Stage Heart Failure Research Articles

The condition of myocardium reserves score from a cloud-based analytics platform of Holter ECG data indicates better cardiometabolic function in heart failure

Abstract Introduction Cardiometabolic dysregulation, particularly type 2 diabetes mellitus (T2DM), is associated with subtle myocardial pathologies, even in individuals without known cardiovascular disease. These subclinical changes, often undetectable by standard electrocardiogram (ECG) analytics, can offer valuable insights into the relationship between metabolic health and cardiac function. Novel ECG markers, developed through machine learning and artificial intelligence (AI), may provide the sensitivity needed to detect such changes. Aim This study aims to evaluate novel composite cardiac parameters from an analytics platform in the context of heart failure (HF), seeking to understand their relationship to cardiometabolic dysregulation. Methods Data from the MyoVasc study, a prospective cohort on HF, were analysed. Participants underwent extensive clinical phenotyping, including a Holter ECG assessment. Holter ECG data was processed based on machine learning and AI models on a cloud-based analytics platform (Cardiolyse, Helsinki, Finland), generating both traditional and proprietary ECG, and heart rate variability cardiac health markers. LASSO-penalized logistic regression adjusted for sex and age was performed to select the marker most strongly associated with T2DM. The identified marker was then evaluated in relation to cardiac function and structure as well as HF-related outcome. Results A total of 953 subjects (mean±SD age 64.6±10.5 years; 35.7% women) were included in the analyses. Symptomatic HF stage C/D was present in 54.8% (n=522) of subjects and diabetes mellitus in 22.4% (n=213). The Condition of Myocardium Reserves Score (CMRS) was the novel composite cardiac parameter selected based on its relationship with T2DM. In a Poisson regression model with robust variance adjusted for sex and age, a lower score was associated with T2DM (Prevalence ratio per SD 1.24, 95% confidence interval [1.14;1.36], P=0.0002). In multivariable linear regressions adjusted for traditional cardiovascular risk factors, comorbidities, and medication, a higher CMRS was associated with better global longitudinal strain (β per SD –0.82 [–1.11;–0.53], P<0.0001), diastolic function (left ventricular E/e’; β per SD –0.04 [–0.06;–0.01], P=0.0059) and systolic function (LV ejection fraction; β per SD 2.06 [1.46;2.67], P<0.0001). A lower CMRS independently predicted all-cause death (Hazard ratio per SD 1.25 [1.09;1.45], P=0.0020) and worsening of HF (HR per SD 1.44 [1.21;1.72], P<0.0001) in Cox regression analysis adjusted for the same confounders. Conclusion The Condition of Myocardium Reserves Score exhibited a strong association with cardiometabolic dysregulation. A higher CMRS indicated preserved cardiac function, while a lower score independently predicted increased risk of all-cause death and worsening HF. This novel score offers potential as a non-invasive tool for assessing cardiometabolic health and stratifying risk in patients with HF.

Association between heart failure in asymptomatic stages and skeletal muscle function assessed by ultrasonography in community-dwelling older adults

BackgroundSymptomatic heart failure (HF) negatively affects the quantity and quality of skeletal muscles. However, the association between asymptomatic HF and skeletal muscle function remains unclear. We aimed to use ultrasonography to elucidate the association between asymptomatic HF and skeletal muscle function in community-dwelling older adults.MethodsThis cross-sectional study comprised community-dwelling older adults aged ≥ 60 years who could perform activities of daily living independently and had never had symptomatic HF (n = 52, 76.3 ± 6.1 years). The participants were classified into three groups namely, non-HF (n = 26), stage A (n = 19), and stage B (n = 7) according to the HF stage criteria of the American Heart Association /American College of Cardiology /Heart Failure Society of America guideline. Skeletal muscle quantity and quality were assessed using ultrasonography (thickness and echo intensity) of the rectus femoris (RF) and vastus intermedius (VI) muscles. The group effects on muscle thickness and echo intensity in each group were assessed using a multivariate analysis.ResultsBoth muscles consistently demonstrated significant group effects on the thickness and echo intensity. Thicknesses of the RF (p = 0.020) and VI (p = 0.035) were lower in the stage B group than that in the non-HF group. The echo intensities in the RF (p = 0.006) and VI (p = 0.009) were higher in the stage B group than that in the non-HF group.ConclusionAsymptomatic HF negatively associated with the characteristics of skeletal muscle function, as assessed by ultrasonography in community-dwelling older adults. The stage B HF contributes to reduced skeletal muscle function as well as symptomatic HF.

Myocardial Abnormalities Across the AHA/ACC Stages of Heart Failure in Patients With Diabetes

BackgroundCardiac magnetic resonance imaging (CMR) could serve as a robust tool for comprehensive evaluation of early changes across heart failure (HF) stages classified by the American Heart Association/American College of Cardiology guideline in diabetes mellitus (DM). ObjectivesThe authors aimed to explore phenotypic imaging features characterizing DM participants at different HF stages by CMR. MethodsDM participants with preserved ejection fraction who underwent CMR examination between January 2020 and December 2021 were evaluated. Left ventricular strain analysis and myocardial fibrosis was evaluated by CMR. ResultsA total of four hundred seventy-five DM participants at different HF stages (mean age 56 ± 12 years; 326 men) and 78 healthy control subjects were evaluated. Significantly decreased absolute strain values with rising HF stage were identified in DM. In addition, early diastolic strain rates were significantly lower in stage B and C HF than in stage A HF and control subjects. Myocardial extracellular volume increased with advancing HF stage in DM (stage A, 27.0% ± 2.9%; stage B, 29.1% ± 3.5%; stage C, 30.5% ± 4.1%; P < 0.05). In multivariable logistic regression analysis, early diastolic longitudinal strain rate (OR: 2.184; 95% CI: 1.378-3.461; P < 0.001) was a significant contributor that independently distinguished DM participants at stage A from control subjects, with an area under the receiver-operating characteristic curve of 0.726. For global longitudinal strain and extracellular volume, each 1% increase was associated with 1.333 and 1.300 times adjusted odds of diagnosis of stage B HF (both P < 0.05). ConclusionsSubclinical dysfunction and myocardial fibrosis derived from CMR were progressively remarkable with advancing HF stage in DM. Comprehensive CMR provided sensitive tools for better delineation of DM patients with pre-HF and at risk for HF.

Targeting MuRF1 to Combat Skeletal Muscle Wasting in Cardiac Cachexia: Mechanisms and Therapeutic Prospects.

Cardiac cachexia, the terminal stage of chronic heart failure, is characterized by severe systemic metabolic imbalances and significant weight loss, primarily resulting from skeletal muscle mass depletion. Despite the detrimental consequences, there is no standardized and clinically-approved intervention currently available for cardiac cachexia. In the context of cardiac cachexia, accelerated protein turnover, that is, inhibited protein synthesis and enhanced protein degradation, plays a crucial role in skeletal muscle wasting. This process is primarily mediated by various proteins encoded by atrogenes. Among them, the atrogene Trim63 (tripartite motif family 63) and its encoded protein MuRF1 have been extensively studied. This review article aims to elucidate the pathogenic mechanisms underlying skeletal muscle wasting in cardiac cachexia, describe the biochemical characteristics of MuRF1, and provide an overview of the investigation into MuRF1-targeting inhibitors. The ultimate goal is to offer novel strategies for the clinical treatment for skeletal muscle wasting associated with cardiac cachexia.

The Prevalence of Various Stages of Heart Failure in Individuals Over 40 Years Old: The Findings from Yazd Health Study

identification and prevention of HF. Therefore, this study aims to evaluate the prevalence of various stages of HF in individuals over 40 years old within a large population of Iranian adults. Methods: In this descriptive cross-sectional study, a random sub sample of Yazd Health Study (YaHS) participants aged 40-70 years was evaluated. History and clinical examination of the patients was conducted by a cardiologist and then, the participants underwent echocardiography to determine the stages of heart failure. Results: Among 410 Yazd population -the representative sample with mean age 58.0±9.2 years, 183 patients (44.6%) were in stage 0, 121 (29.5%) in stage A, 77(18.8%) in stage B, and 29 (7.1%) in stage C heart failure. No individuals were in stage D. There was a significant difference between the frequency of individuals with different stages of HF in terms of diabetes, hypertension, obesity, and history of ischemic heart disease (p&lt;0.05). In addition, the frequency of HF increased in the age group &gt;60 years and the obesity group (p&lt;0.05). Conclusion: According to these, about half of the patients with HF were in stage A and B. Therefore, appropriate measures are needed to identify these groups of patients, especially individuals with risk factors of diabetes, hypertension, obesity and those over 60 years to prevent the progression of the disease to higher stages which lead to poorer outcome.

Role of Na+-K+ ATPase Alterations in the Development of Heart Failure.

Na+-K+ ATPase is an integral component of cardiac sarcolemma and consists of three major subunits, namely the α-subunit with three isoforms (α1, α2, and α3), β-subunit with two isoforms (β1 and β2) and γ-subunit (phospholemman). This enzyme has been demonstrated to transport three Na and two K ions to generate a trans-membrane gradient, maintain cation homeostasis in cardiomyocytes and participate in regulating contractile force development. Na+-K+ ATPase serves as a receptor for both exogenous and endogenous cardiotonic glycosides and steroids, and a signal transducer for modifying myocardial metabolism as well as cellular survival and death. In addition, Na+-K+ ATPase is regulated by different hormones through the phosphorylation/dephosphorylation of phospholemman, which is tightly bound to this enzyme. The activity of Na+-K+ ATPase has been reported to be increased, unaltered and depressed in failing hearts depending upon the type and stage of heart failure as well as the association/disassociation of phospholemman and binding with endogenous cardiotonic steroids, namely endogenous ouabain and marinobufagenin. Increased Na+-K+ ATPase activity in association with a depressed level of intracellular Na+ in failing hearts is considered to decrease intracellular Ca2+ and serve as an adaptive mechanism for maintaining cardiac function. The slight to moderate depression of Na+-K+ ATPase by cardiac glycosides in association with an increased level of Na+ in cardiomyocytes is known to produce beneficial effects in failing hearts. On the other hand, markedly reduced Na+-K+ ATPase activity associated with an increased level of intracellular Na+ in failing hearts has been demonstrated to result in an intracellular Ca2+ overload, the occurrence of cardiac arrhythmias and depression in cardiac function during the development of heart failure. Furthermore, the status of Na+-K+ ATPase activity in heart failure is determined by changes in isoform subunits of the enzyme, the development of oxidative stress, intracellular Ca2+-overload, protease activation, the activity of inflammatory cytokines and sarcolemmal lipid composition. Evidence has been presented to show that marked alterations in myocardial cations cannot be explained exclusively on the basis of sarcolemma alterations, as other Ca2+ channels, cation transporters and exchangers may be involved in this event. A marked reduction in Na+-K+ ATPase activity due to a shift in its isoform subunits in association with intracellular Ca2+-overload, cardiac energy depletion, increased membrane permeability, Ca2+-handling abnormalities and damage to myocardial ultrastructure appear to be involved in the progression of heart failure.

Machine learning in the prevention of heart failure.

Heart failure (HF) is a global pandemic with a growing prevalence and is a growing burden on the healthcare system. Machine learning (ML) has the potential to revolutionize medicine and can be applied in many different forms to aid in the prevention of symptomatic HF (stage C). HF prevention currently has several challenges, specifically in the detection of pre-HF (stage B). HF events are missed in contemporary models, limited therapeutic options are proven to prevent HF, and the prevention of HF with preserved ejection is particularly lacking. ML has the potential to overcome these challenges through existing and future models. ML has limitations, but the many benefits of ML outweigh these limitations and risks in most scenarios. ML can be applied in HF prevention through various strategies such as refinement of incident HF risk prediction models, capturing diagnostic signs from available tests such as electrocardiograms, chest x-rays, or echocardiograms to identify structural/functional cardiac abnormalities suggestive of pre-HF (stage B HF), and interpretation of biomarkers and epigenetic data. Altogether, ML is able to expand the screening of individuals at risk for HF (stage A HF), identify populations with pre-HF (stage B HF), predict the risk of incident stage C HF events, and offer the ability to intervene early to prevent progression to or decline in stage C HF. In this narrative review, we discuss the methods by which ML is utilized in HF prevention, the benefits and pitfalls of ML in HF risk prediction, and the future directions.

Characteristics of gene expression in epicardial adipose tissue and subcutaneous adipose tissue in patients at risk for heart failure undergoing coronary artery bypass grafting

BackgroundEpicardial adipose tissue (EAT) surrounds the heart and is hypothesised to play a role in the development of heart failure (HF). In this study, we first investigated the differences in gene expression between epicardial adipose tissue (EAT) and subcutaneous adipose tissue (SAT) in patients undergoing elective coronary artery bypass graft (CABG) surgery (n = 21; 95% male). Secondly, we examined the association between EAT and SAT in patients at risk for HF stage A (n = 12) and in pre-HF patients, who show signs but not symptoms of HF, stage B (n = 9).ResultsThe study confirmed a distinct separation between EAT and SAT. In EAT 17 clusters of genes were present, of which several novel gene modules are associated with characteristics of HF. Notably, seven gene modules showed significant correlation to measures of HF, such as end diastolic left ventricular posterior wall thickness, e’mean, deceleration time and BMI. One module was particularly distinct in EAT when compared to SAT, featuring key genes such as FLT4, SEMA3A, and PTX3, which are implicated in angiogenesis, inflammation regulation, and tissue repair, suggesting a unique role in EAT linked to left ventricular dysfunction. Genetic expression was compared in EAT across all pre-HF and normal phenotypes, revealing small genetic changes in the form of 18 differentially expressed genes in ACC/AHA Stage A vs. Stage B.ConclusionsThe roles of subcutaneous and epicardial fat are clearly different. We highlight the gene expression difference in search of potential modifiers of HF progress. The true implications of our findings should be corroborated in other studies since HF ACC/AHA stage B patients are common and carry a considerable risk for progression to symptomatic HF.

Cardiac power output associated with hospitalization and mortality in coronary artery disease patients at stage B heart failure

BackgroundCardiac power output (CPO) predicts outcomes in advanced heart failure (HF) and cardiogenic shock, but its role in early HF stages is unclear. This study assessed the prognostic value of CPO in coronary artery disease patients with asymptomatic left ventricular systolic dysfunction (ALVSD) at stage B HF. MethodsWe conducted a retrospective analysis of coronary artery disease patients who underwent coronary and pulmonary artery catheterization between 2006 and 2016. Stage B HF with ALVSD was defined as left ventricular ejection fraction < 50 %, without HF symptoms, signs, or prior HF hospitalization. CPO was derived from invasive hemodynamic parameters. Endpoints included HF hospitalization, cardiovascular mortality, and all-cause mortality over a 5-year follow-up. ResultsA total of 783 coronary artery disease patients with ALVSD at stage B HF were enrolled. Incidence rates (per 1000 person-years) were 13.9 for HF hospitalization, 14.5 for cardiovascular mortality, and 23.7 for all-cause mortality.Multivariate analysis adjusting for covariates demonstrated that CPO was independent associated with all endpoints. Patients with a low CPO (<0.97 Watts) were at significantly higher risk for HF hospitalization (adjusted hazard ratio [HR]: 4.04; 95 % CI: 1.53 – 10.6; p = 0.005), cardiovascular mortality (adjusted HR: 2.73; 95 % CI: 1.19 – 6.27; p = 0.018), and all-cause mortality (adjusted HR: 1.86; 95 % CI: 1.05 – 3.30; p = 0.035) compared to those with higher CPO, regardless of subgroup classification. ConclusionResting CPO in patients with ALVSD is significantly associated with adverse events, including HF hospitalization and mortality, highlighting its value in early-stage HF management.

Application of the AHA/ACC/HFSA Heart Failure Staging Guidelines in CKD

Application of the AHA/ACC/HFSA Heart Failure Staging Guidelines in CKD

BEEAF2 Score: A New Risk Stratification Score for Patients With Stage B Heart Failure From the KUNIUMI Registry Chronic Cohort.

Stage B heart failure (HF) refers to structural heart disease without signs or symptoms of HF, so that early intervention may delay or prevent the onset of overt HF. However, stage B HF is a very broad concept, and risk stratification of such patients can be challenging. We conducted a prospective study of data for 1646 consecutive patients with HF from the KUNIUMI (Kobe University Heart Failure Registry in Awaji Medical Center) registry chronic cohort. The definition of HF stages was based on current guidelines for classification of 29 patients as stage A HF, 761 as stage B HF, 827 as stage C HF, and 29 patients as stage D HF. The primary end point was the time-to-first-event defined as cardiovascular death or HF hospitalization within 2.0 years of follow-up. A maximum of 6 adjustment factor points was assigned based on Cox proportional hazards analysis findings for the hazard ratio (HR) of independent risk factors for the primary end point: 1 point for anemia, estimated glomerular filtration rate <45 mL/min per 1.73 m2, brain natriuretic peptide ≥150 pg/mL, and average ratio of early transmitral flow velocity to early diastolic mitral annular velocity >14, and 2 points for clinical frailty scale >3. Patients with stage B HF were stratified into 3 groups, low risk (0-1 points), moderate risk (2-3 points), and high risk (4-6 points). Based on this scoring system (BEEAF2 [brain natriuretic peptide, estimated glomerular filtration rate, ratio of early transmitral flow velocity to early diastolic mitral annular velocity, anemia, and frailty]), the outcome was found to become worse in accordance with risk level. High-risk patients with stage B HF and patients with stage C HF showed similar outcomes. Our scoring system offers an easy-to-use evaluation of risk stratification for patients with stage B HF.

Sodium-dependent glucose transporter 2 inhibitors effects on myocardial function in patients with type 2 diabetes and asymptomatic heart failure.

Sodium-dependent glucose transporter 2 inhibitors (SGLT2i) have shown efficacy in reducing heart failure (HF) burden in a very heterogeneous groups of patients, raising doubts about some contemporary assumptions of their mechanism of action. We previously published a prospective observational study that evaluated mechanisms of action of SGLT2i in patients with type 2 diabetes who were in HF stages A and B on dual hypoglycemic therapy. Two groups of patients were included in the study: the ones receiving SGLT2i as an add-on agent to metformin and the others on dipeptidyl peptidase-4 inhibitors as an add-on to metformin due to suboptimal glycemic control. To evaluate the outcomes regarding natriuretic peptide, oxidative stress, inflammation, blood pressure, heart rate, cardiac function, and body weight. The study outcomes were examined by dividing each treatment arm into two subgroups according to baseline parameters of global longitudinal strain (GLS), N-terminal pro-brain natriuretic peptide, myeloperoxidase (MPO), high-sensitivity C-reactive protein (hsCRP), and systolic and diastolic blood pressure. To evaluate the possible predictors of observed changes in the SGLT2i arm during follow-up, a rise in stroke volume index, body mass index (BMI) decrease, and lack of heart rate increase, linear regression analysis was performed. There was a greater reduction of MPO, hsCRP, GLS, and blood pressure in the groups with higher baseline values of mentioned parameters irrespective of the therapeutic arm after 6 months of follow-up. Significant independent predictors of heart rate decrease were a reduction in early mitral inflow velocity to early diastolic mitral annular velocity at the interventricular septal annulus ratio and BMI, while the predictor of stroke volume index increase was SGLT2i therapy itself. SGLT2i affect body composition, reduce cardiac load, improve diastolic/systolic function, and attenuate the sympathetic response. Glycemic control contributes to the improvement of heart function, blood pressure control, oxidative stress, and reduction in inflammation.

Alcohol consumption and heart failure: a dose-response meta-analysis.

This is a protocol for a Cochrane Review (prototype). The objectives are as follows: Main objective To assess the effects of alcohol consumption on the progression to symptomatic (stage C) heart failure in people at risk for heart failure (stage A) or in people with pre-heart failure (stage B). Secondary objectives To assess the effects of alcohol consumption on progression of left ventricular dysfunction in people with stage A or stage B heart failure. We will assess the effect of alcohol consumption on the development of heart failure with reduced ejection fraction, mildly reduced ejection fraction, and preserved ejection fraction. We also aim to evaluate the effects of alcohol consumption on the development of symptomatic (stage C) heart failure over the short, medium and long term.

PROGNOSTIC VALUE OF BIOMARKERS IN PATIENTS WITH ISCHEMIC HEART FAILURE

Modern clinical recommendations of medical associations attach great importance to the improvement of methods of early diagnosis, prevention and individualized treatment of heart failure (HF). It is assumed that biological markers that reflect different pathophysiological stages of HF retain their value as a powerful tool for diagnosing acute and chronic HF, stratifying patients into high-risk groups for the occurrence and progression of the specified pathology, and as a probable predictor of treatment effectiveness. Along with this, the levels and prognostic value of serum biomarkers in patients with HF of different etiologies at different stages of treatment remain unclear.The purpose. To study the prognostic value of biomarkers in patients with HF of ischemic origin.Material and methods. 398 were examined with HF aged 45-65 years (54.3±7.2 years. All 398 patients with HF were divided into two groups. The 1st group included 219 (55%) patients who did not have re-hospitalization (RG) due to HF decompensation during the year of observation. The II group consisted of 179 (45%) patients with PG. 226 (56.8%) patients had a permanent form of atrial fibrillation (AF), 102 (25.6%) had type 2 diabetes. Among the examined - 198 (49,7%) women and 200 (50,2%) men. A standardized echocardiographic study was performed to determine the left ventricular ejection fraction (LV EF) and LV dimensions during hospitalization. The levels of thyroid-stimulating hormone, free T3, free T4, blood glucose, glycated hemoglobin, galectin-3, ST-2, BNP, NT-proBNP were determined. The ratios: ST-2 / Galectin-3 (UO), NT-proBNP / BNP (UO), NT-proBNP / ST-2 (UO) and NT-proBNP / Galectin-3 (UO) were calculated. During 1 year, patients were observed, taking into account the presence of repeated hospitalization (RG) due to HF decompensation, mortality. Patients were divided into two groups. The 1st group included 219 (55%) of patients who did not have re-hospitalization (PG) due to HF decompensation. II group - 179 (45%) patients with PG.Results. Compared to patients with a favorable short-term course of the disease, patients with HF of ischemic genesis, who had PG during the year of observation, have HF III and IV PK according to NYHA, diabetes mellitus, and a permanent form of AF more often; higher heart rate, serum levels of galectin-3 (by 11.1%), NT-proBNP (by 31.8%), higher values of NT-proBNP / BNP (by 40.6%) and NT-proBNP / ST- 2 (by 21.1%), but a smaller value of the ST-2 / Galectin-3 ratio (by 9.3%), as well as a higher risk of death during the first year (OR = 3.81). The risk of PG increases when the level of NT-proBNP &gt; 652.6 pg/ml is reached and the ratios: ST-2/Galectin-3 ≤ 17.95 IU, NT-proBNP / BNP &gt; 10.17 IU and NT-proBNP / ST-2 &gt; 13.79 UO. The level of ST-2 &gt; 41.37 ng/ml is prognostically significant for the one-year death of patients within a year.Conclusions. In patients with HF of ischemic genesis, the ratio of NT-proBNP / BNP has a greater prognostic significance regarding the risk of re-hospitalization, compared to NT-proBNP and NT-proBNP / ST-2.

Propelling Nurse-Led Structured Intervention to Enhance Self-Care among Patients with Chronic Heart Failure (PROACT-HF): A Cluster Randomized Controlled Trial Study Protocol.

Heart Failure (HF) is a common chronic disease that has a high readmission rate and is associated with worsening symptoms and major financial impacts. Disease management implemented during or after an HF hospitalization has been shown to reduce hospitalization and mortality rates. Particularly for outpatients, it is necessary to provide self-care interventions. Structured nurse-led support such as timely follow-ups, including phone calls, is beneficial for improving self-care assessments. Evidence for nurse-led support has been investigated but is less than conclusive. The aim of this study is to compare the effectiveness of a nurse-led structured intervention for outpatients with chronic HF against the usual medical care in terms of self-care behaviors and occurrence of symptom exacerbation or rehospitalization. This is a cluster-randomized controlled trial. A total of 40 facilities with certified HF nurses will be allocated to two-arm clusters at a 1:1 ratio, randomly to the intervention or usual care arms. A total of 210 participants will be assigned from the hospital. Participants will be adults aged 18 years or older diagnosed with chronic HF who are classified as Stage C according to the ACCF/AHA Heart Failure staging system. In the intervention group, patients will receive structured nursing support. This begins with weekly support, including phone calls, for the first month, then transitions to monthly support thereafter. The aim is to ensure the stability of their living conditions, promote medication adherence, and encourage self-management. In the control group, patients will receive the usual care. Primary outcomes will assess the improvement or continuation of self-care behavior as measured by changes in EHFScBS (European Heart Failure Self-Care Behavior Scale) scores. Secondary outcomes include occurrence of readmission within 30 days, 3 months, 6 months, and 1 year after discharge, duration of home care until readmission, and blood levels of BNP and NT-proBNP.

The Multicenter STudy On a Precise algorithm for diagnosis of heart failure with preserved ejection fraction, STOP-HFPEF study: study protocol and design.

This study aims to develop a new heart failure with preserved ejection fraction (HFpEF) diagnostic algorithm tailored to Asian populations, addressing limitations of current diagnostic models. Existing HFpEF diagnostic algorithms primarily target patients with dyspnea and metabolic comorbidities, such as obesity, which are more prevalent in Western populations. However, in Asian countries, HFpEF cases are less frequently associated with obesity, leading to less prominent dyspnea and more noticeable symptoms such as fatigue. By incorporating exercise stress echocardiography and focusing on early-stage HFpEF, particularly in patients with symptoms beyond dyspnea, we seek to enable early diagnosis and intervention, ultimately extending healthy life expectancy and improving quality of life. The STOP-HFPEF (The Multicenter STudy On a Precise algorithm for diagnosis of Heart Failure with Preserved Ejection Fraction) study is a multicenter prospective observational investigation in Japan. Certified by the Japanese Society of Echocardiography, the study includes participants aged 20 and older who undergo exercise stress echocardiography. The primary goal is to develop a scoring model for diagnosing HFpEF in heart-failure stages A, B, and C. Secondary outcomes will assess the clinical utility of the new diagnostic score by comparing heart-failure incidence, cardiovascular events, and mortality rates.Study registration: Registered at the UMIN registry (UMIN000054565) on 1 July 2024.

Pulmonary hypertension in ischemic heart failure: a pilot study

Aim. To evaluate the role of cardiopulmonary system assessment in a group of patients with pulmonary hypertension (PH) associated with ischemic heart failure (HF) with the right ventricular-pulmonary arterial (RV-PA) coupling.Material and methods. Forty stable patients were examined. The patients were divided into 3 groups depending on the left ventricle ejection fraction (LVEF). PH was established by using expert transthoracic echocardiography. RV-PA coupling was calculated by 2 following ways: as tricuspid annular plane systolic excursion (TAPSE)/pulmonary artery systolic pressure (PASP) ratio and as TAPSE´Pulmonary Artery Aceleration Time (pACT) multiplication.Results. The patients included in the study were mainly men (73,8%), functional class PH II-III (95,2%), stage IIB CHF (62%). The highest values of TAPSE (18,6±3 mm) and RV-PA coupling (0,64±0,42 mm/mm Hg) were found in the patients with preserved LVEF. In the general cohort, high level of NT-proBNP corresponds to reduced values of RVPA coupling (rs=-0,563) and TAPSE (rs=-0,666; p&lt;0,01). The severity of PH directly affects the level of NT-proBNP (p&lt;0,01). As the stage of HF and PH functional class increases, the indicators of PASP, inferior vena cava diameter and NT-proBNP level significantly increase, as well as TAPSE and RV-PA coupling decrease (p&lt;0,05). Different calculating methods of RV-PA coupling has a strong correlation (rs=0,832; p&lt;0,01).Conclusion. The right heart and RV-PA coupling assessment in patients with ischemic HF of origin is of significant value for the early diagnosis of PH and timely clinical decision-making.

Expression of Osteopontin and Gremlin 1 Proteins in Cardiomyocytes in Ischemic Heart Failure.

A relevant role of osteopontin (OPN) and gremlin 1 (Grem1) in regulating cardiac tissue remodeling and formation of heart failure (HF) are documented, with the changes of OPN and Grem1 levels in blood plasma due to acute ischemia, ischemic heart disease-induced advanced HF or dilatative cardiomyopathy being the primary focus in most of these studies. However, knowledge on the early OPN and Grem1 proteins expression changes within cardiomyocytes during remodeling due to chronic ischemia remains insufficient. The aim of this study was to determine the OPN and Grem1 proteins expression changes in human cardiomyocytes at different stages of ischemic HF. A semi-quantitative immunohistochemical analysis was performed in 105 myocardial tissue samples obtained from the left cardiac ventricles. Increased OPN immunostaining intensity was already detected in the stage A HF group, compared to the control group (p < 0.001), and continued to increase in the stage B HF (p < 0.001), achieving the peak of immunostaining in the stages C/D HF group (p < 0.001). Similar data of Grem1 immunostaining intensity changes in cardiomyocytes were documented. Significantly positive correlations were detected between OPN, Grem1 expression in cardiomyocytes and their diameter as well as the length, in addition to positive correlation between OPN and Grem1 expression changes within cardiomyocytes. These novel findings suggest that OPN and Grem1 contribute significantly to reorganization of cellular geometry from the earliest stage of cardiomyocyte remodeling, providing new insights into the ischemic HF pathogenesis.

Association between self-reported and objectively assessed physical functioning in the general population

Knowledge about a patient’s physical fitness can aid in medical decision-making, but objective assessment can be challenging and time-consuming. We aimed to investigate the concordance of self-reported health status and physical functioning with the 6 minute walking distance (6MWD) as objective measure of physical performance. The prospective characteristics and course of heart failure stages A/B and determinants of progression (STAAB) cohort study iteratively follows a representative sample of residents of the city of Würzburg, Germany, aged 30–79 years, without a history of heart failure (HF). The 6MWD was measured in 2752 individuals (aged 58 ± 11 years, 51% women) from a population-based cohort under strictly standardized conditions. Self-reported health status and physical functioning were assessed from items of the short form 36 (SF-36). After the respective classification of self-reported health status and physical functioning into ‘good’, ‘moderate’, and ‘poor’, we determined the association of these categories with 6MWD by applying a generalized linear model adjusted for age and sex. Prevalence of self-reported good/moderate/poor general health and physical functioning was 41/52/7% and 45/48/7%, respectively. Mean 6MWD in the respective categories was 574 ± 70/534 ± 76/510 ± 87 m, and 574 ± 72/534 ± 73/490 ± 82 m, with significant sex-specific differences between all categories (all p < 0.001) as well as significant differences between the respective groups except for the categories ‘moderate’ and ‘poor’ health status in men. This cross-sectional analysis revealed a strong association between self-reported health status and physical functioning with the objective assessment of 6MWD, suggesting that physicians can rely on their patients’ respective answers. Nevertheless, sex-specific perception and attribution of general health and physical functioning deserve further in-depth investigation. Decision-making based on self-reported health requires prospective evaluation in population-based cohorts as well as adult inpatients.

Sixteen-Frame Gated Myocardial Perfusion SPECT as a Surrogate for Equilibrium Radionuclide Angiography in Measurement of Systolic and Diastolic Indices: A Cross-Sectional Study

Abstract Introduction Equilibrium radionuclide angiography (ERNA) has long been assumed as the preferred method to assess cardiac volumes as well as left ventricular systolic and diastolic indices. ERNA was used to diagnose subtle changes in cardiac function during chemotherapy or early stages of heart failure. Gated myocardial perfusion SPECT (GMPS) was introduced as a more feasible and versatile alternative to ERNA, but the precision of GMPS to assess systolic and diastolic indices has not yet been fully reviewed. Method We studied the left ventricular systolic and diastolic functional indices measured by a 16-frame GMPS and compared the results with those of ERNA in 25 patients. All the images were analyzed visually, semi-quantitatively, and quantitatively using quantitative gated SPECT (QGS), quantitative blood pool SPECT (QBS), and planar gated blood pool (PGBP) software. The left ventricular functional indices calculated using QGS compared with those obtained using QBS and PGBP Result Our study found a significant correlation between the left ventricular ejection fraction (LVEF) calculated using the PGBP, QGS, and QBS methods. There was a significant correlation between the LV peak ejection rate (LVPER) calculated by the PGBP and QGS analyses, and there was no significant difference in the LVPER calculated with the QGS and QBS methods. This study also revealed a significant correlation between the LV peak filling rate (LVPFR) calculated by QBS and QGS, with no significant difference between them. We also found a significant correlation between LV end systolic volume (LVESV) calculated using QGS and QBS and between LV end diastolic volume (LVEDV) calculated using QGS and QBS software. This study also revealed a significant correlation between the LV mean filling rate over the first third of diastole (LVMFR/3) calculated using the QGS and QBS software. Conclusion Considering the significant correlation between LVEF, LVPER, LVPFR, LVESV, LVMFR/3, and LVEDV calculated using the QGS and QBS methods in our study, the 16-frame GMPS could be regarded as an acceptable substitute for ERNA in the investigation of systolic and diastolic indices.