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BACKGROUND: Heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF) are challenging conditions to treat due to complex pathophysiology and associated comorbidities. However, recent trials have demonstrated improved outcomes with guideline-directed medical therapy (GDMT) for each subtype of heart failure. OBJECTIVE: We investigated the relationship of determinants of health and risk factors with GDMT use for HFrEF and HFpEF in a large, diverse US cohort. METHODS: Using the NIH-sponsored All of Us Program, we compared demographics, risk factors (e.g., hypertension, diabetes, smoking), and SDOH measures between HFrEF and HFpEF in US adults aged 18 years and older. We examined the proportions of HFrEF patients receiving fewer than four or all four GDMTs. HFpEF patients receiving two medications were compared with those receiving less than two recommended medications. Multiple logistic regression was used for data analysis. RESULT: Of 6049 HFrEF patients, 5838 (97 %) received fewer than four GDMTs, and 210 (3 %) received quadruple therapy. Of 3774 HFpEF patients, 162 (4 %) were on 2/3 GDMT, and only 38 (1 %) were on all three recommended medications. Patients with ASCVD and diabetes had higher odds of being on more than half of the recommended GDMT for both HFrEF and HFpEF. Additionally, females had higher odds of being on 2/3 GDMT for HFpEF (1.46 [1.08, 2.00]). Race, income, education, and health insurance types did not predict GDMT optimization. CONCLUSION: HFrEF and HFpEF GDMT remain underutilized. Future efforts to address comorbidities and system-wide healthcare interventions may improve heart failure GDMT.

Heart failure with improved ejection fraction (HFimpEF) has better outcomes than HF with reduced EF (HFrEF). However, factors contributing to HFimpEF remain unclear. This study aimed to evaluate clinical and longitudinal characteristics associated with subsequent HFimpEF. This was a single-center retrospective HFrEF cohort study. Data were collected from 2014 to 2022. Patients with HFrEF were identified using International Classification of Diseases codes, echocardiographic data, and natriuretic peptide levels. The main end points were HFimpEF (defined as EF >40% at ≥3 months with ≥10% increase) and mortality. Cox proportional hazards and mixed effects models were used for analyses. The study included 1,307 patients with HFrEF with a median follow-up of 16.3 months (interquartile range 8.0 to 30.6). The median age was 65 years; 68% were male whereas 57% were White. On follow-up, 38.7% (n = 506) developed HFimpEF, whereas 61.3% (n = 801) had persistent HFrEF. A multivariate Cox regression model identified gender, race, co-morbidities, echocardiographic, and natriuretic peptide as significant covariates of HFimpEF (p

Sodium-glucose cotransporter 2 inhibitors were shown to reduce morbidity and mortality in patients with heart failure. This study aims to assess potential effects of dapagliflozin in nondiabetic patients with heart failure with reduced ejection fraction (HFrEF) and heart failure with mildly reduced ejection fraction (HFmrEF) on cardiac function assessed by speckle tracking echocardiography (STE). This randomized, prospective, single-center, open-label trial compared consecutive nondiabetic outpatients with HFrEF or HFmrEF receiving dapagliflozin with patients treated with optimal medical therapy (OMT) except sodium-glucose cotransporter type 2 inhibitors. Primary endpoint was the presence of a significant modification of left ventricular global longitudinal strain, diastolic function (as peak atrial longitudinal strain) and right ventricular function by STE from baseline to 6 months. Cardiovascular events and parameters of congestion were assessed as safety-exploratory endpoints. 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 the dapagliflozin group after 6 months, whereas there was a nonsignificant improvement in OMT group. Moreover, when comparing the modification of STE parameters at follow-up in patients with HFrEF and HFmrEF, only the main treatment effect resulted statistically significant in both groups (P < 0.0001), indicating a significant difference between dapagliflozin and OMT. This study provided randomized data on the beneficial effect of dapagliflozin in nondiabetic patients with HFrEF and HFmrEF in terms of myocardial performance measured by the most sensitive echocardiographic technique, ie, STE. This suggests its usefulness for left ventricular reverse remodeling and better quality of life in patients with HFrEF and HFmrEF. (Effects of Dapagliflozin on cardiac deformation and clinical outcomes in heart failure with reduced and mildly reduced ejection fraction [DAPA ECHO trial]; EudraCT number: 2021-005394-66) [Display omitted] [ABSTRACT FROM AUTHOR]

Heart failure (HF) is defined as the inability of the heart to meet body oxygen demand requiring an elevation in left ventricular filling pressures (LVP) to compensate. LVP increase can be assessed in the cardiac catheterization laboratory, but this procedure is invasive and time-consuming to the extent that physicians rather rely on non-invasive diagnostic tools. In this work, we assess the feasibility to develop a novel machine-learning (ML) approach to predict clinically relevant LVP indices. Synchronized invasive (pressure–volume tracings) and non-invasive signals (ECG, pulse oximetry, and cardiac sounds) were collected from anesthetized, closed-chest Göttingen minipigs. Animals were either healthy or had HF with reduced ejection fraction and circa 500 heartbeats were included in the analysis for each animal. The ML algorithm showed excellent prediction of LVP indices estimating, for instance, the end-diastolic pressure with a R2 of 0.955. This novel ML algorithm could assist clinicians in the care of HF patients. [ABSTRACT FROM AUTHOR]

Background: This is the first study to examine the clinical utility of measuring plasma secretoneurin (SN) levels in patients with heart failure with reduced ejection fraction (HFrEF), as a predictor of unplanned hospitalization, and all-cause mortality independently, and as a composite endpoint at one-year follow-up. Methods: The study group includes 124 caucasian patients in New York Heart Association (NYHA) classes II to IV. Plasma SN concentrations were statistically analyzed in relation to sex, age, BMI, etiology of HFrEF, pharmacotherapy, clinical, laboratory and echocardiographic parameters. Samples were collected within 24h of admission to the hospital. Key results: In the 12-month follow-up, high SN levels were noted for all three endpoints. Conclusions: SN positively correlates with HF severity measured by NYHA classes and proves to be a useful prognostic parameter in predicting unplanned hospitalizations and all-cause mortality among patients with HFrEF. Patients with high SN levels may benefit from systematic follow-up and may be candidates for more aggressive treatment. [ABSTRACT FROM AUTHOR]

Purpose of Review: Heart failure (HF) represents a growing global burden of morbidity and mortality. Identifying individuals at risk for HF development is increasingly important, particularly given the advent of disease-modifying therapies for HF as well as its major risk factors such as obesity actalnd diabetes. We aim to review the key circulating biomarkers associated with future HF which may contribute to HF risk prediction. Recent Findings: While current guidelines recommend the use of natriuretic peptides and cardiac troponins in HF risk stratification, there are a diverse array of other emerging protein, metabolic, transcriptomic, and genomic biomarkers of future HF development. These biomarkers not only lend insight into the underlying pathophysiology of HF, which spans inflammation to cardiac fibrosis, but also offer an opportunity to further refine HF risk in addition to established biomarkers. Summary: As evolving techniques in molecular biology enable an increased understanding of the complex biologic contributions to HF pathophysiology, there is an important opportunity to construct integrated clinical and multi-omic models to best capture HF risk. Moving forward, future studies should seek to understand the contributions of sex differences, underlying comorbidity burden, and HF subtypes to an individual's HF risk. Further studies are necessary to fully define the clinical utility of biomarker screening approaches to refine HF risk assessment, as well as to link risk assessment directly to preventive strategies for HF. [ABSTRACT FROM AUTHOR]

Background/Objectives: Heart failure (HF) remains a major therapeutic and diagnostic challenge nowadays. Albeit, acute decompensated HF is associated with several clinical signs such as dyspnea or edema, it remains a challenge to use easy accessible and suitable tools, such as biomarkers, to distinguish between patients at risk for an acute decompensation of their heart failure and compensated, stable HF patients. Existing biomarkers, such as natriuretic peptides or troponin, are not specific and can be elevated due to several other disease conditions, such as myocardial infarction, atrial fibrillation, or valve diseases. Therefore, the aim of this study was to analyze the predictive potential of four novel cardiovascular biomarkers—the soluble urokinase-type plasminogen activator receptor (suPAR), heart-type fatty acid binding protein (H-FABP), vascular cell adhesion molecule 1 (VCAM-1), and growth/differentiation factor 15 (GDF-15) for the detection of cardiac decompensation in patients with HF. Methods: In this study, 146 patients were prospectively enrolled and the serum biomarker concentrations were analyzed using Enzyme Linked Immunosorbent Assay (ELISA). We correlated the biomarker concentrations with clinical and biochemical parameters of all patients and the predictive value for detection of cardiac decompensation was assessed. Results: A significant increase in the levels of suPAR (1.6-fold-change, p < 0.0001), H-FABP (2.2-fold-change, p = 0.0458), VCAM-1 (1.6-fold-change, p < 0.0001), and GDF-15 (1.7-fold-change, p = 0.0009) was detected in all patients with acute decompensated HF in comparison to patients with compensated HF. Univariate logistic regression analysis revealed a significant association of biomarker plasma concentration with the risk for a cardiac decompensation (suPAR: p < 0.0001; VCAM-1: p < 0.0001, H-FABP: p = 0.0458; GDF-15: p = 0.0009). Conclusions: In conclusion, the investigated novel cardiovascular biomarkers suPAR, GDF-15, VCAM-1, and H-FABP could be a valuable tool to facilitate therapeutic decisions in patients with heart failure and suspicion of a cardiac decompensation. Parameters such as renal function should be taken into account. Further studies on novel biomarkers are required to find reliable, sensitive, and specific tools that will enable the early detection of patients with acute decompensation. [ABSTRACT FROM AUTHOR]

Landiolol, an ultra-short-acting β1-selective blocker, is more effective in controlling heart rate compared with digoxin in patients with atrial tachyarrhythmias and left ventricular dysfunction. However, the effect of atrial tachyarrhythmia type on the effectiveness of landiolol remains unknown. Hence, this study aimed to evaluate the effectiveness of landiolol in patients with atrial fibrillation (AF) and atrial tachycardia (AT), not limited to those with heart failure with a reduced ejection fraction. To this end, we evaluated the efficacy and safety of landiolol in managing tachycardiac AF and tachycardiac atrial flutter/AT in 44 patients with reduced left ventricular function. We found that while landiolol was effective in managing patients with AF and heart failure with a preserved or mid-range ejection fraction, however, it might be more challenging to control heart rate in patients with AT using a similar dosage of landiolol. [ABSTRACT FROM AUTHOR]

Background/Objectives: Advanced calcific aortic stenosis, with or without coronary artery disease [CAD], may lead to severe systolic dysfunction. The aim of the study was to reveal clinical and laboratory parameters that may differentiate patients with severe aortic stenosis with and without systolic dysfunction. Methods: A retrospective, single-center study included all consecutive patients diagnosed with severe aortic stenosis with overt heart failure. Patients with hematological and neoplastic diseases were excluded. Demographic, clinical and laboratory data were analysed. Neutrophil-to-lymphocyte [NLR], monocyte-to-lymphocyte [MLR], and platelet-to-lymphocyte [PLR] ratios were calculated. The study group was divided based on left ventricular ejection fraction [LVEF]. Results: The final study population comprised 301 patients [133 males [44%]; median [Q1–3] age of 80 [75–83] years]. Co-morbidities included CAD [48.8%], arterial hypertension [75.4%], diabetes mellitus [n = 124, 41.2%], atrial fibrillation [39.2%], chronic kidney disease [60.8%]. Fifty-seven patients presented with LVEF ≤ 40% (heart failure with reduced ejection fraction (HFrEF)) and 244 with LVEF > 40%. In the multivariable analysis, N-terminal pro-B-type natriuretic peptide [NTproBNP] [p < 0.001, OR 1.000, 95%CI 1.000–1.000], baseline MLR [p < 0.020, OR 7.393, 95%CI 1.363–40.091] and female sex [p < 0.001, OR 0.308, 95%CI 0.160–0.593] were revealed as significant predictors of HFrEF. Baseline MLR weakly correlated with EuroScore II [Spearman r = 0.141, p = 0.015] and NTproBNP [r = 0.142, p = 0.014]. Cut-off values were established as 0.36 for MLR and 3927 pg/mL for NTproBNP. After excluding 147 patients with CAD, there was still a statistically significant difference in MLR between the subgroups [p = 0.024]. Conclusions: Increased values of MLR and NTproBNP together with female sex are predictive parameters for LVEF ≤ 40% in patients with severe aortic stenosis. [ABSTRACT FROM AUTHOR]

Aims: Non‐ischaemic cardiomyopathy (NICMP), an incurable disease terminating in systolic heart failure (heart failure with reduced ejection fraction [HFrEF]), causes immune activation, however anti‐inflammatory treatment strategies so far have failed to alter the course of this disease. Myeloperoxidase (MPO), the principal enzyme in neutrophils, has cytotoxic, pro‐fibrotic and nitric oxide oxidizing effects. Whether MPO inhibition ameliorates the phenotype in NICMP remains elusive. Methods and results: Prognostic information from MPO was derived from proteomic data of a large human cardiovascular health cohort (n = 3289). In a murine model of NICMP, we studied the mechanisms of MPO in this disease. In a case series, the MPO inhibitor was also evaluated in NICMP patients. Individuals with increased MPO revealed higher long‐term mortality and worsening of heart failure, with impaired prognosis when MPO increased during follow‐up. MPO infusion attenuated left ventricular ejection fraction (LVEF) in mice with NICMP, whereas genetic ablation or inhibition of MPO decreased systemic vascular resistance (SVR, 9.4 ± 0.7 mmHg*min/ml in NICMP vs. 6.7 ± 0.8 mmHg*min/ml in NICMP/Mpo−/−mice, n = 8, p = 0.006, data expressed as mean ± standard error of the mean) and improved left ventricular function (LVEF 30.3 ± 2.2% in NICMP vs. 40.7 ± 1.1% in NICMP/Mpo−/− mice, n = 16, p < 0.0001). Four patients diagnosed with NICMP and treated with an MPO inhibitor over 12 weeks showed increase in LVEF, decline in natriuretic peptides and improved 6‐min walking distance. MPO inhibitor‐related changes in the proteome of NICMP patients predicted reduced mortality when related to the changes in the proteome of the above referenced cardiovascular health cohort. Conclusions: Myeloperoxidase predicts long‐term outcome in HFrEF and its inhibition elicits systemic anti‐inflammatory and vasodilating effects which translate into improved left ventricular function. MPO inhibition deserves further evaluation as a novel, complementary treatment strategy for HFrEF. [ABSTRACT FROM AUTHOR]

This review explores the crucial role of glycosphingolipids (GSLs) in the context of cardiovascular diseases (CVDs), focusing on their biosynthesis, metabolic pathways, and implications for clinical outcomes. GSLs are pivotal in regulating a myriad of cellular functions that are essential for heart health and disease progression. Highlighting findings from both human cohorts and animal models, this review emphasizes the potential of GSLs as biomarkers and therapeutic targets. We advocate for more detailed mechanistic studies to deepen our understanding of GSL functions in cardiovascular health, which could lead to innovative strategies for diagnosis, treatment, and personalized medicine in cardiovascular care. [ABSTRACT FROM AUTHOR]

Patients with heart failure with reduced ejection fraction (HFrEF) are at risk for chronic kidney disease (CKD). Elevated levels of circulating biomarkers soluble urokinase plasminogen activator receptor (suPAR), galectin-3, soluble suppression of tumorigenicity 2 (ST2), and N-terminal prohormone B-type natriuretic peptide (NT-proBNP) are associated with CKD progression and mortality. The predictive value of these biomarkers in a population with HFrEF and kidney disease is relatively unknown. We sought to determine whether these biomarkers were associated with longitudinal trajectory of estimated glomerular filtration rate (eGFR) in HFrEF and assess their association with mortality using a joint model to account for competing risks of ventricular assist device (VAD) implantation and heart transplantation. We included participants from the Registry Evaluation of Vital Information for Ventricular Assist Devices in Ambulatory Life with repeated eGFR measures over 2 years. Of 309 participants, mean age was 59 years, median eGFR 60 ml/min/1.73m², 45 participants died, 33 received VAD, and 25 received orthotopic heart transplantation. Higher baseline serum standardized suPAR (b coefficient =20.36O(ml/min/1.73m²), 95% confidence interval (20.48 to 20.24), p\0.001), standardized galectin-3 (20.14O(ml/min/1.73m²) (20.27 to 20.02), p = 0.02), and log NT-proBNP (20.23O(ml/min/1.73m²) (20.31 to 20.15), p\0.001) were associated with eGFR decline. ST2 and log NT-proBNP were associated with mortality. Higher baseline suPAR, galectin-3, and NT-proBNP are associated with eGFR decline in patients with HFrEF. Only ST2 and NT-proBNP are associated with greater mortality after controlling for other factors including change in eGFR. These biomarkers may provide prognostic value for kidney disease progression in HFrEF and inform candidacy for advanced heart failure therapies. [ABSTRACT FROM AUTHOR]

Background: Heart failure (HF) often disrupts the protein quality control (PQC) system leading to protein aggregate accumulation. Evidence from tissue biopsies showed that exercise restores PQC system in HF; however, little is known about its effects on plasma proteostasis. Aim: To determine the effects of exercise training on the load and composition of plasma SDS-resistant protein aggregates (SRA) in patients with HF with reduced ejection fraction (HFrEF). Methods: Eighteen patients with HFrEF (age: 63.4 ± 6.5 years; LVEF: 33.4 ± 11.6%) participated in a 12-week combined (aerobic plus resistance) exercise program (60 min/session, twice per week). The load and content of circulating SRA were assessed using D2D SDS-PAGE and mass spectrometry. Cardiorespiratory fitness, quality of life, and circulating levels of high-sensitive C-reactive protein, N-terminal pro-B-type natriuretic peptide (NT-proBNP), haptoglobin and ficolin-3, were also evaluated at baseline and after the exercise program. Results: The exercise program decreased the plasma SRA load (% SRA/total protein: 38.0 ± 8.9 to 36.1 ± 9.7%, p = 0.018; % SRA/soluble fraction: 64.3 ± 27.1 to 59.8 ± 27.7%, p = 0.003). Plasma SRA of HFrEF patients comprised 31 proteins, with α-2-macroglobulin and haptoglobin as the most abundant ones. The exercise training significantly increased haptoglobin plasma levels (1.03 ± 0.40 to 1.11 ± 0.46, p = 0.031), while decreasing its abundance in SRA (1.83 ± 0.54 × 1011 to 1.51 ± 0.59 × 1011, p = 0.049). Cardiorespiratory fitness [16.4(5.9) to 19.0(5.2) ml/kg/min, p = 0.002], quality of life, and circulating NT-proBNP [720.0(850.0) to 587.0(847.3) pg/mL, p = 0.048] levels, also improved after the exercise program. Conclusion: Exercise training reduced the plasma SRA load and enhanced PQC, potentially via haptoglobin-mediated action, while improving cardiorespiratory fitness and quality of life of patients with HFrEF. [ABSTRACT FROM AUTHOR]

Aims: The objective of this study was to examine associations between elevated depressive symptoms and increased risk of adverse clinical events patients with heart failure and reduced ejection fraction (HFrEF), as well as the potential contribution of health behaviours. Methods and results: One hundred forty‐two men and women with HFrEF were enrolled through heart failure (HF) clinics and followed over time. At baseline and 6 months, depressive symptoms were assessed by the Beck Depression Inventory‐II (BDI‐II) and HFrEF disease activity by B‐type natriuretic peptide (BNP). The Self‐Care of Heart Failure Index (SCHFI) was used to assess HF self‐care behaviours. Proportional hazards regression models assessed the contribution of depressive symptoms and HFrEF disease biomarkers on death or cardiovascular hospitalization. Over a median follow‐up period of 4 years, 42 patients (30%) died, and 84 (60%) had cardiovascular hospitalizations. A 10‐point higher baseline BDI‐II score was associated with a 35% greater risk of death or cardiovascular hospitalization. Higher baseline BDI‐II scores were associated with poorer HF self‐care maintenance behaviours (R = −0.30, P < 0.001) and fewer daily steps (R = −0.19, P = 0.04), suggesting that elevated depressive symptoms may diminish important health behaviours. Increases in plasma BNP over 6 months were associated with worse outcomes. Changes in BDI‐II and plasma BNP over 6 months were positively related (R = 0.25, P = 0.004). Conclusions: This study confirms that elevated depressive symptoms are associated with an increased likelihood of adverse clinical outcomes in patients with HFrEF. Poor health behaviours may contribute to the adverse association of elevated depressive symptoms with the increased hazard of adverse clinical outcomes. [ABSTRACT FROM AUTHOR]

Abstract Aims The objective of this study was to examine associations between elevated depressive symptoms and increased risk of adverse clinical events patients with heart failure and reduced ejection fraction (HFrEF), as well as the potential contribution of health behaviours. Methods and results One hundred forty‐two men and women with HFrEF were enrolled through heart failure (HF) clinics and followed over time. At baseline and 6 months, depressive symptoms were assessed by the Beck Depression Inventory‐II (BDI‐II) and HFrEF disease activity by B‐type natriuretic peptide (BNP). The Self‐Care of Heart Failure Index (SCHFI) was used to assess HF self‐care behaviours. Proportional hazards regression models assessed the contribution of depressive symptoms and HFrEF disease biomarkers on death or cardiovascular hospitalization. Over a median follow‐up period of 4 years, 42 patients (30%) died, and 84 (60%) had cardiovascular hospitalizations. A 10‐point higher baseline BDI‐II score was associated with a 35% greater risk of death or cardiovascular hospitalization. Higher baseline BDI‐II scores were associated with poorer HF self‐care maintenance behaviours (R = −0.30, P

We present the case of a 52-year-old female patient on optimal medical therapy (OMT) for heart failure with severely reduced ejection fraction. She was diagnosed with dextrocardia and congenital corrected transposition of the great arteries (ccTGA) by echocardiography. Despite 3 months of OMT and a persisting NYHA II functional state, she was referred for primary prevention ICD implantation. At admission echocardiography revealed a hypertrophic systemic ventricle with an ejection fraction of 27%. Cardiac CT confirmed ccTGA, dextrocardia, a normal extracardiac and epicardial venous system. Coronary artery disease was excluded. Our team opted for left-sided VDD-ICD implantation in case of a need for AV-synchronous pacing and to enhance arrhythmia discrimination. An active fixation shock lead was placed in the mid-septal region of the functional right ventricle. The defibrillation threshold test (DFT) was successful at 20 J. No periprocedural complications were observed. At the 12-month ambulatory visit, device interrogation showed good function, no detected arrhythmias, and no antitachycardia therapy was delivered. Preoperative imaging is essential prior to any invasive cardiac procedure in patients with congenital heart disease. Performing a DFT test at adult congenital heart disease patients may be reasonable.

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. [ABSTRACT FROM AUTHOR]

Abstract Aims Heart failure with reduced ejection fraction (HFrEF) significantly impacts health‐related quality of life (HR‐QoL). Existing HR‐QoL questionnaires can show inconsistencies, potentially misrepresenting patient self‐reports. This study examines the variation in HR‐QoL measurement tools for HFrEF patients, identifying related determinants. Methods and results We retrospectively analysed 134 hospitalized patients with acute decompensated HFrEF at a Taiwanese tertiary centre's Heart Failure Post‐Acute‐Care (HF‐PAC) programme. Participants completed the EuroQol‐5 dimension (EQ‐5D) questionnaire, the EQ‐5D visual analogue scale (VAS), and the Minnesota Living with Heart Failure Questionnaire (MLHFQ). Utility values were obtained from the EQ‐5D questionnaire. Demographic features were depicted using descriptive statistics, while multivariate regression was used to ascertain relationships between HR‐QoL measurements and determinants. Average scores for EQ‐5D, MLHFQ, EQ‐5D utility, and VAS were 6.1 ± 1.6, 21.8 ± 21.3, 81.7 ± 27.0, and 59.5 ± 14.6, respectively. Significant correlations were observed among the three tools. The New York Heart Association functional class showed a notable association with all tool scores. Other associations encompassed EQ‐5D with coronary artery disease, mineralocorticoid receptor antagonists, and the 6 min walk test; EQ‐5D VAS with chronic kidney disease; and MLHFQ with age. Conclusions This study illuminates the variance in HR‐QoL measurement tools for Taiwanese HFrEF patients. Using a range of these tools is beneficial in unveiling diverse determinants and approaching comprehensive patient‐centred care. However, for a more precise HR‐QoL assessment in Taiwanese HFrEF patients, recalibrating the EQ‐5D‐derived utility scores might be necessary, emphasizing the importance of patient‐specific considerations within the HF‐PAC programme.

Abstract Aims Patients with HFrEF and worsening HF events (WHFE) are at particularly high risk and urgently need disease‐modifying therapy. CHART‐HF assessed treatment patterns and reasons for medication decisions among HFrEF patients with and without WHFE. Methods and results CHART‐HF collected retrospective electronic medical records of outpatients with HF and EF

Introduction: The use of machine learning is exploding in all areas of healthcare, including the diagnosis and treatment of heart failure. Supervised machine learning can help predict the onset of heart failure, establish the diagnosis, and even predict decompensations. Conversely, unsupervised machine learning is chiefly used for phenotyping of the heart failure population. Several studies have identified distinctive groups of heart failure patients, but the widespread clinical implementation is still lacking. Aims: Our study aims to identify groups with similar characteristics among patients cared for HFrEF at the City Major Heart and Vascular Clinic of Semmelweis University using unsupervised machine learning and to describe the characteristic features of the resulting groups. We then examine the differences in outcome between the resulting groups. Methods: data from outpatients with reduced left ventricular ejection fraction heart failure were collected in a prospective registry. A total of 27 parameters included anamnestic data, laboratory tests, echocardiographic parameters and EQ5D quality of life questionnaire scores. The composite of hospitalization for heart failure and all-cause mortality was considered as the endpoint of the study. Spectral clustering was used to divide the population into three groups. The groups were plotted spatially using principal component analysis. Finally, we compared the groups in terms of parameters and endpoint occurrence. Results: Three characteristic groups were identified in the analysis of 259 patients. The first group consisted of 89 patients with ischemic etiology, more complaining, renal failure, and requiring duck diuretic therapy. The second group of 99 patients consisted of predominantly younger patients with atrial fibrillation, non-ischemic cardiomyopathy, dilated left ventricle, and a lower ejection fraction, almost exclusively on ARNI therapy. The third group of 71 patients included patients with the best ejection fraction, frequently taking ACE inhibitors and MRAs, and not requiring loop diuretics. Group 1 had significantly worse prognosis than group 2 (p=0.013) with a trend to worse prognosis compared to group 3. Conclusion: Our study identified three groups of patients with different characteristics based on a prospectively managed HFrEF registry. After validation on a larger patient cohort, our data may provide a basis for developing targeted treatment strategies.

Background: The role of epicardial adipose tissue (EAT) in heart failure with preserved ejection fraction (HFpEF) remains to be defined. Methods: A consecutive series of outpatients with chronic heart failure—heart failure with reduced ejection fraction (HFrEF) and HFpEF and/or diastolic dysfunction—had EAT assessed by echocardiographic measurement and related to indices of cardiac structure and function. Results: Epicardial fat thickness was significantly (p < 0.05) greater in HFpEF (N = 141) with a mean of 6.7 ± 1.6 mm compared with a mean of 5.1 ± 1.0 mm in HFrEF (n = 40). After adjusting for the relationship with BMI, in HFpEF, epicardial fat was significantly (p < 0.05) negatively correlated with left ventricular internal diameter end diastole (LVIDd), left ventricular internal diameter end systole (LVIDs), left ventricular (LV) end-diastolic volume (EDV) index, lateral e', septal e', right atrial (RA) volume index, and hemoglobin (Hgb). The association with Hgb was no longer significant after adjusting for the effect of age. HFpEF was associated with smaller LVIDd, LVIDs, LV EDV indexes, and left atrial (LA) and RA volume indexes. Conclusions: Epicardial fat is significantly (p < 0.05) greater in HFpEF than HFrEF. Epicardial fat is associated with smaller cardiac chamber sizes in HFpEF suggesting that epicardial fat acts as a constraint to cardiac dilation. [ABSTRACT FROM AUTHOR]

Heart failure (HF) is a significant health burden, with two major clinical subtypes: HF with reduced (HFrEF) and preserved ejection fraction (HFpEF). Blood pressure and lipid profile are established risk factors of HF. We performed univariable and multivariable Mendelian randomization (MR) analyses to assess potential causal effects of blood pressures and lipids on HF subtypes. Genetic instruments for blood pressures and lipids were derived from genome-wide association studies (GWASs) among the European participants of the UK Biobank. GWAS summaries of HFrEF and HFpEF were obtained from the meta-analysis of the European participants from the Million Veteran Program and the Vanderbilt University DNA Databank. Systolic blood pressure exhibited a supportive MR association primarily with HFpEF (odds ratio [OR], 1.14; 95% confidence interval [CI], 1.04–1.23), while diastolic blood pressure had an independent MR association with HFrEF (OR, 1.43; 95% CI, 1.13–1.77). MR associations also supported the observation that higher levels of low-density lipoprotein cholesterol increase the risk for both subtypes (HFrEF OR, 1.10 and 95% CI, 1.05–1.17; HFpEF OR, 1.05 and 95% CI, 1.02–1.09). These findings underscore differences in HF subtype-specific risk profiles and mechanisms, which may lead to different interventional strategies for different HF subtypes. [ABSTRACT FROM AUTHOR]

Congestive heart failure (CHF) as a risk of stroke in patients with atrial fibrillation (AF) mainly referred to patients with left ventricular systolic dysfunction. Whether this should include patients with preserved ejection fraction is debatable. The study aimed to investigate the variation in stroke risk of AF patients with heart failure with preserved ejection fraction (HFpEF), heart failure with mid-range ejection fraction (HFmrEF), and heart failure with reduced ejection fraction (HFrEF) for enhancing risk assessment and subsequent management strategies. In a longitudinal study using the National Taiwan University Hospital integrated Medical Database, 8358 patients with AF were observed for 10 years (mean follow-up, 3.76 years). The study evaluated the risk of ischemic stroke in patients with differing ejection fractions and CHA 2 DS 2 -VASc score, further using Cox models adjusted for risk factors of AF-related stroke. Patients with HFpEF and HFmrEF had a higher mean CHA 2 DS 2 -VASc score compared with patients with HFrEF (4.30 ± 1.729 vs 4.15 ± 1.736 vs 3.73 ± 1.712; P <.001) and higher risk of stroke during follow-up (hazard ratio [HR], 1.40 [1.161–1.688; P <.001] for HFmrEF; HR, 1.184 [1.075–1.303; P =.001] for HFpEF vs no CHF) after multivariate adjustment). In patients with lower CHA 2 DS 2 -VASc score (0–4), presence of any type of CHF increased ischemic stroke risk (HFrEF HR, 1.568 [1.189–2.068; P =.001]; HFmrEF HR, 1.890 [1.372–2.603; P <.001]; HFpEF HR, 1.800 [1.526–2.123; P <.001] vs no CHF). After multivariate adjustment, HFpEF and HFmrEF showed a similar risk of stroke in AF patients. Therefore, it is important to extend the criteria for C in the CHA 2 DS 2 -VASc score to include patients with HFpEF and HFmrEF. In patients with fewer concomitant stroke risk factors, the presence of any subtype of CHF increases risk for ischemic stroke. [Display omitted] [ABSTRACT FROM AUTHOR]

In recent years, thanks to the advent of new classes of drugs (ARNI and SGLT2-i), the prognosis of patients suffering from heart failure with reduced ejection fraction (HFrEF) has gradually improved. Nonetheless, there is a residual risk that is not targeted by these therapies. Currently, it is recognized that vericiguat, an oral stimulator of soluble guanylate cyclase (sGC), can restore the NO-sGC-cGMP pathway, through stimulation and activation of sGC, aiming to increase cGMP levels with a reduction in heart failure-related oxidative stress and endothelial dysfunction. Even though the Victoria trial demonstrated that HFrEF patients in treatment with vericiguat showed a 10% reduction in the composite of cardiovascular mortality and rehospitalization for heart failure, statistically significantly reducing heart failure hospitalization, the international guidelines limit its use as a second-line drug for patients with worsening symptomatology despite optimized medical therapy. Furthermore, vericiguat has proved to be a valid therapeutic ally especially in those patients with comorbidities such that they cannot receive the classic four-pillar therapy of HF (in particular renal failure). In this review, the authors report on randomized clinical trials, substudies, and meta-analysis about vericiguat in HFrEF, emphasizing the strengths that would suggest the possible role of vericiguat as the fifth pillar of the HFrEF treatment, acknowledging that there are still gaps in the evidence that need to be clarified. [ABSTRACT FROM AUTHOR]

Objective: To describe the pharmacology, clinical efficacy, and safety evidence of sotagliflozin, the first approved dual inhibitor of sodium-glucose cotransporter (SGLT) 1 and SGLT2, in heart failure (HF) management. Data sources: A literature search of studies published between January 2012 and September 2023 were identified using PubMed, MEDLINE, and clinicaltrials.gov with search terms of "sotagliflozin," "Inpefa," or "LX4211." Study selection and data extraction: All available studies in English were considered. Studies were included if they investigated drug pharmacology, efficacy, or safety information. Data synthesis: Two phase 3 trials of sotagliflozin, SOLOIST-WHF and SCORED, evaluated sotagliflozin compared with placebo in patients with type 2 diabetes mellitus (T2DM). SOLOIST-WHF reported a statistically decreased rate of cardiovascular and HF events with sotagliflozin (hazard ratio [HR] = 0.67, 95% CI = 0.52-0.85), while SCORED found a statistically significant decrease in incidence of cardiovascular events in patients with T2DM, chronic kidney disease (CKD), and risk factors for cardiovascular disease in patients in the sotagliflozin group (HR = 0.74, 95% CI = 0.63-0.88). Relevance to patient care and clinical practice in comparison to existing agents: While approval of sotagliflozin expands treatment options for patients with HF, the SGLT2 inhibitors, dapagliflozin and empagliflozin, have more data supporting their use in HF, additional risk reduction benefits in patients with CKD, and approval for use in T2DM. Landmark trials of sotagliflozin required a previous diagnosis of T2DM, despite the broader approved indication. Where sotagliflozin will be adopted into the treatment of HF is unclear due to the evidence and benefits of already established SGLT2 inhibitors and the need for comparison with SGLT2 inhibitors. Conclusion: Given the limitations of currently available evidence, including difficulty in fully interpreting the trial results due to changes in primary endpoints, not adjudicating the events, and not reaching the original power calculations, more investigation is warranted to determine the benefit of sotagliflozin compared with SGLT2 inhibitors. [ABSTRACT FROM AUTHOR]

Background: Heart failure (HF) is a highly prevalent syndrome in elderly subjects. Currently, multiple drugs have shown clinical benefits in patients with HF and reduced ejection fraction (HFrEF). However, evidence is scarce in elderly patients (beyond 75 years old), even more so for the latest drugs, such as angiotensin receptor-neprilysin inhibitors (ARNIs). This study aims to evaluate the use and benefits of ARNIs in elderly patients with HFrEF. Methods: A prospective observational cohort study was designed. Patients with left ventricular systolic dysfunction (defined by left ventricular ejection fraction [LVEF] < 40%) and age ≥ 75 years from January 2016 to December 2020 were prospectively included. Patients with an indication for ARNIs at inclusion or throughout follow-up were selected. Clinical, electrocardiographic and echocardiographic variables were collected. Results: A total of 616 patients were included, 34.4% of them female, with a mean age of 83.3 years, mean LVEF of 28.5% and ischemic etiology in 53.9% of patients. Only 14.3% of patients were taking ARNIs. After a mean follow-up of 34 months, 50.2% of patients died, and 62.2% had a cardiac event (total mortality or hospital admission due to HF). Multivariate Cox regression analysis showed that the use of ARNIs was independently and significantly associated with lower rates of mortality [HR 0.36 (95% CI 0.21–0.61)], with similar results in relation to all-cause mortality in a propensity-score-matched analysis [HR 0.33 (95% CI 0.19–0.57)]. Conclusions: We observed an important underuse of ARNIs in a cohort of elderly HFrEF patients, in which treatment with ARNIs was associated with a significant reduction in mortality. Greater implementation of clinical practice guidelines in this group of patients could improve their prognosis. [ABSTRACT FROM AUTHOR]

Background/Objectives: The demographic shift towards an aging population necessitates a reevaluation of surgical interventions like coronary artery bypass grafting (CABG) in octogenarians. This study aims to elucidate the outcomes of CABG in octogenarians with heart failure and reduced ejection fraction (HFrEF), a group traditionally considered at high risk for such procedures. Methods: Conducted across four academic hospitals in Germany from 2017 to 2023, this retrospective multicenter study assessed 100 patients (50 octogenarians ≥80 years and 50 non-octogenarians <80 years) with HFrEF undergoing isolated CABG. Through propensity score matching, the study aimed to compare the incidence of major adverse cardiac and cerebrovascular events (MACCEs), as well as other clinical endpoints, between the two groups. Statistical analyses included chi-square, ANOVA, Mann–Whitney U test, Cox regression, and logistic regression, aiming to identify significant differences in outcomes. Results: The study revealed no significant difference in the combined incidence of MACCEs between octogenarians and non-octogenarians (OR: 0.790, 95% CI: 0.174–3.576, p = 0.759). Mortality rates were similar across groups (7% each, p = 1.000), as were occurrences of postoperative myocardial infarction (2% each, p = 1.000) and stroke (3% total). Secondary outcomes like delirium (17% total, no significant age group difference, p = 0.755), acute kidney injury (18% total, p = 0.664), and the need for dialysis (14% total, p = 1.000) also showed no differences between age groups. Interestingly, non-octogenarians required more packed red blood cells during their stay (p = 0.008), while other postoperative care metrics, such as hospital and ICU length of stay and ventilation hours, were comparable across groups. Conclusion: This multicenter study highlights that CABG is a viable and safe surgical option for octogenarians with HFrEF, challenging prior assumptions about the elevated risks associated with performing this procedure in older patients. The absence of significant differences in the incidence of MACCEs and other postoperative complications across age groups emphasizes the importance of careful patient selection and perioperative management. These findings advocate for a more inclusive approach to surgical treatment for octogenarians with HFrEF, suggesting that age alone should not be a determinant for CABG eligibility. This study contributes critical insights into optimizing care for a high-risk demographic, indicating a need for tailored guidelines that accommodate the aging population with complex cardiac conditions. [ABSTRACT FROM AUTHOR]

Background and Purpose: Cancer therapy‐related cardiovascular adverse events (CAEs) in presence of comorbidities, are in the spotlight of the cardio‐oncology guidelines. Carfilzomib (Cfz), indicated for relapsed/refractory multiple myeloma (MM), presents with serious CAEs. MM is often accompanied with co‐existing comorbidities. However, Cfz use in MM patients with cardiometabolic syndrome (CMS) or in heart failure with reduced ejection fraction (HFrEF), is questionable. Experimental Approach: ApoE−/− and C57BL6/J male mice received 14 weeks Western Diet (WD) (CMS models). C57BL6/J male mice underwent permanent LAD ligation for 14 days (early‐stage HFrEF model). CMS‐ and HFrEF‐burdened mice received Cfz for two consecutive or six alternate days. Daily metformin and atorvastatin administrations were performed additionally to Cfz, as prophylactic interventions. Mice underwent echocardiography, while proteasome activity, biochemical and molecular analyses were conducted. Key Results: CMS did not exacerbate Cfz left ventricular (LV) dysfunction, whereas Cfz led to metabolic complications in both CMS models. Cfz induced autophagy and Ca2+ homeostasis dysregulation, whereas metformin and atorvastatin prevented Cfz‐mediated LV dysfunction and molecular deficits in the CMS‐burdened myocardium. Early‐stage HFrEF led to depressed LV function and increased protein phosphatase 2A (PP2A) activity. Cfz further increased myocardial PP2A activity, inflammation and Ca2+‐cycling dysregulation. Metformin co‐administration exerted an anti‐inflammatory potential on the myocardium without improving LV function. Conclusion and Implications: CMS and HFrEF seem to exacerbate Cfz‐induced CAEs, by presenting metabolism‐related hidden toxicity and PP2A‐related cardiac inflammation, respectively. Metformin retains its prophylactic potential in the presence of CMS, while mitigating inflammation and Ca2+ signalling dysregulation in the HFrEF myocardium. [ABSTRACT FROM AUTHOR]

Heart failure (HF) is a major health issue, affecting up to 2% of the adult population worldwide. Given the increasing prevalence of obesity and its association with various cardiovascular diseases, understanding its role in HFrEF outcomes is crucial. This study aimed to investigate the impact of obesity on in-hospital mortality and prolonged hospital stay in patients with heart failure with reduced ejection fraction (HFrEF). We conducted a retrospective analysis of 425 patients admitted to the cardiology unit at the University Clinical Hospital in Wroclaw, Poland, between August 2018 and August 2020. Statistical analyses were performed to evaluate the interactions between BMI, sex, and comorbidities on in-hospital mortality. Significant interactions were found between sex and BMI as well as between BMI and post-stroke status, affecting in-hospital mortality. Specifically, increased BMI was associated with decreased odds of in-hospital mortality in males (OR = 0.72, 95% CI: 0.55–0.94, p < 0.05) but higher odds in females (OR = 1.18, 95% CI: 0.98–1.42, p = 0.08). For patients without a history of stroke, increased BMI reduced mortality odds (HR = 0.78, 95% CI: 0.64–0.95, p < 0.01), whereas the effect was less pronounced in those with a history of stroke (HR = 0.89, 95% CI: 0.76–1.04, p = 0.12). In conclusion, the odds of in-hospital mortality decreased significantly with each 10% increase in BMI for males, whereas for females, a higher BMI was associated with increased odds of death. Additionally, BMI reduced in-hospital mortality odds more in patients without a history of cerebral stroke (CS) compared to those with a history of CS. These findings should be interpreted with caution due to the low number of observed outcomes and potential interactions with BMI and sex. [ABSTRACT FROM AUTHOR]

Purpose of Review: People with HIV have an elevated risk of developing heart failure even with optimally controlled disease. In this review, we outline the various mechanisms through which HIV infection may directly and indirectly contribute to heart failure pathology and highlight the emerging relationship between HIV, chronic inflammation, and cardiometabolic disease. Recent Findings: HIV infection leads to chronic inflammation, immune dysregulation, and metabolic imbalances even in those with well controlled disease. These dysregulations occur through several diverse mechanisms which may lead to manifestations of different phenotypes of heart failure in people with HIV. Summary: While it has long been known that people with HIV are at risk of developing heart failure, recent studies have suggested numerous complex mechanisms involving chronic inflammation, immune dysregulation, and metabolic derangement through which this may be mediated. Further comprehensive studies are needed to elucidate the precise relationship between these mechanisms and the development of different subtypes of heart failure in people with HIV. [ABSTRACT FROM AUTHOR]

Aims: Patients with HFrEF and worsening HF events (WHFE) are at particularly high risk and urgently need disease‐modifying therapy. CHART‐HF assessed treatment patterns and reasons for medication decisions among HFrEF patients with and without WHFE. Methods and results: CHART‐HF collected retrospective electronic medical records of outpatients with HF and EF < 45% between 2017–2019 from a nationwide panel of 238 cardiologists (458 patients) and the Geisinger Health System (GHS) medical record (1000 patients). The index visit in the WHFE cohort was the first outpatient cardiologist visit ≤6 months following the WHFE, and in the reference cohort was the last visit in a calendar year without WHFE. Demographic characteristics were similar between patients with and without WHFE in both the nationwide panel and GHS. In the nationwide panel, the proportion of patients with versus without WHFE receiving ≥50% of guideline‐recommended dose on index visit was 35% versus 40% for beta blocker, 74% versus 83% for ACEI/ARB/ARNI, and 48% versus 49% for MRA. The proportion of patients receiving ≥50% of guideline‐recommended dose was lower in the GHS: 29% versus 34% for beta‐blocker, 16% versus 31% for ACEI/ARB/ARNI, and 18% versus 22% for MRA. For patients with and without WHFE, triple therapy on index date was 42% and 44% of patients from the nationwide panel, and 14% and 17% in the GHS. Comparing end of index clinic visit with 12‐month follow‐up in the GHS, the proportion of patients on no GDMT increased from 14% to 28% in the WHFE cohort and from 14 to 21% in the non‐WHFE group. Conclusions: Major gaps in use of GDMT, particularly combination therapy, remain among US HFrEF patients. These gaps persist during longitudinal follow‐up and are particularly large among patients with recent WHFE. [ABSTRACT FROM AUTHOR]

Aims: Heart failure with reduced ejection fraction (HFrEF) significantly impacts health‐related quality of life (HR‐QoL). Existing HR‐QoL questionnaires can show inconsistencies, potentially misrepresenting patient self‐reports. This study examines the variation in HR‐QoL measurement tools for HFrEF patients, identifying related determinants. Methods and results: We retrospectively analysed 134 hospitalized patients with acute decompensated HFrEF at a Taiwanese tertiary centre's Heart Failure Post‐Acute‐Care (HF‐PAC) programme. Participants completed the EuroQol‐5 dimension (EQ‐5D) questionnaire, the EQ‐5D visual analogue scale (VAS), and the Minnesota Living with Heart Failure Questionnaire (MLHFQ). Utility values were obtained from the EQ‐5D questionnaire. Demographic features were depicted using descriptive statistics, while multivariate regression was used to ascertain relationships between HR‐QoL measurements and determinants. Average scores for EQ‐5D, MLHFQ, EQ‐5D utility, and VAS were 6.1 ± 1.6, 21.8 ± 21.3, 81.7 ± 27.0, and 59.5 ± 14.6, respectively. Significant correlations were observed among the three tools. The New York Heart Association functional class showed a notable association with all tool scores. Other associations encompassed EQ‐5D with coronary artery disease, mineralocorticoid receptor antagonists, and the 6 min walk test; EQ‐5D VAS with chronic kidney disease; and MLHFQ with age. Conclusions: This study illuminates the variance in HR‐QoL measurement tools for Taiwanese HFrEF patients. Using a range of these tools is beneficial in unveiling diverse determinants and approaching comprehensive patient‐centred care. However, for a more precise HR‐QoL assessment in Taiwanese HFrEF patients, recalibrating the EQ‐5D‐derived utility scores might be necessary, emphasizing the importance of patient‐specific considerations within the HF‐PAC programme. [ABSTRACT FROM AUTHOR]

(1) Background: The validation of new lines of therapy for the elderly is required due to the progressive ageing of the world population and scarce evidence in elderly patients with HF with reduced ejection fraction (HFrEF). The purpose of our study is to analyze the effect of SGLT2 inhibitors (SGLT2i) in this subgroup of patients. (2) Methods: A single-center, real-world observational study was performed. We consecutively enrolled all patients aged ≥ 75 years diagnosed with HFrEF and for treatment with SGLT2i, and considered the theoretical indications. (3) Results: A total of 364 patients were recruited, with a mean age of 84.1 years. At inclusion, the mean LVEF was 29.8%. Median follow-up was 33 months, and there were 122 deaths. A total of 55 patients were under SGLT2i treatment. A multivariate Cox logistic regression test for all-cause mortality was performed, and only SGLT2i (HR 0.39 [0.19–0.82]) and glomerular filtration rate (HR 0.98 [0.98–0.99]) proved to be protective factors. In parallel, we conducted a propensity-score-matched analysis, where a significant reduction in all-cause mortality was associated with the use of SGLT2i treatment (HR 0.39, [0.16–0.97]). (4) Conclusions: Treatment with SGLT2i in elderly patients with HFrEF was associated with a lower rate of all-cause mortality. Our data show that SGLT2i therapy could improve prognosis in the elderly with HFrEF in a real-world study. [ABSTRACT FROM AUTHOR]

Background: Heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF) are challenging conditions to treat due to complex pathophysiology and associated comorbidities. However, recent trials have demonstrated improved outcomes with guideline-directed medical therapy (GDMT) for each subtype of heart failure. Objective: We investigated the relationship of determinants of health and risk factors with GDMT use for HFrEF and HFpEF in a large, diverse US cohort. Methods: Using the NIH-sponsored All of Us Program, we compared demographics, risk factors (e.g., hypertension, diabetes, smoking), and SDOH measures between HFrEF and HFpEF in US adults aged 18 years and older. We examined the proportions of HFrEF patients receiving fewer than four or all four GDMTs. HFpEF patients receiving two medications were compared with those receiving less than two recommended medications. Multiple logistic regression was used for data analysis. Result: Of 6049 HFrEF patients, 5838 (97 %) received fewer than four GDMTs, and 210 (3 %) received quadruple therapy. Of 3774 HFpEF patients, 162 (4 %) were on 2/3 GDMT, and only 38 (1 %) were on all three recommended medications. Patients with ASCVD and diabetes had higher odds of being on more than half of the recommended GDMT for both HFrEF and HFpEF. Additionally, females had higher odds of being on 2/3 GDMT for HFpEF (1.46 [1.08, 2.00]). Race, income, education, and health insurance types did not predict GDMT optimization. Conclusion: HFrEF and HFpEF GDMT remain underutilized. Future efforts to address comorbidities and system-wide healthcare interventions may improve heart failure GDMT.

AbstractBackground This is the first study to examine the clinical utility of measuring plasma secretoneurin (SN) levels in patients with heart failure with reduced ejection fraction (HFrEF), as a predictor of unplanned hospitalization, and all-cause mortality independently, and as a composite endpoint at one-year follow-up.Methods The study group includes 124 caucasian patients in New York Heart Association (NYHA) classes II to IV. Plasma SN concentrations were statistically analyzed in relation to sex, age, BMI, etiology of HFrEF, pharmacotherapy, clinical, laboratory and echocardiographic parameters. Samples were collected within 24 h of admission to the hospital.Key results In the 12-month follow-up, high SN levels were noted for all three endpoints.Conclusions SN positively correlates with HF severity measured by NYHA classes and proves to be a useful prognostic parameter in predicting unplanned hospitalizations and all-cause mortality among patients with HFrEF. Patients with high SN levels may benefit from systematic follow-up and may be candidates for more aggressive treatment.

Background: Cardiac remodeling is an adverse phenomenon linked to heart failure (HF) progression. Cardiac remodeling could represent the real therapeutic goal in the treatment of patients with HF and reduced ejection fraction (HFrEF), being potentially reversed through different pharmacotherapies. Currently, there are well-established drugs such as ACEi/ARBs and β-blockers with anti-remodeling effects. More recently, ARNI effects on cardiac remodeling were also demonstrated; additional potential benefits of gliflozins remain non clearly demonstrated. Aim of study: To evaluate possible changes in cardiac remodeling in patients with HFrEF/HFmrEF in treatment with ARNI or ARNI plus SGLT2i and the potential benefit on cardiac remodeling of adding SGLT2i to ARNI. Methods: Between June 2021 and August 2023, 100 consecutive patients with HFrEF/HFmrEF underwent conventional and advanced echocardiography (TDI, 2DSTE): patients were therefore divided into three groups according to therapy with neither ARNI nor SGLT2i, just ARNI or both. After 3 months, all patients underwent echocardiographic follow-up. Results: After a 3 months of therapy, significant improvements were observed for LVEF, LVEDD, LVEDV, LVESV, LV mass, E/e’, LV GLS, TAPSE (ANOVA p

The article in the Journal of Physiology discusses the pathophysiological features of pre-clinical models of heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). The study compares the effects of different interventions, such as high-fat diet and angiotensin II infusion, on cardiac function in animal models. The findings suggest that both HFrEF and HFpEF models exhibit impairments in systolic and diastolic function, with distinct molecular and structural changes. The research highlights the importance of selecting appropriate animal models to study specific aspects of heart failure and provides insights for potential therapeutic interventions. [Extracted from the article]

Abstract Circulating proteins may provide insights into the varying biological mechanisms involved in heart failure (HF) with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF). We aimed to identify specific proteomic patterns for HF, by comparing proteomic profiles across the ejection fraction spectrum. We investigated 4210 circulating proteins in 739 patients with normal (Stage A/Healthy) or elevated (Stage B) filling pressures, HFpEF, or ischemic HFrEF (iHFrEF). We found 2122 differentially expressed proteins between iHFrEF-Stage A/Healthy, 1462 between iHFrEF–HFpEF and 52 between HFpEF-Stage A/Healthy. Of these 52 proteins, 50 were also found in iHFrEF vs. Stage A/Healthy, leaving SLITRK6 and NELL2 expressed in lower levels only in HFpEF. Moreover, 108 proteins, linked to regulation of cell fate commitment, differed only between iHFrEF–HFpEF. Proteomics across the HF spectrum reveals overlap in differentially expressed proteins compared to stage A/Healthy. Multiple proteins are unique for distinguishing iHFrEF from HFpEF, supporting the capacity of proteomics to discern between these conditions.

Abstract Aims This study aimed to characterize a contemporary population with subtypes of incident or prevalent heart failure (HF) based on reduced (HFrEF), mildly reduced, or preserved (HFpEF) left ventricular ejection fraction (LVEF) and to assess how outcomes, healthcare, treatments, and healthcare costs vary between each subtype of incident HF. Methods and results Using Swedish data from the CardioRenal and Metabolic disease Heart Failure (CaReMe HF) study, updated to cover a more recent time period, this population‐based study characterized patients from Stockholm County, Sweden, with incident HF (patients with a first HF diagnosis between 1 January 2015 and 31 December 2019) or prevalent HF (patients with a first HF diagnosis before 1 January 2020). Patients with incident HF had LVEF measured by echocardiography within ±90 days of their first HF diagnosis, and patients with prevalent HF within 5 years prior to the index date. The 13 375 patients with prevalent HF (39.2% women, mean age 73.9 years) had multiple comorbidities (cardiovascular diseases, chronic kidney disease, diabetes, and cancer). These were already highly prevalent at the time of the first HF diagnosis in the 8042 patients with incident HF (40.5% women, mean age 72.3 years). Patients with incident HFpEF received less specialist HF care at outpatient secondary care facilities following their first HF diagnosis than those with incident HFrEF. Patients with HFrEF had higher risks of complications and exerted a higher burden, in terms of care for and costs of HF, on the healthcare system. Conclusions This study of contemporary patients with incident HF demonstrates that those with HFpEF and HFrEF differ considerably in terms of clinical presentation, prognosis, and care, highlighting a potential to improve HF outcomes.

Abstract Heart failure is a devastating syndrome affecting an increasingly high number of patients worldwide. Its aetiology and pathogenesis are complex with the involvement of factors ranging from the genetic material through valvular dysfunctions to numerous organs beyond the entire cardiovascular system. Based on continuous efforts of the heart failure scientific community we have witnessed major advances in many related disciplines during the last year. For example, epidemiological aspects—paving the road for improved risk prevention—have been thoroughly analysed for various geographical regions. Additionally, evidence‐based approaches now allow the introduction of novel guideline recommended medical therapies (i.e. sodium‐glucose transporter 2 inhibitors, and iron supplementation) while basic and translational research aim to explore additional molecular targets for future heart failure diagnostics and medications. All above aspects are addressed in this article, where a selection of articles published in the ESC Heart Failure journal in 2023 are highlighted. The editors are confident that the scientific contributions of ESC Heart Failure effectively served a highly relevant area of cardiovascular research last year.

Abstract Aims We aim to explore the associations between serum tyrosine (Tyr) to threonine (Thr) ratio and chronic heart failure (HF) with reduced or mildly reduced ejection fraction (EF) (HFrEF or HFmrEF). Methods and results The study recruited 418 subjects (77.5% males, mean age 65.2 ± 12.5 years), including 318 HF subjects (HFrEF or HFmrEF) and 100 cardiovascular subjects without acute or chronic HF [including heart failure with preserved ejection fraction (HFpEF)] as controls. Serum levels of 21 kinds of amino acids (AAs) were measured by mass spectrometry. Logistic regression analysis was conducted to measuring the association between the AAs levels and the presence of HF. Event‐free survival was determined by Kaplan–Meier curves and differences in survival were assessed using log‐rank tests. Cox regression analysis was used to assess the prognostic value of AAs in HF. Receiver‐operating characteristic (ROC) curve was performed to further confirm regression analysis. Along with the control, HFmrEF, and HFrEF subjects, serum tyrosine (Tyr) gradually increased (64.43 ± 15.28 μmol/L vs. 71.79 ± 18.74 μmol/L vs. 77.32 ± 25.90 μmol/L, P

Abstract Aims Regulation of the renin‐angiotensin system (RAS) in heart failure (HF) with reduced ejection fraction (HFrEF) still raises questions, as a large proportion of patients show normal renin levels despite manifest disease. Experimental venous congestion results in reduced renal perfusion pressure and stimulates renin secretion. We hypothesized that excess renin levels are mainly a result of right ventricular failure as a sequalae of left ventricular dysfunction. The study aimed to link right ventricular function (RVF) with renin levels and to investigate further contributors to excess RAS activation. Methods and results Three hundred thirty‐two chronic HFrEF patients undergoing routine ambulatory care were consecutively enrolled in a prospective, registry‐based, observational study. Laboratory parameters, including cardiac‐specific markers renin, aldosterone, and N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), echocardiographic examination (n = 247), and right heart catheterization (n = 85), were documented. The relationship between renin and its respective parameters was analysed. Renin concentration was not associated with the New York Heart Association class or NT‐proBNP. Systolic blood pressure, systemic vascular resistance, serum sodium, aldosterone, and lactate dehydrogenase were associated with increased renin levels (P

Abstract Aims In patients with heart failure (HF), we aimed to assess (i) the time trends in N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) testing; (ii) patient characteristics associated with NT‐proBNP testing; (iii) distribution of NT‐proBNP levels, focusing on the subgroups with (WHFE) vs. without (NWHFE) a worsening HF event, defined as an HF hospitalization; and (iv) changes of NT‐proBNP levels over time. Methods and results NT‐proBNP testing and levels were investigated in HF patients enrolled in the Swedish Heart Failure Registry (SwedeHF) linked with the Stockholm CREAtinine Measurements project from January 2011 to December 2018. Index date was the first registration in SwedeHF. Patterns of change in NT‐proBNP levels before (in the previous 6 ± 3 months) and after (in the following 6 ± 3 months) the index date were categorized as follows: (i)

Abstract Aims The aims of this sub‐study of the SMARTEX trial were (1) to evaluate the effects of a 12‐week exercise training programme on serum levels of high sensitivity cardiac troponin I (hs‐cTnI) in patients with moderate chronic heart failure (CHF), in New York Heart Association class II‐III with reduced ejection fraction (HFrEF) and (2) to explore the associations with left ventricular remodelling, functional capacity and filling pressures measured with N‐terminal pro brain natriuretic peptide (NT‐proBNP). Methods and results In this sub‐study, 196 patients were randomly assigned to high intensity interval training (HIIT, n = 70), moderate continuous training (MCT, n = 59) or recommendation of regular exercise (RRE), (n = 67) for 12 weeks. To reveal potential difference between structured intervention and control, HIIT and MCT groups were merged and named supervised exercise training (SET) group. The RRE group constituted the control group (CG). To avoid contributing factors to myocardial injury, we also evaluated changes in patients without additional co‐morbidities (atrial fibrillation, hypertension, diabetes mellitus, and chronic obstructive pulmonary disease). The relationship between hs‐cTnI and left ventricular end‐diastolic diameter (LVEDD), VO2peak, and NT‐proBNP was analysed by linear mixed models. At 12 weeks, Hs‐cTnI levels were modestly but significantly reduced in the SET group from median 11.9 ng/L (interquartile ratio, IQR 7.1–21.8) to 11.5 ng/L (IQR 7.0–20.7), P = 0.030. There was no between‐group difference (SET vs. CG, P = 0.116). There was a numerical but not significant reduction in hs‐cTnI for the whole population (P = 0.067) after 12 weeks. For the sub‐group of patients without additional co‐morbidities, there was a significant between‐group difference: SET group (delta −1.2 ng/L, IQR −2.7 to 0.1) versus CG (delta −0.1 ng/L, IQR −0.4 to 0.7), P = 0.007. In the SET group, hs‐cTnI changed from 10.9 ng/L (IQR 6.0–22.7) to 9.2 ng/L (IQR 5.2–20.5) (P = 0.002), whereas there was no change in the CG (6.4 to 5.8 ng/L, P = 0.64). Changes in hs‐cTnI (all patients) were significantly associated with changes in; LVEDD, VO2peak, and NT‐proBNP, respectively. Conclusions In patients with stable HFrEF, 12 weeks of structured exercise intervention was associated with a modest, but significant reduction of hs‐cTnI. There was no significant difference between intervention group and control group. In the sub‐group of patients without additional co‐morbidities, this difference was highly significant. The alterations in hs‐cTnI were associated with reduction of LVEDD and natriuretic peptide concentrations as well as improved functional capacity.

Abstract Aims Recent updates of international treatment guidelines for heart failure with reduced ejection fraction (HFrEF) differ regarding the use of angiotensin receptor neprilysin inhibitor (ARNI) as first‐line treatment. The American Heart Association/American College of Cardiology/Heart Failure Society of America (AHA/ACC/HFSA) 2022 guidelines gives ARNI a Class IA recommendation for HFrEF patients while the European Society of Cardiology's guidelines are less clear when ARNI could be considered as first line treatment option in de novo patients. This study aimed to model the clinical and budgetary outcomes of implementing these guidelines, comparing conservative ARNI prescription patterns with less conservative in Sweden and in the United Kingdom. Methods and results A health economic model was developed to compare different treatment patterns for HFrEF. Incident cohorts were included on an annual basis and followed over 10 years. The model included treatment specific all‐cause mortality and hospitalization rates, as well as drug acquisition, monitoring, and hospitalization costs. Increasing the use of ARNI could lead to about 7000–12 300 life years gained and 2600–4600 hospitalizations prevented in Sweden. These health benefits come with an additional cost of 112–195 million euros. Similar results were estimated for the United Kingdom, albeit on a larger population. Conclusions Increasing the proportion of patients receiving ARNI instead of angiotensin converting enzyme inhibitors as first‐line treatment of HFrEF will lead to a considerable number of additional life years gained and prevented hospitalizations but with additional cost in terms of health care expenditure in Sweden and in the United Kingdom.

Background: In patients with preserved left ventricular ejection fraction (LVEF), small ventricular size has been associated with reduced functional capacity, but its impact on clinical outcomes is unclear. Objectives: The goal of this study was to determine the relationship between small heart size and premature mortality within a large multicenter adult patient cohort with transthoracic echocardiographic examinations. Methods: We divided 366,484 individuals with LVEF ≥50% (including a subset of 279,442 individuals with high-normal LVEF ≥60%) by sex and increasing quartiles for LV end-diastolic volume (LVEDV), LVEDV indexed to body surface area (LVEDVi), and LV end-diastolic diameter to assess associations with 5-year mortality through linkage with the National Death Index. Results: During approximately 2 million person-years of follow-up, 65,241 deaths occurred. Increasing LV chamber size was associated with reduced odds of 5-year all-cause mortality, particularly for higher LVEF. As compared with the larger quartiles, the smallest cardiac size quartiles were associated with higher 5-year all-cause mortality, even after adjusting for age. The smallest LVEDVi quartile was associated with a 14% to 18% higher odds of 5-year all-cause mortality, with a greater effect with high-normal LVEF. There was a U-shaped relationship between LV chamber size and all-cause mortality. For cardiovascular-related mortality, females in the smallest LVEDVi quartile had a 17% increased odds of mortality, which increased to 30% in those with LVEF ≥60%. In men, there was no significant association between smallest cardiac size and cardiovascular-related mortality. Conclusions: In individuals with normal LVEF, small ventricular size is associated with increased mortality, particularly among females and those with higher LVEF.

IntroductionGuideline-directed medical therapy (GDMT) is the recommended treatment for heart failure with reduced ejection fraction (HFrEF). However, the implementation remains limited, with suboptimal use and dosing. The study aimed to assess the feasibility and effect of a remote monitoring titration program on GDMT implementation.MethodsHFrEF patients were randomly assigned to receive either usual care or a quality-improvement remote titration with remote monitoring intervention. The intervention group used wireless devices to transmit heart rate, blood pressure, and weight data daily, which were reviewed by physicians and nurses every 2-4 weeks. Medication tolerance was assessed via phone, and dosage instructions were given. This workflow was repeated until target doses were reached or further adjustments were not tolerated. A 4-GDMT score measured use and target dosage, with the primary endpoint being the score at 6 months follow-up.ResultsBaseline characteristics were similar (n = 55). A median of 85% of patients complied with transmitting device data every week. At the 6-month follow-up, the intervention group had a 4-GDMT score of 64.6% compared to 56.5% in the usual care group (p = 0.01), with a difference of 8.1% (95% CI: 1.7%-14.5%). Similar results were seen at the 12-month follow-up [difference 12.8% (CI: 5.0%-20.6%)]. The intervention group showed a positive trend in ejection fraction and natriuretic peptides, with no significant difference between groups.ConclusionsThe study suggests that a full-scale trial is feasible and that utilizing a remote titration clinic with remote monitoring has the potential to enhance the implementation of guideline-directed therapy for HFrEF.