Mid-range Ejection Fraction Research Articles

Effects of Dapagliflozin on myocardial performance in non-diabetic patients with Heart failure with reduced and mid-range ejection fraction (DAPA ECHO trial)

Abstract Background Sodium-glucose cotransporter type-2 inhibitors (SGLT2i) showed to reduced morbidity andmortality in HF patients. The aim of this study was to assess potential effects of dapagliflozin in non-diabetic patients with heart failure (HF) with reduced and mildly reduced ejection fraction (HFrEF and HFmrEF) on cardiac function assessed by speckle tracking echocardiography (STE). Methods This randomized, prospective, single-center, open-label trial compared consecutive non-diabetic outpatients with HFrEF or HFmrEF receiving dapagliflozin with patients treated with optimal medical therapy (OMT) except SGLT2i (Fig.1). Primary endpoint was the modification of left ventricular (LV) global longitudinal strain (GLS), diastolic function (as peak atrial longitudinal strain, PALS) and right ventricular (RV) function by STE from baseline to 6 months. Cardiovascular events and parameters of congestion were assessed as safety-exploratory endpoints. Results Overall, 88 patients (38% HFmrEF) were enrolled and randomized to start dapagliflozin on top of OMT (n=44) or to continue with OMT (n=44). All STE values improved in dapagliflozin group after 6 months, while there was a non-significant improvement in OMT group (Fig.1). Moreover, when comparing the modification of STE parameters at follow up in HFrEF and HFmrEF patients, only the main treatment effect resulted statistically significant in both groups (p<0.0001), indicating a significant difference between dapagliflozin and OMT. Conclusions This study provided randomized data on the beneficial effect of dapagliflozin in non-diabetic patients with HFrEF and HFmrEF in terms of myocardial performance measured by the most sensitive echocardiographic technique i.e. STE. This suggests its usefulness for LV reverse remodeling and better quality of life in patients with HFrEF and HFmrEF.

Automated digital counselling promotes therapeutic change in mental health in patients with chronic heart failure or chronic kidney disease: ODYSSEE-vCHAT study

Abstract Background The efficacy of digital programs to improve the management of chronic heart failure (CHF) and chronic kidney disease (CKD) is not established. Building on related studies in digital health, behavioural counselling, and social support, we evaluated whether an automated digital counselling program with social network support (ODYSSEE-vCHAT) could improve mental health and health-related quality of life in patients with CHF or CKD. Purpose The primary objective was to examine whether engagement with ODYSSEE-vCHAT was associated with a minimal clinically important difference for improvement in the Mental Component Summary (MCS) of the SF-36 at end-of-study. Secondary outcomes included: ENRICHD Social Support Index (ESSI), Patient Health Questionnaire for Depression (PHQ-9) Godin-Shephard Leisure Time Physical Activity Scale (GSLTPAQ), and an index of the frequency to which patients engaged in goal-directed activities for living well (EUROIA). Methods ODYSSEE-vCHAT was a multi-centre, single group, open label study with assessments at baseline and end-of-study (approximately 11 months). Inclusion criteria were: ≥18 years of age, diagnosis of CHF (reduced ejection fraction (EF) ≤ 40%, mid-range EF, 41-49%, or preserved EF ≥ 50%); or CKD diagnosis (>10% risk for dialysis using the 4-variable, 2-year Kidney Failure Risk Equation, or on dialysis). Exclusion was based on inability to participate due to co-morbidities. The digital counselling protocol taught self-care skills to improve mental health, quality of life, and adherence to medications, exercise, diet, and smoke-free living (Figure 1). Patient engagement with ODYSSEE-vCHAT was defined as Not Engaged (0 logon minutes) vs. Engaged (> 0 logon minutes). The primary outcome was a minimal clinically important difference for MCS change: ΔMCS ≥ 3.8 or MCS ≥ 65 at baseline and study endpoint. It was assessed using multivariable binary logistic regression, controlling for exposure to COVID-19 and health literacy. Secondary outcomes were assessed using multivariable linear regression analyses with the same covariates. Results 215 patients were enrolled. There were 7 deaths and 34 withdrew. In our sample of 174 patients, mean age = 54.4 years (95% Confidence Interval, CI, 25, 81), gender identity as women, n = 68 (39%), ethno-racial group other than White, n = 83, (48%), primary diagnosis, CHF, n = 68 (39%), and CKD, n = 106 (61%). Duration of enrolment to end-of-study: median = 352 days, (95% CI, 159, 496). Engagement with ODYSSEE was associated with therapeutic change on the MCS (for both CHF and CKD patients, and CHF patients alone), GSLTPAQ, and EUROIA, but not the PHQ9 or ESSI (Figure 2). Conclusions Automated digital counselling with social network support promotes improvement in indices of mental health for patients with CHF and CKD. These findings support a follow-up randomized controlled trial.Figure 1.ODYSSEE-vCHAT Study ProtocolFiFigure 2.ODYSSEE-vCHAT Study Outcomes

Diagnostic and prognostic value of microRNA423-5p in patients with heart failure

ObjectivesMicroRNAs are considered as a class of potential biomarkers for HF. This study aimed to retrospectively evaluate the diagnostic and prognostic value of microRNA423-5p in patients with HF.MethodsThe observational group comprised 98 patients diagnosed with HF due to coronary atherosclerotic heart disease (n = 45), hypertension (n = 26), or cardiac valve insufficiency (n = 27). Conversely, the control group consisted of 30 healthy volunteers without any history of HF. These patients were further classified into heart function class II (n = 33), class III (n = 32), and class IV (n = 33) according to the NYHA classification. Of these patients, 33 were diagnosed with HF with mid-range ejection fraction (HFmrEF) and the remaining 65 with HF with reduced ejection fraction (HFrEF). The diagnostic and prognostic significance of microRNA423-5p in patients with HF was assessed through laboratory parameter assessments (microRNA423-5p and B-type natriuretic peptide test, BNP), cardiac ultrasound evaluations (left ventricular ejection fraction, LVEF), and subsequent follow-up assessments.ResultsIn this study, we found that patients with HF exhibited notably elevated levels of microRNA423-5p and BNP, as well as significantly lower LVEF values. A significant positive correlation between microRNA423-5p and BNP indicators was validated. In addition, our study also revealed an elevation in the level of microRNA423-5p correlating with the progression of the HF. The combined evaluation of LEVF, BNP, and microRNA423-5p demonstrated superior diagnostic efficacy in comparison to the solitary use of BNP.ConclusionsElevated levels of microRNA423-5p in the serum of patients with HF suggest its potential utility as a novel biomarker for both the diagnosis and prognosis of this condition.

Myocardial mechanical function measured by cardiac magnetic resonance in patients with heart failure

AimStrain analysis offers a valuable tool to assess myocardial mechanics, allowing for the detection of impairments in heart function. This study aims to evaluate the pattern of myocardial strain in patients with heart failure (HF). MethodsIn the present study, myocardial strain was measured by cardiac magnetic resonance imaging feature tracking in 35 control subjects without HF and 195 HF patients. The HF patients were further categorized as HF with preserved ejection fraction (HFpEF, n=80), with mid-range ejection fraction (HFmrEF, n=34), and with reduced ejection fraction (HFrEF, n=81). Additionally, quantitative tissue evaluation parameters, including native T1 relaxation time and extracellular volume (ECV), were examined. ResultsCompared to controls, patients in all HF groups (HFpEF, HFmrEF, and HFrEF) demonstrated impaired left ventricular (LV) strains and systolic and diastolic strain rates in all three directions (radial, circumferential, and longitudinal) (p < 0.05 for all). LV strains also showed significant correlations with left ventricular ejection fraction and brain natriuretic peptide levels (p < 0.001 for all). Notably, septal contraction was significantly affected in HFpEF compared to controls. While LV torsion was slightly increased in HFpEF, it was decreased in HFrEF. Native T1 relaxation times and ECV fractions were significantly higher in HFrEF compared to HFpEF (p < 0.05). Overall, myocardial strain parameters demonstrated good performance in differentiating HF categories. ConclusionsThe myocardial strain impairments exhibit a spectrum of severity in patients with HFpEF, HFmrEF, and HFrEF compared to controls. Assessment of myocardial mechanics using strain analysis may offer a clinically useful tool for monitoring the progression of systolic and diastolic dysfunction in HF patients.

How the Crystal Ball Helps to Beat Ejection Fraction as Predictor of Mortality After Myocardial Infarction.

Ejection fraction (EF) is an incomplete metric and requires consideration of an associated companion (EFC) metric. This figure is based on 96 cardiac patients, including those with acute myocardial infarction (MI). For mid-range EF (with values ranging from 40% to 50%) the brown-colored area indicates the distribution of the EFC for these patients. Only the combination of EF and EFC can define the unique location of each patient. Likewise, data points are spread for any other EF range, for example, those with 55<EF<60% (see yellow area). Volume data obtained by cardiac magnetic resonance imaging (courtesy of Prof. R. A. Diaz-Navarro).

Cardiomyopathy-Associated Chronic HeartFailure in Infants Aged

There have been few large-scale studies on the outcomes of cardiomyopathy-associated heart failure (HF) in infants aged <1 year. This study aimed to assess longitudinal echocardiographic outcomes of infants with HF secondary to cardiomyopathy who survived for >1 year. A prospective observational study following 327 infant patients up to 5 years in 2 large pediatric heart centers in Northern China between January 2010 and December 2018. A total of 236 (72.2%) patients had reduced left ventricular ejection fraction (LVEF) (HF with reduced ejection fraction group; LVEF <40%), 91 (27.8%) patients had midrange LVEF (HF with midrange ejection fraction group; LVEF ≥40% but <55%). LVEF improved significantly within the first year and remained stable in years 2 through 5 for both groups. The HF with midrange ejection fraction group had a higher rate of LVEF normalization (hazard ratio, 1.65; P<0.001). Baseline LVEF ≥40%, baseline left ventricular end-diastolic diameter Z score <7.8, the absence of left bundle-branch block, and the absence of β-blocker use were 4 independent favorable predictors for future LVEF normalization. A total of 62.4% of enrolled patients were diagnosed with left ventricular noncompaction. No significant difference in LVEF normalization was found among the different types of cardiomyopathy studied. A significant number of infants with cardiomyopathy who survived >1 year were found to improve with medical therapies during the first year of diagnosis. Poorer outcomes were associated with decreased LVEF and increased heart size at diagnosis baseline, the presence of left bundle-branch block and use of β blockers. The Northern Chinese pediatric population may have a high proportion of left ventricular noncompaction.

Clinical outcomes of conduction system pacing compared to biventricular pacing in patients with mid-range ejection fraction.

There is a paucity of data comparing conduction system pacing (CSP) to biventricular pacing (BiVP) in patients with heart failure (HF) with mid-range left ventricular ejection fraction (LVEF). Compare the clinical outcomes of patients with mid-range LVEF undergoing CSP versus BiVP. Patients with mid-range LVEF (> 35 to 50%) undergoing CSP or BiVP were retrospectively identified. Lead performance, LVEF, HF hospitalization, and clinical composite outcome including upgrade to cardiac resynchronization therapy and mortality were compared. A total of 36 patients (20 BiVP, 16 CSP--14 His bundle pacing, 4 left bundle branch area pacing) were analyzed. The mean age was 73 ± 15, 44% were female, and the mean LVEF was 42 ± 5%. Procedural and fluoroscopy time was comparable between the two groups. QRS duration was significantly shorter for the CSP group compared to the BiVP group (P < 0.001). During a mean follow-up of 47 ± 36months, nosignificant differences were found in thresholds or need for generator change due to early battery depletion. LVEF improved in both groups (41.5 ± 4.5% to 53.9 ± 10.9% BiVP, P < 0.001; 41.6 ± 5.3% to 52.5 ± 8.3% CSP, P < 0.001). There were no significant differences in HF hospitalizations (P = 0.71) or clinical composite outcomes (P = 0.07). Among patients with HF with moderately reduced ejection fraction, CSP appears associated with similar improvements in LVEF and had similar clinical outcomes as BiVP in mid-term follow-up.

Clinical Characteristics and Long-Term Outcomes of Patients With Heart Failure With Mid-Range Ejection Fraction: Insights From a Prospective Cohort Study

Clinical Characteristics and Long-Term Outcomes of Patients With Heart Failure With Mid-Range Ejection Fraction: Insights From a Prospective Cohort Study

Outcomes of Left Bundle Branch Area Pacing in Heart Failure With Mid-Range Ejection Fraction in Comparison to Right Ventricular Pacing

Outcomes of Left Bundle Branch Area Pacing in Heart Failure With Mid-Range Ejection Fraction in Comparison to Right Ventricular Pacing

Comprehensive review of the heart failure management guidelines presented by the American College of Cardiology and the current supporting evidence.

Heart failure (HF) is a chronic condition that affects the heart's functional capacity, resulting in symptoms such as fatigue, edema, and dyspnea. It affects millions of adults in the United States and presents challenges in optimizing treatment and coordinating care among clinicians. Additionally, the various classifications for HF and limited research on treatment outcomes in heart failure with midrange ejection fraction (HFmrEF) and heart failure with preserved ejection fraction (HFpEF) further complicate the pharmacological management of patients with this disease. The objectives of this article are to review the pharmacotherapy guidelines for HF provided by the American College of Cardiology (ACC) and offer an update on the current trials conducted on these agents. The paper includes a post hoc analysis of established randomized controlled trials (RCTs), current RCTs, analysis of HF registries, and the guidelines published by the ACC. The gathering of research began in June 2023 and completed in August 2023. PubMed was utilized with the following search items: "treatment for HFrEF" (heart failure with reduced ejection fraction), "treatment for HFmrEF," and "treatment for HFpEF." The screening process was completed by one author. The automation tools utilized were "clinical trials," "randomized control trials," and "five years". Meta-analyses, systematic reviews, and case reports were excluded from the screening process. This review does not include research regarding medical devices, interventional therapies, and lifestyle modifications. Finally, research regarding additional comorbidities, nonpharmacological focused research, and agents not recommended by the ACC are not included in this paper. The search began with 6,561 records identified from PubMed, with 407 records screened after automation tools were utilized to filter for "clinical trials," "randomized control trials," "one year," and "five years". A total of 22 duplicates were reviewed, 318 were sought for screening after trials from 2019 were removed, and 31 studies were ultimately included in the review. A detailed summary of the most recent recommendations by the ACC are provided. The discussion includes indications, mechanisms of action, side effects, and contraindications for the selected agents. Additionally, recent clinical trials are included to provide evidence on the efficacy of the recommended classes of drugs. The current guidelines for managing HFrEF have been consistent, but there is limited consensus on treating HFmrEF and HFpEF. Large RCTs have provided compelling evidence supporting the use of the recommended pharmacological agents. However, despite the new effective treatment protocols, slow clinical inertia and underoptimization of HF management persist. Thus, it is crucial to synchronize care among clinicians involved in managing patients with this disease.

Sacubitril with valsartan, a modern pharmacotherapy in heart failure - a literature review

Introduction and purpose: Heart failure is one of the most common cardiovascular diseases worldwide. It is an important factor leading to a reduced, health-related quality of life (HRQoL) not only because of its various symptoms but also due to loss of jobs or increase in medical expenses impairing the socioeconomic status of the sick. Nowadays scientists face this problem and are trying to invent specific pharmacotherapy that allows it to extend life and improve its quality. One of the elements of modern pharmacotherapy is the combination of sacubitril with valsartan. This work aims to evaluate the effect of this drug on the length and quality of life of patients with heart failure.Materials and methods: This article is a literature review based on publications from PubMed, Cochrane Library, ClinicalKey released since 2014, keywords included: sacubitril/valsartan; angiotensin receptor–neprilysin inhibitor; ARNI; heart failure.The state of knowledge: The use of sacubitril/valsartan drugs is an established agent used to reduce the risk of death from any cause in all patients with heart failure with reduced ejection fraction, death from cardiovascular causes and the rate of hospitalization due to exacerbation of symptoms. Some study analyses also indicate the utility of using sacubitril/valsartan in HFmrEF and HFpEF to reduce the rate of cardiovascular events and hospitalization because of heart failure.Conclusions: The use of sacubitril/valsartan is recognized to improve prognosis in patients with HFrEF. Evidence supporting its efficacy in the subgroup of patients with mid-range and preserved ejection fraction is still insufficient and requires further investigation.

Prevalence and Risk Factors of Heart Failure with Preserved Ejection Fraction in Middle-Aged Maintenance Haemodialysis Patients on a Twice-Weekly Schedule: Experience from a Single Indian Centre.

Background. Data on the prevalence of cardiac failure with preserved ejection in the haemodialysis population, which impacts treatment strategy, mortality, and morbidity, are scarce. Aims and Objectives. Estimate the prevalence of heart failure with preserved ejection fraction (HFpEF) in haemodialysis patients Classify cardiac failure and ascertain the risk factors influencing HFpEF in haemodialysis patients. Methods. All consenting individuals on haemodialysis over 18 years of age were included. Lung ultrasound was performed as per the LUST study protocol, and the labs were documented. Echocardiographic parameters were measured using two-dimensional (2D ECHO). Results. A total of 102 patients consented to participate in the study, which included 63 males (61.8%) and 39 females (38.2%). The mean patient age was 53 ± 13.1 years. The dialysis vintage of the participants was 38.92 ± 6.947 months. 47 (46.1%) patients had diabetes and 88 (80.4%) had hypertension. ECG findings included sinus rhythm (51/102, 50%), sinus tachycardia (22/102, 21.6%), ST-T wave abnormalities (18/102, 17.6%), and atrial fibrillation (11/102, 10.8%). Heart failure with preserved ejection fraction (HFpEF) was present in 44/102 (43.14%), heart failure with mid-range EF in 14/102 (13.72%), and heart failure with reduced EF in 13/102 (12.7%) patients. The ejection fraction was positively associated with haemoglobin (r = 0.23; p = 0.044), and calcium levels (r = 0.25; p =0 .03). E/lateral e' ratio was positively correlated with NT pro-BNP (r = 0.63; p < 0.001), systolic blood pressure (r = 0.44; p = 0.003) and age (r = 0.353; p = 0.003) and negatively correlated with transferrin saturation (r = -0.353; p = 0.027) and diastolic blood pressure (r = -0.31; p = 0.040). Binary logistic regression analysis revealed that the odds of diastolic dysfunction increased by 2.3 times with each unit increase of creatinine, and diabetics have 7.66 times higher risk for diastolic dysfunction. Binary logistic regression involving ejection fraction (EF) and all laboratory and clinical parameters revealed odds of HFpEF increased by 1.93 times with each unit increase in age, odds of HFpEF increases by 1.53 times with each unit increase in phosphorous and odds of HFpEF increased by 1.1 times with a unit increase of systolic blood pressure. Conclusion. HFpEF is the predominant form of heart failure in haemodialysis patients. Haemoglobin and calcium were positively associated with ejection fraction. Advancing age, elevated creatinine and diabetes mellitus levels are independent predictors of diastolic dysfunction in haemodialysis patients.

Clinical Characteristics and Segmental Qualities of Young Patients with Heart Failure in a Tertiary Care Centre

Background: The prevalence and hospitalizations of patients with heart failure aged &lt;55 years have increased. The study aims to evaluate the clinical traits and segmental qualities of young patients experiencing heart failure at a tertiary care center. Methods: This cross-sectional study design enrolled 83 individuals who had recently developed heart failure at a young age. The study encompassed individuals aged 18 to 55 years, from whom clinical indicators and potential risk elements were obtained followed by 2D transthoracic echocardiography performed as part of the routine assessment. Results: The study comprised of 83. The participants with a mean age of 51.5 ± 4.0 years. A significant proportion of the individuals were noted to have diabetes (65%), while 74.7% were identified with hypertension. A statistically significant association was noted between patients who had a prior history of Ischemic heart disease (IHD) and their probability of developing Heart failure (HF) (p-value = 0.02). The primary and the most prevalent cause of heart failure among these study participants was dilated cardiomyopathy. Patients with reduced Ejection fraction (EF) had a notably higher occurrence (68%) compared to mid-range EF (14%) and preserved EF (23%). Conclusion: The study comprised of involved individuals those belonging to the age group between 45-55 years, exhibited higher rates of hypertension and diabetes. Heart Failure with reduced Ejection Fraction (HFrEF) was dominant, wherein dilated cardiomyopathy invariably being the most common cause of heart failure in younger patients. Notably, a significant portion of these individuals had a past history of IHD, which contributed a substantial role in the development of HF

Sex differences in clinical characteristics and long-term clinical outcomes in Asian hospitalized heart failure patients.

Sex differences in long-term post-discharge clinical outcomes in Asian patients hospitalized for acute decompensated heart failure (HF) persist despite the world-wide implementation of guideline-directed medical therapy for decades. The present study aims to elucidate the puzzling dilemma and to depict the directions of solution. Between 2011 and 2020, a total of 12428 patients (6518 men and 5910 women, mean age 73.50±14.85) hospitalized for acute decompensated HF were retrospectively enrolled from a university HF cohort. Compared with men, women hospitalized for acute decompensated HF were older in age (76.40±13.43 vs. 71.20±15.67years old, P<0.0001) with more coexisting hypertension, diabetes, hyperlipidaemia and moderate to severe chronic kidney disease, but less with ischaemic heart disease, cerebrovascular disease and chronic obstructive pulmonary disease (P<0.0001). In echocardiography measurement parameters, women had smaller left ventricular and left atrial dimensions, higher left ventricular mass index, higher left ventricular ejection fraction (LVEF) and more in HF with preserved ejection fraction (EF) category (LVEF>50%) than men (P<0.0001). In HF therapy, women compared with men received more guideline-directed medical HF therapies including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, angiotensin receptor-neprilysin inhibitors and sodium-glucose cotransporter-2 inhibitors, but similar beta-blockers and mineralocorticoid receptor antagonists (P<0.0001). Post-discharge long-term clinical outcomes after multivariate-adjusted analysis revealed that women compared with men had lower all-cause mortality [adjusted hazard ratio (aHR): 0.89, 95% confidence interval (CI): 0.84-0.93], lower cardiovascular mortality (aHR: 0.89, 95% CI: 0.80-0.99) and lower 1year mortality (aHR: 0.91, 95% CI: 0.84-0.99) but similar HF rehospitalization rate (aHR: 1.02, 95% CI: 0.95-1.09) over 8years of follow-up. The superiority of women over men in all-cause mortality was shown in HF with preserved EF (>50%) and HF with mildly reduced EF (40%-50%), but not in HF with reduced EF (<40%) category. Subgroup forest plot analysis showed body mass index, coexisting hypertension and chronic obstructive pulmonary disease as significant interacting factors. With more coronary risk factors and medical comorbidities, less cardiac remodelling and better adherence to guideline-directed HF therapy, women hospitalized for acute decompensated HF demonstrated superiority over men in long-term post-discharge clinical outcomes, including all-cause mortality, cardiovascular mortality and 1year mortality, and mainly in HF with preserved and mid-range EF categories, in the Asian HF cohort.

Machine learning in heart failure diagnosis, prediction, and prognosis: review

Globally, cardiovascular diseases take the lives of over 17 million people each year, mostly through myocardial infarction, or MI, and heart failure (HF). This comprehensive literature review examines various aspects related to the diagnosis, prediction, and prognosis of HF in the context of machine learning (ML). The review covers an array of topics, including the diagnosis of HF with preserved ejection fraction (HFpEF) and the identification of high-risk patients with HF with reduced ejection fraction (HFrEF). The prediction of mortality in different HF populations using different ML approaches is explored, encompassing patients in the ICU, and HFpEF patients using biomarkers and gene expression. The review also delves into the prediction of mortality and hospitalization rates in HF patients with mid-range ejection fraction (HFmrEF) using ML methods. The findings highlight the significance of a multidimensional approach that encompasses clinical evaluation, laboratory assessments, and comprehensive research to improve our understanding and management of HF. Promising predictive models incorporating biomarkers, gene expression, and consideration of epigenetics demonstrate potential in estimating mortality and identifying high-risk HFpEF patients. This literature review serves as a valuable resource for researchers, clinicians, and healthcare professionals seeking a comprehensive and updated understanding of the role of ML diagnosis, prediction, and prognosis of HF across different subtypes and patient populations.

The role of pyroptosis in heart failure and related traditional chinese medicine treatments.

Pyroptosis is a type of programmed cell death that is mediated by both typical and atypical pathways and ultimately leads to the lysis and rupture of cell membranes and the release of proinflammatory factors, triggering an intense inflammatory response. Heart failure (HF) is a serious and terminal stage of various heart diseases. Myocardial hypertrophy, myocardial fibrosis, ventricular remodeling, oxidative stress, the inflammatory response and cardiomyocyte ionic disorders caused by various cardiac diseases are all risk factors for and aggravate HF. Numerous studies have shown that pyroptosis can induce and exacerbate these reactions, causing progression to HF. Therefore, targeting pyroptosis is a promising strategy to treat HF. This paper summarizes the role of pyroptosis in the development of HF and the underlying mechanism involved. Recent research progress on the ability of traditional Chinese medicine (TCM) extracts and formulas to inhibit pyroptosis and treat HF was summarized, and some traditional Chinese medicine extracts and formulas can alleviate different types of HF, including heart failure with preserved ejection fraction (HFpEF), heart failure with reduced ejection fraction (HFrEF), and heart failure with midrange ejection fraction (HFmrEF), by targeting pyroptosis. These findings may provide new ideas and evidence for the treatment or adjuvant treatment of HF by targeting pyroptosis.

#2970 Heart failure with preserved ejection fraction on chronic kidney patients: innocent bystander? A cohort study in Portuguese population

Abstract Background and Aims Heart failure (HF) consists in a significant public health challenge, with high prevalence worldwide and a substantial impact on morbidity and mortality. In chronic kidney disease (CKD), HF can act both as a risk factor and a complication, exacerbating the overall outcomes for affected individuals. This study aims to elucidate the prevalence of distinct types of heart failure, encompassing preserved ejection fraction (HFpEF), mid-range ejection fraction (HFmrEF), and reduced ejection fraction (HFrEF) in CKD patients. Moreover, we purpose to identify the potential of these subtypes to influence the outcomes of mortality and start of kidney replacement therapy (KRT), as a different therapeutic approach is suitable for each. Method Observational retrospective cohort study of 3008 CKD patients, with follow-up in Nephrology out-patient clinic in a Portuguese hospital, from February, 2012 to October, 2019. Ejection fraction was accessed by echocardiogram and information was collected from health records. To access mortality, patients who started KRT along the study were excluded. Results A total of 3008 patients, of which 91.7% Caucasians and 54.5% males, with an average age of 68.2 (±15.9) years was enrolled in the study. The mean follow-up time was 3.21 (±1.97) years and the mean estimated glomerular filtration rate at baseline was 47.63 ± 33.1 ml/min/1.73 m2. Among the participants, 769 individuals (25.5%) were diagnosed with HF. Specifically, 319 patients (41.5%) exhibited HFpEF; 85 patients (11%) had HFmrEF, and 117 patients (15.2%) had HFrEF, while the ejection fraction (EF) was unknown in 32.2% of cases. In the HF group, the incidence of diabetes was 55.6%, compared to 37.5% in the non-HF group. As for hypertension, the prevalence of was 91.8% in the HF group and 78.6% in the non-HF group. When assessing all-cause mortality during the follow-up, the hazard ratio (HR) for the HF group was 3.54 (95% CI, 2.94-4.26) compared to the non-HF group. Furthermore, for the initiation of KRT, the HR was 1.57 (95% CI, 1.19-2.06), favoring patients without heart failure. Across different types of HF, in comparison to the group without HF, the hazard ratio during follow up were notably different. Specifically, the HR was 5.39 (95% CI, 3.66-7.94) for patients with HFrEF, 3.43 (95% CI, 2.18-5.40) for patients with HFmrEF and 2.99 (95% CI, 2.32-3.87) for the HFpEF. When assessing the initiation of kidney replacement therapy (KRT), HFrEF and HFpEF also exhibited statistically different data comparing to those without HF. Specifically, HFrEF showed a HR of 2.14 (95%, 1.27-3.63), while HFpEF had a HR of 1.79 (95%, 1.25-2.56). The Kaplan-Meier analysis demonstrated a steeper descent curve for both survival and start of KRT for the HF group compared to the non-HF group (log-rank p &amp;lt; 0.0001) over the study period. Within the HF group, the worst survival outcomes were observed in the HFrEF subgroup, followed by HFmrEF and HFpEF (log-rank p &amp;lt; 0.0001). Conclusion Heart failure is a prevalent condition in CKD patients and worsens outcomes. Our analysis of real-world data suggests a threefold higher risk of mortality among for patients with HF, and a fivefold increase in the subgroup of HFrEF, comparing to patients without HF. Notably, preserved EF yielded a HR of 3.3 for mortality when compared to those without heart failure, underscoring the importance of clinical accurate assessment, since both entities may present with preserved ejection fraction in echocardiogram. Despite the study's sample limitations and the fact that it is unicentric, we believe this work holds significance as it highlights the importance of the establishment of different degrees of HF as it can change the prognosis in terms of mortality and progression to kidney replacement therapy in CKD patients. In addition to the established association between reduced EF and mortality, the HFpEF showed to exert a notable influence on outcomes comparing to patients without HF. This emphasizes the importance of not neglecting this entity, as it should treated appropriately.

The impact of atrial fibrillation on clinical outcomes in heart failure with mid-range and preserved ejection fraction patients

BackgroundThe combined effect of left ventricular ejection fraction (LVEF) and atrial fibrillation (AF) on clinical outcomes in heart failure (HF) remains complex. ObjectiveIn this post hoc analysis of the TOPCAT trial, we aimed to evaluate the impact of AF on clinical outcomes in patients with HF stratified by LVEF range. MethodsA total of 3442 patients were included, stratified into 3 groups according to LVEF range—HF with mid-range ejection fraction (HFmrEF), LVEF of 45%–50% (n = 823); HF with preserved ejection fraction (HFpEF), LVEF of 51%–60% (n = 1682); and HF with normal ejection fraction (HFnEF), LVEF >60% (n = 937)—and subdivided according to the presence of AF at enrollment. Cox regression analysis was used to define independent associations between AF and clinical outcomes. ResultsAF was prevalent in 38.6% in HFmrEF, 34.6% in HFpEF, and 33.7% in HFnEF (P = .07). AF was associated with worse primary outcome in each subgroup and with HF hospitalizations and worse cardiovascular mortality in HFpEF and HFnEF. The hazard ratio for the primary outcome in those with AF compared with sinus rhythm (SR) was 1.11 (1.01–1.22; P = .03) in HFmrEF, 1.20 (1.11–1.29; P < .001) in HFpEF, and 1.16 (1.05–1.28; P = .004) in HFnEF. When LVEF was treated as a continuous variable, there was a linear negative association between LVEF and the effect of AF vs SR for the primary end point and HF hospitalizations and a linear positive association for cardiovascular mortality. ConclusionCompared with SR, AF was independently associated with worse outcomes across all LVEF ranges.

Prognostic value of growth differentiation factor-15 in heart failure among whole ejection fraction phenotypes.

The utility of growth differentiation factor-15 (GDF-15) in predicting long-term adverse outcomes in heart failure (HF) patients is not well established. This study explored the relationship between GDF-15 levels and adverse outcomes in HF patients across various ejection fraction (EF) phenotypes associated with coronary heart disease (CHD) and evaluated the added prognostic value of incorporating GDF-15 into the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) risk score-based model. This single-centre cohort study included 823 HF patients, categorized into 230 (27.9%) reduced EF (HFrEF), 271 (32.9%) mid-range EF (HFmrEF), and 322 (39.1%) preserved EF (HFpEF) groups. The median age was 68.0years (range: 56.0-77.0), and 245 (29.8%) were females. Compared with the HFrEF and HFmrEF groups, the HFpEF group had a higher GDF-15 concentration (P=0.002) and a higher MAGGIC risk score (P<0.001). We examined the associations between GDF-15 levels and the risks of all-cause mortality and HF rehospitalization using Cox regression models. The C-index, integrated discrimination improvement (IDI), and net reclassification improvement (NRI) metrics were employed to assess the incremental prognostic value. During the 9.4year follow-up period, 425 patients died, and 484 were rehospitalized due to HF. Multivariate Cox regression analysis revealed that elevated GDF-15 levels were significantly associated with an increased risk of all-cause mortality [hazard ratio (HR)=1.36, 95% confidence interval (CI): 1.20-1.54; P<0.001] and HF rehospitalization (HR=1.75, 95% CI: 1.57-1.95; P<0.001) across all HF phenotypes. This association remained significant when GDF-15 was treated as a categorical variable (high GDF-15 group: all-cause death: HR=1.73, 95% CI: 1.40-2.14; P<0.001; HF rehospitalization: HR=3.37, 95% CI: 2.73-4.15; P<0.001). Inclusion of GDF-15 in the MAGGIC risk score-based model provided additional prognostic value for all HF patients (Δ C-index=0.021, 95% CI: 0.002-0.041; IDI=0.011, 95% CI: 0.001-0.025; continuous NRI=0.489, 95% CI: 0.174-0.629) and HF rehospitalization (Δ C-index=0.034, 95% CI: 0.005-0.063; IDI=0.021, 95% CI: 0.007-0.032; continuous NRI=0.307, 95% CI: 0.147-0.548), particularly in the HFpEF subgroup. GDF-15 is identified as an independent risk factor for adverse outcomes in HF patients across the entire EF spectrum in the context of CHD. Integrating GDF-15 into the MAGGIC risk score-based model enhances its prognostic capability for adverse outcomes in the general HF population. This incremental prognostic effect was observed specifically in the HFpEF subgroup and not in other subgroups.

Evaluation of Perfusion and Function in Cardiac Radionuclide Imaging in Cases of Heart Failure with Mid-Range Ejection Fraction

Objective: Heart failure with mid-range ejection fraction (HFmrEF) poses a significant clinical challenge due to its diverse etiology and variable prognosis. Patients with HFmrEF exhibit an intermediate level of left ventricular dysfunction, making their management and prognosis less well-defined compared to those with heart failure with reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF). Coronary artery disease (CAD) is a common underlying cause of HFmrEF and can further exacerbate myocardial dysfunction under stress conditions. In this study, we aimed to evaluate the change in left ventricular ejection fraction with stress in the presence of coronary artery disease in cases of heart failure with mid-range ejection fraction. Material and Methods: In this retrospective study, we included 507 patients diagnosed with coronary artery disease and an left ventricular ejection fraction (LVEF) of 41-49% measured by echocardiography. All patients underwent a treadmill exercise test using the Bruce protocol, with progressively increasing speed and incline. Myocardial perfusion was assessed using stress gated myocardial perfusion scintigraphy (MPS), and fixed and reversible defects were identified in cases of coronary artery disease. Cardiac scintigraphic images were acquired from the right anterior oblique to the left posterior oblique. We calculated post-stress LVEF and the percentage decrease in LVEF to evaluate cardiac function. Results: Resting LVEF was measured as 46 (43-50), while post-stress LVEF was 35 (25-47) in all patients. Myocardial perfusion was evaluated using stress gated MPS in all patients, with 200 (39.5%) patients showing both fixed and reversible perfusion defects. The rate of decrease in LVEF due to stress was significantly higher in patients with reversible perfusion defects (15.90 (6-30.43) vs. 28.26 (24-43.18), p: 0.0005). Post-stress LVEF was lower in patients with reversible perfusion defects (40 (31-47) vs. 33 (25-38), p: 0.0005). Conclusion: In cases of impaired left ventricular perfusion, quantitative calculations of LVEF may vary, and their reliability may decrease as the ejection fraction decreases under stress conditions. Clinicians should consider this variability in the follow-up of patients with heart failure and mid-range ejection fraction.