Clinical Outcomes In Heart Failure Research Articles

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 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.

The impact of platelet-to-lymphocyte ratio on clinical outcomes in heart failure: a systematic review and meta-analysis.

Inflammation has been suggested to play a role in heart failure (HF) pathogenesis. However, the role of platelet-to-lymphocyte ratio (PLR), as a novel biomarker, to assess HF prognosis needs to be investigated. We sought to evaluate the impact of PLR on HF clinical outcomes. English-published records in PubMed/Medline, Scopus, and Web-of-science databases were screened until December 2023. Relevant articles evaluated PLR with clinical outcomes (including mortality, rehospitalization, HF worsening, and HF detection) were recruited, with PLR difference analysis based on death/survival status in total and HF with reduced ejection fraction (HFrEF) patients. In total, 21 articles (n = 13,924) were selected. The total mean age was 70.36 ± 12.88 years (males: 61.72%). Mean PLR was 165.54 [95% confidence interval (CI): 154.69-176.38]. In total, 18 articles (n = 10,084) reported mortality [either follow-up (PLR: 162.55, 95% CI: 149.35-175.75) or in-hospital (PLR: 192.83, 95% CI: 150.06-235.61) death rate] and the mean PLR was 166.68 (95% CI: 154.87-178.50). Further analysis revealed PLR was significantly lower in survived HF patients rather than deceased group (152.34, 95% CI: 134.01-170.68 versus 194.73, 95% CI: 175.60-213.85, standard mean difference: -0.592, 95% CI: -0.857 to -0.326, p < 0.001). A similar trend was observed for HFrEF patients. PLR failed to show any association with mortality risk (hazard ratio: 1.02, 95% CI: 0.99-1.05, p = 0.289). Analysis of other aforementioned outcomes was not possible due to the presence of few studies of interest. PLR should be used with caution for prognosis assessment in HF sufferers and other studies are necessary to explore the exact association.

Hypokalemia, Kidney Function, and Clinical Outcomes in Heart Failure With Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is an increasing health problem associated with high morbidity and mortality rates. Several reports have shown an association between hypokalemia and clinical outcomes in patients with heart failure (HF). However, the association of hypokalemia with kidney function and clinical outcomes in patients with HFpEF remains unclear. We measured serum potassium levels and kidney function in 454 patients with HFpEF (mean age 76 years; 55% men) at admission. Hypokalemia (K+<3.5 mmol/L) and hyperkalemia (K+>5.0 mmol/L) were identified in 58 (12.7%) and 11 (2.4%) patients, respectively. Patients with hypokalemia showed renal tubular damage (RTD), defined as a urinary β2-microglobulin to creatinine ratio ≥300 μg/gCr, preserved estimated glomerular filtration rate (eGFR), and plasma volume expansion. Multivariate logistic analysis demonstrated that RTD, preserved eGFR, and plasma volume expansion were significantly associated with hypokalemia. During the median follow-up period of 1,000 days, 82 HF-related events occurred. Kaplan-Meier analysis showed that patients with hypokalemia had a higher rate of HF-related events than those without hypokalemia. Multivariate Cox proportional hazard regression analysis demonstrated that hypokalemia was significantly associated with HF-related events after adjusting for confounding factors. Hypokalemia is affected by kidney function, notably RTD, in patients with HFpEF. Hypokalemia is a risk factor for HF-related events in patients with HFpEF.

Association between hyponatremia and adverse clinical outcomes of heart failure: current evidence based on a systematic review and meta-analysis.

Heart failure (HF) is a global health challenge. The perturbations in fluid and electrolyte equilibrium, particularly the compromised sodium balance associated with HF lead to high mortality rates. Hence, elucidating the correlation between serum sodium levels and the prognosis of HF is of paramount importance. This study aimed to conduct a comprehensive meta-analysis to thoroughly investigate the interplay between hyponatremia and the prognostic outlook of individuals with HF. A comprehensive search of bibliographic databases including PubMed, Embase, and the Cochrane Central Register of Controlled Trials was conducted to identify relevant observational studies examining the association between hyponatremia and prognosis of HF. Data extraction, synthesis, and assessment of risk of bias were conducted. Meta-analytic methods, sensitivity analyses, and heterogeneity test were employed as appropriate to synthesize the data. A total of 43,316 patients with HF were included spanning 25 selected studies. The pooled data revealed a notable association between hyponatremia and elevated risks across short and long-term mortality of HF. Specifically, hyponatremia was found to significantly increase the likelihood of all-cause mortality (Hazard ratio [HR] = 1.94, 95% confidence interval [CI]: 1.78-2.12); 1-year mortality (HR = 1.67, 95%CI: 1.46-1.90); 30-day mortality (HR = 2.03, 95%CI: 1.73-2.25); cardiac mortality (HR = 2.11, 95%CI: 1.81-2.46); and in-hospital mortality (HR = 1.64, 95%CI: 1.15-2.34). Our meta-analysis emphasizes the significant impact of hyponatremia on mortality in the HF patient population, highlighting the critical importance of maintaining stable serum sodium levels in HF management.

THE ASSOCIATIONS OF β-ADRENORECEPTORS GENES POLYMORPHISMS WITH THE COURSE OF HEART FAILURE AND WITH THE LOW TRIIODOTHYRONINE SYNDROME (LITERATURE REVIEW AND OWN OBSERVATIONS)E

The systematization of literature data on the associations of β-adrenoreceptors (β-AR) genes polymorphisms with the course of heart failure (HF) and with the development of low triiodothyronine syndrome (LT3S), and the results of our own study were presented. The study of associations of β-AR system genes polymorphisms with the clinical outcome of HF and the effectiveness of β-adrenoblockers (β-AB) has been continued. It has been demonstrated that carrier state of the A allele of the Ser49Gly (c.145A &gt; G) polymorphism of the b1-AR gene leads to a decrease in the risk of combined end point. At the same time, the carrier state of the G allele of the Gln27Glu (c.79C&gt; G) polymorphism of the b2-AR gene increases the risk of combined end point. Administration of bisoprolol at a dose of &gt; 5 mg leads to a reduction of the risk of the combined endpoint, provided the G/A genotype of the Ser49Gly (c.145A &gt; G) polymorphism of the β1-AR gene is present. The use of bisoprolol at this dose also reduces the risk of re-hospitalisation and combined endpoint, provided the homozygous genotype (C/C) of the Gln27Glu (c.79C &gt; G) polymorphism of the β2-AR gene is present. The probability of the low triiodothyronine syndrome increases with the homozygous G/G genotype of the Gln27Glu polymorphism of the β2-AR gene and in the presence of the C/T polymorphism of the Serβ75 GNβ3 gene. The genotype C/G of the Gln27Glu polymorphism of the β2-AR gene is associated with a decreased risk of LT3S.

Sex-specific cardiovascular protein levels and their link with clinical outcome in heart failure.

This study aims to provide insight into sex-specific cardiovascular protein profiles and their associations with adverse outcomes, which may contribute to a better understanding of heart failure (HF) pathophysiology and the optimal use of circulating proteins for prognostication in women and men. In 250 stable patients with HF with reduced ejection fraction (HFrEF), we performed trimonthly blood sampling (median follow-up: 26 [17-30] months). We selected all baseline samples and two samples closest to the primary endpoint (PEP; composite of cardiovascular death, heart transplantation, left ventricular assist device implantation, and HF hospitalization) or one sample closest to censoring and applied the Olink Cardiovascular III panel. We used linear regression to study sex-based differences in baseline levels and joint models to study differences in the prognostic value of serially measured proteins. In 66 women and 184 men (mean age of 66 and 67years, respectively), 21% and 28% reached the PEP, respectively. Mean baseline levels of fatty acid-binding protein 4, secretoglobin family 3A member 2, paraoxonase 3, and trefoil factor 3 were higher in women (Pinteraction : 0.001, 0.007, 0.018, and 0.049, respectively), while matrix metalloproteinase-3, interleukin 1 receptor-like 1, and myoglobin were higher in men (Pinteraction : <0.001, 0.001, and 0.049, respectively), independent of clinical characteristics. No significant differences between sexes were observed in the longitudinal associations of proteins with the PEP. Only peptidoglycan recognition protein 1 showed a suggestive interaction with sex for the primary outcome (Pinteraction =0.028), without multiple testing correction, and was more strongly associated with adverse outcome in women {hazard ratio [HR] 3.03 [95% confidence interval (CI), 1.42 to 6.68], P=0.008} compared with men [HR 1.18 (95% CI, 0.84 to 1.66), P=0.347]. Although multiple cardiovascular-related proteins show sex differences at baseline, temporal associations with the adverse outcome do not differ between women and men with HFrEF.

Impact of worsening renal function in patients with incident heart failure across the spectrum of ejection fraction: a population-based longitudinal study

Abstract Background Renal dysfunction is a common occurrence in patients with heart failure (HF) and may impact on HF treatment and outcomes. HF clinical trial data suggest that worsening renal function (WRF) is associated with worse prognosis, however many of the medications used in HF cause a short-term decline in renal function that may improve in the longer-term. The real-world incidence and implications of WRF following an initial diagnosis of HF across the spectrum of ejection have not been well-characterised. Purpose The present study was designed to establish the incidence and outcomes associated with WRF in patients with incident HF on the risk of mortality and HF hospitalisation (hHF) in a real-world setting. Methods Electronic health records were linked to echocardiography data between 2016 to 2021 to define incident HF with reduced/mildly reduced/preserved EF (HFrEF/HFmrEF/HFpEF). Incidence of WRF at 6 months was determined as a composite endpoint of (i) having two consecutive eGFR declined by 40% or greater; (ii) having an eGFR &amp;lt;15 mL/min/1.73m^2; (iii) on sustained dialysis; or (iv) receiving kidney transplantation. Incidence of hHF and all-cause mortality were compared in HF patients with versus without WRF. We performed a stratified analysis according to baseline renal function (eGFR: &amp;gt;60, 45-59, 30-44, 15-29, or &amp;lt;15 mL/min/1.73m2). Results 4254 individuals were identified, 1100 HFrEF, 650 HFmrEF, 1252 HFpEF, and 1252 HF with unknown EF. Within 6 months of HF diagnosis, 592 patients died and 349 had WRF. Baseline eGFR &amp;lt;60 was present in 32% of individuals with HFrEF, 32% in HFpEF, 27% in HFmrEF, and 37% in HF with unknown EF. The incidence of WRF was similar in HFrEF (20.7 [95% CI: 16.9 – 25.1] per 100 person-years) and in HF with unknown EF (20.9 [17.1 – 25.3]), but was significantly lower in HFmrEF (13.6 [9.8 – 18.4]) and HFpEF (16.8 [13.7 – 20.5]). Patients with WRF were more likely to be female (adjusted hazard ratio [aHR]: 1.32 [1.06 – 1.64], p=0.014), having diabetes (1.34 [1.07 – 1.69], p = 0.012), and with lower baseline renal function (eGFR categories 45-59, 30-44, 15-29, or &amp;lt;15 compared with &amp;gt;60: aHR 1.75 [1.29 – 2.38], p&amp;lt;0.001; 1.64 [1.12 – 2.42], p=0.012; 5.65 [4.06 – 7.87], p&amp;lt;0.001; 90.74 [63.2 – 130.28], p&amp;lt;0.001). Individuals with WRF had significantly higher incidence of subsequent hHF (HR adjusted for age, sex, baseline renal function, and diabetes: 1.79 [1.35 – 2.39], p&amp;lt;0.001) and all-cause death (2.18 [1.66 – 2.88], p&amp;lt;0.001), compared to those without WRF. This was driven by patients diagnosed with HFrEF (2.46 [1.45 – 4.18], p&amp;lt;0.001) or HFpEF (3.45 [2.21 – 5.40], p&amp;lt;0.001), but was not seen in HFmrEF (1.91 [0.91 – 3.99], p=0.086) or HF within unknown EF (1.28 [0.65 – 2.52], p=0.484). Conclusion WRF is an important and common consequence following initial diagnosis of HF across the spectrum of EF with associated severe clinical outcomes in HF. Priority should be given to prevention of WRF in patients with incident HF.Impact of WRF on Clinical Outcomes

The prognostic impact of cardiac Metaiodobenzylguanidine imaging related to left ventricular geometry in patients with acute decompensated heart failure: a prospective study

Abstract Background It is known that changes in the geometry of the left ventricle (LV), such as dilation or hypertrophy, are associated with cardiovascular events. The sympathetic nervous system also plays a crucial role in exacerbating these changes. Cardiac iodine-123 metaiodobenzylguanidine (MIBG) imaging can evaluate cardiac sympathetic neuronal activity and has been strongly associated with poor clinical outcomes in heart failure (HF). However, the prognostic significance of cardiac MIBG imaging related to LV geometry is still unclear, particularly in patients admitted for acute decompensated HF (ADHF). Methods We studied consecutive 575 patients admitted for ADHF and echocardiography were performed just before discharge. In cardiac MIBG imaging, the heart-to-mediastinum ratio (HMR) was measured on the delayed image. We divided the patients into four groups according to the relative wall thickness (RWT) and LV mass index (LVMI) based on the ASE/EACVI classification as follows: normal (n=75), normal RWT and LVMI; concentric remodeling (n=56), high RWT and normal LVMI; eccentric hypertrophy (n=298), normal RWT and high LVMI; and concentric hypertrophy (n=146), high RWT and LVMI. The endpoint of this study was all cause death (ACD). Results During a follow-up period of 4.2 ± 2.5 years, 272 patients had ACDs (normal [n=32], concentric remodeling [n=28], eccentric hypertrophy [n=137] and concentric hypertrophy [n=75]). There was no significant association between LV geometry and ACDs. At univariate Cox analysis, late HMR was significantly and independently associated with ACDs in the subgroup of patients with eccentric hypertrophy (p=0.0004). However, there was no significant association between late HMR and ACDs in those with other subgroups of LV geometry. At multivariate Cox analysis, late HMR was also significantly associated with ACDs even after adjusting for major HF confounders in the subgroup of patients with eccentric hypertrophy (p=0.0042). Furthermore, Kaplan-Meier analysis revealed that patients with lower late HMR (&amp;lt;1.524: determined by ROC curve analysis) had a significantly higher risk of ACDs in the subgroup with eccentric hypertrophy (61% vs 37%, p&amp;lt;0.0001). Conclusions LV geometry has an impact on the prognostic value of cardiac MIBG imaging in patients admitted for ADHF.

Clinical outcomes of cardiac devices in heart failure patients hospitalized with COVID-19: insights from the united states national inpatient database

Abstract Background COVID-19 has caused global impact especially in patients with cardiac devices(CD). Moreover, since the onset of the COVID-19 pandemic, physicians have suspended nonurgent procedures. Scarce date is available with respect to CD implantations in patients with active COVID-19. Purpose We aimed to investigate the impact of COVID-19 on implantation rates and clinical outcomes in heart failure (HF) patients hospitalized for COVID-19. Methods Data from National Inpatient Sample database from 2020 was used to identify hospitalizations for COVID in HF patients. Clinical outcomes of CD implantations were compared using univariate and multivariate logistic regression analysis. Results From March-December 2020, a total of 20,426 CD were performed in HF patients in the United States, of which 0.9 % were among those with active COVID-19 infection. Patients with COVID were younger, more hispanic and black population, and had a higher prevalence of comordities such as ventricular fibrillation and complete heart block when compared to patients without COVID. CD implantation in patients with COVID had significantly increased in-hospital mortality, longer lengths of stay, higher hospitalization costs, and outcomes such as incidence of acute stroke, thromboembolism, and sepsis. Device related complications and the need for revisions were comparable in the two cohorts. After adjustment for baseline characteristics, COVID cohort had increased odds of in-hospital mortality. Conclusion Patients with active COVID-19 infection who underwent device implantation had increased in-hospital mortality, longer lengths of stay and higher hospitalization costs with comparable outcomes of device complications.Figure 1Figure 2

Abstract 13565: Long-Term Prognostic Value of the Combination of Systemic Immune-Inflammation Index and AHEAD Score and in Patients Admitted for Acute Decompensated Heart Failure

Backgrounds: Systemic inflammation plays a critical role in the outcomes of heart failure patients. A newly defined index, which is named as systemic immune-inflammation index (SII), had been reported to have prognostic value in patients with cardiovascular disease. On the other hand, comorbidities are strongly associated with poor clinical outcome in heart failure patients (pts). AHEAD (A: atrial fibrillation; H: hemoglobin; E: elderly; A: abnormal renal parameters; D: diabetes mellitus) score was known to be related to clinical outcomes in acute decompensated heart failure (ADHF) patients. We sought to investigate the prognostic value of the combination of SII and AHEAD in patients admitted for ADHF. Methods and Results: We studied 263 patients admitted for ADHF and discharged with survival. At the discharge, we obtained SII, which is computed as neutrophils x platelets / lymphocytes, and AHEAD score (range 0-5, atrial fibrillation, hemoglobin &lt;13 mg/dL for men and 12 mg/dL for women, age &gt;70 years, creatinine &gt;130 μmol/L, and diabetes mellitus). During a follow-up period of 5.0±4.2 yrs, 67 patients had cardiovascular death (CVD). At multivariate Cox analysis, SII and AHEAD score were significantly independently associated with CVD, independently of prior heart failure hospitalization, systolic blood pressure and left ventricular dimension index. The patients with both greater SII (≥571 determined by ROC analysis: AUC 0.632[0.553-0.712]) and AHEAD score (≥3: AUC 0.635[0.562-0.707]) had a significantly increased risk of CVD than those with either and none of them (51% vs 28% vs 16%, p&lt;0.0001, respectively). Conclusion: The combination of SII and AHEAD score would be useful for stratifying patients at risk for cardiovascular-renal poor outcome in ADHF patients.

Abstract 12486: Predictive Value of Chronotropic Incompetence for Clinical Outcomes in Heart Failure: Findings From the MyoVasc Study

Introduction: Chronotropic incompetence (CI), an important aspect of exercise intolerance, is related to adverse clinical outcomes in heart failure (HF). However, the lack of standardized evaluation of CI results in inconsistent evidence. Aim: To evaluate CI with regard to clinical and medical determinants and relationship to clinical outcomes in HF. Methods: Data from the MyoVasc study (NCT04064450), a prospective cohort on HF, were analyzed. Subjects underwent deep clinical phenotyping, including cardiopulmonary exercise testing on a cycle ergometer. Measures of CI were evaluated, with continuous predicted heart rate reserve (pHRR) emerging as the most clinically relevant definition for operationalizing CI. Clinical and medical determinants of CI were assessed in multivariable linear regression models and outcomes in Cox regression models. Results: The analysis sample included 886 subjects (median age 63 years [interquartile range (IQR) 55; 72]; 29.9% women) who achieved maximal exertion (respiratory exchange ratio&gt;1.0). Symptomatic HF stage C/D was present in 42.8% (379) of the subjects. Sixteen drug groups were identified as CI modulators including β-blockers (β-estimate per SD -0.83 [95% confidence interval -0.95;-0.70], p&lt;0.0001) and antiarrhythmics (β SD -0.93 [-1.30;-0.56], p&lt;0.0001). New York Heart Association functional class, smoking, fatty liver index (FLI), and diabetes mellitus (DM) were the strongest determinants of CI in all subjects independently of sex, age, and previously identified medication. Determinants differed according to left ventricular ejection fraction [LVEF] (≥50 vs &lt;50%), being strongly associated with markers of HF (NT-proBNP) and lung function (FEV1) in HF with reduced EF and more linked to DM or the FLI in HF with preserved EF. In Cox regression analysis adjusted for clinical profile, pHRR independently predicted all-cause death (HR SD 1.86 [1.41;2.45], p&lt;0.0001) and worsening of HF (HR SD 1.37 [1.04;1.81], p=0.025). Conclusions: CI strongly predicted clinical outcomes and revealed relevant differences between HF with preserved and reduced EF. This highlights the relevance of impaired response to exercise in the clinical course of HF with implication for risk stratification and intervention.

Abstract 13828: Aptamer Proteomics for Biomarker Discovery in Heart Failure With Preserved Ejection Fraction: The PARADIGM-HF Proteomic Sub-Study

Introduction: Prognostic markers and biological pathways linked to detrimental clinical outcomes in heart failure with preserved ejection fraction (HFpEF) remain incompletely defined. Goal: To identify serum proteins associated with risk for HF hospitalization (HFH) and cardiovascular (CV) death in patients with HFpEF, including proteins with differential associations with clinical outcomes in HFpEF compared to HFrEF. Methods: We measured serum levels of 4123 unique proteins in 1117 patients with HFpEF in the PARAGON-HF trial using a modified aptamer proteomic assay. Baseline protein concentrations significantly associated with total HFH and CV death were identified by recurrent events regression, accounting for multiple testing, adjusted for age, sex, treatment, and anticoagulant use, and compared to 2515 patients with HFrEF from the PARADIGM-HF and ATMOSPHERE trials. Results: We identified 288 proteins to be robustly associated with the risk of HFH and CV death (335 events over an average of 2.7 years of follow-up) in a HFpEF trial population. Proteins most strongly related to HFpEF outcomes included B2M, TIMP1, SERPINA4, and SVEP1 ( Figure ). Protein-outcome associations in patients with HFpEF did not markedly differ compared to HFrEF. Just 3 proteins (APOE, RTF1, and VWF) were differentially associated with outcomes between the HF subtypes (FDR &lt;0.05). A proteomic risk score derived in HFpEF patients was not superior to a previous proteomic score derived in HFrEF nor to clinical risk factors, NT-proBNP, or high-sensitivity cardiac troponin. Conclusions: Numerous serum proteins linked to metabolic, coagulation, and extracellular matrix regulatory pathways were associated with worse HFpEF prognosis. SVEP1, a cell adhesion protein recently identified as a HFrEF prognosis biomarker, also strongly predicted risk in HFpEF. Our results demonstrate substantial similarities in serum proteomic risk markers across the EF spectrum.

Abstract 15808: Sodium Glucose Co-Transporter-2 Inhibitors and Clinical Outcomes in Cancer Patients Treated With Anthracyclines

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been proven to improve clinical outcomes in heart failure (HF). However, there remains a paucity of data on the potential cardioprotective impact of SGLT2i in cancer patients receiving anthracyclines. Aim: To evaluate if SGLT2i use is associated with improved outcomes in anthracycline-treated cancer patients. Methods: Using TriNetX Global Research Network from 2013 to 2021, patients diagnosed with cancer and receiving anthracycline therapy were identified and categorized into those who were taking SGLT2i versus those who were not. A 1:1 propensity score matching was used to control for baseline characteristics between the two groups. Patients were followed for 2 years. The primary endpoint was all-cause mortality and secondary endpoints were new-onset HF, acute HF exacerbation, myocardial infarction, new-onset atrial fibrillation/flutter, and all-cause hospitalization. Results: A total of 82,369 anthracycline-treated cancer patients were identified. After propensity score matching application, 1,412 patients were included in our analysis (706 patients in each group). Patients on SGLT2i had lower rates of all-cause mortality (OR: 0.7 [95% CI: 0.56, 0.88]; P=0.002), acute HF exacerbation (OR: 0.64 [95% CI: 0.41-1]; P=0.048), and new-onset atrial fibrillation/flutter (OR: 0.52 [95% CI: 0.33, 0.8]; P=0.003) compared to those not on SGLT2i. The incidence of myocardial infarction, new-onset HF, and all-cause hospitalization were similar between the two groups (Figure). Conclusion: Among cancer patients receiving anthracyclines, SGLT2i were associated with lower rates of mortality, acute HF exacerbations, and new-onset atrial fibrillation/flutter and similar rates of myocardial infarction, new-onset HF, and hospitalization.

Differential Associations of A-/B-Type Natriuretic Peptides With Cardiac Structure, Function, and Prognosis in Heart Failure

BackgroundNatriuretic peptide (NP) elevations are prognostic in heart failure (HF), but relative atrial NP deficiency in acute HF has been suggested. ObjectivesThe authors compared plasma concentrations and relative strength of associations of A- and B-type NPs with cardiac structure/function and clinical outcomes in HF. MethodsMidregional pro–atrial natriuretic peptide (MR-proANP), B-type natriuretic peptide (BNP), and N-terminal pro–B-type natriuretic peptide (NT-proBNP) were measured in patients with compensated HF in a prospective, multicenter study. The primary outcome was a composite of HF-hospitalization or all-cause mortality. Secondary outcomes included individual primary outcome components and cardiovascular admission. ResultsAmong 1,278 patients (age 60.1 ± 12.1 years, 82% men, left ventricular ejection fraction [LVEF] 34% ± 14%), median concentrations of MR-proANP were 990 pg/mL (Q1-Q3: 557-1,563 pg/mL), NT-proBNP 1,648 pg/mL (Q1-Q3: 652-3,960 pg/mL), and BNP 291 pg/mL (Q1-Q3: 103-777 pg/mL). No subpopulation with inappropriately low MR-proANP (relative to BNP/NT-proBNP) was observed. Clinical event rates were similar for biomarker tertiles. Increments in MR-proANP exhibited steeper associations with concurrent shifts in left ventricular size, diastolic indexes and LVEF than BNP/NT-proBNP at baseline and serially (P < 0.05), and lower odds of beneficial left ventricular reverse remodeling: OR: 0.35 (95% CI: 0.18-0.70). In single-biomarker models, MR-proANP(log10) was associated with the highest hazard (4 to 6 times) for each outcome. In multimarker models, independent associations were observed for the primary outcome (MR-proANP and NT-proBNP), HF-hospitalization and cardiovascular admission (MR-proANP only), and all-cause mortality (NT-proBNP only) (P < 0.05). The discriminative value of MR-proANP was superior to BNP/NT-proBNP (HF-hospitalization) and BNP (primary outcome) (P < 0.05). ConclusionsMR-proANP was not inappropriately low relative to concurrent BNP/NT-proBNP values. Proportional increments in MR-proANP were more pronounced than for B-peptides for given decrements in cardiac structure/function. MR-proANP offered greater independent predictive power overall.

International Physical Activity Questionnaire Short Form and accelerometer-assessed physical activity: concurrent validity using six cut-points in HF patients.

Physical activity (PA) is an important target for improving clinical outcomes in heart failure (HF) patients. Nonetheless, assessing the daily PA profile in this population is a challenging task, traditionally performed using self-report questionnaires such as the International PA Questionnaire Short Form (IPAQ-SF). This study aimed to evaluate the concurrent validity of the IPAQ-SF and accelerometer-assessed PA using six published cut-points in patients with HF and reduced or mildly reduced ejection fraction. The concordance between the IPAQ-SF and a hip-worn accelerometer regarding daily time spent performing moderate to vigorous PA in bouts of at least 10min was assessed in 53 participants for seven consecutive days using six different cut-points (Barnett, Dibben, Mark, Sanders, Troiano, and Vaha-Ypya). Spearman's correlation and Bland-Altman plots were used to evaluate concurrent validity between methods. Regressions were used to study the association between patient variables, wear protocol (waking hour or 24h), and absolute bias. The kappa index was used to evaluate the concordance between IPAQ-SF and accelerometry for classifying patients as active or non-active. All analyses were re-run using non-bouted metrics to investigate the effect of bouted versus non-bouted analysis. The IPAQ-SF and accelerometry showed low to negligible correlation (ρ=0.12 to 0.37), depending on the cut-point used. The regression analysis showed that the absolute bias was higher in participants following the waking-hour protocol at all cut-points except Dibben's (P≤0.007). The concordance between the two methods to classify patients as active and non-active was low when using Mark (κ=0.23) and Barnett (κ=0.34) cut-points and poor for the remaining cut-points (κ=0.03 to 0.18). The results of the sensitivity analysis showed negligible to low correlation using non-bouted metrics (ρ=0.27 to 0.33). Moderate to vigorous PA measures using IPAQ-SF and accelerometers are not equivalent, and we do not encourage researchers to use IPAQ-SF alone when assessing PA in HF patients. Moreover, applying personalized collection and processing criteria is important when assessing PA in HF patients. We recommend following the 24h protocol and selecting cut-points calibrated in patients with cardiovascular diseases. Finally, it is necessary to develop a new tailored questionnaire that considers walking intensity and is adjusted to the current World Health Organisation recommendations, which use non-bouted metrics.