Heart Failure Research Articles

Dual pathway inhibition in patients with atherosclerosis with and without heart failure: insights from the XATOA Registry

Abstract Introduction Patients with atherosclerotic cardiovascular disease (ASCVD) are at a high-risk of experiencing a major adverse cardiovascular event, with 1 in 10 individuals experiencing an event within four years (1). To address this risk of secondary cardiovascular events, there have been renewed efforts to enhance secondary prevention therapies through the application of guideline-directed medical therapy. One secondary prevention strategy is the use of dual pathway inhibition (DPI) therapy with aspirin and vascular-dose rivaroxaban (2.5mg twice daily), which simultaneously targets both the platelet activation and thrombin generation pathways. Patients with concomitant ASCVD and heart failure (HF) are a subgroup with a higher risk for ischemic events, but have not been adequately represented in recent clinical trials. Purpose To explore the risks and benefits of DPI therapy in a generalizable population of patients with concomitant ASCVD and HF. Methods The Xarelto plus Acetylsalicylic acid Treatment patterns and Outcomes in patients with Atherosclerosis (XATOA) registry is a prospective, multicentre registry of patients with either coronary artery or peripheral artery disease that were initiated on DPI (2). The primary endpoint was a composite of cardiovascular death, myocardial infarction or stroke and the safety outcome was major bleeding. Multivariable logistic regression was performed to assess the association of HF status and ejection fraction (EF) on the outcomes of interest. Results Of 5532 participants, 4022 (72.7%) had documentation of HF status. Of those 873 (21.5%) had a history of heart failure (EF >40% - 461; EF ≤40% - 181, EF unknown – 231). Over a median follow-up of 465 days (IQR – 372-576), the primary outcome occurred in 4.9% of participants with HF compared to 2.4% in those without HF (aHR 1.57 95% CI 1.02-2.41). The safety outcome was similar in patients with and without HF (0.9% versus 1.11%; aHR 0.7 95% CI 0.31-1.67). Among patients with HF, those with an EF of ≤40% demonstrated a non-significant trend towards higher rates of adverse events including MACE (8.8% versus 3.5%; aHR 1.38; 95% CI 0.59-3.22) compared to those with an EF of > 40%. Conclusion In a generalizable cohort of patients with atherosclerotic disease and HF, the use of DPI is associated with similar outcomes to those observed in recent randomised controlled clinical trials.Table 1 - Demographics by HF statusFigure 1 - MACE by HF status

Association between self-care behaviour and multiple frailty domains in older patients with heart failure

Abstract Background/Introduction Heart failure (HF) self-care is important for the effective management of HF, reducing clinical events such as all-cause mortality and hospitalizations. HF self-care behaviours encompass comply with a regimen involving medication, diet, and exercise, symptom monitoring, and seeking assistance when symptoms occur. Frailty, prevalent among older patients with HF, involves physical, social, and cognitive domains. Identified factors influencing self-care behaviours in patients with HF include age, social support, and knowledge of the condition. Despite research on the association between self-care behaviours and frailty, there is a notable gap in studies that explore the relationship between self-care behaviour and multiple domains of frailty, particularly with adjustments for clinical characteristics. Purpose The aim of this study was to assess the association between self-care behaviour and multiple domains of frailty in older patients with HF. Methods The study included 182 patients with HF who were aged 65 years or older. Self-care behaviour was assessed 5 months after their discharge using the European Heart Failure Self-Care Behaviour Scale (EHFScBS), a self-report questionnaire. Frailty was assessed using the revised Japanese version of the Cardiovascular Health Study criteria (J-CHS) for physical frailty, and using Makizako’s five items for social frailty, and using Mini-Cog for cognitive decline. We used multiple regression analysis to assess the association between self-care score and multiple frailty domains and the number of frailty domains. The adjusted model was constructed based on age, gender, body mass index, New York Heart Association Classification, left ventricular ejection fraction, log-transformed B-type natriuretic peptide, estimated glomerular filtration rate and history of HF. In addition, we used multiple regression analysis to assess the association between the EHFScBS subitems score complying with regimen, asking for help, and adapting activities and multiple frailty domains and the number of frailty domains. Results According to the results of a multiple regression analysis, poor self-care behaviour was significantly associated with physical and social frailty and the number of frailty domains (all p < 0.05), even after adjusting for clinical characteristics. Poor complying with regimen was also significantly associated with physical and social frailty and the number of frailty domains (all p < 0.05). Poor asking for help was significantly associated with social frailty and the number of frailty domains (all p < 0.05). Conclusion The study indicates that poor self-care behaviour is linked to physical and social frailty, in addition to the cumulative number of frailty domains in older patients with HF, even when clinical characteristics are taken into consideration. This underscores the importance of factoring in the frailty status when guiding patients with HF in disease management.

Circulating secretoneurin concentrations predict cardiovascular death in ambulatory patients with heart failure

Abstract Background Secretoneurin (SN) is a novel biomarker, which predicts cardiovascular (CV)-related mortality in patients with acute dyspnea and sepsis. Higher SN concentrations have also been found associated with all-cause death in outpatients with heart failure (HF), but whether SN primarily reflects cardiovascular (CV)-related mortality in HF outpatients is not known. Objectives To evaluate the relation between SN concentrations and CV- & non-CV death in ambulatory patients with HF. Methods We studied 184 consecutive patients who attended our HF clinic for routine follow up and had stored blood samples available for SN analysis. SN concentrations were measured with a CE-marked SN ELISA assay. We assessed the associations between SN concentrations and CV & non-CV death. Mortality was ascertained using medical records, autopsy reports and death certificates, and CV deaths included sudden cardiac deaths or mortality due to myocardial infarction, HF or stroke. We assessed association with CV & non-CV death by Kaplan-Meier curves and by Cox proportional hazard regression analysis. Results Median age was 76 years (range: 38-94 years) and two thirds were male. Sixty-three percent had HF with reduced ejection fraction, 22% had NYHA III/IV symptoms and median NT-proBNP was 1079 (interquartile range: 462-2347) ng/L. Median SN level was 60 (range: 21-134) pmol/L. In multivariable linear regression analysis, impaired renal function and lower body-mass index were significantly associated with increasing (log)SN concentration. During median follow up of 540 days, there were 18 CV deaths, including 15 HF deaths, and 7 non-CV deaths. A higher SN concentration was associated with higher risk of CV death, while we did not find statistically significant association between SN concentrations and non-CV deaths (Figure). Patients with SN concentration in the top tertile had 15-fold increased risk of CV death compared to patients with SN concentration in the lowest tertile. In multivariable Cox regression analysis that adjusted for age, NYHA functional class, frailty status, increasing SN concentrations were independently associated with CV death: hazard ratio per logSN (95% CI): 3.01 (1.02-8.90), p=0.04. Conclusion In ambulatory patients with HF, circulating SN concentrations were predictive of CV death. Higher SN concentrations in ambulatory HF patients seemed to be linked to impaired renal function and lower body-mass index. Figure: Kaplan Meier curves illustrating the relation between SN tertiles and (A) CV mortality (B) Non-CV mortality.

Associations of Cardiac myosin binding protein C to Troponin I in patients with chronic heart failure during exercise. A substudy of the SMARTEX-HF trial

Abstract Aim Cardiac myosin binding protein C (cMyC) has shown promise being more sensitive than cardiac troponins, rising faster after myocardial infarction[i]. Its association to hs-cTnI in heart failure patients during physical activity is not known. The aim of this study was to assess the association between a novel biomarker: cMyC and the clinically used high sensitivity cardiac Troponin I (hs-cTnI) during a 12-week exercise training program in patients with chronic symptomatic heart failure with reduced ejection fraction (HFrEF). The changes of biomarkers in plasma levels in an intervention group, performing structured exercise programs, were compared to those in a control group, instructed to perform regular recommended exercise (RRE) according to current guidelines. Methods and results This was a post hoc analysis of the SMARTEX-HF trial in 215 patients with symptomatic heart failure (HF) with Left Ventricular Ejection Fraction (LVEF) <35% and NYHA II-III. The patients were randomly assigned to High Intensity Interval Training (HIIT, n=77), Moderate Continuous Training (MCT, n=65) or RRE, (n=73) for 12 weeks. Measurements and clinical data were acquired before and after the 12-week intervention. In 191 patients, plasma was available for hs-cTnI testing and in 189 patients plasma was available for cMyC testing. Due to the lack of a normal distribution, the values were log transformed. There was a significant association of change in log hs-cTnI and change in log cMyC (Pearson correlation R=0.52 (95% CI 0.37- 0.66) p<0.001) (Figure 1). For any 10% increase in cMyC level, the ratio of the hs-cTnI level increased with approximately 5% (Figure 2). There was no association between the levels of cMyC at baseline and change in hs-cTnI at 12 weeks. Conclusion Changes in levels of the novel biomarker cMyC was significantly associated with hs-cTnI plasma levels in patients with symptomatic chronic HFrEF during a structured 12 week exercise training program. Being more sensitive, it may indicate a role as a future marker of subclinical myocardial damage.Models with adjustmentsMarginal effect at the mean

Heart failure and renal outcomes in patient treated with GLP1 agonists

Abstract Introduction Glucagon-like peptide-1 receptor (GLP1) agonists are emerging as a primordial treatment for diabetes and to reduce cardiovascular burden, both of them factors that play an important role in the developing of renal chronic disease and heart failure, and vice versa. The debut of renal chronic disease and the manifestation of acute renal injury/failure can lead to the discontinuation of treatment, which in patients suffering from heart failure who tend to be polymedicated could end up in lessening their survival. Methods A metanalysis of randomized clinical trials (RCT) comparing GLP1 agonists with placebo was performed. The endpoint of the study was to analyze all-cause mortality, hospitalization or urgent medical visit for heart failure, a kidney outcome composite, which is slightly heterogenic depending on the RCT, and the manifestation of acute renal injury/failure as an adverse effect or that lead to the discontinuation of treatment. The meta-analysis was performed using the inverse variance method, using the fixed effects model when there was no heterogeneity and the random effects model when heterogeneity is significant. Results A sum of 9 randomized controlled trial were included where a GLP1 agonists such as albiglutide, dulaglutide, exenatide, liraglutide, lixinatide or semaglutide compared with placebo. 77684 patients were incorporated, while 39497 were treated with a GLP1 agonists. The mean age was of 63.7 years (SD ± 1.97 years), 60080 (77.3%) suffered from diabetes, 60552 (77.9%) from cardiovascular disease and 14367 from chronic heart failure (18.4%). The mean eGFR was 77.3 mL/min (SD ± 3.3 mL/min). As showed in the forest plots, treatment with GLP1 agonists reduced all-cause mortality by 12% (RR: 0.88, 95% CI 0.83-0.92; p<0.001), hospitalization or urgent medical visit for heart failure by 10% (RR: 0.90, 95% CI 0.83-0.98; p<0.001), the kidney composite outcome by 22% (RR: 0.78, 95% CI 0.70-0.87; p<0.001), while it showed no statistical reduction in acute renal injury/failure (RR: 0.89, 95% CI 0.79-1.01; p=0.069). Conclusion Treatment with a GLP1 agonists reduced the incidence of all-cause mortality by 12%. In addition, hospitalization or urgent medical visit for heart failure was decreased by 10%. In terms of renal asessment, the composite of kidney function was reduced by 22%, while the manifestation of acute renal injury/failure, though no statistical signification was accomplished, showed some evidence of beneficial effect but more RCTs are needed to prove it. Hence, GLP1 analogues appear as a possible new pillar of treatment for heart failure and renal disease in determined patients.

Survival in patients with chronic congestive heart failure and correlation of presence of risk factors and all-cause mortality

Abstract Background Right heart function is known to be an independent risk factor for early mortality in patients with acute and chronic heart failure (HF). The prognostic value of cardiopulmonary exercise testing (CPET) is established for risk stratification in patients with Heart Failure. Further, markers of inflammation may predict clinical outcomes. Purpose We performed a single-center retrospective analysis of a large single center cohort and assessed all-cause mortality. A simple score including presence of RVD, systemic inflammation and reduced O2 uptake was applied to all patients and a subgroup survival analysis was performed. Methods A total of 612 patients with HF across the whole spectrum of left ventricular ejection fraction (LVEF) were analyzed. We stratified patients according to RV function, peak relative oxygen consumption in ml/min/kg (VO2max) and CRP levels. Patients were classified as RV Dysfunction when a right ventricular dilation (RVEDD > 40 mm or RVOT > 30 MM) or decreased tricuspid annular systolic excursion (TAPSE < 17 mm) was seen in the echocardiography. All patients were followed up by phone or by hospital records if available. The primary end-point of all-cause mortality was assessed. Results For the primary analysis, 612 patients (mean age 59.8 ± 13.8 years, 71.41% male) were included. According to LVEF 248 (40.5%) patients had preserved LVEF (HFpEF), 82 (13.0%) had mid-range LVEF (HFmrEF) and 282 (46.0%) had reduced LVEF (HFrEF). HF etiology was in 27% ischemic. Mean BNP values were 514.1 ± 827.1 pg/l. Mean VO2max 15,9 ± 5,9 ml/min per kg. Patients were followed up for a median of 4.0 years (IQR: 3.4 - 4.9 years). Over this period, the primary end-point occurred in 17.6% of patients. 135 (22%) of patients had evidence of RV dysfunction, 26% had increased CRP-levels and 256 (41.8%) had a VO2max < 14 ml/min per kg. Patients with elevated CRP, VO2max < 14 ml/min/kg and RV-dysfunction showed worse survival according to the Kaplan-Meier-Estimate with a significant difference (Log Rank: Chi²: 1480, p = 0.013) compared to patients with only RV dysfunction low VO2 max or only increased CRP values. Conclusion A combined evaluation of systemic inflammation, cardiopulmonal exercise testing and right ventricular dysfunction is useful in predicting long-term outcomes of patients with HF. Patients with both risk factors show worse survival than patients with signs of inflammation or RV dysfunction only.Kaplan-Meier-Estimates

Telehealth-aided outpatient management of acute heart failure in a specialist virtual ward compared to standard care

Abstract Background/Introduction Acute decompensated heart failure (ADHF) leads to hospitalisations, frequent re-hospitalisations and mortality. The safety and efficacy of telehealth-guided outpatient ADHF management (virtual ward-VW) as an alternative to hospitalisation has not been assessed previously. Aim The aim of this study was to assess the safety and outcomes of our acute heart failure virtual ward (HFVW) pathway (Figure 1) when compared to hospitalised ADHF patients. Methods This cohort study (May 2022-October 2023) assessed the outcomes of telehealth-guided outpatient ADHF management using bolus intravenous furosemide in a HF-specialist VW. We compared baseline patient characteristics, NTproBNP, ejection fraction, NYHA Class, clinical risk score (Get With the Guidelines-Heart Failure-GWTG-HF), comorbidities (Charlson Co-morbidity Index-CCI), frailty (Rockwood Clinical Frailty Score-CFS), HF therapies and measured clinical outcomes at 1, 3, 6 and 12 months (re-hospitalisations, mortality) in the HFVW cohort versus standard care (ADHF patients managed without telehealth in 2021). Results 554 HFVW ADHF patients (age 73.1±10.9 years; 46% female) were compared with 402 ADHF patients (74.2±11.8; p=0.15 and 49% female) in the standard care cohort (SC). Despite similar baseline patient characteristics, GWTG-HF score, CCI and CFS, re-hospitalisations were significantly lower in the HFVW compared to standard care (1 month - 11.6% vs. 21%, p=0.002; 3 months - 20.4% vs. 30%, p=0.001; 6 months -29.3% vs 41%, p=0.02 and 12 months-48% vs. 57%,p=0.03) whereas mortality was lower at 1 month (6% vs. 14%; p<0.001), 3 months (10.5% vs. 15%; p=0.02) and 6 months (15.5% vs. 21%; p=0.04) (Figure 2). Multivariate logistic regression analysis showed that an increased daily step count whilst on HFVW independently predicted reduced odds of re-hospitalisations at 1 month (OR 0.85; 95% CI 0.7-0.9; p=0.005), 3 months [OR 0.95 (0.93-0.98); p=0.003] and 1 month mortality [OR 0.85 (0.7-0.95), p=0.01]. Whereas CCI predicted adverse 12-month outcomes [OR 1.2 (1.1-1.4), p=0.03]. Higher GWTG-HF score independently predicted increased odds of re-hospitalisation [1-month OR 1.2 (1.1-1.3), p=0.01; 12-month OR 1.1, 1.05-1.2, p=0.03) as well as mortality [1-month OR 1.2 (1.1-1.4), p=0.01; 12-month OR 1.3 (1.1-1.7), p=0.02]. Similarly higher CFS also independently predicted increased odds of re-hospitalisations [1-month OR 1.5 (1.1-2.2), p=0.03; 12-month OR 1.9 (1.2-3, p=0.01] and mortality [1-month OR 2 (1.1-3.5), p=0.02; 12-month OR 2.6 (1.6-10); p=0.02] throughout the follow-up period. Conclusions A telehealth-guided specialist HFVW management strategy for ADHF may offer a safe and efficacious alternative to hospitalisation in suitable patients. Daily step count, GWTG, CCI and CFS can play a vital role in assessing suitability for VW and in predicting risk of adverse clinical outcomes.Heart Failure Virtual Ward PathwayMortality & Re-hospitalisations outcomes

A practical risk score for prediction of 6-month mortality in patients with acute heart failure: CHAM2P2

Abstract Background Admission with acute heart failure carries a poor prognosis. Multiple predictive risk scores exist in heart failure presentation, however the utility of these scores in acute heart failure setting among older adults is limited. Aim The purpose of this study was to develop a practical risk score to predict 6-month mortality in patients presenting with acute heart failure. Methods Between January-August 2020, 474 consecutive patients (mean age 80 ± 11 years) admitted with acute heart failure to a large tertiary hospital in the South-West of England were identified. Data was retrospectively collected on admission bloods, comorbidities, imaging, echocardiography and post discharge mortality. Prediction modelling with multivariate Cox regression was then used to identify clinically relevant predictors of six-month mortality. Continuous variables were dichotomised around the mean/median for simplification. Variables were assigned points proportional to hazard ratios on Cox regression. Results Mortality at six months was 34% (161/474). Cox regression identified five significant (p<0.05) predictors of mortality: C: Clinical Frailty Score>5, H: hospital stay >10 days, A: age >80yrs, M: malignancy (current or previous) history and P: NT pro-BNP>4500pg/ml. In our final model, malignancy and NT pro-BNP were assigned two points with the remainder being assigned one. In total, 304 patients had data available to generate CHAM2P2 scores. Mortality increased sequentially from 16.0% in patients with CHAM2P2 0-2, 44.4% in patients with CHAM2P2 scores of 3-5 and 94.1% in patients with CHAM2P2 scores of 6 or 7 (log rank <0.01). AUC demonstrated good discriminatory value of the CHAM2P2 score in predicting six-month mortality (AUC 0.74). Conclusion The CHAM2P2 score is a readily available and simple tool to predict 6-month mortality in patients admitted with acute heart failure.

Usefulness of preoperative NT-proBNP for prediction of acute heart failure, perioperative myocardial infarction/injury and mortality after non-cardiac surgery

Abstract Background Predicting cardiac complications after non-cardiac surgery is challenging. Purpose to determine the predictive accuracy of N-Terminal Pro–B-Type Natriuretic Peptide (NT-proBNP) and, to assess the utility of existing NT-proBNP cutoffs of the 2021 ESC Guidelines for the diagnosis of acute and chronic heart failure for prediction of postoperative acute heart failure (pAHF), perioperative myocardial infarction/injury (PMI) and mortality following non-cardiac surgery. Methods we prospectively determined preoperative NT-proBNP concentrations in consecutive patients at high cardiac risk undergoing inpatient non-cardiac surgery. Uni- and multivariable regression models were constructed to test the association between NT-proBNP concentrations and the outcomes (pAHF, PMI, 30-day and one-year mortality), using NT-proBNP as a continuous variable. We further stratified NT-proBNP into 5 categories according to guidelines (<125 pg/ml, 125 to 299pg/ml, 300 to 900 pg/ml, 901 to 1800pg/ml and >1800 pg/ml). Receiver operating characteristic curves were constructed to determine the predictive value of NT-proBNP. Results Among the 2,334 cases included, pAHF occurred in 83 (3.6%), PMI in 381 (17%), 45 (2.5%) patients died within 30 days and 179 (10%) within one year. After adjusting for confounders, NT-proBNP concentrations were independent predictors of pAHF (adjusted hazard ratio [aHR] 1.8 [95%CI, 1.5-2.1], p<0.001), PMI (aHR 1.3 [95%CI, 1.2-1.4],p<0.001) and 30 day/one year mortality (aHR 1.6[95%CI, 1.3-2.0], p<0.001)/aHR 1.5 [95%CI 1.4-1.7], p<0.001). By quintiles, higher the NT-proBNP levels were strongly associated with adverse outcome (Figure). Accuracy of preoperative NT-proBNP for prediction of pAHF was excellent (area under the curve [AUC] 0.825) and better than accuracy of the Revised Cardiac Risk Index score (AUC 0.692, p<0.001), whereas accuracy of NT-proBNP for prediction of PMI (AUC 0.654) and mortality (AUC 0.787) was only moderate. Conclusion NT-proBNP concentrations are independent predictors of pAHF, PMI and short and long-term mortality following non-cardiac surgery. Stratifying NT-proBNP concentrations using current recommended cut-offs could help to further determine the magnitude of the risk, mainly of pAHF.

Cardiovascular risks of PD1 inhibitor therapy in cancer: impact of prior ischemic events on heart failure - a retrospective cohort study

Abstract Introduction Immune checkpoint inhibitors (ICIs) have transformed cancer therapy, but concerns remain about their cardiac risks. Limited recent basic evidence suggests a possible link between ICIs that target PD1 and adverse cardiac events such as heart failure. Purpose This study explores the connection between PD1 inhibitor therapy and incident heart failure in cancer patients. Methods In our retrospective study at a tertiary medical center, 1,671 cancer patients receiving PD1 inhibitors were analyzed. Individuals with a history of heart failure, who developed myocarditis on PD-1, or had missing data were excluded. Data from pharmacy records and the Research Patient Data Registry provided clinical and ICI-related details. Cases were defined as patients who developed incident heart failure after ICI started. Controls were patients who did not develop incident heart failure after ICI start. Sensitivity analyses, including propensity score matching and comparison with non-ICI-treated cancer patients, ensured result robustness. Multivariate logistic regressions were performed. Results Among 1,671 ICI treated patients, 109 (6.5%) developed heart failure without evidence of myocarditis over a median follow-up of 332.0 days. In both the full cohort and the 3:1 matched cohort (n=380), multivariate logistic regression showed increased odds of incident heart failure in patients with prior ischemic cardiac events: 2.34 (95%CI 1.26-4.16, p=0.005) and 2.11 (95%CI 1.05-4.2, p=0.033) respectively. Among the non-ICI treated cancer patients, multivariate logistic regression found no association between prior ischemic events and incident heart failure (1.23, 95%CI 0.53-2.63, p=0.6), but hypertension showed an association (1.74, 95%CI 1.07-2.87, p=0.027). Conclusion This study emphasizes vigilance for cardiovascular complications in PD1 inhibitor-treated cancer patients. The incidence of heart failure was 6.5% over a follow-up period of less than 1 year. Prior ischemic events correlate with increased heart failure risk, suggesting a need for nuanced patient management. Understanding ICIs' cardiovascular safety is crucial for risk assessment, treatment optimization, and patient well-being.

Hyponatremia and risk of new-onset heart failure in patients with type 2 diabetes - a real-world study of 70,000 patients

Abstract Background Hyponatremia is common in patients with heart failure and in patients with type 2 diabetes (T2D), and is a risk marker for increased morbidity and mortality. However, it is unclear whether hyponatremia in patients with T2D is associated with an increased risk of new-onset heart failure. Purpose To investigate whether hyponatremia is associated with an increased risk of new-onset heart failure in patients with T2D. Methods From Danish nationwide registers, all patients with T2D with no history of heart failure were identified from 2013-2021. Patients with at least two samples of plasma sodium measured (at least one month apart), during the first six months following their T2D diagnosis, were included with follow-up start six months after T2D diagnosis as well. Patients were categorized in two groups according to the mean plasma sodium concentration at baseline: 1) sodium >137 mmol/L; and 2) sodium <137mmol/L. Cumulative incidence curves and Cox proportional hazards models (crude and adjusted for age, sex, comorbidities, and potential hyponatremia-inducing medications including diuretics, anticonvulsants, and antidepressants) were used to investigate the association of sodium concentration with the incidence of heart failure during follow-up. Incidence rates of heart failure per 1000 person-years were calculated across the spectrum of the measured sodium levels. Results We included 69,750 patients where 57% were male and the median age was 63 (interquartile range: 54-71). At index, 57,723 (83%) patients had a mean sodium concentration of >137 mmol/L and 12,027 (17%) patients had a mean sodium concentration <137 mmol/L (hyponatremia). Patients with a sodium level <137 mmol/L were associated with a significantly higher hazard rate of heart failure compared to patients with sodium concentrations >137 mmol: adjusted hazard ratio (HR) 1.27 (95% confidence interval 1.15-1.41, p-value <0.001). In analyses where sodium concentration was considered a continuous variable, increasing concentration of 1 mmol/L was associated with a decreasing hazard rate of heart failure: adjusted HR 0.96 (0.94-0.97, p-value <0.001). Conclusions Hyponatremia was common and associated with a significantly higher risk of new-onset heart failure in patients newly diagnosed with T2D. Whether hyponatremia could be a new treatment target to prevent heart failure in T2D remains to be determined.Cumulative incidence of heart failureIncident heart failure

Right ventricular pulmonary artery uncoupling independently associated with 5 year outcome following AHF hospitalisation

Abstract Background Right ventricular pulmonary artery (RV-PA) uncoupling is associated with poor outcome across a range of conditions, but its role in acute heart failure (AHF) remains incompletely investigated. Purpose To investigate if RV-PA uncoupling is independently associated with mortality following hospitalisation for AHF. Methods 418 patients were recruited. 391/418 (93.5%) had measurable TAPSE and SPAP and were followed up for 5 years to assess for all-cause mortality. Patients were recruited if they displayed signs and symptoms of AHF, had point-of-care brain-natriuretic peptide >100pg/ml and had evidence of HF on TTE. We identified a study-specific cut-off for TAPSE/SPAP of 0.24mm/mmHg on ROC analysis and performed univariate analysis to assess for an association with outcome. 30 covariates encompassing comorbidities, medications, echo parameters and observations were assessed and logistic regression analysis performed including variables associated with outcome. Results Patient average age at presentation was 79 years, 53.3% were male, 55.5% had hypertension, 30.7% had diabetes and 36.8% had CAD with a mean LVEF of 42.6% and BNP of 1363pg/ml. The mean TAPSE was 15.6mm and SPAP of 52.5mmHg. The average TAPSE/SPAP was 0.34mm/mmHg. 252/391 (64.5%) presented with TAPSE/SPAP <0.24mm/mmHg. These individuals were at higher risk of 5-year mortality compared to >0.24mm/mmHg: HR 1.94 (95% CI 1.49-2.54 [p<0.0001]), which persisted when adjusted for significant covariates – HR 1.35 (95% CI 1.02-1.80 [p<0.0395]). Conclusion TAPSE/SPAP ratio is an independent predictor of mortality in patients admitted with AHF. Our cut-off, a lower value than others have suggested in the literature for chronic conditions such as pulmonary hypertension, could identify those at risk of poor outcome in the acute setting. This may offer an exciting therapeutic target and help risk stratify patients. These results should focus the attention of those managing AHF patients onto the RV, pulmonary pressures and their interrelationship. It is time we moved beyond the LVEF.

Liver function tests in patients receiving high-intensity care after hospital admission for acute heart failure: the STRONG-HF trial

Abstract Background/Introduction Episodes of acute heart failure (AHF) unfavorably affect extra-cardiac organs such as the liver due to altered hemodynamics and neurohormonal activation. In AHF, elevated levels of levels of alanine aminotransferase (ALT) and total bilirubin (tBil) may reflect congestion and impaired liver function, while lower levels of ALT (which is also produced in muscle cells) correlate with malnutrition and sarcopenia. Thus, the clinical importance of these markers in AHF and the post-discharge period is unclear. Purpose To assess circulating concentrations of ALT and tBil in patients with AHF before discharge and during high-intensity care (HIC) vs usual care follow-up in association with clinical outcomes. Methods ALT and tBil concentrations were measured 1-2 days before discharge in patients hospitalized for AHF (baseline), and again after 90 days of either HIC or usual care according to the STRONG-HF protocol. Baseline values and changes in ALT and tBil were analyzed in association with the primary outcome of all-cause death or HF readmission by day 180. Results At baseline, the median (Q1-Q3) concentrations of ALT and tBil were 21 (15-32) U/L and 14 (10-21) umol/L, respectively. Lower levels of both ALT and tBil were associated with female sex, Black race, lower BMI, higher LVEF, lower hemoglobin, lower creatinine and less frequent atrial fibrillation/flutter, while there were no significant associations with age. Patients with lower ALT, but not tBil, were more likely to have edema, elevated JVP and orthopnea, and used higher loop diuretic doses and less beta-blockers, pre-randomization (Figure, panel A). ALT was inversely associated with risk for the primary outcome (HR 0.81 [95%CI 0.65,1.00) per log increment, p=0.05), while there was no association with risk for tBil (HR 1.04 [95%Ci 0.84-1.28], p=0.73) (Figure, panel B). After 90 days, ALT and tBil concentrations were lower than at baseline, with a greater reduction in tBil in the HIC group vs usual care group (mean -1.7 [95%CI -3.0,-0.4] umol/L, p=0.01), while there was no significant between-group differences in ALT changes (mean -0.6 [95%CI -4.7,3.4] U/L, p=0.75) (Figure, panel C). The treatment effect of HIC over usual care on the primary outcome was consistent across the range of baseline ALT (P-interaction=0.30) and tBil (P-interaction=0.80) (Figure, panel D). Conclusion Contrary to our hypothesis of higher liver function tests with hepatic congestion in AHF, lower ALT was associated with more congestion and worse outcomes among patients hospitalized for AHF in STRONG-HF. There was no prognostic value from tBil levels. This suggests that ALT may be a marker of sarcopenia in these patients. Importantly, the beneficial effect of HIC on clinical outcomes is consistent irrespective of ALT and tBil levels at discharge.Figure

Prognostic value of albumin-bilirubin score in patients with chronic heart failure

Abstract Background Liver dysfunction is one of the common comorbidities, and associated with worse clinical outcomes in patients with chronic heart failure (CHF). Recently, the albumin-bilirubin (ALBI) score has been developed as an effective and convenient scoring system for assessing liver function. However, the prognostic significance of the ALBI score in patients with CHF remained to be clarified. Purpose We sought to investigate the clinical significance of ALBI score on outcome prediction in patients with CHF. Methods We prospectively examined 1567 symptomatic CHF patients (median age 74, inter quartile range [IQR] 64-82 years, mean left ventricular ejection fraction [LVEF] 49 ± 15.9 %, median N-terminal pro-brain natriuretic peptide [NT-pro BNP] 801 [IQR 372-1820] pg/ml) in a multicentre registry with 27 Japanese sites between January 2020 and December 2023. The ALBI score was calculated according to the following formula: log10 total bilirubin (mg/dl) × 0.06 + albumin (g/dL) × 10 × (-0.085). Studied patients were divided into three groups according to the ALBI grade; ALBI score ≤ -2.60 (Grade1, n = 691), -2.60 < ALBI score ≤ -1.39 (Grade 2, n = 864), ALBI score > -1.39 (Grade3, n = 12). Primary outcome of interest was a composite of all-cause death and hospitalisation due to worsening heart failure. Results Patient with higher ALBI grade had higher age, New York Heart Association functional class, NT-pro BNP level, prevalence of atrial fibrillation and chronic obstructive pulmonary disease, and lower body mass index, systolic blood pressure, haemoglobin level, serum albumin level and estimated glomerular filtration rate compared to those with lower ALBI grade. LVEF was comparable between the groups. During a median follow-up period of 537 (IQR 285-701) days, the primary outcome occurred in 267 patients (17%). Higher ALBI grade were significantly related to increased incidence of the primary outcome (P for trend < 0.001) (Figure 1). Multivariable Cox regressions showed that a higher ALBI score was independently associated with higher risk of the primary outcome (hazard ratio 2.8, 95% confidential interval (CI) 2.08-3.77, P < 0.001), even after adjustment for the MAGGIC score as an established risk prediction model, NT-pro BNP, aspartate aminotransferase, and platelet counts. Furthermore, addition of the ALBI score to the MAGGIC score significantly increased c-index from 0.70 (95% CI 0.66-0.74) to 0.73 (95% CI 0.69-0.76) (P < 0.001) (Figure 2). The net reclassification improvement afforded by the ALBI score was 26% for the primary outcome (P<0.001). Conclusions Liver dysfunction assessed by the ALBI score was independently associated with worse clinical outcomes in patients with CHF. Moreover, addition of the score to the existing risk prediction model significantly increased the ability of outcome prediction, suggesting beneficial clinical application of the ALBI score in patients with CHF.

Prognostic value of soluble urokinase plasminogen activator receptor (suPAR) in patients admitted with acute heart failure

Abstract Introduction The inflammatory marker, soluble urokinase plasminogen activator receptor (suPAR), has emerged as a promising prognostic biomarker of heart failure (HF). Higher levels of suPAR in plasma are indicative of hospital readmissions and mortality. Currently little is known about suPAR-values upon admission in patients with acute heart failure (AHF). Purpose This study investigates the prevalence of elevated suPAR and prognostic value in patients hospitalized with AHF. Methods In this prospective cohort study, all patients ≥ 18 years old admitted at the Emergency Department at a large University Hospital in Denmark, were consecutively included from March 10, 2020, to March 31, 2022. The follow-up period was 365 days. The biomarker suPAR was measured in all patients upon admission (median time from admission to suPAR measurement was two hours (IQR 3: 3,9-6,9)). Patient data was extracted from the electronic patient record system, and a cardiologist adjudicated whether the patients had AHF. Patients were stratified according to validated cut-off values of suPAR above or below 6 ng/mL. Kaplan-Meier survival analysis and Cox Regression were used to assess the association between suPAR levels and one-year mortality outcomes. Results A total of 408 (5%) AHF patients, from a total population of 6,715, were included in the study. 40 patients were excluded due to missing suPAR-values and the final analysis comprised of 368 AHF patients. Among AHF patients upon admission, the mean suPAR value was 6.2 ng/mL (standard deviation [SD] = 4.8 ng/mL), and non-AHF patients had a mean value of 4.5 ng/mL (SD = 3.1 ng/mL). A suPAR level above 6 ng/mL was significantly associated with mortality (figure 1), log-rank test p-value < 0.0001. Furthermore, Cox regression analysis demonstrated that elevated suPAR levels were independently associated with increased risk of mortality with a hazard ratio (HR): 2.09 (95% CI: 1.59-2.90), p-value < 0.001 after adjusting for potential confounders: age, sex, atrial fibrillation, Chronic Obstructive Pulmonary Disease, and Creatinine levels. Conclusion The inflammatory biomarker suPAR measured upon hospital admission in AHF patients is significantly associated with one-year mortality in patients admitted with AHF. The potential of suPAR as a valuable prognostic marker in AHF is offering clinicians a tool to identify high-risk patients and tailor management strategies, accordingly, thereby improving patient outcomes.Figure 1 - 1 year mortality

Right ventricular failure following left ventricular assist device implantation

Abstract Background Left ventricular assist device (LVAD) therapy is a lifesaving option for patients with medical therapy-refractory advanced heart failure.(1) Right ventricular failure (RVF) is a cause of major morbidity and mortality after LVAD implantation.(2,3) Our objective was to get the outcomes and predictors of RVF in adult patients undergoing LVAD implantation. Methods This retrospective study enrolled 73 adult patients with LVAD (Heart Mate III) implantation, of them 24(32.9%) patients had RVF after LVAD implantation. Results The patients with RVF had statistically significant more frequencies of acute kidney injyry (p<0.001), new need for dialysis(p<0.001), RVAD insertion (p<0.001), total mortality (p=0.012) and on-VAD mortality(p=0.018) with prolonged ICU stay (p<0.001) compared to the non-RVF group respectively. The pre-LVAD pulmonary vascular resistance(PVR) ≥3 WU (OR:2.4, 95%CI: 1.52-7.38, p=0.04) and diastolic pulmonary gradient(DPG) ≥ 7 mmHg (OR:6.4,95%CI: 5.49-18.6, p<0.001) were the independent predictors of RVF after LVAD implantation. Cox proportional regression analysis revealed that RVF was associated with increased risk of death (HR:3.12,95%CI:1.42-6.85, p=0.005). Conclusion Early RVF post-LVAD carries significant risks of mortality and multiple morbidities. Concomitant BiVAD implantation needs to be considered in patients with elevated DPG and PVR to avoid post-LVAD RVF.The significant variables of patients.Kaplan-Meier curves of the 2 groups.

Basal natriuresis as a predictor of diuretic resistance and clinical evolution in acute heart failure

Abstract Introduction Current clinical guidelines recommend serial measurement of natriuresis to detect diuretic resistance (DR) and to adjust the dose of furosemide in patients with acute heart failure (AHF) (1-5). However, multiple natriuretic dosages could make more complex the AHF management. Our objective was to correlate a single measurement of basal natriuresis (BN) on admission with the development of DR and cardiovascular (CV) events in patients hospitalized for AHF and during early outpatient follow-up (6-11). Methodology Prospective, multicenter study that included patients admitted to the coronary care unit (CCU) for AHF. Patients in shock or with creatinine >2.5 mg% at admission were excluded. Patients included received 40 mg of intravenous furosemide on admission, BN was measured in the first urination (the result was blinded to the treating physician), and subsequent diuretic treatment was guided by a pre-established protocol. The BN was considered low if it was <70 meq/L. The DR was defined as a combined endpoint composed of the requirement for intravenous furosemide ≥240 mg/day, tubular diuretic blockade (TB), hypertonic saline solution (HSS) or renal replacement therapy (RRT). In-hospital CV mortality was evaluated, as well as CV mortality and AHF readmissions at 60-day post-discharge follow-up. Results 157 patients were included, 56% men, with a median age of 74 years. The median BN was 103 meq/L (IQR 74-122), and BN was low in 22% of the cohort (N=34). DR was presented in 19% (N=30), 12.7% (N=20) required furosemide ≥240 mg/day, 8% (N=13) TB, 1 patient HSS and 4% (N=6) RRT. In-hospital CV mortality was 5.7%, CV mortality at 60-day follow-up 6.8%, and AHF readmissions at 60-day follow-up 12.2%. The group with low BN presented more DR (44% vs 12%; p 0.0001; RR 0.27; 95% CI 0.15-0.5), persistence of congestion at 48 hs (26.5% vs 11.4%; p 0.05; RR 0.48; IC 95% 0.22-1), administration of furosemide ≥240 mg/day (29% vs 8%; RR 0.27; 95% CI 0.12-0.61; p 0.003), more cumulative dose of furosemide at 72 hours (220mg [IQR 180-440] vs 160mg [IQR 100-180]; p 0.0001), use of TB (20.6 vs 4.9%; p 0.008; RR 0.23; 95%CI 0.08-0.65) and RRT (11.8 vs 1.6%; p 0.02; RR 0.14; 95%CI 0.02-0.72). Low BN was associated with in-hospital worsening of AHF (26.5% vs 9%; p 0.016; RR 0.34; 95%CI 0.15-0.74), inotropics use (21% vs 7%; p 0.048; RR 0.36; 95%CI 0.14 -0.88) or mechanical respiratory assistance (12% vs 2%; p 0.02; RR 0.14; 95%CI 0.02-0.72). Low BN presented higher in-hospital CV mortality (12% vs 4%; p 0.1), without association with endpoints in outpatient 60-day follow-up. Conclusions In patients hospitalized for AHF, low BN was associated with DR, persistence of congestion, need for more aggressive decongestion strategies, and a worse in-hospital clinical outcome

Effects of dapagliflozin in heart failure according to duration of type 2 diabetes: a patient-level meta-analysis of DAPA-HF and DELIVER

Abstract Introduction Type 2 diabetes (T2D) is a common comorbidity in heart failure (HF), and long-standing T2D is associated with worse outcomes. Purpose To investigate the efficacy and safety of dapagliflozin, compared with placebo, according to duration of T2D in patients with HF and established T2D. Methods We conducted a patient-level pooled analysis of the DAPA-HF and DELIVER trials, which evaluated the effects of dapagliflozin, compared with placebo, in patients with HF with reduced ejection fraction and HF with mildly reduced/preserved ejection fraction, respectively. T2D duration was categorized as <5 years, 6-10 years, and >11 years. The primary outcome was a composite of worsening HF or cardiovascular death. Results Of the 4,784 patients with a history of T2D, 1,879 (39.3%) had a T2D duration of <5 years, 1,074 (22.4%) 5-10 years, and 1,831 (38.3%) >11 years. Patients with longer-duration T2D were older, more often female, and White, and had a higher HbA1c, body mass index, and left ventricular ejection fraction. They were more likely to have ischaemic heart disease, peripheral artery disease, hypertension, and chronic kidney disease, but were less likely to have atrial fibrillation/flutter. Although patients with longer-duration T2D had longer duration of HF, they were not more likely to have a prior HF hospitalization or worse New York Heart Association functional class. Despite similar N-terminal pro-B-type natriuretic peptide levels, patients with longer-duration T2D had a higher risk of the primary outcome, even after adjustment for potential confounders (<5 years, reference; 6-10 years, HR 1.25 [95% CI, 1.06-1.46]; >11 years, HR 1.33 [1.15-1.54]). The benefit of dapagliflozin on the primary outcome was consistent across T2D duration category: <5 years, HR 0.85 (95% CI, 0.69-1.04); 5-10 years, HR 0.65 (0.51-0.83); >11 years, HR 0.84 (0.70-1.01) (Pinteraction=0.18). Dapagliflozin reduced the risk of secondary clinical outcomes and increased (improved) mean KCCQ scores from baseline to 8 months, regardless of T2D duration (Table). Adverse events and treatment discontinuation were not more frequent with dapagliflozin than with placebo irrespective of T2D duration. Conclusions Dapagliflozin reduced the risk of worsening HF or cardiovascular death, and improved symptoms, in patients with HF and T2D, irrespective of T2D duration.

The impact of heart failure caregiver burden and patient heart failure severity: analysis of the needs assessment tool: advanced heart failure (NAT: PD-HF)

Abstract Background Not only patients with heart failure (HF), but also their caregivers have reported experiencing distress, depression, anxiety, social isolation, and health problems related to caring for a patient. Needs assessment tools have been used in clinical practice to identify patients' problems and needs from an early stage, however, their relationship with caregiver burden and the severity of the HF patients they care for has not been well investigated. Purpose The purpose of this study is to examine the relationship between distress and HF severity in patients and their caregivers using the Needs Assessment Tool: Progressive Disease-Heart Failure (NAT: PD- HF). Methods We enrolled consecutive 106 chronic HF patients who were admitted to a university hospital and assessed needs by the NAT: PD-HF between February 2023 and July 2023. We also enrolled 95 of their caregivers. The NAT: PD-HF is administered by the health care provider in the form of an interview with the patient and their caregiver. The questionnaire consists of an assessment of the patient's well-being and an assessment of the caregiver's ability to care for the patient. The healthcare provider completes the tool by indicating the level of distress (none, mild, significant) for each section. The severity of the New York Heart Association (NYHA) functional classification is examined in each patient. Results The median age was 72 years (interquartile range 59-81), and 41% were in NYHA class III or IV. The most common relationship between patients and their primary caregivers was partners (53%), followed by children (26%), parents (8%), and siblings (5%). There were 100 patients (94%) with more than mild distress, 57 with NYHA I or II and 43 with NYHA III or IV (P = 0.037). There were also 84 (88%) caregivers with more than mild distress, 47 with NYHA I or II, and 37 with NYHA III or IV of the patients they cared for (P = 0.026). Twenty-four patients (22.6%) were in severe distress, of which 10 were NYHA I or II and 14 were NYHA III or IV (P = 0.044). Among caregivers, 18 (18.9%) were in severe distress, of whom 6 with NYHA I or II and 12 with NYHA III or IV for whom they are caring (P = 0.010). Conclusions Regardless of the severity of HF, caregivers were found to experience distress as similar rate as that in the HF patients they cared for. The proportion of patients and caregivers experiencing distress was found to increase with the severity of HF. It is important to introduce palliative care for HF from the early stage of the disease and to support not only the patient but also the caregivers by using screening tools to identify distress.

Impact of heart failure diagnosis on recorded healthcare resource use by older people in Wales; is primary care shouldering a hidden burden?

Abstract Background Heart failure (HF) is associated with high healthcare resource use and mortality. Most of the evidence focuses on hospital admission data. The impact on primary care interactions and outpatient attendance is less well described, but this information is important in understanding resource utilisation, patient pathways, and in planning services. Purpose To examine how a diagnosis of HF impacts healthcare resource use and outcomes for older people in Wales. Methods We conducted a retrospective, population-level, observational study using linked anonymised electronic health record (EHR) data in Wales (2015-22). 737,230 individuals were aged 65y+ in the study period in primary and secondary care data. Of these, 65,010 had a code for HF in their primary or secondary care records. To evaluate changes in resource use, we excluded 13,990 individuals with fewer than 12 months health data pre- and post-diagnosis. We summarised general practice (GP) interactions, emergency department (ED) attendance, outpatient (OP) attendance, inpatient (IP) episodes and days, time between HF diagnosis and death, and place of death. Results The final cohort comprised 51,020 individuals 65y and over with a diagnosis of HF between 2015-2022. Incidence and prevalence of HF increased across the study period (1.4-1.5% and 8.5-9.1% respectively). Figure 1 shows the percentage change in healthcare resource use for the cohort when HF was diagnosed (12 months pre-and post-diagnosis comparison). Table 1 shows the average number of healthcare utilisation events per person. After a diagnosis of HF, there are fewer ED attendances (-28.2%) and IP admissions (-9.3%) but more OP appointments (31%) and GP interactions (20.3%). When admissions occur, hospital stays tend to be longer (55.4%). Median time (IQR) from HF diagnosis to death from any cause was 247(34-840) days, and with HF listed as a cause 186(25-780) days. In this cohort, the place of death was recorded as NHS establishment (20,379, 67.8%), community (5,450, 18.1%), non-NHS establishment (3,789,12.6%) and unknown (450, 1.5%). Conclusions In Wales, a diagnosis of HF in those 65y+ increases primary care interactions and OP attendances. The change in volume of primary care interactions is considerable (increase from 1,047,920 to 1,315,080). Longer hospital stays may suggest difficulty in managing patients or discharging back to community settings. Majority of those with HF die in NHS establishments. It is unclear whether this reflects deficits in end-of-life care. These results are important in planning effective health service delivery and in establishing baseline data from which to monitor quality improvements.