Myocardial fibers of the left ventricle (LV) play a pivotal role in electrical conduction, mechanical contraction, and numerous clinical malfunctions. While the general fiber orientation of the LV has been revealed through histological analysis and magnetic resonance diffusion tensor imaging, its impact on LV deformation remains largely unknown. In this paper, we adopt an idealized hollow semi-ellipsoid LV model, allowing for adjustable fiber orientations using a widely-accepted rule-based method. Simulations are conducted using a robustly coupled excitation-contraction nonlinear finite element algorithm. Our primary focus is on exploring the orientation angle of regularly-distributed fibers and the proportion of chaotic fibers, whose orientation angles are randomly assigned, on the end-systolic volume and ejection fraction of the LV.‌ By employing this model, we successfully recreate the changes in LV volume over a cardiac cycle and capture the typical twisting motion observed in clinical practice. Furthermore, our findings reveal that when myocardial fibers are regularly distributed and the orientation angle increases, the ejection fraction of the LV decreases along with an increase in end-systolic volume, indicating a decline in LV contractility. Additionally, both the proportion and spatial distribution of chaotic fibers within the LV influence its contractility. Specifically, an LV with a higher proportion of chaotic fibers in the basal area exhibits weaker contractility. These results provide deeper insights into the quantitative influence of myocardial fibers on LV contractility and failure, offering valuable information for further research and clinical applications.

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome with vast prevalence worldwide. Despite recent advances in understanding its pathophysiology, HFpEF remains under-diagnosed in clinical practice. Obesity-related HFpEF is a distinct and frequent phenotype with an additionally challenging diagnosis. We address the importance of overweight and obesity in HFpEF, focusing on the influence of adipose tissue in inflammation and neurohormonal activity. We also discuss atrial and ventricular remodelling in obesity-related HFpEF and potential clinical implications. Obesity is an independent risk factor for HFpEF. Adipose tissue synthesizes aldosterone, causing lower levels of natriuretic peptide. Adipocytes dysfunction promotes a pro-inflammatory state and leads to extracellular matrix remodelling and consequently stiffening of the heart and vessels. Thus, the quantity, distribution and quality of the excess fat influences cardiovascular risk. Visceral and epicardial adipose tissue are often associated with an increased likelihood of developing HFpEF. Obesity-related HFpEF presents higher risk of left ventricular concentric remodelling and inadequate accommodation of the expanded volume due to the obesity, resulting in higher left ventricular filling pressure. Nevertheless, microvascular endothelium inflammation modifies cardiomyocyte elasticity and increases collagen deposition, which enhances myocardial fibrosis and results in HFpEF. Furthermore, neurohormonal activation may also contribute to cardiac remodelling by inducing plasma volume expansion. In turn, leptin also stimulates aldosterone synthesis and enhances renin-angiotensin-aldosterone system. Obesity-related HFpEF presents worse overall prognosis, with increased risk of heart failure hospitalization and all-cause mortality. Intentional weight loss through caloric restriction, physical activity, pharmacological intervention and/or bariatric surgery are promising strategies.

Palliative care is a component of high-quality care for people with heart failure (HF). However, how best to deliver specialist palliative care (SPC) within ambulatory settings is unknown. Such information could help healthcare systems expand access to these services.

We aimed to understand the preferred components and characteristics of ambulatory SPC delivery for people with HF and their non-medical family caregivers, as well as to identify barriers to its utilization.

We conducted a qualitative descriptive study employing content analysis among people with HF and caregivers. We enrolled 20 participants with current use of ambulatory SPC from 3 Department of Veterans Affairs (VA) medical centers.

The sample (N = 20; patients = 16, caregivers = 4) mean age was 64.3 years (standard deviation = 16.5 years), 80% were male, 85% were White, and 10% were Black. Participants valued three key components of ambulatory SPC: 1) providing comprehensive education about HF; 2) care coordination of medical and social services, and 3) serious illness conversations including discussions of goals of care, the selection of surrogate decision-makers, and the completion of advance directives and related documentation. For participants, important characteristics of ambulatory SPC delivery included 1) collaboration and communication among SPC and cardiology clinicians, 2) the accessibility and availability of the SPC team, and 3) flexibility in visit logistics. Barriers to engagement were conflating SPC with hospice, and logistical concerns with appointment delivering and scheduling.

People with HF and their caregivers prefer and value specific components and characteristics of ambulatory SPC. Implementation of ambulatory SPC should be educational, collaborative, and incorporate logistical preferences.

The Care Transitions Scale for Patients With Heart Failure (CTS-HF) is a scale that registered nurses working in the cardiovascular ward use to assess patients' readiness for hospital discharge; CTS-HF has shown sufficient reliability and validity for use.

In this study, our aim was to test the relationship between assessments using CTS-HF by nurses and patients' difficulties of symptom management and self-care 1 week after discharge.

In this longitudinal study we paired responses from nurses and patients with heart failure between 2022 and 2023. A nurse assessed a patient's readiness for hospital discharge using CTS-HF. One week after discharge, patients with heart failure completed a questionnaire about their daily difficulties at home. The relationship between the nurse-reported CTS-HF scores and patients' difficulties at home was analyzed.

Twenty-three dyads of nurse-patient responses were included in the analysis. Nurse-assessed CTS-HF scores were significantly correlated with patients' symptom management difficulties at home (r = -0.471, P = .012), degree of interference with daily life due to symptoms (r = -0.530, P = .005), daily healthy ways to manage symptoms (r = 0.561, P = .003), and emotional support at home (r = 0.435, P = .019).

Nurse-reported CTS-HF scores showed a relationship with patients' difficulties after discharge. Because nurses' assessment before discharge may predict patients' difficulties managing symptoms after discharge, such discharge readiness assessment by nurses using CTS-HF may be useful in transitional care from hospital to home. Further studies on patients with complex care needs are warranted.

Myocardial remodeling, a complex adaptive response to pathological stimuli, plays a pivotal role in the progression of various cardiovascular diseases, including arrhythmias and heart failure. Significant progress has been made in understanding the molecular mechanisms of myocardial remodeling and exploring the efficacy of single and multicomponent agents. Myocardial remodeling entails a complex signaling network that incorporates certain identified critical "bridge nodes," which are also significant drug targets in classical pharmacological approaches. Nonetheless, some multicomponent drugs that have undergone clinical trials, such as Qili Qiangxin capsules, may suggest the presence of a new and feasible drug development path. The potential of multicomponent agents lies in their ability to achieve a synergistic effect through the coordinated regulation of multiple up- and downstream molecules in signaling pathways involved in myocardial remodeling. However, the development of multicomponent agents presents several challenges, such as identifying active compounds, defining their mechanisms of action, and determining the optimal proportions of each component. Delving deeper into the synergistic, multitarget effects of multicomponent agents in the realm of future research holds the promise to chart a new course toward the development of more effective and safer therapeutic strategies for managing myocardial remodeling and its associated cardiovascular diseases.

Ischemic heart disease has long been established as the leading cause of heart failure, typically as a result of hemodynamically significant and obstructive coronary anatomy. Since, the role of dysfunctional coronary microvascular pathophysiologic mechanisms have also been associated with the development of congestive heart failure (CHF), most notably heart failure with preserved ejection fraction (HFpEF) although with limited clinical evidence. Conventional cardiometabolic and behavioral risk factors common to HFpEF such as diabetes mellitus (DM), obesity, hypertension, dyslipidemia, smoking, and chronic kidney disease foster a pro-inflammatory environment conducive to endothelial dysfunction and improper regulation of vasoactive substances. The impaired relaxation and increased vasoconstriction of damaged endothelium gives rise to impaired coronary blood flow and episodes of transient ischemia. Such coronary microvascular dysfunction (CMD) has its own implication on cardiovascular pathophysiologic mechanisms beyond symptomatic coronary and myocardial ischemia, and thus its own potential prevention goals and treatment targets for patients with HFpEF, where previous management had been limited. As such, we conducted a literature review to address the current landscape of data which links CMD to HFpEF. Furthermore, we considered the implications of biopsychosocial elements such as race, ethnicity, sex, gender, and the social determinants of health as they relate to the disparate health outcomes of those most at risk for CMD and HFpEF.

Heart failure with preserved ejection fraction (HFpEF) is defined by heart failure (HF) with a left ventricular ejection fraction (LVEF) of at least 50%. HFpEF has a complex and heterogeneous pathophysiology with multiple co-morbidities contributing to its presentation. Establishing the diagnosis of HFpEF can be challenging. Two algorithms, the 'Heavy, 2 or more Hypertensive drugs, atrial Fibrillation, Pulmonary hypertension, Elderly age >60, elevated Filling pressures' (H2FPEF) and the 'Heart Failure Association Pre-test assessment, Echocardiography and natriuretic peptide, Functional testing, Final aetiology' (HFA-PEFF), can help to determine the likelihood of HFpEF in individuals with symptoms of HF. Phenotype clusters defined largely by the total number and types of co-morbidities may delineate groups of patients with HFpEF with different management needs. It is important to recognize alternative diagnoses or HFpEF mimics such as infiltrative cardiomyopathies, coronary artery disease, lung disease, anxiety, depression, anaemia, severe obesity, and physical deconditioning, among others. Treatment with sodium-glucose co-transporter 2 inhibitors (dapagliflozin and empagliflozin) is recommended for all patients with HFpEF unless contraindicated. Future research should consider alternative approaches to guide the initial diagnosis and treatment of HFpEF, including phenotype clustering models and artificial intelligence, and consider whether LVEF is the most useful distinguishing feature for categorizing HF. Ongoing clinical trials are evaluating novel pharmacological and device-based approaches to address the pathophysiological consequences of HFpEF.

Patients with cardiomyopathies are a heterogeneous group of patients who experience high morbidity and mortality. Early cardiac assessment and intervention with access to genetic counselling in a multidisciplinary Cardiomyopathy Clinic may improve outcomes and prevent progression to advanced heart failure.

Our prospective cohort study was conducted at a multidisciplinary Cardiomyopathy Clinic with 421 patients enrolled (42.5% female, median age 58 years), including 224 patients with dilated cardiomyopathy (DCM, 42.9% female, median age 57 years), 72 with hypertrophic cardiomyopathy (HCM, 43.1% female, median age 60 years), 79 with infiltrative cardiomyopathy (65.8% female, median age 70 years) and 46 who were stage A/at risk for genetic cardiomyopathy (54.3% female, median age 36 years). Patients were seen in follow-up at a median of 18 months. A pathogenic/likely pathogenic variant was identified in 28.5% of the total cohort, including 33.3% of the DCM cohort (28% TTN mutations) and 34.1% of the HCM cohort (60% MYBPC3 and 20% MYH7) who underwent genetic testing. The use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor neprilysin inhibitor (48.3-69.5% of total cohort, P < 0.001), β-blockers (58.4-72.4%, P < 0.001), mineralocorticoid receptor antagonists (33.9-41.4%, P = 0.0014) and sodium/glucose cotransporter-2 inhibitors (5.3-27.9%, P < 0.001) all increased at follow-up. Precision-based therapies were also implemented, including tafamidis for transthyretin amyloidosis (n = 21), enzyme replacement therapy for Fabry disease (n = 14) and mavacamten (n = 4) for HCM. Optimization of medications and devices resulted in improvements in left ventricular ejection fraction (LVEF) from 27% to 43% at follow-up for DCM patients with reduced LVEF at baseline (P < 0.001) and reduction in left ventricular mass index (LVMI) from 156 g/m2 to 128 g/m2 at follow-up for HCM patients with abnormal LVMI at baseline (P = 0.009). Optimization of therapies was associated with stable plasma biomarkers in stage B patients while lowering levels of BNP (619-517.5 pg/mL, P = 0.048), NT-proBNP (777.5-356 ng/L, P < 0.001) and hsTropT (31-22 ng/L, P = 0.005) at follow-up relative to baseline values for stage C patients. Despite stage B patients having overt cardiomyopathy at baseline, stage A and B patients had a similarly high probability of survival (χ2 = 0.204, P = 0.652). The overall cardiovascular mortality rate was low at 1.7% for the cohort (0.5% for stage B and 3.3% for stage C) over a median of 34-month follow-up.

Our study demonstrates that a multidisciplinary cardiomyopathy clinic can improve the clinical profiles of patients with diverse genetic cardiomyopathies.

Patients hospitalized for heart failure (HF) experience impairments in functional status, primarily affecting basic activities of daily living (ADL). We investigated the independent effect of functional status for ADL on patient-centered outcomes (i.e., home discharge) and conventional clinical outcomes in HF. We analyzed 2936 consecutive hospitalized patients with HF from a prospective multicenter registry. The functional status of ADL was assessed before discharge by using the Barthel index (BI). Patients were categorized into the lower BI group (≤85; the lowest tertile) and higher BI group (>85). We evaluated the risk-adjusted association between BI and non-home discharge, as well as the two-year all-cause mortality. Exploratory subgroups included patients categorized by age, sex, HF hospitalization, left ventricular ejection fraction, body mass index, and estimated glomerular filtration rate (eGFR). Of the participants (age: 79 [69-85] years; 41.1% women), 86.3% were discharged home. A lower BI was independently associated with non-home discharge (OR: 5.12, 95% CI 3.86-6.80) and higher all-cause mortality rates (HR: 1.96, 95% CI 1.58-2.45). Two-year cardiac and non-cardiac mortality rates were higher in the lower BI group; however, the proportion of cardiac causes in two-year deaths did not differ between the lower and higher BI groups (48.8% vs. 49.5%, P = 0.891). Subgroup analyses consistently demonstrated an association between two-year mortality and lower BI; however, this association was stronger among patients with a higher eGFR (P-value for interaction = 0.004). A lower BI was independently associated with non-home discharge and higher mortality rates because of cardiac- and non-cardiac-related causes in hospitalized patients with HF.

ST-segment elevation myocardial infarction (STEMI) is responsible for high morbidity and mortality rates globally. Although the use of angiotensin-converting enzyme inhibitors (ACEIs) remains the cornerstone treatment for patients with STEMI, the use of angiotensin-receptor neprilysin inhibitors (ARNIs) may offer better outcomes than ACEIs. This meta-analysis compares the efficacy and safety of ARNIs versus ACEIs in patients with STEMI.

Randomized controlled trials (RCTs) were pooled from PubMed and Cochrane databases. A random-effects model calculated risk ratios (RRs) and weighted mean differences (WMDs) with 95% confidence intervals (CIs).

Five trials (n = 4,915) were included. ARNIs significantly reduced major adverse cardiovascular events (MACE) (RR: 0.66, 95% CI [0.50, 0.86]; p = 0.002) and hospitalizations for heart failure (HHF) (RR: 0.67, 95% CI [0.49, 0.92]; p = 0.01). ARNIs also improved left ventricular ejection fraction (LVEF) (WMD: 2.60, 95% CI[1.53, 3.68]; p < 0.00001) and lowered NT-proBNP levels (WMD: -268.89, 95% CI[-422.35, -115.42]; p = 0.0006). No significant differences were observed in recurrent myocardial infarction, cardiovascular death, or safety outcomes - except for hypotension, which was significantly more common with ARNI use.

ARNI therapy reduces MACE, HHF, and NT-proBNP levels and improves LVEF in patients with STEMI without increasing safety risks, except for hypotension. Further RCTs are needed to confirm these findings.

The study aims to examine characteristics and outcomes associated with health-related quality of life (HRQoL) in patients with heart failure (HF) with preserved, mildly reduced and reduced ejection fraction (EF) (HFpEF, HFmrEF and HFrEF).

Data on HRQoL were collected in the Swedish Heart Failure Registry (SwedeHF; 2000-2021) using the EuroQoL 5-dimensional visual analogue scale (EQ 5D-vas). Baseline EQ 5D-vas scores were categorized as 'best' (76-100), 'good' (51-75), 'bad' (26-50) and 'worst' (0-25). Independent associations between patients' characteristics and EQ 5D-vas, as well as between EQ 5D-vas and outcomes were assessed. Of 40 809 patients (median age 74 years; 32% female), 29% were in the 'best', 41% in the 'good', 25% in the 'bad' and 5% in the 'worst' EQ 5D-vas categories, similarly distributed across all EF categories. Higher New York Heart Association (NYHA) class was strongly associated with lower EQ 5D-vas regardless of EF categories, followed by chronic obstructive pulmonary disease, smoking, body mass index, higher heart rate, anaemia, previous stroke, ischaemic heart disease, use of diuretics and living alone, whereas higher income, male sex, outpatient status and higher systolic blood pressure were inversely associated with lower EQ 5D-vas categories. Patients in the 'worst' EQ 5D-vas category as compared with the 'best' had the highest risk of all-cause death [adjusted hazard ratios 1.97, 95% confidence interval (CI) 1.64-2.37 in HFrEF, 1.77, 95% CI 1.30-2.40 in HFmrEF and 1.43 95% CI 1.02-2.00 in HFpEF].

Most patients were in the two highest EQ 5D-vas categories. Higher NYHA class had the strongest association with lower EQ 5D-vas categories, across all EF categories. Patients in the worst EQ 5D-vas category were at the highest risk of mortality.

The challenge in heart failure medical practice is to address the clinical and laboratory method integrations for the shared decision-making process in caring for patients and families. Furthermore, stressful life events may worsen outcomes in patients with heart failure. This study aimed to explore patient perceptions regarding cardiac care analyzing the individual needs and features of adverse life event experiences.

A mixed-methods design was used in this study. This quantitative research focuses on clinical (medical and psychological) data. Giorgi's phenomenological method was applied to the interview analysis.

Qualitative analyses highlighted the role of patient-engagement strategies powered by cardiologists in a personalized approach that favors adherence to complex medical therapies. Active patient involvement and associated engagement based on cardiologists' confidence are focal points for facilitating management-therapy strategies to improve outcomes and reduce the perception of the frailty burden. The quality of therapeutic relationships with cardiologists is a key protective factor for accurate risk stratification and therapeutic decision-making in patients, addressing the potential benefits of therapeutic interventions.

In conclusion, the engaged patient contributes to more efficient cardiological care and the personalized patient-centered approach leads to the more efficient 'cure and care' clinical model. In adverse life events, acute psychological and physiological stress responses intensify detrimental outcomes for patients with cardiovascular disorders. Integrative management of physical risks and mental resilience factors in the development of cardiac disease appears to be strategic for patients with a positive quality of life (QoL) and clinical management of heart failure (HF).

Soluble suppression of tumorigenicity 2 (sST2) is a critical biomarker for heart failure (HF) diagnosis and prognosis, yet conventional antibody-based detection methods suffer from time-consuming protocols and high costs and involve complex detection procedures. To address these challenges, we first screened high-affinity aptamers under clinically relevant conditions and then coupled with the CRISPR/Cas12a system to develop a fluorescence aptasensor for rapid and sensitive sST2 detection. A serum matrix was introduced during aptamer selection to enhance specificity and anti-interference performance in real biological environments. Three sST2-specific aptamers (Apt-1, Apt-2, and Apt-3) were identified with dissociation constants (KD) of 8.42, 46.08, and 25.02 nM, respectively. Among these, Apt-1 demonstrated superior performance, which was utilized to construct a fluorescence biosensor combining aptamer recognition with CRISPR/Cas12a trans-cleavage signal amplification. The sensor achieved a broad linear detection range (5-120 ng/mL) and an ultralow limit of detection (LOD, 0.816 ng/mL) when applied in detecting sST2 in both the buffer and human serum. Notably, the platform exhibited exceptional resistance to interference from HF-related proteins and maintained high accuracy in clinical serum samples, showing a strong correlation (R2 = 0.9794) with enzyme-linked immunosorbent assay (ELISA) results. By integration of serum-matrix screening and CRISPR-based signal enhancement, this work establishes a robust, cost-effective, and rapid diagnostic tool for sST2 detection.

Left-sided heart disease is the leading etiology of tricuspid regurgitation (TR) in heart failure (HF); however, the association between different HF phenotypes and the adverse effects of TR remains unclear.

The authors aimed to elucidate the association between TR and outcomes across the subtypes of left-sided heart disease in patients hospitalized for HF.

We analyzed data from the multicenter West Tokyo Heart Failure registry between January 2006 and December 2021. Moderate or severe mitral or aortic valve disease was defined as left-sided valve dysfunction (LVD). Patients with congenital heart disease, secondary cardiomyopathy, systemic conditions related to HF, or those with incomplete datasets were excluded. Using a multivariable Cox hazard model, the survival effect of TR on mortality in patients with LVD was examined.

Overall, 3,040 presented with LVD (median age, 80 years; 45.9% female), and 2,438 had no LVD (median age, 74 years; 27.8% female). The prevalence of moderate and severe TR was 27.6% and 6.5% in patients with LVD and 9.2% and 1.5% in those without LVD, respectively. The adjusted HRs of moderate and severe TR for mortality were 1.25 (95% CI: 1.03-1.52) and 1.72 (95% CI: 1.30-2.29) in those with LVD, respectively, and 2.15 (95% CI: 1.62-2.84) and 3.09 (95% CI: 1.87-5.09) in those without LVD, respectively. Significant interactions between the subtypes were observed (P = 0.005).

TR severity stratified mortality after acute decompensated HF better in patients without LVD than in those with LVD.

The liver and heart are closely interconnected organs, and their bidirectional interaction plays a central role in cardiometabolic disease. In this review, we summarize current evidence linking liver dysfunction-particularly metabolic dysfunction-associated steatotic liver disease, alcohol-associated liver disease, and cirrhosis-with an increased risk of heart failure and other cardiovascular diseases. We discuss how these liver conditions contribute to cardiac remodeling, systemic inflammation, and hemodynamic stress and how cardiac dysfunction in turn impairs liver perfusion and promotes hepatic injury. Particular attention is given to the molecular mediators of liver-heart communication, including hepatokines and cardiokines, as well as the emerging role of advanced research methodologies, including omics integration, proximity labeling, and organ-on-chip platforms, that are redefining our understanding of interorgan cross talk. By integrating mechanistic insights with translational tools, this review aims to support the development of multiorgan therapeutic strategies for cardiometabolic disease.

To apply the American College of Cardiology (ACC) and American Heart Association (AHA) heart failure (HF) staging system to patients with transthyretin cardiac amyloidosis (TTR-CA) in order to assess diagnostic delay and evaluate prognosis.

Consecutive patients with TTR-CA enrolled in an Italian registry were classified according to the ACC/AHA HF staging system at diagnosis. Outcome was assessed as all-cause mortality during a 3-year follow-up.

At diagnosis, of 549 patients with TTR-CA, 115 (20.9%) presented with HF stage B, 172 (31.3%) with stage C1, 198 (36.1%) with stage C2, and 64 (11.7%) with stage D. Patients with stages B, C1, C2, and D presented with hierarchically higher prevalence of left ventricular systolic impairment, advanced diastolic dysfunction, advanced New York Heart Association functional class, hospitalization for HF, and N-terminal pro-B-type natriuretic peptide values. At 3 years, the survival rate was 94% in patients with stage B HF, decreasing to 69% with stage C1, 43% with stage C2, and 17% with stage D. At multivariable analysis, considering stage B as the reference, risk increase for all-cause mortality was 4, 5, and 11 for stages C1, C2, and D, respectively.

At diagnosis, almost half of patients with TTR-CA present with advanced stages of HF (C2 or D), suggesting marked diagnostic delay. The ACC/AHA HF staging system accurately stratifies prognosis and may be usefully added to the multiparametric evaluation of patients with TTR-CA.

Patients with chronic heart failure (HF) and left ventricular ejection fraction (LVEF) less than 40% who experience LVEF improvement to 40% or higher (HFimpEF) may still face residual risks.

To assess the clinical profiles, risk, and treatment response to finerenone in participants with HFimpEF.

A total of 6001 patients with HE, LVEF of 40% or higher, New York Heart Association class II to IV symptoms, and elevated natriuretic peptide levels, were enrolled between September 14, 2020, and January 10, 2023. Patients with a prior history of LVEF less than 40% were included. Data analysis was conducted between September 1 to December 10, 2024.

Participants received finerenone (titrated to 20 mg or 40 mg) or placebo.

The primary end point was the composite of cardiovascular (CV) death and total (first and recurrent) worsening HF events.

Of the 6001 participants (mean [SD] age, 72 [9.7], years; 3269 male [55%]), 273 (5%) had a prior LVEF less than 40%. Among those with a prior LVEF of less than 40%, the median recorded prior LVEF was 35% [IQR, 30%-37%], with a median improvement of 12% [IQR, 8%-17%]. Over a median follow-up of 2.6 years, those with a history of LVEF of less than 40% experienced higher rates of the primary outcome of a composite of CV death and worsening of HF events (21.4 per 100 patient-years vs 16.0 per 100 patient-years) than did those whose LVEF was consistently 40% or higher. After adjustment for clinically relevant covariates; however, this rate ratio (RR) was not statistically different (absolute RR, 1.13; 95% CI, 0.85-1.49, P = .39). The treatment effect of finerenone on the primary outcome was consistent among those with a history of LVEF less than 40% and those with LVEF that was consistently 40% or higher (P for interaction = .36). Owing to higher baseline risk, the absolute risk reduction was greater among those with HFimpEF (9.2 vs 2.5 per 100 patient-years). Patients with HFimpEF tended to develop more hypotension with finerenone treatment, but otherwise, the safety profile of finerenone was similar in patients with and without previous LVEF less than 40%.

In this prespecified analysis of a randomized clinical trial, patients with HFimpEF remained at high risk of CV events, underscoring the need for continued management despite LVEF improvement. The treatment benefits of finerenone observed among the overall population of patients with HF with preserved EF were consistent among patients with HFimpEF.

ClinicalTrials.gov Identifier: NCT04435626.

Cardiac autonomic dysfunction is associated with heart failure (HF). Reduced heart rate recovery (HRR) indicates impaired parasympathetic reactivation after physical activity. Heart rate recovery 60 seconds after peak effort (HRR60) is linked to autonomic dysfunction, but data on its relevance across HF phenotypes are scarce. This study aimed to identify clinical determinants of HRR60 in an HF cohort and assess its relationship with clinical outcomes.

Data from the MyoVasc study (NCT04064450; N=3289) were analyzed. Participants underwent standardized clinical phenotyping including cardiopulmonary exercise testing. HRR60 was defined as the heart rate decline 60 seconds after exercise termination. Clinical determinants of HRR60 were evaluated using multivariate regression, whereas Cox regression analyses assessed all-cause death and worsening of HF.

The analysis sample comprised 1289 individuals (median age, 66.0 [interquartile range {IQR}, 58.0-73.0] years, 30.4% women) ranging from stage B to stage C/D according to the universal definition of HF. Age, sex, smoking, obesity, peripheral artery disease, and chronic kidney disease were identified as determinants of HRR60. HRR60 showed a strong association with all-cause death (hazard ratio [HR]HRR60 [10 bpm], 1.56 [95% CI, 1.32-1.85]; P<0.0001) and worsening of HF (HRHRR60 [10 bpm], 1.36 [95% CI, 1.10-1.69]; P=0.0052) independent of age, sex, and clinical profile. Sensitivity analysis showed a stronger association with worsening HF in HF with preserved left ventricular ejection fraction (Pinteraction=0.027).

HRR60 was associated with clinical outcome in chronic HF. Because it showed a stronger association with outcomes in HF with preserved ejection fraction, future research should consider phenotype-specific differences.

This study investigates the causal relationship between Asialoglycoprotein receptor 1 (ASGR1) inhibitors, inflammation, and heart failure (HF). Leveraging data from the Global Lipids Genetics Consortium (2021) and the UK Biobank, we identified instrumental variables for ASGR1 and validated these genetic instruments using coronary heart disease (CHD) patients as positive controls. We employed Instrumental variable weighted (IVW) and Summary-data-based Mendelian Randomization (SMR) methods to assess the association of ASGR1 with HF and its associated risk factors, comparing efficacy with PCSK9 and LDLR. Mediation analysis of inflammatory biomarkers was conducted using a two-step Mendelian randomization approach, with sensitivity analyses performed using conventional MR methods. IVW analysis demonstrates a significant positive correlation between ASGR1 expression and HF, myocardial infarction, non-ischemic cardiomyopathy, and calcific aortic valvular stenosis. Patients with HF comorbid with CHD showed an increased likelihood of benefit. ASGR1 exhibited a stronger effect on HF compared to PCSK9. Similar conclusions were drawn from SMR analysis. Additionally, LDLR shows no causal relationship with HF but appears negatively correlated with non-ischemic cardiomyopathy. Among the 91 inflammatory proteins studied, Leukemia inhibitory factor receptor (LIF-R) and Urokinase-type plasminogen activator (uPA) were found to mediate the effects of ASGR1 on HF. Sensitivity analyses indicate no evidence of pleiotropy in reported results. This study supports a causal association between ASGR1 inhibitors and HF, providing genetic evidence for the anti-inflammatory role of ASGR1 inhibitors in reducing HF risk. LIF-R and uPA, identified as potential mediators, introduce a novel therapeutic pathway for HF management.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with heart failure (HF), independent of shared risk factors. Our aim was to describe the incidence of HF in patients with biopsy-proven MASLD.

We followed patients with biopsy-proven MASLD from the prospective Duke NAFLD Biorepository and Clinical Database from liver biopsy (2007-2013) until death or 5 January 2023. Clinical and echocardiographic data were abstracted via manual chart review. Incident HF was defined as one of the following: (1) hospitalization for HF, (2) medical record diagnosis of HF, (3) ≥1 sign/symptom of HF and elevated natriuretic peptide, or (4) diastolic dysfunction on transthoracic echocardiography with ≥1 sign/symptom of HF. Univariable and multivariable logistic regression models were evaluated. Overall, 570 patients with biopsy-proven MASLD were included. The mean age was 49.5 years, 42.5% were male and 87.0% were non-Hispanic White. Ten patients (1.8%) had baseline HF, leaving 560 patients to assess for incident HF. Over a median follow up of 4009 days (11.0 years) (interquartile range 2270-4672 days), 100 (17.9%) patients developed incident HF while 268 (47.9%) met criteria for HF suspicion. In a multivariable model, increasing age (odds ratio [OR] 1.05, 95% confidence interval [CI] 1.02-1.08, p < 0.001) and female sex (OR 1.85, 95% CI 1.12-3.04, p = 0.02) were associated with incident HF.

We found a high incidence of HF in patients with biopsy-proven MASLD. Despite nearly half of patients having suspected HF, very few carried a chart diagnosis. Screening for HF in high-risk patients and establishment of formal care pathways to address early HF may reduce morbidity and mortality.

Tirzepatide, a dual agonist of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, has shown promise in improving metabolic and cardiovascular profiles in patients with obesity. However, its potential benefits in patients with heart failure with preserved ejection fraction (HFpEF) remain unclear. We conducted a real-world, retrospective cohort study using the TriNetX global database. A total of 14,154 patients with HFpEF were included after 1:1 propensity score matching. Tirzepatide use was associated with significantly lower risks of the primary composite outcome of heart failure exacerbation and all-cause mortality (HR 0.52), as well as reductions in major adverse cardiovascular events (HR 0.64) and major adverse kidney events (HR 0.44). Subgroup analyses demonstrated consistent benefits across different strata. Sensitivity analyses using alternative exposure definitions confirmed the robustness of the findings. These results support the potential clinical utility of tirzepatide in HFpEF management and warrant further investigation in randomized controlled trials.

Heart failure (HF) is a complex disease and a major cause of morbidity and mortality worldwide. Natriuretic peptides (NPs) are involved in the pathogenesis of HF, but their activity may be modified by polymorphisms in the genes encoding them. Aim: To examine the associations of NPPA:rs5065 and NPPB:rs198389 polymorphisms with the risk of HF and cardiovascular phenotypes in Polish patients with HF. The study group comprised 330 HF patients, and the control group comprised 206 healthy newborns. Genomic DNA was extracted from blood, and genotyping of both polymorphisms was performed using polymerase chain reaction-restriction fragment length polymorphism. There were no significant differences in the distributions of NPPA and NPPB genotypes between HF patients and controls. Within the HF group, there were no significant associations between the frequencies of type 2 diabetes, hypertension, left ventricular hypertrophy, or categories of left ventricular ejection fraction (LVEF) and the NPPA or NPPB variants. However, LVEF was significantly higher in NPPA CC homozygotes than in carriers of at least one T allele. The results of our study did not confirm an association between the NPPA:rs5065 or NPPB:rs198389 polymorphisms and predisposition to HF or HF intermediate phenotypes, except for LVEF.

Unplanned admissions for worsening heart failure (WHF) are the largest resource cost in heart failure (HF) management. Despite advances in pharmacological agents and interventional therapy, HF remains a global epidemic. One crucial-and costly-gap in HF management is the inability to obtain objective information to identify and quantify congestion and personalize treatment plans to effectively manage WHF events without resorting to expensive, invasive methods. Although the causes of WHF are varied and complex, the universal effect of HF decompensation is the significant decline in quality of life due to symptoms of hypervolemic congestion and the resultant reduction in cardiac output, which can be quantified via increased pulmonary venous congestion due to high intracardiac filling pressures. Accessible and reliable markers of congestion could more precisely quantify the severity of WHF events and stabilize patients earlier by interrupting and reversing this process with timely introduction or modification of evidence-based treatments. Pulmonary artery and cardiac pressure sensing tools have gained evidential credence and increased clinical uptake in recent years for the prevention and treatment of WHF, as studies of implantable hemodynamic devices have iteratively and reliably demonstrated substantial reductions in WHF events. Recent advances in sensing technologies have ranged from single-parameter invasive pulmonary artery monitors to completely non-invasive multi-parameter devices incorporating multi-sensor concept technologies aided by machine learning or artificial intelligence, although many remain investigational. This review aims to evaluate the potential for novel pulmonary artery and cardiac pressure sensing technology to reshape the management of WHF from within the hospitalized and ambulatory care environments.

The study aimed to explore the association between type 2 diabetes (T2D) and heart failure (HF) using echocardiography and NT-proBNP. The study also derived an NT-proBNP cut-off for diagnosing HF by echo in Asian Indians with T2D.

A retrospective study was performed using data from individuals with T2D, aged ≥ 18 years, who visited diabetes clinics in India between March 2019 and December 2023. NT-proBNP levels were quantified by chemiluminescence, and left ventricular ejection fraction (LVEF) was assessed from echo using two-dimensional (2D) echocardiography. Heart failure was classified based on the European Society of Cardiology (ESC) guidelines. Receiver operating characteristic (ROC) curve was performed to determine the optimal NT-proBNP cut-off for diagnosing HF by echo.

Among the 1189 study individuals included in the study (714 men and 475 women), 5.9% were identified as having HF with reduced ejection fraction (HFrEF), 5.5% had mildly reduced ejection fraction (HFmrEF), and 14.1% had HF with preserved ejection fraction (HFpEF) while the rest (74.5%) had LVEF > 50%. Elevated NT-proBNP levels were observed in those with reduced ejection fraction. ROC analysis identified an optimal NT-proBNP threshold of 398 pg/mL for diagnosing HF, with 87% sensitivity and 78% specificity. HF prevalence increased with age, peaking at 30.6% in individuals aged 61-70 years. Women with HF had higher NT-proBNP levels than men.

In this diabetes clinic population, 11.5% of individuals with T2D had moderate to reduced LVEF. Early identification of HF using echocardiography and NT-proBNP in a diabetes clinic could help improve prognosis.

Background/Objectives: Patients hospitalized for de novo heart failure with reduced ejection fraction (HFrEF) may experience improvement in left ventricular function, a phenomenon associated with improved morbidity and mortality outcomes. However, the factors influencing this improvement remain unclear. This study aimed to investigate the association between clinical and therapeutic factors and short-term improvement or recovery of left ventricular ejection fraction (LVEF) in patients hospitalized with newly diagnosed heart failure with reduced ejection fraction (HFrEF). Methods: This was a prospective observational study conducted in two referral centers in Spain. All patients admitted with de novo HFrEF between March 2021 and December 2023 were included. Improved myocardial function (HFimpEF) was defined as an initial LVEF ≤ 40% and a follow-up echocardiogram showing LVEF > 40%, with an increase of ≥10 points from baseline. Results: In total, 157 patients (63.3%) met the criteria for HFimpEF. Among the various etiologies of heart failure, significant differences were found between groups for tachycardiomyopathy (HFimpEF: 29.3% vs. non-HFimpEF: 13.1%, p = 0.006), valvular (HFimpEF: 7.6% vs. non-HFimpEF: 1.1%, p = 0.05), and ischemic (HFimpEF: 17.2% vs. non-HFimpEF: 43.9%, p < 0.0001) etiologies. Multivariate analysis showed that non-ischemic etiologies significantly favored myocardial improvement compared to ischemic cardiomyopathy. NT-proBNP values were consistently higher in the non-HFimpEF group at all time points measured with statistically significant differences, except at admission. Event-free survival curves (hospitalization for HF, worsening HF, and all-cause mortality) diverged early, showing statistically significant differences between groups. Conclusions: Overall, 63% of patients hospitalized for de novo HFrEF achieved myocardial improvement within an average of 3-4 months, with improvement favored by valvular and tachycardiomyopathy etiologies. This improvement has a significant prognostic impact.

To develop and validate a risk prediction model for adverse outcomes in patients with angina with non-obstructive coronary arteries (ANOCA) confirmed by invasive coronary angiography.

Retrospective cohort study.

A tertiary cardiovascular care centre in China.

From 17 816 consecutive patients undergoing coronary angiography for suspected coronary artery disease, 5934 met ANOCA criteria after rigorous exclusion: (1) significant stenosis (≥50% luminal narrowing), (2) established coronary artery disease history, (3) incomplete baseline/follow-up data, (4) non-cardiovascular life-limiting conditions.

The primary outcome was a composite of all-cause death, non-fatal myocardial infarction (MI), stroke and repeat percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). The secondary outcome was major adverse cardiovascular events, defined as cardiac-related death, non-fatal MI, non-fatal stroke, repeat PCI and CABG.

The derivation cohort (n=4452) and validation cohort (n=1482) demonstrated comparable baseline characteristics. The nomogram incorporated eight prognosticators: age, haemoglobin, serum urea, serum sodium, alanine aminotransferase/aspartate aminotransferase ratio, N-terminal pro-B-type natriuretic peptide (NT-proBNP), left atrial diameter and left ventricular ejection fraction. The prediction model showed robust discrimination for primary endpoint, achieving area under the curve (AUC) values of 0.82 (1 year), 0.90 (2 years) and 0.89 (3 years) in the derivation cohort, with corresponding validation cohort AUCs of 0.75, 0.77 and 0.78. Calibration plots revealed close alignment between predicted and actual event-free survival probabilities in both cohorts. Risk stratification identified two distinct prognostic groups with significant survival differences (log-rank p<0.0001).

This predictive model integrates routinely available clinical parameters to accurately stratify mortality and cardiovascular risk in ANOCA patients, providing a potential valuable decision-support tool for personalised therapeutic strategies.

Heart failure (HF) secondary to tachycardia-induced cardiomyopathy (TIC) is often underdiagnosed due to inconsistent definitions and perceived reversibility. The treatment focuses on early arrhythmia control, but the impact of guideline-directed medical therapy (GDMT) on left ventricular ejection fraction (LVEF) improvement has not been fully explored.

This multicentric prospective registry study included patients with newly onset HF and reduced ejection fraction (HFrEF). Data were collected on clinical characteristics, echocardiographic and laboratory parameters, pharmacological treatment, and follow-up events. The statistical analyses focused on TIC patients, analyzing the event rates and the influence of GDMT on LVEF improvement according to sinus rhythm (SR) restoration.

Among 808 patients, 174 (21.5%) were diagnosed with TIC, with an age of 67.2 (SD: 9.4) years. After a median follow-up of 3.5 months [IQR: 2.6-4.3], SR was restored in 56.8% of patients, and LVEF improved from 29.6 to 49%. The increase was more pronounced in patients who restored SR compared to those remaining in atrial fibrillation (AF) (22.4% vs. 15.1%; p < 0.05). The natriuretic peptides significantly decreased in the SR group (- 1883.7 pg/mL) but did not in the AF group. The overall readmission rate was 25.1% and the overall mortality rate was 3.6%, with no significant differences between patients who achieved SR and those with persistent AF at the end of up-titration. HF readmission was infrequent (4%) despite AF persistence. Early GDMT was initiated in TIC patients, regardless of SR recovery and significantly improved LVEF, especially in AF patients [RR = 4.24 (95% CI: 1.44-12.45)] compared to SR patients [(RR = 1.41 95% CI: 1.02-1.92)].

TIC represents a significant proportion of HFrEF patients, with early restoration of SR leading to greater LVEF improvement. Despite AF persistence, HF readmissions were rare, highlighting the efficacy of early quadruple therapy. Enhanced adherence to GDMT should be prioritized, particularly in patients with persistent AF.

Cardiac sarcoidosis (CS) affects between 5 % to 25 % of systemic sarcoid cases. CS patients may present with heart failure (HF), with ultimate progression to advanced heart failure (AHF) associated with heightened mortality.

American guidelines emphasise using the 'I NEED HELP' criteria to identify AHF patients. The European Society of Cardiology (ESC) have alternative AHF diagnostic criteria. Both have demonstrated prognostic value, but their utility in prognosticating CS is unknown. This study aimed to address this.

109 patients, with baseline left ventricular ejection fraction (LVEF) <50 %, referred to the Royal Brompton Hospital between 2006 and 2019, were analysed. 48 patients had ≥1 'I NEED HELP' criteria consistent with AHF. Comparisons were made between the AHF and non-AHF CS patients. Sub-analysis was performed between the AHF patients that did or did not meet ESC-AHF criteria. Primary combined outcome measure was all-cause-mortality, urgent orthotopic cardiac transplant or urgent left ventricular assist device insertion. Secondary outcome measure was sustained ventricular tachycardia.

The AHF cohort had significantly lower LVEF and higher brain natriuretic peptide values. More AHF CS patients reached combined primary outcome measure (AHF 16/48 [33 %]), than the non-AHF group (8/61 [13 %]), p < 0.019. The AHF group had shorter time to both primary and secondary events on Kaplan-Meier analysis (logrank p < 0.014 and p < 0.040 respectively). Sub-analysis revealed the ESC-AHF group had the poorest prognoses according to both outcome measures.

In this study, both the AHA and ESC-AHF criteria had prognostic value. The ESC-AHF criteria best identifies CS patients with poorest prognoses.

The management of a chronic total occlusion (CTO) of a coronary artery has been a conundrum in interventional cardiology, as revascularization has not been proven to provide a mortality benefit. However, there are subgroups of patients with a CTO that have high levels of ischemia on myocardial perfusion imaging and high circulating levels of high sensitivity troponin-I (hsTn-I) and N terminal pro-brain natriuretic peptide (NT pro-BNP) that are at a particularly high-risk for adverse cardiovascular events. These high-risk subgroups of patients with a CTO may have not been well represented in prior clinical trials, and may gain a mortality benefit from revascularization of the CTO. Conversely, patients with low levels of ischemia and these biomarkers are at lower risk and may not gain a mortality benefit from revascularization of their CTO. It is important for future randomized controlled trials to investigate the efficacy of CTO PCI in patients with elevated biomarkers and high ischemic burden on myocardial perfusion imaging to determine if patients at high-risk gain a mortality benefit from revascularization.

As there is limited evidence regarding the prognostic impact of prior left ventricular ejection fraction (LVEF) in patients with heart failure with mildly reduced ejection fraction (HFmrEF), this study investigates the prognostic impact of longitudinal changes in LVEF in patients with HFmrEF.

Consecutive patients with HFmrEF (i.e. LVEF 41-49% with signs and/or symptoms of HF) were included retrospectively in a monocentric registry from 2016 to 2022. Based on prior LVEF, patients were categorized into three groups: stable LVEF, improved LVEF, and deteriorated LVEF. The primary endpoint was 30-months all-cause mortality (median follow-up). Secondary endpoints included in-hospital and 12-months all-cause mortality, as well as HF-related rehospitalization at 12 and 30 months. Kaplan-Meier and multivariable Cox proportional regression analyses were applied for statistics.

Six hundred eighty-nine patients with HFmrEF were included. Compared to their prior LVEF, 24%, 12%, and 64% had stable, improved, and deteriorated LVEF, respectively. None of the three LVEF groups was associated with all-cause mortality at 12 (p ≥ 0.583) and 30 months (31% vs. 37% vs. 34%; log rank p ≥ 0.376). In addition, similar rates of 12- (p ≥ 0.533) and 30-months HF-related rehospitalization (21% vs. 23% vs. 21%; log rank p ≥ 0.749) were observed. These findings were confirmed in multivariable regression analyses in the entire study cohort.

The transition from HFrEF and HFpEF towards HFmrEF is very common. However, prior LVEF was not associated with prognosis, likely due to the persistently high dynamic nature of LVEF in the follow-up period.

Although hypertension is a risk factor for cardiovascular (CVD) events in stage B heart failure (HF), data on the prognostic value of home blood pressure (BP) measurements in stage B HF are limited. We retrospectively analyzed the cases of 568 patients with stage B HF and at least one cardiovascular risk factor who underwent home BP monitoring. Stage B HF was defined as BNP ≥ 35 pg/mL or NT-proBNP ≥125 pg/mL, Troponin T > 0.014 ng/mL, LVEF < 50%, enlarged left ventricular dimensions in diastole (men: ≥60 mm; women: ≥54 mm), enlarged left atrium (men: >40 mm; women: >38 mm), or increased left ventricular mass (men: >115 g/m2; women: >95 g/m2). Office hypertension was defined as systolic BP ≥ 140 mmHg. Home BP was measured in the morning, evening, and nighttime; morning/evening home hypertension was defined as ≥135 mmHg and nighttime home hypertension as ≥120 mmHg. During a mean follow-up of 7.8 ± 3.6 years, 66 CVD events occurred. An unadjusted Cox regression model gave the following hazard ratios (HRs) and 95% confidence intervals (CIs) for CVD-events risk in patients with office, morning, evening, and nighttime home hypertension: HR 1.69 (95% CI 1.03-2.78), 1.73 (1.02-2.95), 1.44 (0.89-2.33) and 2.33 (1.34-4.04), respectively. In a multivariate Cox regression analysis adjusting for significant variables, the association with CVD events remained only for nighttime home hypertension (HR 1.89; 95% CI 1.06-3.38), not other hypertension types. In conclusion, hypertension defined based on nighttime home BP was associated with CVD-events risk in stage B HF patients.

With rising incidence, mortality and limited therapeutic options, heart failure with preserved ejection fraction (HFpEF) remains one of the most important topics in cardiovascular medicine today. Characterised by left ventricular diastolic dysfunction partially due to impaired Ca2+ homeostasis, one ion channel in particular, SarcoEndoplasmic Reticulum Ca2+-ATPase (SERCA2a), may play a significant role in its pathophysiology. A better understanding of the complex mechanisms interplaying to contribute to SERCA2a dysfunction will help develop treatments targeting it and thus address the growing clinical challenge HFpEF poses. This review examines the conflicting evidence present for changes in SERCA2a expression and activity in HFpEF, explores potential underlying mechanisms, and finally evaluates the drug and gene therapy trials targeting SERCA2a in heart failure. Recent positive results from trials involving widely used anti-diabetic agents such as sodium-glucose co-transporter protein 2 inhibitors (SGLT2i) and glucagon-like peptide-1 (GLP-1) agonists offer advancement in HFpEF management. The potential interplay between these agents and SERCA2a regulation presents a novel angle that could open new avenues for modulating diastolic function; however, the mechanistic research in this emerging field is limited. Overall, the direct role of SERCA2a dysfunction in HFpEF remains undetermined, highlighting the need for well-designed pre-clinical studies and robust clinical trials.

Heart failure is the leading cardiovascular cause of hospitalization with an increasing prevalence, especially in older patients. About 50% of patients with heart failure have preserved ventricular function, a form of heart failure that, until a few years ago, was orphaned by pharmacological treatments effective in reducing hospitalization and mortality. New trials, which have tested the use of gliflozins in patients with heart failure with preserved ejection fraction (HFpEF), have for the first time demonstrated their effectiveness in changing the natural history of this insidious and frequent form of heart failure. Therefore, diagnosing those patients early is crucial to provide the best treatment. Moreover, the diagnosis is influenced by the patient's comorbidities, and some HFpEF patients have symptoms common to other rare diseases that, if unrecognized, develop an unfavourable prognosis. This position paper aims to provide the clinician with a useful tool for diagnosing and treating patients with HFpEF, guiding the clinician towards the most appropriate diagnostic and therapeutic pathway.