Search Results (3,448)

Background/Objectives: Historically, echocardiographic imaging of the right heart has been challenging because its abnormal geometry is not conducive to reproducible anatomical and functional assessment. With the development of advanced echocardiographic techniques, it is now possible to complete an integrated assessment of the right heart that has fewer assumptions, resulting in increased accuracy and precision. Echocardiography continues to be the first-line imaging modality for diagnostic analysis and the management of acute and chronic right heart failure because of its portability, versatility, and affordability compared to cardiac computed tomography, magnetic resonance imaging, nuclear scintigraphy, and positron emission tomography. Virtually all echocardiographic parameters have been well-validated and have demonstrated prognostic significance. The goal of this narrative review of the echocardiographic parameters of the right heart chambers and hemodynamic alterations associated with right ventricular dysfunction is to present information that must be acquired during each examination to deliver a comprehensive assessment of the right heart and to discuss their clinical significance in right heart failure. Methods: Using a literature search in the PubMed database from 1985 to 2025 and the Cochrane database, which included but was not limited to terminology that are descriptive of right heart anatomy and function, disease states involving acute and chronic right heart failure and pulmonary hypertension, and the application of conventional and advanced echocardiographic modalities that strive to elucidate the pathophysiology of right heart failure, we reviewed randomized control trials, observational retrospective and prospective cohort studies, societal guidelines, and systematic review articles. Conclusions: In addition to the conventional 2-dimensional echocardiography and color, spectral, and tissue Doppler measurements, a contemporary echocardiographic assessment of a patient with suspected or proven right heart failure must include 3-dimensional echocardiographic-derived measurements, speckle-tracking echocardiography strain analysis, and hemodynamics parameters to not only characterize the right heart anatomy but to also determine the underlying pathophysiology of right heart failure. Complete and point-of-care echocardiography is available in virtually all clinical settings for routine care, but this imaging tool is particularly indispensable in the emergency department, intensive care units, and operating room, where it can provide an immediate assessment of right ventricular function and associated hemodynamic changes to assist with real-time management decisions. Full article

Background: Clinical outcomes among older adults hospitalized with heart failure with preserved ejection fraction (HFpEF) in the setting of metabolically healthy obesity (MHO) remain insufficiently explored. This study aimed to evaluate whether MHO status is associated with different rates of major adverse cardiac and cerebrovascular events (MACCEs) during HFpEF-related hospitalizations compared to patients without MHO. Methods: Data from the 2019 National Inpatient Sample (NIS) database was analyzed using relevant ICD-10 codes to identify HFpEF admissions in older adults. Propensity score matching (1:1) was applied to generate balanced cohorts of patients with and without MHO. Multivariable adjustments were performed to assess primary outcomes, including MACCEs, all-cause mortality (ACM), acute myocardial infarction (AMI), dysrhythmia, cardiac arrest (CA), and stroke. Statistical significance was set at p < 0.05. Results: Each MHO cohort included 22,405 patients with a median age of 75 years. The MHO+ group demonstrated a significantly higher risk of dysrhythmia (OR 1.32, 95% CI 1.21–1.43, p < 0.001). Interestingly, an “obesity paradox” was observed, as the MHO+ cohort had lower odds of MACCEs (OR 0.70, 95% CI 0.61–0.81, p < 0.001), ACM (OR 0.66, 95% CI 0.54–0.82, p < 0.001), and AMI (OR 0.71, 95% CI 0.59–0.86, p = 0.001) compared to MHO−. No significant differences were found for CA or stroke between the groups. Conclusions: Although the MHO+ group had an elevated risk of dysrhythmia, they exhibited more favorable outcomes in terms of MACCEs, ACM, and AMI—supporting the concept of an “obesity paradox.” Further research is needed to better understand the role of MHO as a comorbid condition in patients with HFpEF. Full article

Background: Standard room temperature housing (~22 °C) represents a stress for laboratory mice, resulting in an increased metabolic rate, calorie consumption, heart rate, and catecholamine levels compared to thermoneutral conditions (29–32 °C). Using a recently established two-hit model of heart failure with preserved ejection fraction (HFpEF) (Angiotensin II + High-fat diet for 28 days; MHS), we investigated how housing temperature modulates cardiac remodelling and function in male and female C57Bl/6J mice. Methods: Using the MHS mouse model, we investigated cardiac remodelling and function in 8-week-old C57BL/6J mice of both sexes housed at 10 °C, 22 °C, and 30 °C for four weeks. Control mice were analyzed in parallel. Before the MHS, the animals were allowed to acclimate for a week before the MHS started. Results: Mice housed at 10 °C consumed more food and had increased fat mass compared to those at 22 °C or 30 °C. This was accompanied by increased heart weight, stroke volume, heart rate, and cardiac output. Mice housed at 22 °C and 30 °C were similar for these cardiac parameters. Following MHS, mice at 10 °C and 22 °C developed marked cardiac hypertrophy, whereas thermoneutral housing attenuated this response and reduced left atrial enlargement. Cold-exposed females showed more diastolic dysfunction after MHS (increased E’ wave, E/E’, and isovolumetric relaxation time) than those at 22 °C or 30 °C. Ejection fraction and cardiac output declined significantly at 10 °C after MHS but were preserved at 22 °C and 30 °C in females. Conclusions: Cold housing exacerbates cardiac dysfunction in mice subjected to HFpEF-inducing stress, with pronounced effects in females. In contrast, thermoneutrality limits the cardiac hypertrophic response. Full article

The aim of the present observational study was to evaluate the early effect of free-form essential amino acid (EAA) supplementation on cardiac and muscular performance in elderly patients with chronic heart failure (HF) with reduced ejection fraction (HFrEF) and sarcopenia, as add-on to the optimized medical therapy (OMT) for HF. The present study included 60 elderly Caucasian patients suffering from HFrEF and sarcopenia. At the baseline and at follow-up, all patients underwent complete physical examination with the determination of the main anthropometric and hemodynamic parameters. After 6 months of supplementation with EAAs, we observed significant improvements in the parameters of sarcopenia. In addition, there was a significant improvement in glycol-metabolic parameters, and in inflammatory index as high sensitivity C-reactive protein (hs-CRP). In accordance with these results, significant decreases were observed in circulating levels of oxidative stress biomarkers Nox-2 (p < 0.001) and 8-Isoprostane (p < 0.001), and platelet aggregation biomarkers such as sP-Selectin (p < 0.001) and Gp-VI (p < 0.001). Of particular interest, after 6 months’ follow-up, there was a significant improvement in LVEF and global longitudinal strain (GLS). In conclusion, this study demonstrates that targeted nutritional intervention with EEAAs represents a viable therapeutic strategy for addressing the complex interplay between cardiac dysfunction and skeletal muscle wasting in elderly HF patients. Full article

Background: Minimally invasive cardiac surgery (MICS) via right minithoracotomy is a safe, reproducible approach with excellent outcomes and reduced costs compared to median sternotomy. Despite careful patient selection, conversion to sternotomy occurs in 1–3% of cases and is associated with significantly higher morbidity and mortality. Small body habitus, particularly a short anteroposterior (AP) diameter, may increase the risk of conversion, but this has not been previously studied. This study aims to identify preoperative factors associated with conversion to improve patient selection for MICS. As cardiovascular surgery becomes increasingly personalized, identifying anatomical factors that predict technical complexity is essential. Methods: This retrospective study included 254 adult patients who underwent elective MICS between 2015 and 2024 at a tertiary hospital. Patient characteristics, computed tomography (CT) scans, intraoperative parameters, and postoperative outcomes were reviewed. AP diameter was defined as the distance from the posterior sternum to the anterior vertebral body at the mitral valve level on CT. Statistical analyses included Mann−Whitney and Fisher’s exact/chi-square tests. Results: Conversion to sternotomy occurred in 1.6% of patients (n = 4). All converted patients were female. The converted group had a significantly shorter median AP diameter (100 mm vs. 124 mm, p = 0.020). Conversion was associated with higher rates of stroke and infection (25.0% vs. 0.8%, p = 0.047 for both), but no significant differences in hospital stay, bleeding, or renal failure. Conclusions: An AP diameter of less than 100 mm was associated with a higher risk of conversion to sternotomy in MICS. Incorporating simple, reproducible preoperative imaging metrics into surgical planning may advance precision-guided cardiac surgery and optimize patient outcomes. Full article

The image represents the post-mortem heart of a 28-year-old female patient, diagnosed in childhood with complete common atrioventricular canal defect. At time of diagnosis, the family refused surgery, as did the patient during her adulthood. Despite being advised against pregnancy, she became pregnant. On presentation to hospital, she was cyanotic, with clubbed fingers, and hemodynamically unstable, in sinus rhythm, with Eisenmenger syndrome and respiratory failure partially responsive to oxygen. During pregnancy, owing to systemic vasodilatation, the right-to-left shunt is increased, with more severe cyanosis and low cardiac output. Echocardiography revealed the complete common atrioventricular canal defect, with a single atrioventricular valve with severe regurgitation, right ventricular hypertrophy, pulmonary artery dilatation, severe pulmonary hypertension and a hypoplastic left ventricle. The gestational age at delivery was 38 weeks. She gave birth to a healthy boy, with an Apgar score of 10. The vaginal delivery was chosen by an interdisciplinary team. The cesarean delivery and the anesthesia were considered too risky compared to vaginal delivery. Three days later, the patient died. The autopsy revealed hepatomegaly, a greatly hypertrophied right ventricle with a purplish clot ascending the dilated pulmonary arteries and a hypoplastic left ventricle with a narrowed chamber. A single valve was observed between the atria and ventricles, making all four heart chambers communicate, also insufficiently developed interventricular septum and its congenital absence in the cranial third. These morphological changes indicate the complete common atrioventricular canal defect, with right ventricular dominance, which is a rare and impressive malformation that requires mandatory treatment in early childhood in order for the condition to be solved. Full article

Hibiscus syriacus L. (HS), native to Eastern and Southern Asia, has been traditionally used in Asian herbal medicine for its anticancer, antimicrobial, and anti-inflammatory properties. Despite these recognized bioactivities, its potential cardioprotective effects, particularly in the setting of heart failure (HF), remain largely unexplored. This study aimed to investigate the effects of HS extracts and its bioactive constituents on angiotensin II (Ang II)-induced cardiac injury using an in vitro model with H9c2 rat cardiomyocytes. Cells exposed to Ang II were pretreated with HS extracts, and assays were performed to assess cell viability, reactive oxygen species (ROS) generation, protein synthesis, and secretion of inflammatory mediators, including tumor necrosis factor-alpha, interleukin 1β (IL-1β), and interleukin 6 (IL-6), as well as chemokine (CCL20) and HF-related biomarkers, such as brain natriuretic peptide (BNP) and endothelin-1. The results demonstrated that HS extracts significantly and dose-dependently attenuated Ang II-induced ROS accumulation and suppressed the secretion of pro-inflammatory cytokines, chemokines, BNP, and endothelin-1. Additionally, HS and its purified components inhibited Ang II-induced protein synthesis, indicating anti-hypertrophic effects. Collectively, these findings highlight the antioxidative, anti-inflammatory, and antihypertrophic properties of HS in the context of Ang II-induced cardiac injury, suggesting that HS may represent a promising adjunctive therapeutic candidate for HF management. Further in vivo studies and mechanistic investigations are warranted to validate its clinical potential. Full article

Background/Objectives: Iron deficiency (ID) is a common and prognostically relevant comorbidity in heart failure with reduced ejection fraction (HFrEF). It contributes to reduced functional status, exercise capacity, and survival. Intravenous ferric carboxymaltose (FCM) improves symptoms, but its effect on cardiac structure and function remains incompletely understood. The aim of this study was to assess the impact of intravenous FCM on echocardiographic indices of left ventricular (LV), left atrial (LA), and right ventricular (RV) morphology and function in HFrEF patients with ID and determine whether these changes correlate with improvements in exercise capacity. Methods: This sub-analysis of the RESAFE-HF registry (NCT04974021) included 86 HFrEF patients with ID (median age 71.8 years, 83% male). Transthoracic echocardiography was performed at baseline and 12 months post-FCM. Parameters assessed included LV ejection fraction (LVEF), LV global longitudinal strain (GLS), LV diastolic function grade, LAVi, LA strain, TAPSE, and RV free wall strain (FWS). Peak VO₂ was measured to assess exercise capacity. Results: LVEF improved from 29.3 ± 7.8% to 32.5 ± 10.6% (p < 0.001), LV GLS from −7.89% to −8.62%, and the LV diastolic dysfunction grade improved (p < 0.001). LAVi, peak LA strain, TAPSE, and RV FWS also showed significant improvement. Peak VO₂ increased from 11.3 ± 3.2 to 12.1 ± 4.1 mL/min/kg (p < 0.001). Improvements in LVEF, RV FWS, and LV GLS were independent predictors of VO₂ increase (p < 0.001, p < 0.001, and p = 0.01, respectively), explaining 42% of the variance. Conclusions: FCM therapy improves biventricular and atrial function, with echocardiographic gains correlating with an enhanced exercise capacity in HFrEF patients with ID. Full article

Aims: Sinus tachycardia after heart transplantation (HTX) due to cardiac graft denervation is associated with reduced post-transplant survival and requires adequate treatment. We analyzed the long-term effects of heart rate control with ivabradine or metoprolol succinate in HTX recipients. Methods: This observational retrospective single-center study analyzed the ten-year results of 110 patients receiving ivabradine (n = 54) or metoprolol succinate (n = 56) after HTX. Analysis included comparison of demographics, medications, heart rates, blood pressure values, echocardiographic features, cardiac catheterization data, cardiac biomarkers, and post-transplant survival including causes of death. Results: Both groups showed no significant differences concerning demographics or medications (except for ivabradine and metoprolol succinate). At 10-year follow-up, HTX recipients with ivabradine showed a significantly lower heart rate (72.7 ± 8.5 bpm) compared to baseline (88.8 ± 7.6 bpm; p < 0.001) and to metoprolol succinate (80.1 ± 8.1 bpm; p < 0.001), a significantly lower NT-proBNP level (588.4 ± 461.4 pg/mL) compared to baseline (3849.7 ± 1960.0 pg/mL; p < 0.001) and to metoprolol succinate (1229.0 ± 1098.6 pg/mL; p = 0.005), a significantly lower overall mortality (20.4% versus 46.4%; p = 0.004), and mortality due to graft failure (1.9% versus 21.4%; p = 0.001). Multivariate analysis showed a significantly decreased risk of death within 10 years after HTX in patients with post-transplant use of ivabradine (HR 0.374, CI 0.182–0.770; p = 0.008). Conclusions: In this single-center trial, patients with ivabradine revealed a significantly more pronounced heart rate reduction, a lower NT-proBNP level, and a superior 10-year survival after HTX. Full article

Background/Objectives: Pulmonary vein isolation (PVI) via cryoballoon ablation (CBA) is a recommended therapeutic strategy for patients with symptomatic paroxysmal and persistent atrial fibrillation (AF) who are refractory to antiarrhythmic drugs. Although PVI has demonstrated efficacy in reducing AF recurrence and improving patients’ quality of life, its impact on respiratory function is not well understood, particularly in patients with comorbid conditions. The aim of the study was to search for functional predictors of the respiratory system in the process of evaluating the efficiency of clinical assessment of CBA in patients with AF. Methods: We conducted a prospective study on 42 patients with symptomatic AF who underwent CBA, assessing their respiratory function through spirometry before and 30 days after the procedure. Exclusion criteria included pre-existing lung disease and cardiac insufficiency. The impact of variables such as body mass index (BMI), coronary artery disease (CAD) and heart failure (HF) on spirometry parameters was analyzed using statistical tests. Results: No significant changes were observed in overall post-PVI spirometry parameters for the full cohort. However, post hoc analyses revealed a significant decline in ΔMEF₇₅ in patients with CAD and BMI ≥ 30 kg/m², whereas ΔFEV₁/FVCex was significantly increased in patients with HF, as well as in patients with ejection fraction (EF) < 50%. Conclusions: CBA for AF does not universally affect respiratory function in the short term, but specific subgroups, including patients with CAD and a higher BMI, may require post-procedure respiratory monitoring. In addition, PVI may improve lung function in patients with HF and reduced EF. Full article

Pathologies of the heart (e.g., ischemic disease, valve fibrosis and calcification, progressive myocardial fibrosis, heart failure, and arrhythmogenic disorders) stem from the irreversible deterioration of cardiac tissues, leading to severe clinical consequences. The limited regenerative capacity of the adult myocardium and the architectural complexity of the heart present major challenges for tissue engineering. However, recent advances in biomaterials and biofabrication techniques have opened new avenues for recreating functional cardiac tissues. Particularly relevant in this context is the integration of biomimetic design principles, such as structural anisotropy, mechanical and electrical responsiveness, and tissue-specific composition, into 3D bioprinting platforms. This review aims to provide a comprehensive overview of current approaches in cardiac bioprinting, with a focus on how structural and functional biomimicry can be achieved using advanced hydrogels, bioprinting techniques, and post-fabrication stimulation. By critically evaluating materials, methods, and applications such as patches, vasculature, valves, and chamber models, we define the state of the art and highlight opportunities for developing next-generation bioengineered cardiac constructs. Full article

Introduction: Congestive heart failure (CHF), a complex clinical syndrome characterized by the heart’s inability to pump blood effectively due to structural or functional impairments, is a growing public health concern, with profound implications for patients’ physical and emotional well-being. In India, the burden of CHF is rising due to aging demographics and increasing prevalence of lifestyle-related risk factors. Among the subtypes of CHF, heart failure with preserved ejection fraction (HFpEF), i.e., heart failure with left ventricular ejection fraction of ≥50% with evidence of spontaneous or provokable increased left ventricular filling pressure, and heart failure with reduced ejection fraction (HFrEF), i.e., heart failure with left ventricular ejection fraction of 40% or less and is accompanied by progressive left ventricular dilatation and adverse cardiac remodeling, may present differing impacts on health-related quality of life (HRQoL), i.e., an individual’s or a group’s perceived physical and mental health over time, yet comparative data remains limited. This study assesses HRQoL among CHF patients using the Minnesota Living with Heart Failure Questionnaire (MLHFQ), one of the most widely used health-related quality of life questionnaires for patients with heart failure based on physical and emotional dimensions and identifies sociodemographic and clinical variables influencing these outcomes. Methods: A cross-sectional analytical study was conducted among 233 CHF patients receiving inpatient and outpatient care at the Department of Cardiology at a quaternary care teaching hospital in coastal Karnataka in India. Participants were enrolled using convenience sampling. HRQoL was evaluated through the MLHFQ, while sociodemographic and clinical characteristics were recorded via a structured proforma. Statistical analyses included descriptive measures, independent t-test, Spearman’s correlation and stepwise multivariable linear regression to identify associations and predictors. Results: The mean HRQoL score was 56.5 ± 6.05, reflecting a moderate to high symptom burden. Patients with HFpEF reported significantly worse HRQoL (mean score: 61.4 ± 3.94) than those with HFrEF (52.9 ± 4.64; p < 0.001, Cohen’s d = 1.95). A significant positive correlation was observed between HRQoL scores and age (r = 0.428; p < 0.001), indicating that older individuals experienced a higher burden of symptoms. HRQoL also varied significantly across NYHA functional classes (χ² = 69.9, p < 0.001, ε² = 0.301) and employment groups (χ² = 17.0, p < 0.001), with further differences noted by education level, gender and marital status (p < 0.05). Multivariable linear regression identified age (B = 0.311, p < 0.001) and gender (B = –4.591, p < 0.001) as significant predictors of poorer HRQoL. Discussion: The findings indicate that patients with HFpEF experience significantly poorer HRQoL than those with HFrEF. Older adults and female patients reported greater symptom burden, underscoring the importance of demographic-sensitive care approaches. These results highlight the need for routine integration of HRQoL assessment into clinical practice and the development of comprehensive, personalized interventions addressing both physical and emotional health dimensions, especially for vulnerable subgroups. Conclusions: CHF patients, especially those with HFpEF, face reduced HRQoL. Key factors include age, gender, education, employment, marital status, and NYHA class, underscoring the need for patient-centered care. Full article

Tricuspid regurgitation (TR) is a well-recognized factor contributing to adverse outcomes and mortality. Recent developments in transcatheter valve repair techniques, with the emergence of tricuspid transcatheter edge-to-edge repair (TEER) devices, have altered the treatment algorithm of TR and now offer a safe and feasible alternative for the effective management of the disease and an improvement in patient symptoms. Evidence from large studies and registries showcases the benefit of tricuspid interventions in terms of heart failure hospitalization and quality of life; however, most studies do not report a significant benefit in terms of hard outcomes. Even though longer-term follow-up may be needed to identify such differences, it is important to also identify distinct patient phenotypes that would benefit the most from such interventions, moving from pure anatomical criteria to an overall assessment of the patient’s clinical status. Therefore, the aim of this review is to provide updates on potential moderators of the effect of tricuspid TEER, focusing on novel anatomical criteria, right cardiac function, and renal physiology, in order to guide patient selection and provide an insightful discussion on the optimal patient phenotype for future trial design. Full article

(1) Background: Comparison of clinical outcomes between patients with moderate-severe aortic valve stenosis and those with mild or no aortic valve stenosis undergoing surgical revascularization for critical limb threating ischemia (CLTI). (2) Methods: Single center retrospective analysis of consecutive patients undergoing surgical lower limb revascularization with femoro-distal bypass for critical ischemia between 2016 and 2022. All patients were evaluated preoperatively by echocardiographic examination and divided into two cohorts: group A with moderate-severe aortic valve stenosis (AVA-cm² < or =1.5 cm²) and group B with mild or absent stenosis (AVA-cm² > 1.5 cm²). Primary outcomes were major limb amputation and mortality between the two groups. The rate of major cardiovascular events (stroke, myocardial infarction, sudden cardiac death) and change in “preoperative functional status” were the secondary outcomes. Descriptive statistics for continuous variables were performed by calculating means, standard deviation (SD) medians, and interquartile range (IQR) while, for categorical variables, frequencies and percentages were performed. Intergroup comparison tests, for continuous variables, were performed by t-test or corresponding nonparametric tests (Mann-Whitney test) while, for categorical variables, Chi-square test was used. Evaluation of cut-offs for the variable AVA-fx-cm², in terms of predictive of outcome outcomes, was calculated by ROC curves. Comparison between clinical and outcome variables was performed using logistic regression models. A total of 316 patients were analyzed and divided in two groups: 50 (16%) patients with moderate or severe aortic valve stenosis (group A) and 266 (84%) with no or mild aortic valve stenosis (AVA > 1.5 cm²). Patients in group A were significantly older than those in group B (78 years vs. 74 years, p value = 0.005); no other significant comorbidity differences were found between the two groups. The mean follow-up was 1178 days (SD 991 days; 2–3869 days). There were no statistically significant differences between group A and group B in terms of major amputation rate (20% vs. 16.5%; p = 0.895) and overall mortality (48.0% vs. 40.6%; p = 0.640). In the total cohort, the statistically significant variables associated with the major amputation were systemic perioperative complication (OR 5.83, 95% CI: 2.36, 14.57, p < 0.001), bypass-related complication within 30 days of surgery (OR 2.74, 95% CI: 1.17, 6.45, p = 0.020), surgical revascularization below the knee (OR 7.72, 95% CI: 1.53, 140.68, p = 0.049), and the presence of a previous cardiovascular event (OR 2.65, 95% CI: 1.14, 6.26, p = 0.024). In patients undergoing surgical revascularization for CLTI, no significant difference in major amputation rate and overall mortality was found between subjects with mild or no aortic valve stenosis and those with moderate/severe stenosis. As expected, overall mortality was higher in older patients with worse functional status. A significantly higher rate of limb amputation was found in those subjects undergoing subgenicular revascularization, early bypass failure, or previous cardiovascular event. Full article

Background: TNF receptor 1 (TNF-R1) mediates the proinflammatory and proapoptotic effects of TNF-alpha, with its soluble form predicting incident heart failure (HF). While there is evidence linking TNF pathway activation to cardiac dysfunction, the mechanisms involved remain unclear. This study aimed to investigate the association between TNF-R1, exercise capacity, and cardiac function in asymptomatic patients with hypertensive heart disease (HHD). Methods: We enrolled 80 patients (mean age 55 ± 12 years) with HHD and no clinical symptoms of HF (stages A and B). Echocardiography, including tissue Doppler and left atrial and left ventricular (LV) strain assessment, was performed at rest. Peripheral venous blood samples were collected to measure serum TNF-R1 concentration. Results: The study population was divided into two subsets based on the median exercise capacity (peak VO₂) value. Patients with higher VO₂ had lower serum TNF-R1 concentration and higher early peak mitral annular velocity (e’) and peak atrial longitudinal strain (PALS). After adjusting for other covariates, multivariable regression analysis identified TNF-R1 as an independent determinant of peak VO₂. Mediation analysis revealed that the relationship between TNF-R1 and peak VO₂ was mediated by LV diastolic function (PALS or e’), with a decrease in the beta coefficient after including mediator variables from 0.37 (p < 0.001) to 0.30 (p < 0.006) and 0.31 (p = 0.004), respectively. Conclusions: In patients with HHD, higher TNF-R1 levels are associated with lower exercise capacity, which may be mediated by impaired LV diastolic function. These findings might suggest a role of TNF signalling in early HF development, justifying further studies to evaluate TNF-R1 as a biomarker for risk of HF progression. Full article