Different Stages Of Heart Failure Research Articles

CircRNA Interference Pathway: A New Target for Intervention in Different Stages of Heart Failure.

Cardio-cerebrovascular disease has seen a rapid rise in recent years, with Heart Failure (HF) -- a terminal stage of various cardiovascular diseases -- also on the rise. HF has a complex pathogenesis involving multiple factors, such as inflammation, fibrosis, and oxidative stress. Due to its unique reverse shear mechanism, HF exhibits distinct expression patterns across different diseases. CircRNA has been linked to conditions like cancer, diabetes, and osteoarthritis. This article briefly introduces the mechanisms of circRNA biogenesis and its associated biological functions, focusing on CircSLC8A1-1, CircRNA_000203, and others at the early stage of HF, CircRNA PAN3, CircRNA (ACR), and others during the progression of HF, and CircHIPK3, CircNfix, and others at the end stage of HF. These circRNAs play a participatory role in the exact mechanism. As a research method, circRNA can be utilized to study the pathogenesis of heart failure and serve as a target for drug discovery and development. Therefore, circRNA's ability to mark the disease at different stages has significant guiding implications for HF monitoring, treatment, and prognosis.

Electrocardiography changes and different stages of heart failure in central Iran: A cross-sectional study from Yazd Health Study.

Electrocardiography (ECG) is a widely accessible, noninvasive, and cost-effective diagnostic instrument used to evaluate patients with suspected heart failure (HF). The aim of this study is to investigate electrocardiographic changes in patients with different stages of HF in a random population of Yazd city. This prospective cross-sectional study included 319 individuals, randomly selected, aged 40 years and more, registered in the Yazd Health Study was conducted from March 2022 to May 2023 at Afshar Hospitals. In accordance with the AHA/ACC guidelines, HF was classified into four stages (A, B, C, and D). The 159 individuals were classified in the stage 0 group, 77 were in Stage A, 65 were in Stage B, and 18 were in Stage C of HF. In the Stage 0, the PR interval (PRi) was 130.5 ± 18.1 ms, while in Stage C, it was 143.3 ± 21.9 ms, with a significant difference (p = 0.047). Similarly, the QRS interval (QRSi) increased with HF staging (p = 0.001). The frequency of diabetes mellitus (DM), hypertension (HTN), hyperlipidemia (HLP), chronic heart disease, alcoholism, and PRi, QRSi, QT interval levels were independent predictors of HF stage in multivariate regression analysis. The prevalence of HF stages, as classified by the AHA/ACC guidelines, was observed, with significant correlations between ECG parameters and HF progression. abnormal rhythms, left bundle branch block, ischemia, hypertrophy, and left atrial enlargement increased with higher HF stages. Major risk factors like DM and HTN exhibited a heightened prevalence in advanced HF stages, accentuating their pivotal role in the progression of HF.

Behavior of Hypertrophied Right Ventricle during the Development of Left Ventricular Failure Due to Myocardial Infarction.

In order to determine the behavior of the right ventricle, we have reviewed the existing literature in the area of cardiac remodeling, signal transduction pathways, subcellular mechanisms, β-adrenoreceptor-adenylyl cyclase system and myocardial catecholamine content during the development of left ventricular failure due to myocardial infarction. The right ventricle exhibited adaptive cardiac hypertrophy due to increases in different signal transduction pathways involving the activation of protein kinase C, phospholipase C and protein kinase A systems by elevated levels of vasoactive hormones such as catecholamines and angiotensin II in the circulation at early and moderate stages of heart failure. An increase in the sarcoplasmic reticulum Ca2+ transport without any changes in myofibrillar Ca2+-stimulated ATPase was observed in the right ventricle at early and moderate stages of heart failure. On the other hand, the right ventricle showed maladaptive cardiac hypertrophy at the severe stages of heart failure due to myocardial infarction. The upregulation and downregulation of β-adrenoreceptor-mediated signal transduction pathways were observed in the right ventricle at moderate and late stages of heart failure, respectively. The catalytic activity of adenylate cyclase, as well as the regulation of this enzyme by Gs proteins, were seen to be augmented in the hypertrophied right ventricle at early, moderate and severe stages of heart failure. Furthermore, catecholamine stores and catecholamine uptake in the right ventricle were also affected as a consequence of changes in the sympathetic nervous system at different stages of heart failure. It is suggested that the hypertrophied right ventricle may serve as a compensatory mechanism to the left ventricle during the development of early and moderate stages of heart failure.

Development and Phenotype of Heart Failure in Long-Term Survivors of Childhood Cancer: The CVSS Study.

Background The CVSS (Cardiac and Vascular Late Sequelae in Long-Term Survivors of Childhood Cancer) study aimed to investigate the prevalence of different stages of heart failure (HF) in childhood cancer survivors (CCSs) compared with the general population. Methods and Results A total of 1002 CCSs (age range, 23-48 years) diagnosed with neoplasia before an age of 15 years underwent a comprehensive cardiovascular screening. An age- and sex-matched sample from the population-based GHS (Gutenberg Health Study) served as a comparison group. Although prevalence of HF was significantly higher in CCSs, prevalence of different HF stages varied strongly by specific tumor history. Compared with the population, the prevalence ratio was 2.6 (95% CI, 2.4-2.8) for HF stage A and 4.6 (95% CI, 4.1-5.1) for the composite of HF stage B to D in an age- and sex-adjusted Poisson regression model. Multivariable linear regression, adjusting for tumor entities, age, sex, and cardiovascular risk factors, revealed a lower left ventricular ejection fraction in patients with history of bone tumors (β, -4.30 [95% CI, -5.70 to -2.80]), soft tissue sarcoma (β, -1.60 [95% CI, -2.90 to -0.30]), and renal tumors (β, -1.60 [95% CI, -2.80 to -0.29]) compared with the population. The same model for the diastolic marker, ratio of the peak early diastolic filling velocity/lateral mitral annular early diastolic velocity, showed an association only with cardiovascular risk factors but not with tumor entities. Conclusions The prevalence of HF stage A to D was significantly higher among long-term CCSs compared with the population and varied strongly by tumor entity. Systolic dysfunction was primarily associated with tumor entities, whereas diastolic dysfunction was associated with a higher burden of cardiovascular risk factors in CCSs.

Cardioprotective efficacy of Xin-shu-bao tablet in heart failure with reduced ejection fraction by modulating THBD/ARRB1/FGF1/STIM1 signaling

Traditional Chinese medicine offer unique advantages in mitigating and preventing early or intermediate stage for treating heart failure (HF). The purpose of this study was to assess the in vivo therapeutic efficacy of Xin-shu-bao (XSB) at different stages of HF following induction of a myocardial infarction (MI) in mice and use mass spectrometry-based proteomics to identify potential therapeutic targets for different stages of HF based on the molecular changes following XSB treatment. XSB had high cardioprotective efficacy in the pre-HF with reduced ejection fraction (HFrEF) stages, but had a weak or no effect in the post-HFrEF stages. This was supported by echocardiographic measurements showing that XSB decreased ejection fraction and fractional shortening in HF. XSB administration improved cardiac function in the pre- and post-HFrEF mouse model, ameliorated deleterious changes to the morphology and subcellular structure of cardiomyocytes, and reduced cardiac fibrosis. Proteomics analysis showed that XSB intervention exclusively targeted thrombomodulin (THBD) and stromal interaction molecule 1 (STIM1) proteins when administered to the mice for both 8 and 6 weeks. Furthermore, XSB intervention for 8, 6, and 4 weeks after MI induction increased the expression of fibroblast growth factor 1 (FGF1) and decreased arrestin β1 (ARRB1), which are classic biomarkers of cardiac fibroblast transformation and collagen synthesis, respectively. Overall, the study suggests that early intervention with XSB could be an effective strategy for preventing HFrEF and highlights potential therapeutic targets for further investigation into HFrEF remediation strategies.

Self-efficacy and barriers to exercise across the different stages of heart failure with a preserved ejection fraction

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): FWO - Research Foundation – Flanders. Background Exercise is a key therapy for patients across all the stages of heart failure with preserved ejection fraction (HFpEF). Despite being a class I recommendation, the EUROASPIRE registry showed that only a third of patients is sufficiently active, with numbers being even lower among patients with symptomatic HFpEF (stage C). Knowledge of barriers and confidence to exercise is needed to increase the uptake of exercise and a physically active lifestyle. Objective To assess barriers to exercise and self-efficacy in patients along the continuum of HFpEF and to detect possible differences between patients in different HFpEF stages. Methods The first 60 patients (n = 20 HFpEF stage A, 20 HFpEF stage B, 20 HFpEF stage C) from the PRIORITY randomized controlled trial (PeRsonalIzed remOtely guided preventive exeRcIse therapy for a healThY heart) were included. Barriers to exercise and self-efficacy were evaluated using the Exercise Barrier Questionnaire and the Exercise Self-Efficacy Scale. Results Patients with HFpEF stage C were older (72 ± 9.41 years), more likely to be female (70%) and were less physically fit (peak VO2 14.09 ± 2.58 ml/min/kg) compared to patients with HFpEF stage A (63.5 ± 9.10 years, 40% women and peak VO2 21.43 ± 4.94 ml/min/kg) and stage B (70.5 ± 5.25 years, 40% women and peak VO2 17.84 ± 5.15 ml/min/kg). As shown in Figure 1, patients with HFpEF stage C reported more barriers to exercise compared to patients with HFpEF stage A or HFpEF stage B. In particular, 50% of HFpEF stage C reported that they would not exercise when they perceived the exercise as boring (vs A:21%, B:22%), not fun (vs A: 21%, B:21%), if supervised by a bad instructor (vs A:32%, B:33%) or during holidays (vs A:26%, B:17%). Almost 40% of patients with HFpEF stage C reported that having to exercise alone would be a barrier for them (vs A:11%, B:22%). As shown in Figure 2, patients with HFpEF stage C were less confident that they 1) could overcome barriers to exercise by finding appropriate exercise resources (A:0%, B:6%, C:11%), 2) would exercise when feeling tired (A:5%, B:24%, C:28%), 3) would exercise without family support (A:5%, B:6%, C: 17%) or 4) without professional support (A:11%, B:18%, C:17%). Conclusion Barriers to exercise and self-efficacy were rated differently by the 3 stages of HFpEF. Patients with more advanced stages of HFpEF experienced more challenges to be physically active.

Mechanical and hemodynamic effects of left bundle branch area versus biventricular pacing in virtual heart failure patients with left bundle branch block

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The Dutch Research Council (NWO) Background Left bundle branch area pacing (LBBAP) has been introduced as an alternative, more physiological pacing strategy to biventricular pacing (BiVP). LBBAP can result in selective LBB pacing (sLBBP), non-selective LBB pacing (nsLBBP), or LV septal pacing (LVSP). Direct comparison between the different pacing strategies is challenging due to the practical implications of performing multiple pacing procedures within the same patients, as well as the large heterogeneity of underlying disease in patients. Computational models can be used to perform controlled in silico experiments and to compare all possible pacing modalities under the same conditions. Aim To investigate the effects of LBBAP strategies versus BiVP on cardiac mechanics and hemodynamics in a set of well-defined virtual heart failure patients. Methods An electrophysiological model was used to calculate biventricular electrical activation maps during LBBB and the different pacing strategies. The resulting regional activation times were imposed to the well-validated CircAdapt model of the human four-chamber heart and circulation. A set of virtual patients at different stages of heart failure are then defined within the CircAdapt framework, which is achieved by decreasing the contractility of the LV myocardium, such that LVEF≤35%. The CircAdapt model is then used to compute regional ventricular strain patterns and myocardial work as well as global ventricular pump function during LBBB, BiVP and the different LBBAP modalities. Results Selective LBBP is best at restoring mechanical homogeneity in LV contraction as evidenced by simulated wall strains waveforms (Fig 1, Left). NsLBBP increases septal dyssynchrony and introduces small pre-stretch in the LVfw (1.3±0.3%). This effect is more pronounced in LVSP (2.4±1.4%). In BiVP, pre-stretch occurs only in a single LV free wall (LVfw) segment, but all septal segments display a distinct oscillatory pattern. Work load homogeneity (Fig 1, Center) was best restored in sLBBP (4.9±1.1 kPa). NsLBBP lead to reduced homogeneity (4.9±1.8 kPa). LVSP reduced this further (4.8±2.6kPa), while BiVP performed similarly (4.6±2.6kPa) to LVSP. All modalities vastly improved on the baseline LBBB (4.06±5.6 kPa). Hemodynamically (Fig 1, Right), sLBBP showed greatest improvement in LV function (LVESV:-8.1%; LVEF:+6.8%; MLAP:-16.4%; LVdp/dtmax:+12.8%), followed by nsLBBP (LVESV:-7.2%; LVEF:+6.0%; MLAP:-14.5%; LVdp/dtmax:+12.5%), LVSP (LVESV:-5.6%; LVEF:+4.6%; MLAP:-11.7%; LVdp/dtmax:+12.358%) and finally BiVP (LVESV: -4.6%; LVEF:+3.8%; MLAP:-9.3%; LVdp/dtmax:+9.8%) Conclusion We were able to simulate LBBB and subsequent pacing strategies in virtual heart failure patients. This approach allowed direct comparison of mechanical and hemodynamic effects of BiVP and LBBAP modalities without confounding variables. Our results indicate that all LBBAP modalities perform at least similar to bi-ventricular pacing regardless of mechanical viability.

Relationship between diffuse fibrosis assessed by CMR and depressed myocardial strain in different stages of heart failure

ObjectivesTo investigate the extent of the left ventricular (LV) diffuse myocardial fibrosis and the association with the degree of impaired myocardial strain in different stages of heart failure. BackgroundThe increased diffuse myocardial fibrosis impairs the LV systolic and diastolic function. Previous studies found that the global longitudinal strain (GLS) impacted survival in patients with heart failure with preserved ejection fraction (HFpEF). However, limited data are available regarding the association between the degree of diffuse myocardial fibrosis and the severity of impaired myocardial strain in HFpEF. MethodsSixty-six consecutive participants with heart failure (HF), and 15 healthy controls underwent cardiac magnetic resonance (CMR) examination. T1 mapping to calculate extracellular volume fractions (ECV) were used to assess diffuse myocardial fibrosis. ECV and myocardial strains were compared among the 3 groups. Associations between these two factors were also explored. ResultsThe patients with HFpEF showed increased myocardial ECV fractions (32.9 % ± 3.7 % vs. 29.2 % ± 2.9 %, p < 0.001) compared with the control group. The patients with HFm + rEF also had increased myocardial ECV fractions (36.8 % ± 5.4 % vs. 32.9 % ± 3.7 %, p < 0.001) compared with HFpEF. The myocardial ECV was significantly correlated with the GLS (r = 0.422, p = 0.020), global circumferential strain (GCS) (r = 0.491, p = 0.006), and global radial strain (GRS) (r = −0.533, p = 0.002) in the HFpEF groups, but no significant correlation was found in the HFm + rEF group (GLS: r = −0.002, p = 0.990; GCS: r = 0.153, p = 0.372; GRS: r = 0.070, p = 0.685) ConclusionsIn patients with HF, only patients with HFpEF exhibited a significant correlation between increased diffuse myocardial fibrosis and impaired myocardial strain. Diffuse myocardial fibrosis plays a unique role in affecting myocardial strain in patients with HFpEF.

Prevalence of Quality of Life and Physical Activity in Patients with Different Stages of Heart Failure – An Observational Cross-Sectional Study

Background: Heart failure (HF) is an escalating health problem around the world. HF is a highly prevalent disorder worldwide, with a high morbidity and mortality rate. Maintaining a good quality of life (QOL) and physical activity are as important as survival to patients living with HF. Individuals with HF have markedly impaired QOL compared with other chronic diseases and healthy population. Different stages of HF in physical activity and QOL have not been studied in India. Hence, aim of the study was to find out the prevalence of physical activity and QOL patients with HF. Methodology: After calculating the sample size, 301 patients diagnosed with HF who were managed medically were selected for this study with fulfilling criteria. The Minnesota Living with Heart Failure Questionnaire and International PhysicalActivity Questionnaire were used to screen the patients. Outcome measures were QOL, physical activity, ejection fraction (EF), Heart Failure Classification (HFC) New York Heart Association and American Heart Association (AHA) Stages. Results: The mean age of the patients was 53 ± 13.56, including 53.82% males and 45.84% females. Among them, occupation data show 58.13% have labourer work, socioeconomical data show 28.30% of patients have upper middle class. Co-morbidity data shows 13.28% patients have hypertension (HTN), 39.20% have diabetes mellitus (DM), and 22.25% patients have both. Among 301, 30.23% of patients have HFC 3 and 38.53% of patients have AHA Stages B. This study shows 19.60%, 46.17%, and 34.21% good, moderate, and poor QOL, respectively. The prevalence of physical Activity was found to be 81.06% low, 15.61% moderate, and 3.32% high. According to EF prevalence, 79.73% have a reduced EF. Conclusion: Patients with different HF stages experienced impaired QOL and lowest physical activity. Low physical activity and moderate QOL can be improved by early rehabilitation.

Role of left atrial strain response to exercise in the transition from the preclinical to overt heart failure

Abstract Impaired left ventricular (LV) functional reserve has been shown to contribute to exercise intolerance in heart failure. Little is known about the role of left atrial (LA) functional response to exertion in this context. LA strain has recently emerged as a valuable diagnostic marker reflecting both LA and LV performance. Aim To investigate the association between LA strain response to exercise and exercise capacity across different stages of heart failure with preserved ejection fraction (HFpEF). Methods Transthoracic echocardiography (including peak atrial longitudinal strain (PALS) and LV global longitudinal strain (GLS) assessment) was performed at rest and immediately post exercise test in 55 patients with stage A, 62 patients with stage B and 54 patients with stage C HFpEF. Results There was a progressive worsening of peak oxygen uptake from stage A through stage B to stage C, which was accompanied by a gradual impairment of changes from rest to exercise in PALS, GLS, tissue early diastolic velocity e', LA ejection fraction and E/e' ratio (Table 1). In multivariable analysis including LV and LA components of cardiac functional reserve, changes from rest to exercise in PALS (beta 0.34, SE 0.07, p&amp;lt;0.001), e' (beta 0.29, SE 0.07, p&amp;lt;0.001) and GLS (beta 0.17, SE 0.07, p=0.014) were among the independent correlates of exercise capacity. However, after adjustment for age, sex and beta-blocker treatment, only the former two remained statistically significant. Conclusions LA strain response to exercise progressively deteriorates from stage A through stage B to stage C HFpEF, and is independently associated with exercise capacity. Accordingly, it might be considered in the risk stratification of the transition from the asymptomatic phase to overt HFpEF. Funding Acknowledgement Type of funding sources: None.

Markers of bone metabolism are associated in all-cause mortality in heart failure with reduced ejection fraction

Abstract Background In patients with heart failure an increased risk of fracture-related mortality has been reported. A growing body of evidence suggests that, heart failure (HF) itself may be related to disturbances in bone metabolism, but the exact mechanism remains unclear. In patients with HF previous studies indicated a loss of renal function and alterations in bone micro-architecture, but the clinical relevance remains unclear. Purpose We aimed to evaluate the association between markers of bone metabolism with mortality and pro-brain natriuretic peptide (proBNP) in patients with HF with reduced ejection fraction (HFrEF). Methods We analysed participants of a prospective cohort study of patients referred to coronary angiography (CA). The baseline examination was performed at a tertiary care centre in Germany. Indications for CA were based on clinical routine. For the current analysis only patients with HFrEF were included. Patients were selected based on echocardiographic left ventricular (LV)-EF≤40%, symptoms of heart failure and elevated proBNP concentrations, as recommended by current clinical guidelines. We estimated the risk associated with parathyroid hormone (PTH), osteocalcin (OC), beta-crosslaps (βCL) and alkaline phosphatase (AP) and all-cause mortality using Cox proportional hazard models. Adjustments for demographic and clinical characteristics from the index hospital presentation were used as covariates. We included all individuals who had complete data for all variables in the study in our primary analysis. Additionally, we used linear regression analysis to investigate the correlation between proBNP and its association with PTH, OC, βCL and AP. Results A total of 297 participants (63.9±9.9 years; 17.9% females) were included in the analysis. Median follow-up was 10 years. Median LV-EF was 35%, median New York Heart Association functional class was 2 (IQR=1–3), mean pulmonary capillary wedge pressure was 15.3±7.4 mmHg and median proBNP levels of 2282 (IQR 1875–3758) ng/ml. Participants had in 42.3% multi-vessel atherosclerotic CAD (with stenosis of ≥50% considered diagnostic) with 66.4% had a previous myocardial infarction. In multivariate cox proportionate hazard models OC, βCL and AP were statistically significant associated with an increased risk for all-cause mortality (hazard ratio (HR)=1.6 [95% CI 1.2–2.2], HR=1.8 [95% CI 1.1–2.9] and HR=2.1 [95% CI 1.5–2.9], respectively). In multivariate analysis proBNP was associated with PTH (β-coefficient = 0.076; P≤0.001), AP (β-coefficient = 0.125; P=0.001) and βCL (β-coefficient = 0.062; P=0.046), but not with osteocalcin (β-coefficient = −0.055; P=0.145). Conclusion In patients with HFrEF markers of bone metabolism were significantly associated with mortality and proBNP concentrations. Future studies should focus on different aspects of bone metabolism, fracture rates and fracture related mortality in patients with different stages of heart failure. Funding Acknowledgement Type of funding sources: None.

Perspective on the Role of Four Beta-blockers in Heart Failure.

The current recommendations of the American College of Cardiology/ American Heart Association and a previous Bayesian analysis clearly show a mortality benefit with the use of β- blockers in chronic HF, especially for bisoprolol, carvedilol, and sustained-release metoprolol succinate. The main objective was to report the evidence on the use of the afore-mentioned β-blockers in subjects with heart failure and to characterize the stages of heart failure in response to the four different β-blockers. Furthermore, it shed light on the patient's satisfaction and improved quality of life using the afore-mentioned β-blockers in subjects with heart failure. The current perspective presented the clinical outcomes, including hospitalization, morbidity, mortality, patient's satisfaction, and quality of life, of four beta (β)-blockers, namely bisoprolol, carvedilol, metoprolol succinate, and nebivolol in different stages of heart failure. The use of these three agents should be recommended for all stable subjects with current or previous symptoms of heart failure and heart failure with reduced ejection fraction unless there is any contraindication. The fore-mentioned β-blockers (bisoprolol, carvedilol, and metoprolol succinate) can be initiated early, even in stable and symptom-free (at rest) subjects with heart failure. β-blockers in heart failure should be commenced at small doses and then titrated upward as tolerated to achieve the desired clinical effects on heart rate and symptom control. Cardiologists should weigh the benefit-risk in subjects with heart failure and other coexisting cardiovascular problems such as atrial fibrillation and diabetes.

Inverse Associations Between Circulating Secreted Frizzled Related Protein 2 (sFRP2) and Cardiometabolic Risk Factors.

Background: Secreted frizzled-related protein 2 (sFRP2) plays an important role in metabolic syndrome and cardiovascular diseases (CVDs); However, its relevance with cardiometabolic diseases remains to be elucidated. We aimed to determine the serum levels of sFRP2 in patients at different stages of heart failure (HF) with or without type 2 diabetes mellitus (T2DM), and assess the correlation between circulating sFRP2 levels and cardiometabolic risk factors.Methods: In this study, serum samples from 277 patients visiting Zhongshan Hospital affiliated to Fudan University were collected. These patients were clinically diagnosed and categorized as five groups, including the control group, pre-clinical HF group, pre-clinical HF+T2DM group, HF group and HF+T2DM group. Serum sFRP2 levels were measured with enzyme-linked immunosorbent assay (ELISA) tests and the clinical characteristics of each patient were recorded. Spearman rank correlation analysis and multiple stepwise linear regression analysis were conducted. Univariate and multivariate logistic regression analysis were performed to screen risk factors for HF in patients with CVDs.Results: Serum sFRP2 levels were significantly lower in the HF+T2DM group compared with the other four groups. Spearman rank correlation analysis showed that sFRP2 was negatively correlated with parameters including patients' age, fasting plasma glucose (FPG), glycated hemoglobin A1c (HbA1c), cardiac troponin T (cTNT), N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hs-CRP), left atrial dimension (LAD) and left ventricular posterior wall (LVPW), and positively correlated with hemoglobin, estimated glomerular filtration rate (eGFR), albumin, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and left ventricular ejection fraction (LVEF). However, in multiple regression analysis, significant associations with ln(sFRP2) were observed only in FPG, hs-CRP and LAD. Higher serum sFRP2 was significantly linked to lower odds of HF in patients with CVDs.Conclusion: sFRP2 progressively decreased when glucose homeostasis and cardiac function deteriorated. sFRP2 acted as a risk factor for HF in patients with CVDs, especially in those with concomitant T2DM.

Development of heart failure in long-term survivors of childhood cancer: results from the cvss study

Abstract Background Long-term survivors of childhood cancer (CCS) are at increased risk for cardiovascular sequelae, including heart failure (HF) as the largest non-malignant contributor to excess death. Yet, little is known about the risk factors, mechanisms of cardiac dysfunction and prevalence of different stages of HF in these patients. Purpose To investigate the development and prevalence of HF phenotypes in CCS compared to the general population. Methods The CVSS study is a prospective single-center cohort study investigating cardiovascular sequelae of CCS. Patients were eligible for the study when they were diagnosed with a neoplasia according to the International Classification of Childhood Cancer (ICCC 3) at an age prior to 15 years between 1980 and 1990, survived more than five years after initial cancer diagnosis and received antineoplastic treatment. Between 2013 and 2016, study individuals underwent a comprehensive, standardized clinical investigation in the CVSS cohort study including echocardiographic examination. HF was categorized as stages A to D according to current HF guidelines of the American Heart Association (AHA). A population-based sample free of cancer (age- and sex matched) serves as control group. Results From 1,002 individuals, all CCS with history of chemo- or radiotherapy and no subsequent neoplasia (n=877) were included (mean age 34.2 (±5.5) years, 44.7% (N=392) female). Age at diagnosis was 6.28 years (±4.24) and the mean interval from the date of diagnosis of cancer to the date of completion of baseline examination 28.5±3.2 years. Based on echocardiographic examination, clinical data and biomarker assessment, 26.6% of CCS were diagnosed with HF stage A, 21.1% with HF stage B and 2.1% with symptomatic HF, i.e. HF stage C/D. Importantly, prevalence of different HF stages varied strongly by specific tumor history. Compared to the population, the prevalence ratio (PR) was 1.16 [95% confidence interval 1.02/1.31] for stage A HF and 1.91 [1.63/2.23] for the composite of stage B to D HF in an age- and sex-adjusted Poisson regression model. Multivariable linear regression with the systolic marker left ventricular ejection fraction as dependent variable and adjustment for tumor entities, age, sex, and cardiovascular risk factors (CVRF) revealed a lower EF in patients with history of bone tumors (β −6.0 [−8.1/−3.0]), soft tissue sarcoma (β −2.2 [−4.1/−0.35]), leukemia (β −0.84 [−1.8/0.08]) and renal tumors (β −1.8 [−4.0/0.27]) compared to the population. In contrast, the same model for the diastolic marker E/E', showed an association only with CVRF, but not with tumor entities. Conclusion The prevalence of stage B to D HF was significantly higher among long-term CCS in the 3rd to 5th age decade compared to the population and varied strongly by tumor entity. Systolic dysfunction was primarily associated with history of tumor entities, whereas diastolic dysfunction was associated with the higher burden of CVRF in CCS. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This study is funded by the Deutsche Forschungsgemeinschaft (DFG) (SP 1381/2-1&amp;2, FA 1038/2-1&amp;2, WI 3881/2-1&amp;2)

Role of Irisin in Myocardial Infarction, Heart Failure, and Cardiac Hypertrophy.

Irisin is a myokine derived from the cleavage of fibronectin type III domain-containing 5. Irisin regulates mitochondrial energy, glucose metabolism, fatty acid oxidation, and fat browning. Skeletal muscle and cardiomyocytes produce irisin and affect various cardiovascular functions. In the early phase of acute myocardial infarction, an increasing irisin level can reduce endothelial damage by inhibiting inflammation and oxidative stress. By contrast, higher levels of irisin in the later phase of myocardial infarction are associated with more cardiovascular events. During different stages of heart failure, irisin has various influences on mitochondrial dysfunction, oxidative stress, metabolic imbalance, energy expenditure, and heart failure prognosis. Irisin affects blood pressure and controls hypertension through modulating vasodilatation. Moreover, irisin can enhance vasoconstriction via the hypothalamus. Because of these dual effects of irisin on cardiovascular physiology, irisin can be a critical therapeutic target in cardiovascular diseases. This review focuses on the complex functions of irisin in myocardial ischemia, heart failure, and cardiac hypertrophy.

2021 ACC/AHA Key Data Elements and Definitions for Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Data Standards (Writing Committee to Develop Clinical Data Standards for Heart Failure).

2021 ACC/AHA Key Data Elements and Definitions for Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Data Standards (Writing Committee to Develop Clinical Data Standards for Heart Failure).

MicroRNAs as monitoring markers for right-sided heart failure and congestive hepatopathy.

The last decades showed a worrying increase in the evolution of cardiovascular diseases towards different stages of heart failure (HF), as a stigma of the western lifestyle. MicroRNAs (miRNAs), non-coding RNAs, which are approximately 22-nucleotide long, were shown to regulate gene expression at the post-transcriptional level and play a role in the pathogenesis and progression of HF. miRNAs research is of high interest nowadays, as these molecules display mechanisms of action that can influence the course of evolution of common chronic diseases, including HF. The potential of post-transcriptional regulation by miRNAs concerning the diagnosis, management, and therapy for HF represents a new promising approach in the accurate assessment of cardiovascular diseases. This review aims to assess the current knowledge of miRNAs in cardiovascular diseases, especially right-sided heart failure and hepatomegaly. Moreover, attention is focused on their role as potential molecular biomarkers and more promising aspects involving miRNAs as future therapeutic targets in the pathophysiology of HF.

Changes of inflammatory and oxidative stress biomarkers in dogs with different stages of heart failure

BackgroundHeart failure (HF) is associated with changes in inflammatory and oxidative stress biomarkers. This study aimed to evaluate the changes of a panel of inflammatory and oxidative stress biomarkers in dogs with different stages of HF and its relation with the severity of the disease and echocardiographic changes. A total of 29 dogs with HF as a result of myxomatous mitral valve degeneration or dilated cardiomyopathy were included and classified as stage-A (healthy), B (asymptomatic dogs), C (symptomatic dogs) and D (dogs with end-stage HF) according to the ACVIM staging system. In these dogs an ecnhocardiographic examination was performed and cytokines, and inflammatory and oxidative stress markers were evaluated in serum.ResultsKC-like was significantly increased in dogs of stage-C (P < 0.01) and -D (P < 0.05) compared with stage-A and -B. Stage-D dogs showed significantly higher serum CRP and Hp (P < 0.05) but lower serum antioxidant capacity (PON1, TEAC, CUPRAC, and thiol) compared to stage-A and -B (P < 0.05). After the treatment, serum levels of CRP, Hp and KC-like decreased and serum antioxidant levels increased compared to their pre-treatment values. Left ventricular dimension and LA/Ao ratio correlated positively with CRP, MCP-1, and KC-like but negatively with PON1, GM-CSF, IL-7 and antioxidant biomarkers (P < 0.01).ConclusionOur results showed that dogs with advanced HF show increases in positive acute-phase proteins and selected inflammatory cytokines such as KC-like, and decreases in antioxidant biomarkers, indicating that inflammation and oxidative stress act as collaborative partners in the pathogenesis of HF. Some of these biomarkers of inflammation and oxidative stress could have the potential to be biomarkers to monitor the severity of the disease and the effect of treatment.

Proteomic Signatures During Treatment in Different Stages of Heart Failure.

Proteomics have already provided novel insights into the pathophysiology of heart failure (HF) with reduced ejection fraction. Previous studies have evaluated cross-sectional protein signatures of HF, but few have characterized proteomic changes following HF with reduced ejection fraction treatment with ARNI (angiotensin receptor/neprilysin inhibitor) therapy or left ventricular assist devices. In this retrospective omics study, we performed targeted proteomics (N=625) of whole blood sera from patients with American College of Cardiology/American Heart Association stage D (N=29) and stage C (N=12) HF using proximity extension assays. Samples were obtained before and after (median=82 days) left ventricular assist device implantation (stage D; primary analysis) and ARNI therapy initiation (stage C; matched reference). Oblique principal component analysis and point biserial correlations were used for feature extraction and selection; standardized mean differences were used to assess within and between-group differences; and enrichment analysis was used to generate and cluster Gene Ontology terms. Core sets of proteins were identified for stage C (N=9 proteins) and stage D (N=18) HF; additionally, a core set of 5 shared HF proteins (NT-proBNP [N-terminal pro-B type natriuretic peptide], ESM [endothelial cell-specific molecule]-1, cathepsin L1, osteopontin, and MCSF-1) was also identified. For patients with stage D HF, moderate (δ, 0.40-0.60) and moderate-to-large (δ, 0.60-0.80) sized differences were observed in 8 of their 18 core proteins after left ventricular assist devices implantation. Additionally, specific protein groups reached concentration levels equivalent (g<0.10) to stage C HF after initiation on ARNI therapy. HF with reduced ejection fraction severity associates with distinct proteomic signatures that reflect underlying disease attributes; these core signatures may be useful for monitoring changes in cardiac function following initiation on ARNI or left ventricular assist device implantation.

P825 Multi-modality imaging for noninvasive diagnosis of transthyretin amyloid cardiomyopathy-single centre experience

Abstract Background Thransthyretin amyloidosis (ATTR) is a rare progressive disease that may present as heart failure with preserved ejection fraction, severe aortic stenosis, hypertrophic cardiomyopathy (HCM) or resctrictive cardiomyopathy. There are two types of ATTR: hereditary ATTR (hATTR) caused by mutations in the TTR gene and wild-type ATTR (wtATTR) resulting from deposition of wild-type TTR protein. Purpose We describe the clinical heterogeneity of ATTR patients from our centre diagnosed noninvasively in 2018-2019. Methods All patients presented intensive cardiac uptake at 99mTc-DPD scintigraphy. Light chain amyloidosis was excluded. Results 8 patients were diagnosed with ATTR (Table 1). Three unrelated male patients were diagnosed with hATTR due to rare mutations: 2 of them had Phe33Leu, 1 patient had Glu89Lys mutation. Five patients (males) were diagnosed with wtATTR. Age of onset differed among the patients. Characteristic clinical features included cardiomyopathy with increased left and right ventricular wall thickness. Only 2 patients had restrictive filling pattern, 3 patients had atrial fibrillation. Laboratory examination showed increased level of troponin T and NT-proBNP. Three patients had bilateral carpal tunnel syndrome. Thanks to DPD-scintygraphy we excluded ATTR in two patients with false-positive results of histological exam for TTR-related amyloid deposits. Conclusions Although ATTR is known for its broad clinical spectrum, patients from our center presented mostly as HCM phenocopies but in different stages of heart failure. Appropriate diagnosis of ATTR is crucial and have direct therapeutic impact. Echocardiography raise the suspicion of amyloid cardiomyopathy, while other imaging technique (DPD-scintigraphy) confirm it or exclude it in noninvasive way. Patient 1 2 3 4 5 6 7 8 Mutation Glu89Lys Phe33Leu Phe33Leu wild type wild type wild type wild type wild type Sex male male male male male male male male Age of onset 57 56 55 77 78 80 77 76 Electrocardiogram AF low QRS voltage low QRS voltage AF, RBBB LVH LVH pseudoinfarct pattern, low QRS voltage AF, LVH Maximal wall thickness [mm] 23 20 18 28 22 23 18 20 LVEF% 45 40 40 60 65 60 45 55 Asymmetric hypertrophy pattern + - - - + + - + NYHA III II II II III II II II NT-proBNP pg/ml 2122 1200 1500 2755 222 2630 2426 hs-Troponin T ng/l 50 98 42 65 35 63 64 Abstract P825 Figure 1