Marker Of Heart Failure Research Articles

EP21.04: The correlation between amniotic fluid biochemical marker of fetal heart failure and staging of Twin–twin transfusion syndrome in recipient fetuses

EP21.04: The correlation between amniotic fluid biochemical marker of fetal heart failure and staging of Twin–twin transfusion syndrome in recipient fetuses

Inflammation as a Prognostic Marker in Heart Failure.

Background: Heart failure (HF) is a chronic cardiac disease of great importance worldwide and responsible for one-fifth of hospitalizations for cardiovascular disease in Brazil. Pro-inflammatory mediators are involved in the pathophysiology of HF. However, the impact of inflammatory markers on the prognosis of the disease remains uncertain.Objective: We aimed to evaluate inflammation as a prognostic marker in chronic HF.Methods: In this prospective, single-center, observational cohort study conducted from June 2018 through December 2019, we included outpatients with HF from a specialized service of a teaching hospital. Patients with decompensated HF requiring hospitalization in the last 30 days were excluded. At the time of inclusion, serum C-reactive protein (CRP) and albumin were collected and the presence of inflammation was defined as CRP/albumin ≥1.2. Patients with CRP/albumin ratio <1.2 (group A) and CRP/albumin ratio ≥1.2 (group B) were compared. The primary outcome was all-cause mortality. The secondary outcomes were hospitalization for decompensated HF, number of hospitalizations, and number of days of hospitalization in the 12-month follow-up.Results: We included 77 patients, 49 (63.3%) in group A and 28 (3.4%) in group B. Six patients in group A (12.2%) and 10 patients in group B (35.7%) required at least one hospitalization during follow-up (p=0.01). The rate of hospitalizations for decompensated HF for every 100 patients was 16.3 in group A vs 50.0 in group B (p=0.0001) and the average in-hospital length of stay was 12.2 vs 14.2 days per hospitalized patient (p=0.36) in groups A and B, respectively. The mortality rate was 6.1% in group A vs 7.1% in group B (p=0.86).Conclusion: In HF outpatients with inflammation evidentiated by the CRP/albumin ratio ≥1.2, the risk of death was similar to patients without inflammation criteria. However, the presence of inflammation led to a three-fold higher risk of hospitalization for HF decompensation.

Predictors of heart failure and all-cause mortality in asymptomatic patients with moderate and severe aortic regurgitation.

Class I indications for aortic valve replacement (AVR) for severe chronic aortic regurgitation (AR) include AR attributable symptoms or left ventricular (LV) ejection fraction <50%. As noninvasive estimates of elevated LV filling pressures (LVFP's) have been noted to predict heart failure (HF) readmission and all-cause mortality (ACM) in HF patients, we hypothesize that elevated LVFP's may also be independent predictors of HF and ACM in chronic AR. We developed a single center patient database of moderate or greater AR diagnoses between 2003 and 2008 and followed each patient through January 2013. We included patients with >30 days follow-up with interpretable Doppler-echocardiograms. We recorded demographic variables, EuroScore II, incident HF and ACM, and Doppler-echo variables of LV size, systolic and diastolic function. Patients with severe AR (105 patients) and moderate AR (201 patients) had similar EuroScore II values and similar incident HF and ACM. For the 180 patients who developed HF, effective arterial elastance (aHR=1.70 (1.01-2.83), p=.041), LV end-diastolic dimension (aHR=1.83, (1.11-3.03), p=.0176), E/e' (aHR=3.04, (1.83-5.05), p<.0001), eccentric hypertrophy (EH) (aHR=2.39, (1.62-5.12), p=.0004), and tricuspid regurgitation (TR) velocity (aHR=5.75, (3.70-10.36), p<.0001) were independent predictors. For the 118 patients with ACM, EH (aHR=1.73, (1.02-3.28), p=.0414), systolic blood pressure (aHR=.58, (.33-.95), p=.0301), left atrial volume index (aHR=1.82, (1.06-3.06), p=.0293), E/e' (aHR=1.83, (1.07-3.08), p=.0280), and TR velocity (aHR=4.14, (2.22-6.49), p<.0001) were independent predictors. Elevated TR velocity and EH were strong markers of HF and ACM in patients with asymptomatic severe AR and in moderate AR.

Clinical course and decision-making in heart failure by preload stress echocardiography: a preliminary study.

Abnormal left ventricular diastolic response to preload stress can be an early marker of heart failure (HF). The aim of this study was to assess clinical course in patients with HF with preserved ejection fraction (HFpEF) who underwent preload stress echocardiography. In the subgroup analysis, we assessed the prognosis of patients with unstable signs during preload stress classified by treatment strategies. We prospectively conducted preload stress echocardiographic studies between January 2006 and December 2013 in 211 patients with HFpEF. Fifty-eight patients had abnormal diastolic reserve during preload stress (unstable impaired relaxation: unstable IR). Of 58 patients with unstable IR, 19 patients were assigned to additional therapy by increased or additional therapy and 39 patients were assigned to standard therapy. Composite outcomes were prespecified as the primary endpoint of death and hospitalization for deteriorating HF. During a median period of 6.9years, 19 patients (33%) reached the composite outcome. Unstable group with standard therapy had significantly shorter event-free survival than stable group. Patients with uptitration of therapy had longer event-free survival than those with standard therapy group after adjustment of laboratory data (hazard ratio, 0.20, 95% confidence interval, 0.05-0.90; P=0.036); the 10year event-free survival in patients with and without uptitration of therapy was 93% and 51%, respectively (P=0.023). Patients with unstable sign had significantly shorter event-free survival than patients with stable sign. After additional therapy, the prognosis of patients with unstable signs improved. This technique may impact decision-making for improving their prognosis.

GlycA and GlycB as Inflammatory Markers in Chronic Heart Failure

The role of inflammation in heart failure (HF) has been extensively described, but it is uncertain whether inflammation exerts a different prognostic influence according to etiology. We aimed to examine the inflammatory state in chronic HF by measuring N-acetylglucosamine/galactosamine (GlycA) and sialic acid (GlycB), evolving proton nuclear magnetic resonance biomarkers of systemic inflammation, and explore their prognostic value in patients with chronic HF. The primary end point was a composite of all-cause death and HF readmission. A total of 429 patients were included. GlycB correlated with interleukin-1 receptor-like 1 in the whole cohort (r2=0.14, p=0.011) and the subgroup of nonischemic etiology (r2=0.31, p <0.001). No association was found with New York Heart Association functional class or left ventricular ejection fraction. In patients with nonischemic HF (52.2%, n=224), GlycA and GlycB exhibited significant association with the composite end point (hazard ratio [HR] 1.19, 95% confidence interval [CI] 1.06 to 1.33, p=0.004 and HR 2.13, 95% CI 1.43 to 3.13, p <0.001; respectively) and GlycB with HF readmission after multivariable adjustment (HR 2.25, 95% CI 1.54 to 3.30, p <0.001). GlycB levels were also associated with a greater risk of HF-related recurrent admissions (adjusted incidence rate ratio 1.33, 95% CI=1.07 to 1.65, p=0.009). None of the markers were associated with the clinical end points in patients with ischemic HF. In conclusion, GlycA and GlycB represent an evolving approach to inflammation status with prognostic value in long-term outcomes in patients with nonischemic HF.

Increased serum S100A12 levels are associated with higher risk of acute heart failure in patients with type 2 diabetes.

The hyperglycaemic stress induces the release of inflammatory proteins such as S100A12, one of the endogenous ligands of the receptors for advanced glycation end products (RAGE). Chronic activation of RAGE has multiple deleterious effects in target tissues such as the heart and the vessels by promoting oxidative stress, inflammation by the release of cytokines, macrophages infiltration, and vascular cell migration and proliferation, causing ultimately endothelial cell and cardiomyocyte dysfunction. The aim of our study was to investigate the prognostic value of circulating S100A12 beyond established cardiovascular risk factors (CVRF) for heart failure (HF) and major adverse cardiovascular events (MACE) in a cohort of patients with type 2 diabetes. Serum S100A12 concentrations were measured at baseline in 1345 type 2 diabetes patients (58% men, 64±11years) recruited in the SURDIAGENE prospective cohort. Endpoints were the occurrence of acute HF requiring hospitalization (HHF) and MACE. We used a proportional hazard model adjusted for established CVRF (age, sex, duration of diabetes, estimated glomerular filtration rate, albumin/creatinine ratio, history of coronary artery disease) and serum S100A12. During the median follow-up of 84months, 210 (16%) and 505 (38%) patients developed HHF and MACE, respectively. Baseline serum S100A12 concentrations were associated with an increased risk of HHF [hazard ratio (HR) (95% confidence interval) 1.28 (1.01-1.62)], but not MACE [1.04 (0.90-1.20)]. After adjustment for CVRF, S100A12 concentrations remained significantly associated with an increased risk of HHF [1.29 (1.01-1.65)]. In a sub-analysis, patients with high probability of pre-existing HF [N terminal pro brain natriuretic peptide (NT-proBNP) >1000pg/mL, n=87] were excluded. In the remaining 1258 patients, the association of serum S100A12 with the risk of HHF tended to be more pronounced [1.39 (1.06-1.83)]. When including the gold standard HF marker NT-proBNP in the model, the prognostic value of S100A12 for HHF did not reach significance. Youden method performed at 7years for HHF prediction yielded an optimal cut-off for S100A12 concentration of 49ng/mL (sensitivity 53.3, specificity 52.2). Compared with those with S100A12≤49ng/mL, patients with S100A12>49ng/mL had a significantly increased risk of HHF in the univariate model [HR=1.58 (1.19-2.09), P=0.0015] but also in the multivariate model [HR=1.63 (1.23-2.16), P=0.0008]. After addition of NT-proBNP to the multivariate model, S100A12>49ng/mL remained associated with an increased risk of HHF [HR=1.42 (1.07-1.90), P=0.0160]. However, the addition of S100A12 categories on top of multivariate model enriched by NT-pro BNP did not improve the ability of the model to predict HHF (relative integrated discrimination improvement=1.9%, P=0.1500). In patients with type 2 diabetes, increased serum S100A12 concentration is independently associated with risk of HHF, but not with risk of MACE. Compared with NT-proBNP, the potential clinical interest of S100A12 for the prediction of HF events remains limited. However, S100A12 could be a candidate for a multimarker approach for HF risk assessment in diabetic patients.

Biomakers in Chronic Chagas Cardiomyopathy.

The primary objective was to observe the relationship between serum levels of BNP, Ca-125, C-reactive protein and uric acid as prognostic and functional markers in patients with chronic Chagas cardiomyopathy (CCC). Circulating levels of cytokines: IL-1β, TNFα, IL-10, IL6, IL-8 and IL-12 were determined and investigated regarding their association with hemodynamic parameters, clinical signs of heart failure and outcome. Chagas is still a neglected disease that affects numerous individuals, many of them in their most productive years. CCC with left ventricular dysfunction is the most severe presentation of Chagas Disease. BNP is a well-recognized prognostic and clinical biomarker, not only in chronic heart failure patients but also in patients with CCC. Previous studies have shown Ca-125, C-reactive protein, and uric acid to be potentially good prognostic markers in heart failure (HF). Fifty patients with left ventricular fraction less (LVEF) than 55% were selected and followed for a mean period of 18 ± 8.3 months. Patient’s mean age was 43.42 ± 10.3 years (32 male), their BNP was 293 (160–530) pg/mL, Ca-125 8.5 (5.5–16.75) U/mL, uric acid 6.2 ± 2 mg/dL, and C- reactive protein 4.5 (4.5–7.3) mg/L. Patients who had LVEF less than 35% had higher BNP (p = 0.0023), Ca-125 (p = 0.027) and uric acid (p = 0.01) serum levels. Patients who died also showed higher BNP (p = 0.01), uric acid (p = 0.05) and a trend towards higher Ca-125 serum levels (p = 0.056). All markers: BNP, Ca-125, uric acid and C-reactive had good predictability of death in Cox-regression univariate analysis, however, not on the final multivariate model. Of the inflammatory cytokines, IL-8 and IL-12 showed a relation to LVEF of less than 35%. IL-12 was related to adverse cardiovascular events and non-survival. IL-1β was a good predictor of mortality in the final Cox regression model. Determination of Ca-125, uric acid levels and C-reactive protein may add useful clinical and prognostic information and may help clinical decision making for patients with CCC.

Update on Disease-Specific Biomarkers in Transthyretin Cardiac Amyloidosis.

Transthyretin cardiac amyloidosis (ATTR-CM) is an infiltrative cardiomyopathy and an increasingly recognized cause of morbidity and mortality. There remains substantial delay between initial symptoms and diagnosis. With the recent emergence of various targeted therapies proven to reduce morbidity and mortality, there is an imperative to diagnose subclinical disease. Biomarkers may be well-suited for this role. Conventional markers of heart failure, such as natriuretic peptides and cardiac troponins, and estimated glomerular filtration rate are associated with risk in ATTR-CM. Circulating transthyretin (TTR) levels parallel TTR kinetic stability, correlate with disease severity, and may serve as indirect markers of ATTR-CM disease activity and response to targeted treatment. There is also growing evidence for the correlation of TTR to retinol-binding protein 4, a biomarker which independently associates with this disease. The rate-limiting step for ATTR pathogenesis is dissociation of the TTR homotetramer, which may be quantified using subunit exchange to allow for early risk assessment, prognostication, and assessment of treatment response. The protein species that result from the dissociation and misfolding of TTR are known as nonnative transthyretin (NNTTR). NNTTR is quantifiable via peptide probes and is a specific biomarker whose reduction is positively correlated with improvement in neuropathic ATTR amyloidosis. Neurofilament light chain (NfL) is released into the blood after axonal damage and correlates with neuropathic ATTR amyloidosis, but its clinical use in ATTR-CM is uncertain. Conventional markers of heart failure, transthyretin, retinol-binding protein 4, transthyretin kinetic stability, nonnative transthyretin, peptide probes, and neurofilament light chain have potential as biomarkers to enable early, subclinical diagnosis in patients with transthyretin cardiac amyloidosis.

Adrenomedullin is a biological marker of heart failure: review of modern literature&#x0D; Amina M. Alieva*1, Natalia

It has been proven that in patients with heart failure (HF), there is an increased level of adrenomedullin (ADM) in plasma. Biomarker indices correlate with the severity of hemodynamic dysfunction, as well as with neurohumoral indices, which are activated depending on the severity of congestive circulatory failure. In addition, the expression of the ADM gene in the heart and kidneys is increased in experimental and clinical HF. A small number of studies have examined the effect of ADM infusion. These studies have generally shown that hormone infusion has beneficial hemodynamic effects and promotes the maintenance/improvement of renal function, but most of the studies have been short-lived. The available results suggest that increasing ADM levels reduce the negative effects of vasoconstriction and sodium retention. A better understanding of the role of a biological marker in congestive circulatory failure may lead to the development of drugs that target ADM receptors.

Knockout of cardiac troponin I-interacting kinase leads to cardiac dysfunction and remodelling.

Cardiac troponin I-interacting kinase (TNNI3K) is a cardiac-specific kinase that has been identified as a diagnostic marker and a therapeutic target in cardiovascular diseases. However, the biological function of TNNI3K in cardiac dysfunction and remodelling remains elusive. In the present study, a Tnni3k cardiomyocyte-specific knockout (Tnni3k-cKO) mouse model was established. Echocardiography was used to evaluate cardiac function in mice. Heart failure markers were detected using enzyme-linked immunosorbent assay. Haematoxylin and eosin staining, wheat germ agglutinin staining, Masson's trichrome staining, Sirius red staining and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) staining were used to assess histopathological changes, cardiac hypertrophy, collagen deposition and myocardial apoptosis, respectively. Expression levels of TNNI3K, apoptosis-related proteins, and p38 mitogen-activated protein kinase were measured using Western blot analysis. Compared to wild-type controls, cardiac dysfunction and cardiac remodelling of Tnni3k-cKO mice increased gradually with age. Tnni3k-cKO mice exhibited cardiac hypertrophy, cardiac fibrosis and cardiomyocyte apoptosis. Upregulation of cleaved caspase-3 in Tnni3k-cKO mice appeared to be related to phosphorylation and activation of the p38 mitogen-activated protein kinase signalling pathway. In conclusion, this study shows that TNNI3K is essential for cardiac development and function, providing new insights into the development of novel therapeutic strategies for cardiac diseases.

Relaxin-2, pathophysiological insights and outcomes in heart failure with preserved ejection fraction: Findings from the NETDiamond cohort

AimsThe role of relaxin-2 as a circulating marker in heart failure (HF) with preserved ejection fraction (HFpEF) is poorly understood. We aimed to characterize relaxin-2 circulating levels in a population of chronic HFpEF patients and their association with long-term prognosis. MethodsRelaxin-2 serum levels were measured in 85 chronic HFpEF patients from a prospective cohort study (NETDiamond). Clinical, imaging, and analytical data were compared across relaxin-2 tertiles. The primary outcome was a composite of cardiovascular death, HF hospitalisation, acute HF episode or diuretic intensification and the secondary outcome a composite of cardiovascular death and total HF hospitalisations. Cox regression and negative binomial models were used to assess the relation between relaxin-2 and the outcomes. ResultsRelaxin-2 levels were positively associated with left atrial volume, left ventricular mass and peripheral oedema, and negatively associated with ischemic heart disease and statin use. Higher relaxin-2 levels were associated with an increased risk of primary outcome, even after adjustment for age, B-type natriuretic peptide (BNP) and glomerular filtration rate (eGFR) (adjusted HR = 2.80, 95%CI 1.4–7.3, p = 0.034 for tertile 3). They were also associated with the occurrence of the secondary outcome (Incidence Rate Ratio = 5.28, 95%CI 1.2–23.2, p = 0.027), but this significance was lost when simultaneously adjusted for BNP and eGFR. ConclusionIn chronic HFpEF patients, higher relaxin-2 circulating levels were associated with left chambers remodelling, congestion, and adverse prognosis. These findings support a potential role for relaxin-2 as a pathophysiological agent and as a circulating biomarker in HFpEF.

Gamma-glutamyl transpeptidase is a promising biological marker of heart failure

Introduction. Currently, the search and study of new biological markers that can help early diagnosis of heart failure, serve as a laboratory tool for assessing the effectiveness of therapy, be a predictive marker of possible adverse clinical outcomes and a significant criterion for risk stratification is very relevant. While cardiospecific markers, including natriuretic peptides, their precursors, and highly sensitive troponins, are widely used in clinical practice, the need to use other markers does not have sufficient evidence. aspect of a biological marker of heart failure.Gamma-glutamyl transpeptidase is an enzyme localized on the outer side of cell membranes and involved in the metabolism of glutathione and cysteine. This enzyme is a dimeric glycoprotein (68 kDa), consisting of 2 subunits – a large and a small (46 and 22 kDa). Gamma-glutamyl transpeptidase is encoded by a multigene family consisting of at least 7 different genes located on chromosome 22; however, only 1 of these genes is involved in the formation of a functional enzyme. Gamma-glutamyl transpeptidase was found in all cells except erythrocytes. There is a significant variability in enzyme activity, which is especially high in tissues with a secretory and absorptive function, such as the kidneys, biliary tract, intestines, and epididymis.Purpose of the review is to present an overview of current publications devoted to the study of γ-glutamyl transpeptidase in the aspect of a biological marker of heart failure.Materials and methods. The analysis of literature sources (foreign and domestic articles) was carried out in the databases: PubMed, RSCI, MedLine, Google Scholar, Science Direct. The search was performed according to the following keywords: biological markers, heart failure, γ-glutamyl transpeptidase, biological markers, heart failure, γ-glutamyl transpeptidase.Results. In addition to its clinical use as a test for liver disease, biliary tract disease, and alcohol abuse, γ-glutamyl transpeptidase is of great interest because of its association with cardiovascular disease, diabetes, metabolic syndrome, and cancer. In the literature available to us, we found a small number of works devoted to the study of γ-glutamyl transpeptidase in patients with heart failure. In the review, we have presented data from experimental and clinical studies indicating a clear link between γ-glutamyl transpeptidase and heart failure. The pathogenetic mechanism of the possible relationship between γ-glutamyl transpeptidase and heart failure is not completely clear. The localization of this enzyme in tissues with a transport function has led to the assumption that it is involved in the transport of amino acids through the γ-glutamyl cycle.Conclusion. Further deeper understanding of the structure and function of the enzyme is needed, as well as future clinical studies to determine the diagnostic, prognostic and possibly therapeutic significance of this biological marker.

High-density lipoprotein cholesterol: a new marker in heart failure

High-density lipoprotein cholesterol: a new marker in heart failure

Sex-related differences in plasma amino acids of patients with ST-elevation myocardial infarction and glycine as risk marker of acute heart failure with preserved ejection fraction.

Nowadays, the problem of preventing acute heart failure (AHF) in patients with ST-elevation myocardial infarction (STEMI) and preserved left-ventricular ejection fraction (pLVEF) is still not completely resolved, especially in late-presented patients. The purpose of study was: (1) assessment of free plasma amino acid (PAA) alterations in STEMI patients [not receiving reperfusion therapy (RT)], depending on sex and LVEF; (2) analysis of development of late/persistent AHF more than 48h after admission (pAHF) in STEMI patients with pLVEF depending on PAA levels. This prospective cohort study included 92 STEMI patients (33 women and 59 men), not receiving RT. The free PAA were investigated by ion-exchange liquid-column chromatography. The women had significantly higher PAA levels than men in general cohort and cohort with pLVEF (n = 69). There were associations between female sex and pAHF in general cohort (OR 3.7, p = 0.004) and cohort with pLVEF (OR 11.4, p = 0.0001) by logistic regression. The association between pAHF and glycine level [OR 2.5, p < 0.0001; AUC 0.84, p < 0.0001; 86.7% sensitivity and 77.8% specificity for > 2.6mg/dL] was revealed in cohort with pLVEF (including female and male). Glycine remained a predictor of pAHF with pLVEF by multivariable logistic regression adjusting for comorbidities, demographic and clinical variables. Higher rate of pAHF in female than in male STEMI patients with pLVEF is associated with higher plasma glycine in women. The glycine level may be genetically determinated by female sex. The plasma glycine > 2.6mg/dL is a predictor of pAHF in STEMI with pLVEF (including female and male).

Возможности лабораторной диагностики повреждения миокарда при СOVID-19: в фокусе хроническая сердечная недостаточность

Recent studies of patients with COVID-19 have shown that people with cardiovascular disease, hypertension, bleeding disorders, and diabetes have severe symptoms and higher mortality rates. In addition to cardiovascular disease, potential risks also include age, gender, immunosuppressive state, multiple organ dysfunction, chronic respiratory disease, kidney dysfunction, obesity, and cancer. In the practice of a doctor, it is important to be able to predict and prevent the development of complications, so it is necessary to identify the relationship between COVID-19 and cardiovascular diseases at the molecular level. These data will help in the development of markers for the development of complications and provide an opportunity to adjust treatment tactics and prevent their occurrence. This review considers changes in the main markers of heart failure in coronavirus infection, which can be used for risk stratification.

A survey-based triage tool to identify patients potentially eligible for referral to an advanced heart failure centre.

Accurate prevalence data for ambulatory advanced heart failure (HF) in European countries remains limited. This study was designed to identify the population of patients potentially eligible for referral for assessment for advanced surgical HF therapies to a National advanced HF and cardiac transplant centre. A survey comprising 13 potential clinical markers of advanced HF was developed, modified from the 'I NEED HELP' tool from the 2018 position statement of the Heart Failure Association of the European Society of Cardiology, and distributed to all HF clinic services (secondary and tertiary units) nationwide. Each HF clinic unit was asked to complete the survey on consecutive patients over a 3month period fulfilling the following three criteria: (i) age <65years; (ii) ejection fraction <40% and (iii) HF of >3months duration. As a comparison, the number of actual referrals to the advanced HF clinic were also audited over a 9month period. In all, 21 of 26 HF clinic units participated in the survey. Across the period of inclusion, 4950 all-comer HF patients were seen across all sites. Of these, 375 (7.5%) fulfilled the inclusion criteria and were surveyed (74.4% male, median age 57years [IQR: 11years]). In total, 246 (66%) of the surveyed patients had ≥1 potential markers for advanced HF, representing just under 5% of the total all-comer HF population seen across the same time period. Of these, 67 patients (27%) had ≥2, 48 (20%) had 3 and 40 (16%) had ≥4 potential markers. The most frequently noted markers were ≥1 HF hospitalization or unscheduled clinic review (56%), intolerance to renin-angiotensin-aldosterone system inhibitors due to hypotension or renal dysfunction (29%) and intolerance to beta-blockers due to hypotension (27%). Almost one-quarter of patients reported NYHA Class III or IV symptoms. During the advanced HF clinic audit, the number of patients actually referred to the advanced HF clinic during the same time period was <5% of this potentially eligible cohort. In this index prospective National survey, approximately 5% of an all-comer routine HF clinic population and two-thirds of a pre-selected HF with reduced EF under 65years cohort were found to have at least one clinical or biochemical marker suggesting advanced or impending advanced HF. Almost one-quarter of patients in this chronic outpatient 'snapshot' population have NYHA III-IV symptoms. This simple one-page triage survey-modified from the 'I NEED HELP' tool-is useful to identify a population potentially eligible for referral to an advanced HF centre for assessment for advanced surgical therapies, thereby aiding resource and service planning.

Cardiac fibroblasts regulate the development of heart failure via Htra3-TGF-β-IGFBP7 axis

Tissue fibrosis and organ dysfunction are hallmarks of age-related diseases including heart failure, but it remains elusive whether there is a common pathway to induce both events. Through single-cell RNA-seq, spatial transcriptomics, and genetic perturbation, we elucidate that high-temperature requirement A serine peptidase 3 (Htra3) is a critical regulator of cardiac fibrosis and heart failure by maintaining the identity of quiescent cardiac fibroblasts through degrading transforming growth factor-β (TGF-β). Pressure overload downregulates expression of Htra3 in cardiac fibroblasts and activated TGF-β signaling, which induces not only cardiac fibrosis but also heart failure through DNA damage accumulation and secretory phenotype induction in failing cardiomyocytes. Overexpression of Htra3 in the heart inhibits TGF-β signaling and ameliorates cardiac dysfunction after pressure overload. Htra3-regulated induction of spatio-temporal cardiac fibrosis and cardiomyocyte secretory phenotype are observed specifically in infarct regions after myocardial infarction. Integrative analyses of single-cardiomyocyte transcriptome and plasma proteome in human reveal that IGFBP7, which is a cytokine downstream of TGF-β and secreted from failing cardiomyocytes, is the most predictable marker of advanced heart failure. These findings highlight the roles of cardiac fibroblasts in regulating cardiomyocyte homeostasis and cardiac fibrosis through the Htra3-TGF-β-IGFBP7 pathway, which would be a therapeutic target for heart failure.

Lack of correlation between different congestion markers in acute decompensated heart failure

BackgroundHospitalizations for acute decompensated heart failure (ADHF) are commonly associated with congestion-related signs and symptoms. Objective and quantitative markers of congestion have been identified, but there is limited knowledge regarding the correlation between these markers.MethodsPatients hospitalized for ADHF irrespective of left ventricular ejection fraction were included in a prospective registry. Assessment of congestion markers (e.g., NT-proBNP, maximum inferior vena cava diameter, dyspnea using visual analogue scale, and a clinical congestion score) was performed systematically on admission and at discharge. Telephone interviews were performed to assess clinical events, i.e., all-cause death or readmission for cardiovascular cause, after discharge. Missing values were handled by multiple imputation.ResultsIn total, 130 patients were prospectively enrolled. Median length of hospitalization was 9 days (interquartile range 6 to 16). All congestion markers declined from admission to discharge (p < 0.001). No correlation between the congestion markers could be identified, neither on admission nor at discharge. The composite endpoint of all-cause death or readmission for cardiovascular cause occurred in 46.2% of patients. Only NT-proBNP at discharge was predictive for this outcome (hazard ratio 1.48, 95% confidence interval 1.15 to 1.90, p = 0.002).ConclusionNo correlation between quantitative congestion markers was observed. Only NT-proBNP at discharge was significantly associated with the composite endpoint of all-cause death or readmission for cardiovascular cause. Findings indicate that the studied congestion markers reflect different aspects of congestion.Graphical abstract

1081-P: Blood Pressure Variability Is Associated with Risk of Heart Failure, Elevated NT-proBNP, and High-Sensitivity Troponin: Results from MESA

The association between blood pressure variability (BPv) and heart failure (HF) is incompletely studied. This association, and its links with biomarkers of HF and cardiac injury, were examined in the community-based Multi-Ethnic Study of Atherosclerosis (MESA) . Resting seated BP was measured thrice; the average of the last two measures was used for analysis, and visit-to-visit BPv (coefficient of variation-CV) was assessed over 5 visits. Biomarkers of HF (N-terminal B-type natriuretic peptide: NT-proBNP) and cardiac injury (high-sensitivity troponin-T: hs-cTnT) , respectively, at exams 1, 3 and 5 were ascertained. With 9.4 years median follow-up in 6,785 individuals, 385 HF events occurred. In adjusted time-dependent models including CVD risk factors, BMI, BP medications, and cumulative mean BP, BPv (CV-SBP and CV-DBP) was associated with risk of clinical HF (e.g., CV-SBP HR=1.16, p=0.03) . Similar patterns were seen regardless of T2D status. The associations were stronger for HF with reduced ejection fraction (EF) vs. preserved EF. When excluding those with baseline NT-proBNP &amp;gt;450 pg/mL or hs-cTnT &amp;gt;14 ng/L, the association between BPv and HF became stronger. CV-SBP and CV-DBP were also associated with elevated exam 5 NT-proBNP (&amp;gt;450 pg/mL: OR=1.74, and OR = 1.32, p&amp;lt;0.001) . We saw a positive relationship between CV-SBP and exam 1 to exam 5 changes in NT-proBNP (p=0.001) and hs-cTnT (p&amp;lt;0.001) as well as elevated hs-cTnT (&amp;gt;14 ng/L; OR=1.18, p&amp;lt;0.001) . Our data strongly support an association between BPv and both clinical HF and elevated NT-proBNP, and the association was greater in those with reduced vs. preserved EF. The association between BPv and clinical HF was related to deleterious changes in subclinical markers of myocardial injury and heart failure. Disclosure D.S.Nuyujukian: None. J.Zhou: Research Support; Dexcom, Inc. J.Koska: None. C.Nwabuo: None. A.Bertoni: None. S.Shea: Research Support; National Heart, Lung, and Blood Institute. P.Reaven: Research Support; AstraZeneca, Dexcom, Inc. Funding NIH/NHLBI (F32HL156626) NIH/NHLBI (R21HL150374) NIH/NHLBI (R21HL150268) NIH/NHLBI (R01HL138969)

INHIBITION OF RAS COMPONENTS ATTENUATES PROGRESSION OF MYOCARDIAL REMODELING IN BOTH NORMOTENSIVE AND HYPERTENSIVE RATS IN EXPERIMENTAL HEART FAILURE

Objective: New findings in the pathogenesis of heart failure (HF) with a focus on extracellular matrix (ECM) and communication in the heart are still relevant for more effective treatment. We focused on signaling pathways involved in cardiac structural remodeling in HF due to pressure and volume overload, as well as on investigating the efficacy of substances with possible antifibrotic potential. Design and method: We used as experimental model 28-week-old hypertensive (TGR) and normotensive (HSD) rats with created aortocaval fistula (ACF), supplemented with ACE inhibitor (ACEi) (Trandolapril, 15 weeks, 6 mg/L) and AT1 receptor blocker (ARB) (Losartan, 15 weeks, 200 mg/L). Results: Echocardiography confirmed an increase in cardiac output and a decrease in ejection fraction in both strains of rats. BW was higher in TGR vs HSD and it was not affected by VO. ACF-induced cardiac volume overload, elevated markers of heart failure and oxidative damage, ANP, BNP-45, and TBARS, were elevated in the blood serum of both strains. ACF induced profibrotic signaling by increasing TGF-, and mRNA collagen I, and collagen I protein expression in the left and right ventricles of HSD rats. In TGR rats ACF decreased TGF- and SMAD2 protein expression in the right ventricle similar to HSD rats, in which ACF also suppressed MMP-2 protein expression. Heart failure affected protein kinase signaling by reducing the protein expression of PKC, PKG, and in part, PKC in both chambers of the heart of both strains. ACF decreased the protein expression of Cx43 and its phosphorylated form, which is significantly proarrhythmic. Hypertension in TGR rats increased mRNA TGF- expression and collagen I, but decreased PKC and PKC protein expression and increased PKC. Conclusions: A notable finding was that the signaling pathways involved in cardiac remodeling were more normalized by the ARB, while proteins involved in intercellular communication, ACEi. The results of analyzes of both experiments indicate attenuated responses of the signaling pathways monitored by us in the heart of hypertensive strains reflecting adaptation to primarily induced pathophysiology. Scientific Grant Agency of the Ministry of Education, Science, Research and Sport of the Slovak Republic VEGA 2/0158/19, 2/0002/20