m2 and median NT-proBNP 840 pg/mL) followed for a median 33.5 months, there were 3,092 primary outcomes, 2,184 heart failure hospitalisations, 1,465 cardiovascular and 1,049 non-cardiovascular deaths. Participants in lower eGFR categories were more likely to be older, female, and have atrial fibrillation and diabetes (all p<0.001). NT-proBNP levels increased by 9%, 8%, and 23% per 10 mL/min/1.73m2 lower eGFR in patients with baseline eGFR ≥60, 45-60, and <45 mL/min/1.73m2, respectively (P for non-linearity <0.001). For any given NT-proBNP concentration, participants with eGFR <45 mL/min/1.73m2 were at highest risk (Figure 1). Each doubling in NT-proBNP was associated with a 37% relative increase in the primary outcome (HR 1.37, 95% CI 1.34-1.41), consistent across different eGFR categories (P-interaction=0.42). Association between NT-proBNP and other clinical outcomes were also consistent across different levels of kidney function (all P-interaction>0.3; Figure 1). Equivalent risk for the primary outcome was apparent at NT-proBNP levels approximately 2.5- to 3.5-fold lower in patients eGFR <45 mL/min/1.73m2, compared to those with eGFR ≥60 mL/min/1.73m2. (Figure 2). Conclusion NTproBNP is a potent predictor of risk in patients with heart failure with mildly reduced or preserved ejection fraction across the spectrum of kidney function. However, in patients with reduced kidney function, lower NT-proBNP levels confer absolute risk of cardiovascular outcomes similar to substantially higher NT-proBNP levels in patients with normal kidney function. Accordingly, interpretation of NTproBNP levels should vary according to kidney function, particularly in those with eGFR <45 mL/min/1.73m2.

A flexible, calibrated transformer-based risk model for prediction of clinical outcomes in patients with heart failure; an open cohort study using linked UK EHR

Abstract Background Numerous risk scores, both uni- and multi-variable, have been developed to conduct prognostication for a range of clinical outcomes in heart failure (HF) patients [1,2]. However, these models provide only modest discrimination and often depend on complex test data (e.g., ejection fraction) collected outside of routine clinical care [2]. Furthermore, transparency in reporting of key individual-level metrics (e.g., precision, recall) is notably lacking. Purpose We developed and validated a novel deep learning model, the second version of the Transformer-based Risk assessment survival model (TRisk2), for 36-month prediction of all-cause mortality, cardiovascular-related mortality, fatal and non-fatal cardiovascular events, and renal outcomes in patients with HF using routine, linked UK electronic health records (EHR) data. Methods An open cohort of 405 thousand patients with HF between 40 and 90 years of age was identified using linked EHR from 1,063 and 355 English general practices, which were used for TRisk2 model development and external validation, respectively. Comparison was conducted against MAGGIC [2], modified for use on routine linked EHR. Additional analyses compared discriminatory performance in other age groups, by sex, and by baseline disease. All analyses were repeated for prediction of cardiovascular-related mortality, fatal and non-fatal cardiovascular events, and renal outcomes. Results TRisk2 demonstrated superior discrimination with Concordance index (C-index) of 0.828; 95% confidence interval (CI): 0.824 to 0.832 for all-cause mortality prediction outperforming MAGGIC. The proposed model’s performance was found to be stable across stratified analyses by sex, age, and baseline disease status. Both models were overall well-calibrated, and TRisk2 demonstrated greater net benefit than MAGGIC across reasonable decision boundaries in decision curve analyses. At exemplar risk threshold of 50% for 36-month prediction, TRisk2 outperformed MAGGIC by 0.08 for both, precision and recall and identified 10% more events. At the same threshold for 12-month prediction, TRisk2 outperformed MAGGIC by 0.14 and 0.26 precision and recall respectively and captured 70% more events. The well-calibrated TRisk2 similarly outperformed MAGGIC in prediction of cardiovascular-related mortality, fatal and non-fatal cardiovascular events, and renal outcomes. Conclusion Utilising solely routine EHR from primary and secondary care, TRisk2 enabled more accurate prediction than MAGGIC with 10-20% gain in C-index across the four outcome investigations. Integration of TRisk2 into routine clinical care could simultaneously eliminate the reliance of complex tests and improve prognostication of key clinical outcomes, thereby refining management of HF.Models' discrimination on four outcomes

Characteristics, Predictors, and Clinical Outcomes in Heart Failure With Reduced Ejection Fraction According to a 1-Year Left Ventricular Ejection Fraction Following Sacubitril/Valsartan Treatment.

Optimal medical treatment can lead to improvement in left ventricular ejection fraction (LVEF) in patients with heart failure with reduced EF (HFrEF). We investigated the characteristics, predictors, and outcomes of HFrEF according to the 1-year LVEF following angiotensin receptor-neprilysin inhibitors therapy (ARNI). Using the STRATS-HF-ARNI (Strain for Risk Assessment and Therapeutic Strategies in Patients With Heart Failure Treated With Angiotensin Receptor-Neprilysin Inhibitor) registry, we identified 1074 patients with HFrEF who took ARNI and underwent baseline and 1-year echocardiography. Patients were classified as HF with improved ejection fraction (HFimpEF) and persistent HFrEF (perHFrEF) (1-year LVEF >40% and ≤40%). The primary and secondary outcomes were all-cause and cardiac mortality from the 1-year follow-up. Among 1074 included patients, 498 (46.4%) had HFimpEF, and 576 (53.6%) had perHFrEF. Older age, male sex, and large LV end-diastolic volumes were positive predictors of perHFrEF, whereas atrial fibrillation and high systolic blood pressure were identified as inverse predictors. Patients with HFimpEF showed lower all-cause and cardiac mortality rates (both log-rank P<0.001). In the multivariable analysis, perHFrEF (hazard ratio, 2.402 [95% CI, 1.251-4.610]; P=0.008) was an independent predictor of poor outcomes. The risk of all-cause mortality decreased as the 1-year LVEF increased up to 40%; however, no additional risk reduction was observed beyond 40%. Compared with patients taking renin-angiotensin-aldosterone system inhibitors in the STRATS-AHF (Strain for Risk Assessment and Therapeutic Strategies in Patients With Acute Heart Failure) registry, those in the STRATS-HF-ARNI registry demonstrated better outcomes in both HFimpEF and perHFrEF. Patients with HFimpEF had better prognosis than those with perHFrEF, and ARNI treatment in HFrEF could be more beneficial than renin-angiotensin-aldosterone system inhibitors for both HFimpEF and perHFrEF. URL: https://www.who.int/clinical-trials-registry-platform; Unique identifier: KCT0008098.

Prevalence of sarcopenia in heart failure with mildly reduced ejection fraction and its impact on clinical outcomes

Background Sarcopenia is a progressive age-related skeletal muscle disease associated with adverse outcomes in those with cardiovascular disease. In this study, the prevalence of sarcopenia and its effect on clinical outcomes in heart failure with mildly reduced ejection fraction (HFmrEF) patients were examined. Methods A total of 722 patients from three centres who applied to the outpatient clinic with the diagnosis of HFmrEF between 01 January 2020 and 01 June 2021 were included in the study retrospectively. Sarcopenia was diagnosed with a screening test using age, grip srength and calf circumference. At least two-year follow-up results were reviewed from the date the patients were included in the study. Results Of the 722 HFmrEF patients, 169 (23.4%) were sarcopenic. During the follow-up of sarcopenic patients, a higher rate of hospitalisation and two-year mortality was detected compared to the non-sarcopenic group (49.7% vs 33.3%, p < .001 and 23.7% vs 13.2%, p = .001, respectively). Additionally, atrial fibrillation (AF), chronic obstructive pulmonary disease (COPD), chronic renal failure (CRF) and smoking were detected at higher rates in sarcopenic patients. In subgroup analysis, AF was found to be significantly higher in overweight/obese sarcopenia patients compared to other groups. According to Receiver operating characteristic (ROC) analysis, the sarcopenia score cut-off of 73.61 predicted mortality with 65% sensitivity and 63% specificity, and the cut-off level of 71.10 predicted hospitalisation with 68% sensitivity and 69% specificity. Conclusion In HFmrEF patients, sarcopenia is associated with adverse events and is an important prognostic marker.

The role of cardiac acoustic biomarkers in monitoring patients with heart failure: A systematic literature review.

Heart failure (HF) creates a considerable clinical, humanistic and economic burden on patients and caregivers as well as on healthcare systems. To attenuate the significant burden of HF, there is a need for enhanced management of patients with HF. The use of digital tools for remote non-invasive monitoring of heart parameters is gaining traction, and cardiac acoustic biomarkers (CABs) have been proposed as a complementary set of measures to assess heart function alongside traditional methods such as electrocardiogram and echocardiography. We conducted a systematic literature review to evaluate associations between CABs and HF outcomes. Embase and MEDLINE databases were searched for recent studies published between 2013 and 2023 that evaluated CABs in patients with HF. Additional grey literature (i.e., conference, congress and pre-print publications from January 2021 to May 2023) searches were included. Two reviewers independently examined all articles; a third resolved conflicts. Data were extracted from articles meeting inclusion criteria. Extracted studies underwent quality and bias assessments using the Joanna Briggs Institute (JBI) critical appraisal tools. In total, 3074 records were screened, 73 full-text articles were assessed for eligibility and 27 publications were included. Third heart sound (S3) and electromechanical activation time (EMAT) were the CABs most often reported in the literature for monitoring HF. Fifteen publications discussed changes in S3 characteristics and its role in HF detection or outcomes: six studies highlighted S3 assessment among various groups of patients with HF; four studies evaluated the strength or amplitude of S3 with clinical outcomes; five studies assessed the relationship between S3 presence and clinical outcomes; and one study assessed both S3 presence and amplitude in relation to HF clinical outcomes. Eleven publications reported on EMAT and its derivatives: five studies on the relationship between EMAT and HF and six studies on the association of EMAT and HF clinical outcomes. Studies reporting the first and fourth heart sound, left ventricular ejection time and systolic dysfunction index were limited. Published literature supported S3 and EMAT as robust CAB measures in HF that may have value in remote clinical monitoring and management of patients with HF. Additional studies designed to test the predictive power of these CABs, and others less well-characterized, are needed. This work was funded by Astellas Pharma Inc.

Natriuretic Peptides, Kidney Function, and Clinical Outcomes in Heart Failure With Preserved Ejection Fraction

BackgroundN-terminal pro–B-type natriuretic peptides (NT-proBNPs) are guideline-recommended biomarkers for risk stratification in patients with heart failure. However, NT-proBNP levels are often elevated in chronic kidney disease, introducing uncertainty about their prognostic relevance in persons across a broad range of estimated glomerular filtration rate (eGFR). ObjectivesThe aim of this study was to assess the association of NT-proBNP with cardiovascular and mortality outcomes in patients with heart failure and mildly reduced or preserved ejection fraction, stratified by baseline kidney function. MethodsA pooled analysis was conducted of participants with NT-proBNP and eGFR measured at baseline in the I-PRESERVE (Irbesartan in Heart Failure and Preserved Ejection Fraction), TOPCAT (Americas region) (Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function), PARAGON (Prospective Comparison of ARNI with ARB Global Outcomes in HF With Preserved Ejection Fraction), and DELIVER (Dapagliflozin Evaluation to Improve the LIVEs of Patients With PReserved Ejection Fraction Heart Failure) trials. The relationship between NT-proBNP and eGFR was assessed using piecewise linear regression. Using multivariable Cox and Poisson regression models, the association of NT-proBNP with outcomes across a range of eGFR was evaluated. The primary outcome was hospitalization for heart failure or cardiovascular death. ResultsAmong 14,831 participants (mean age: 72.1 years; 50.3% female; mean eGFR: 63.3 mL/min/1.73 m2, and median NT-proBNP: 840 pg/mL) followed up for a median 33.5 months, there were 3,092 primary outcomes. NT-proBNP levels increased by 9%, 8%, and 23% per 10 mL/min/1.73 m2 lower eGFR in patients with baseline eGFR ≥60, 45-<60, and <45 mL/min/1.73 m2, respectively (P for nonlinearity < 0.001). Each doubling in NT-proBNP was associated with a 37% relative increase in the primary outcome (HR: 1.37; 95% CI: 1.34-1.41), consistent across different eGFR categories (P for interaction = 0.42). For the same incidence of the primary outcome, NT-proBNP levels were approximately 2.5- to 3.5-fold lower in patients with eGFR <45 mL/min/1.73 m2, compared with patients with eGFR ≥60 mL/min/1.73 m2. Similar patterns were observed across all outcomes studied, including cardiovascular and noncardiovascular death. ConclusionsThe same NT-proBNP concentration predicts a substantially higher absolute risk of adverse outcomes for people with heart failure and reduced kidney function, compared with those with preserved kidney function. These data call into question proposals for higher NT-proBNP references ranges in people with CKD, and suggest that reduced kidney function per se should not be a reason to disregard higher NT-proBNP levels.

Hypoalbuminaemia and heart failure: A practical review of current evidence.

Hypoalbuminaemia (serum albumin levels ≤3.5 g/dl) is associated with poor outcomes among patients with heart failure (HF). This narrative review includes original articles and reviews published over the past 20 years and retrieved from PubMed using the following search terms (or their combination): 'heart failure', 'hypoalbuminaemia', 'heart failure with reduced ejection fraction', 'heart failure with preserved ejection fraction', 'all-cause mortality', 'in-hospital mortality', 'hospitalization', 'prognosis'. The aims of this review are to provide an overview on the prevalence of hypoalbuminaemia in HF, its impact on clinical outcomes, and potential mechanisms that may suggest future therapeutic strategies. Hypoalbuminaemia is frequent in HF patients, especially among the elderly. However, data about the exact epidemiology of hypoalbuminaemia are scant due to different definitions, and prevalence is estimated between 5% and 70% across the whole spectrum of ejection fraction. Current evidence points to hypoalbuminaemia as a marker of poor outcomes in HF, irrespective of the ejection fraction, and in other cardiovascular diseases. Among patients who suffered from acute coronary syndrome, those with hypoalbuminaemia had an increased risk of new-onset HF and in-hospital mortality. Albumin, however, might also play a role in the natural history of such diseases due to its antioxidant, anti-inflammatory, and antithrombotic properties. Whether albumin supplementation or nutritional support in general would be beneficial in improving clinical outcomes in HF is not completely clear and should be evaluated in adequately designed studies.

Aptamer Proteomics for Biomarker Discovery in Heart Failure With Preserved Ejection Fraction: The PARAGON-HF Proteomic Substudy.

Prognostic markers and biological pathways linked to detrimental clinical outcomes in heart failure with preserved ejection fraction (HFpEF) remain incompletely defined. We measured serum levels of 4123 unique proteins in 1117 patients with HFpEF enrolled in the PARAGON-HF (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction) trial using a modified aptamer proteomic assay. Baseline circulating protein concentrations significantly associated with the primary end point and the timing and occurrence of total heart failure hospitalization and cardiovascular death were identified by recurrent events regression, accounting for multiple testing, adjusted for age, sex, treatment, and anticoagulant use, and compared with published analyses in 2515 patients with heart failure with reduced ejection fraction from the PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) and ATMOSPHERE (Efficacy and Safety of Aliskiren and Aliskiren/Enalapril Combination on Morbidity-Mortality in Patients With Chronic Heart Failure) clinical trials. We identified 288 proteins that were robustly associated with the risk of heart failure hospitalization and cardiovascular death in patients with HFpEF. The baseline proteins most strongly related to outcomes included B2M (β-2 microglobulin), TIMP1 (tissue inhibitor of matrix metalloproteinase 1), SERPINA4 (serpin family A member 4), and SVEP1 (sushi, von Willebrand factor type A, EGF, and pentraxin domain containing 1). Overall, the protein-outcome associations in patients with HFpEF did not markedly differ as compared with patients with heart failure with reduced ejection fraction. A proteomic risk score derived in patients with HFpEF was not superior to a previous proteomic score derived in heart failure with reduced ejection fraction nor to clinical risk factors, NT-proBNP (N-terminal pro-B-type natriuretic peptide), or high-sensitivity cardiac troponin. Numerous serum proteins linked to metabolic, coagulation, and extracellular matrix regulatory pathways were associated with worse HFpEF prognosis in the PARAGON-HF proteomic substudy. Our results demonstrate substantial similarities among serum proteomic risk markers for heart failure hospitalization and cardiovascular death when comparing clinical trial participants with heart failure across the ejection fraction spectrum. URL: https://www.clinicaltrials.gov; Unique Identifiers: NCT01920711, NCT01035255, NCT00853658.

Dapagliflozin Effects on Cardiac Deformation in HeartFailure and Secondary Clinical Outcome.

Sodium-glucose cotransporter 2 inhibitors were shown to reduce morbidity and mortality in patients with heart failure. This study aims to assess potential effects of dapagliflozin in nondiabetic patients with heart failure with reduced ejection fraction (HFrEF) and heart failure with mildly reduced ejection fraction (HFmrEF) on cardiac function assessed by speckle tracking echocardiography (STE). This randomized, prospective, single-center, open-label trial compared consecutive nondiabetic outpatients with HFrEF or HFmrEF receiving dapagliflozin with patients treated with optimal medical therapy (OMT) except sodium-glucose cotransporter type 2 inhibitors. Primary endpoint was the presence of a significant modification of left ventricular global longitudinal strain, diastolic function (as peak atrial longitudinal strain) and right ventricular function by STE from baseline to 6months. Cardiovascular events and parameters of congestion were assessed as safety-exploratory endpoints. Overall, 88 patients (38% HFmrEF) were enrolled and randomized to start dapagliflozin on top of OMT (n=44) or to continue with OMT (n=44). All STE values improved in the dapagliflozin group after 6months, whereas there was a nonsignificant improvement in OMT group. Moreover, when comparing the modification of STE parameters at follow-up in patients with HFrEF and HFmrEF, only the main treatment effect resulted statistically significant in both groups (P< 0.0001), indicating a significant difference between dapagliflozin and OMT. This study provided randomized data on the beneficial effect of dapagliflozin in nondiabetic patients with HFrEF and HFmrEF in terms of myocardial performance measured by the most sensitive echocardiographic technique, ie, STE. This suggests its usefulness for left ventricular reverse remodeling and better quality of life in patients with HFrEF and HFmrEF. (Effects of Dapagliflozin on cardiac deformation and clinical outcomes in heart failure with reduced and mildly reduced ejection fraction [DAPA ECHO trial]; EudraCT number: 2021-005394-66).

Biologically active adrenomedullin as a marker for residual congestion and early rehospitalization in patients hospitalized for acute heart failure: Data from STRONG-HF.

Biologically active adrenomedullin (bio-ADM) is a promising marker of residual congestion. The STRONG-HF trial showed that high-intensity care (HIC) of guideline-directed medical therapy (GDMT) improved congestion and clinical outcomes in heart failure (HF) patients. The association between bio-ADM, decongestion, outcomes and the effect size of HIC of GDMT remains to be elucidated. We measured plasma bio-ADM concentrations in 1005 patients within 2 days prior to anticipated discharge (baseline) and 90 days later. Bio-ADM correlated with most signs of congestion, with the exception of rales. Changes in bio-ADM were strongly correlated with change in congestion status from baseline to day 90 (gamma -0.24; p = 0.0001). Patients in the highest tertile of baseline bio-ADM concentrations were at greater risk than patients in the lowest tertile for the primary outcome of 180-day all-cause mortality or HF rehospitalization (hazard ratio [HR] 2.14, 95% confidence interval [CI] 1.42-3.22) and 180-day HF rehospitalization (HR 2.33, 95% CI 1.38-3.94). Areas under the receiver-operating characteristic curves were 0.5977 (95% CI 0.5561-0.6393), 0.5800 (95% CI 0.5356-0.6243), and 0.6159 (95% CI 0.5711-0.6607) for bio-ADM, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and their combination, respectively, suggesting that both bio-ADM and NT-proBNP provided similarly modest discrimination for this outcome. A trend towards better discrimination by combined bio-ADM and NT-proBNP than NT-proBNP alone was found (p = 0.059). HIC improved the primary outcome, irrespective of baseline bio-ADM concentration (interaction p = 0.37). In contrast to NT-proBNP, the 90-day change in bio-ADM did not differ significantly between HIC and usual care. Bio-ADM is a marker of congestion and predicts congestion at 3 months after a HF hospitalization. Higher bio-ADM was modestly associated with a higher risk of death and early hospital readmission and may have added value when combined with NT-proBNP.

[Translated article] Therapeutic management, adherence, and clinical outcomes of heart failure in Andalucía. ANDALIC Protocol

Heart failure is a prevalent syndrome with high mortality rates, representing a significant economic burden in terms of healthcare. The lack of systematic information about the treatment and adherence of patients with heart failure limits the understanding of these aspects and potentially the improvement of clinical outcomes. ObjectiveTo describe the clinical characteristics, therapeutic management, adherence, persistence, and clinical results, as well as the association between these variables, in a cohort of patients with heart failure in Andalusia. DesignThis study will be an observational, population-based, retrospective cohort study. Data of patients discharged from an Andalusian hospital with a diagnosis of heart failure between 2014 and 2023 will be extracted from the Andalusian population health database. AnalysisThe statistical analysis will incorporate the following strategies: (1) Descriptive analysis of the characteristics of the population cohort, adherence measures, and clinical outcomes. (2) Bivariate analyses to study the association of covariates with adherence, persistence, and clinical results. (3) Multivariate logistic regression and Cox regression analysis including relevant covariates. (4) To evaluate changes over time, multivariate Poisson regression models will be used.By conducting this comprehensive study, we aim to gain valuable insights into the clinical characteristics, treatment management, and adherence of heart failure patients in Andalusia, as well as to identify factors that may influence clinical outcomes. These findings could be critical both for the development of optimised strategies that improve medical care and quality of life of patients and for mitigating the health burden of HF in the region.

The Role of Vortex Flow Analysis by Contrast Echocardiography to Predict Clinical Outcome in Heart Failure with Reduced Ejection Fraction

The Role of Vortex Flow Analysis by Contrast Echocardiography to Predict Clinical Outcome in Heart Failure with Reduced Ejection Fraction

Depressive symptoms are associated with clinical outcomes in heart failure with reduced ejection fraction.

The objective of this study was to examine associations between elevated depressive symptoms and increased risk of adverse clinical events patients with heart failure and reduced ejection fraction (HFrEF), as well as the potential contribution of health behaviours. One hundred forty-two men and women with HFrEF were enrolled through heart failure (HF) clinics and followed over time. At baseline and 6months, depressive symptoms were assessed by the Beck Depression Inventory-II (BDI-II) and HFrEF disease activity by B-type natriuretic peptide (BNP). The Self-Care of Heart Failure Index (SCHFI) was used to assess HF self-care behaviours. Proportional hazards regression models assessed the contribution of depressive symptoms and HFrEF disease biomarkers on death or cardiovascular hospitalization. Over a median follow-up period of 4years, 42 patients (30%) died, and 84 (60%) had cardiovascular hospitalizations. A 10-point higher baseline BDI-II score was associated with a 35% greater risk of death or cardiovascular hospitalization. Higher baseline BDI-II scores were associated with poorer HF self-care maintenance behaviours (R=-0.30, P<0.001) and fewer daily steps (R=-0.19, P=0.04), suggesting that elevated depressive symptoms may diminish important health behaviours. Increases in plasma BNP over 6months were associated with worse outcomes. Changes in BDI-II and plasma BNP over 6months were positively related (R=0.25, P=0.004). This study confirms that elevated depressive symptoms are associated with an increased likelihood of adverse clinical outcomes in patients with HFrEF. Poor health behaviours may contribute to the adverse association of elevated depressive symptoms with the increased hazard of adverse clinical outcomes.

The impact of atrial fibrillation on clinical outcomes in heart failure with mid-range and preserved ejection fraction patients

BackgroundThe combined effect of left ventricular ejection fraction (LVEF) and atrial fibrillation (AF) on clinical outcomes in heart failure (HF) remains complex. ObjectiveIn this post hoc analysis of the TOPCAT trial, we aimed to evaluate the impact of AF on clinical outcomes in patients with HF stratified by LVEF range. MethodsA total of 3442 patients were included, stratified into 3 groups according to LVEF range—HF with mid-range ejection fraction (HFmrEF), LVEF of 45%–50% (n = 823); HF with preserved ejection fraction (HFpEF), LVEF of 51%–60% (n = 1682); and HF with normal ejection fraction (HFnEF), LVEF >60% (n = 937)—and subdivided according to the presence of AF at enrollment. Cox regression analysis was used to define independent associations between AF and clinical outcomes. ResultsAF was prevalent in 38.6% in HFmrEF, 34.6% in HFpEF, and 33.7% in HFnEF (P = .07). AF was associated with worse primary outcome in each subgroup and with HF hospitalizations and worse cardiovascular mortality in HFpEF and HFnEF. The hazard ratio for the primary outcome in those with AF compared with sinus rhythm (SR) was 1.11 (1.01–1.22; P = .03) in HFmrEF, 1.20 (1.11–1.29; P < .001) in HFpEF, and 1.16 (1.05–1.28; P = .004) in HFnEF. When LVEF was treated as a continuous variable, there was a linear negative association between LVEF and the effect of AF vs SR for the primary end point and HF hospitalizations and a linear positive association for cardiovascular mortality. ConclusionCompared with SR, AF was independently associated with worse outcomes across all LVEF ranges.

The effect of sustained-release CARvedilol in patients with hypErtension and heart failure with preserved ejection fraction: a study protocol for a pilot randomized controlled trial (CARE-preserved HF).

Although beta-blockers improve clinical outcomes in heart failure with reduced ejection fraction, the benefit of beta-blockers in heart failure with preserved ejection fraction (HFpEF) is uncertain. Global longitudinal strain (GLS) is a robust predictor of heart failure outcomes, and recent studies have shown that beta-blockers are associated with improved survival in those with low GLS (GLS <14%) but not in those with GLS ≥14% among patients with LVEF ≥40%. Therefore, the objective of this trial is to evaluate the effect of sustained-release carvedilol (carvedilol-SR) on the outcome [N-terminal pro-B-natriuretic peptide (NT-proBNP) concentration] in patients with hypertension and HFpEF and will assess the differential effects of these drugs on the outcome, according to the GLS categories. This prospective randomized double-blind multicenter trial (CARE-preserved HF) will include 100 patients with HFpEF from three tertiary hospitals in South Korea. Patients with HFpEF and hypertension aged ≥20 years who have evidence of functional and structural heart disease on echocardiography and elevated natriuretic peptide will be enrolled. Eligible participants will be randomized 1:1 to either the carvedilol-SR group (n = 50) or the placebo group (n = 50). Patients in the carvedilol-SR group will receive 8, 16, 32, or 64 mg carvedilol-SR once daily for 6 months, and the dose of carvedilol will be up-titrated at the discretion of the treating physicians. The primary efficacy outcome was the time-averaged proportional change in N-terminal pro-B-natriuretic peptide concentration from baseline to months 3 and 6. We will also evaluate the differential effects of carvedilol-SR on primary outcomes according to GLS, using a cut-off of 14% or the median value. This randomized controlled trial will investigate the efficacy and safety of carvedilol-SR in patients with HFpEF and hypertension. ClinicalTrial.gov, identifier NCT05553314.

Implication of geriatric nutritional risk index on treatment response and long-term prognosis in patients with cardiac resynchronization therapy

PurposeGeriatric Nutritional Risk Index (GNRI) is a simple tool for assessing the nutritional status of the aging population. This study aims to explore the clinical implication of GNRI on treatment response and long-term clinical outcomes in heart failure (HF) patients receiving cardiac resynchronization therapy (CRT). MethodsPatients who underwent CRT implantation or upgrade at our hospital were retrospectively included. The association of GNRI and its tertiles with the echocardiographic response, all-cause mortality or heart transplantation, and the first hospitalization due to HF were investigated. ResultsTotally, 647 patients were enrolled, with a median age of 60 [Interquartile Range (IQR): 52–67] years and mean score of GNRI at 107.9 ± 23.7. Super-response rates increased significantly among the GNRI T1, T2, and T3 groups (25.1%, 29.8% vs. 41.1%, P = 0.002). Patients with higher GNRI were more likely to have better LVEF improvement after multiple adjustments (OR = 1.13, 95% CI: 1.04–1.23, P = 0.010). Higher GNRI was independently associated with a lower risk of all-cause mortality or heart implantation (HR = 0.95, 95% CI: 0.93–0.96, P < 0.001) and HF hospitalization (HR = 0.96, 95% CI: 0.95–0.98, P < 0.001). The inclusion of GNRI enhanced the predictability of all-cause mortality based on traditional model, including sex, New York Heart Association functional class, left bundle branch block, QRS reduction, and N-terminal pro-B-type natriuretic peptide level (C statistics improved from 0.785 to 0.813, P = 0.007). ConclusionHigher GNRI was associated with better treatment response and long-term prognosis in HF patients with CRT. Evaluation of nutritional status among CRT population is necessary for individualized choice of potential responders.

Conceptual Approach to Body Fluids and Edema, EducationDetermines Clinical Outcomes in Heart Failure.

In this brief communication, we reemphasize the importance of critical thinking in clinical practice using the example of edema. The common practice of thinking and inquiry by practicing clinicians has beneficial implications for healthcare by improving outcomes and patient care while alleviating the burden of misconceptions in practice. We provide an in-depth and interactive investigation of physiological concepts as a foundation for understanding body fluid dynamics. Finally, we offer a new classification of symptoms of heart failure. DOI: 10.52547/ijkd.8171.

Conceptual Approach to Body Fluids and Edema, EducationDetermines Clinical Outcomes in Heart Failure.

In this brief communication, we reemphasize the importance of critical thinking in clinical practice using the example of edema. The common practice of thinking and inquiry by practicing clinicians has beneficial implications for healthcare by improving outcomes and patient care while alleviating the burden of misconceptions in practice. We provide an in-depth and interactive investigation of physiological concepts as a foundation for understanding body fluid dynamics. Finally, we offer a new classification of symptoms of heart failure. DOI: 10.52547/ijkd.8171.

Temporal evolution of liver function parameters predicts clinical outcome in chronic heart failure patients (Bio-SHiFT study).

Liver dysfunction contributes to worse clinical outcomes in heart failure (HF) patients. However, studies exploring temporal evolutions of liver function parameters in chronic HF (CHF) pa- tients, and their associations with clinical outcome, are scarce. Detailed temporal patterns of alkaline phosphatase (ALP), gamma glutamyl transpeptidase (GGTP), total bilirubin (TBIL) and albumin (ALB) were investigated, and their relation with clinical outcome, in patients with stable CHF with reduced ejection fraction. Tri-monthly plasma samples were collected from 250 patients during 2.2 (1.4-2.5) years of follow-up. ALP, GGTP, ALB, and TBIL were measured in 749 selected samples and the relationship between repeatedly measured biomarker levels and the primary endpoint (PEP; composite of cardiovas- cular death, heart transplantation, left ventricular assist device implantation, and hospitalization for worsened HF) was evaluated by joint models. Mean age was 66 ± 13 years; 74% were men, 25% in New York Heart Association class III-IV. 66 (26%) patients reached the PEP. Repeatedly measured levels of TBIL, ALP, GGTP, and ALB were associated with the PEP after adjustment for N-terminal prohormone B-type natriuretic peptide and high sensitivity troponin T (hazard ratio [95% confidence interval] per doubling of biomarker level: 1.98 [1.32; 2.95], p = 0.002; 1.84 [1.09; 3.05], p = 0.018, 1.33 [1.08; 1.63], p = 0.006 and 1.14 [1.09; 1.20], p < 0.001, respectively). Serial levels of ALP and GGTP, and slopes of the temporal evolutions of ALB and TBIL, adjusted for clinical variables, were also significantly associated with the PEP. Changes in serum levels of TBIL, ALP, GGTP, and ALB precede adverse cardiovascular events in patients with CHF. These routine liver function parameters may provide additional prognostic information in heart failure with reduced ejection fraction patients in clinical practice.