(1) Background: Assessment of right ventricular (RV) function has become increasingly important in echocardiography due to its prognostic significance in cardiac and systemic diseases. (2) Objectives: Tricuspid Annular Plane Systolic Excursion (TAPSE) and Tissue Doppler Imaging (TDI S') are commonly used methods to assess RV function. The aim of this study was to compare the reproducibility of TAPSE and TDI S' among experienced operators. (3) Methods: A study was conducted on 100 consecutive patients with systemic sclerosis undergoing echocardiography evaluation screening for pulmonary hypertension. Standardized echocardiography images were acquired using a Philips EPIQ system (Philips Healthcare, Amsterdam, The Netherlands), measuring TAPSE and TDI S'. Five operators independently analyzed the images, with each blinded to the results. Exclusion criteria included pathological TAPSE or TDI S' values, as well as indirect echocardiography signs of pulmonary hypertension. (4) Results: The study's results indicate that there was superior inter-operator agreement for TDI S' (ICC = 0.891) compared to TAPSE (ICC = 0.47). The mean TAPSE measurements ranged from 23.49 mm to 23.99 mm, while TDI S' values ranged from 12.16 cm/s to 12.35 cm/s, with TDI S' showing narrower confidence intervals. (5) Conclusions: Echocardiographic assessment of right ventricular (RV) function is crucial in clinical practice. Tissue Doppler imaging-derived systolic velocity (TDI S') demonstrated superior reproducibility compared to tricuspid annular plane systolic excursion (TAPSE) in evaluating RV function. This enhanced reproducibility supports the routine incorporation of TDI S' as a highly reproducible parameter within a multiparametric assessment framework.

Heart failure (HF) is a complex systemic syndrome for which the HLM staging system has been proposed to better capture disease complexity. This study investigated the prognostic role of HLM staging according to SGLT2i status and the impact of in-hospital SGLT2i therapy across different stages of HF severity. In this prospective, multicenter, observational study, consecutive patients hospitalized for HF between November 2022 and August 2025 were enrolled and stratified according to HLM stage and according to SGLT2i status at discharge. The primary endpoint was the composite of cardiovascular (CV) death or HF hospitalization at 6-month follow-up. A total of 711 patients were included. The primary endpoint occurred in 82 patients with a significant increase across HLM stages (p < 0.001). Increasing HLM stage was associated with higher risk of adverse outcomes (HR = 1.40; 95% CI 1.02-1.90; p = 0.03), regardless of SGLT2i status. SGLT2i therapy initiation within the index hospitalization was independently associated with a lower risk of the composite endpoint (HR = 0.59; 95% CI 0.38-0.92; p = 0.02) across the HLM severity stages. In this cohort of HF patients, the HLM staging system provided potential clinically meaningful risk stratification irrespective of SGLT2i therapy, and SGLT2i therapy was associated with improved outcomes irrespective of HLM severity. These observations suggest a potential role for integrated pathophysiological staging in risk assessment and therapeutic evaluation.

Introduction: Primary Sjögren’s (pSS) is an autoimmune disease that affects several organs, especially the heart, and raises cardiovascular risk. Investigating the associations of hemoglobin-to-red cell distribution width (RDW) ratio (HRR), vitamin D status, and cardiac function could provide valuable insights and biomarkers regarding early cardiovascular risk in patients with pSS. Method: This cross-sectional study involved 61 patients diagnosed with pSS based on ACR/EULAR criteria. Data on demographics, hematological (Hb, RDW), echocardiography, and serum vitamin D levels were collected. Echocardiograms were conducted by trained cardiologists following established guidelines, while vitamin D levels were measured using ELISA. Statistical analyses, including univariate linear regression, were performed with SPSS in order to identify whether HRR tertiles were related to cardiac function and vitamin D status. Results: A study of 61 pSS patients (mean age 59.8 years, 89% female) revealed that patients with a lower hemoglobin-to-RDW ratio (HRR ≤ 0.98) had significantly higher pulmonary artery pressures (PAPs) and lower values for the tricuspid annular plane systolic excursion (TAPSE)/PAPs ratio, contributing to poor right heart function. These associations were particularly strong in patients with insufficient levels of vitamin D (<30 ng/mL), while differences in other echocardiographic parameters remained nonsignificant between HRR groups. Conclusions: These findings underscore the clinical value of HRR as a composite biomarker that reflects the interplay between anemia, inflammation, and cardiovascular health in primary Sjögren’s disease. They also suggest that vitamin D status may be an important therapeutic consideration to mitigate cardiopulmonary risks in this population.

Although metabolic, renal, and cardiovascular disorders frequently coexist, little is known about how illness combinations affect prognosis. Cardiovascular disease (CVD), which can manifest as coronary artery disease (CAD), stroke, heart failure (HF), arrhythmias, and sudden cardiac death, is more likely to develop in patients with chronic kidney disease (CKD). This link is closer with regard of heart failure (HF) and renal dysfunction, in which a reciprocal relationship has been demonstrated, with the initial illness of one organ causing the progressive dysfunction of the other system. Common risk factors for both illnesses include obesity, diabetes, metabolic disorders, hypertension, and dyslipemia. Theoretically, each of these factors accelerates the atherosclerotic process or directly damages the endothelium through inflammatory, oxidative, and pro-thrombotic pathways, which in turn causes the beginning of heart dysfunction and renal function deterioration. Although the mechanisms and causes have been identified, there are still a number of unanswered questions regarding classification, development, monitoring, and preventive aspects. Furthermore, the absence of reliable data on cardiac and renal outcomes across different stages contributes to creating confusion in CKM classification and management. This paper discusses the current challenges and perspectives in CKM definition and assessment proposing a specific diagnostic and laboratory fingerprint.

Introduction: Sjogren’s is an autoimmune disease that affects several organs, especially the heart, and raises cardiovascular risk. Investigating associations of hemoglobin-to-RDW ratio (HRR), vitamin D status, and cardiac function could provide valuable insights and biomarkers regarding early cardiovascular risk in patients with SD. Method: This cross-sectional study involved 61 patients diagnosed with primary Sjogren’s syndrome (pSS) based on ACR/EULAR criteria. Data on demographics, hematological (Hb, RDW), echocardiography, and serum vitamin D levels were collected. Echocardiograms were conducted by trained cardiologists following established guidelines, while vitamin D levels were measured using ELISA, and statistical analyses, including univariate linear regression, were adjusted for confounders. were performed with SPSS in order to identify whether HRR tertiles were related to cardiac function and vitamin D status. Results: A study of 61 Sjogren’s disease patients (mean age 59.8 years, 89% female) revealed that patients with a lower hemoglobin-to-RDW ratio (HRR ≤0.98) had significantly higher pulmonary artery pressures (PAPs) and lower values for the TAPSE/PAPs ratio, contributing to poor right heart function. These associations were particularly strong in patients with insufficient levels of vitamin D (< 30 ng/mL), while differences in other echocardiographic parameters remained nonsignificant between HRR groups. Conclusion: These findings underscore the clinical value of HRR as a composite biomarker that reflects the interplay between anemia, inflammation, and cardiovascular health in Sjogren’s disease. They also suggest that vitamin D status may be an important therapeutic consideration to mitigate cardiopulmonary risks in this population.

BACKGROUND:Paravalvular leaks (PVLs) are common complications following prosthetic valve implantation, significantly impacting patient outcomes due to associated heart failure and hemolysis. While percutaneous closure is a recognized alternative to surgery, challenging anatomies and multiple leaks can be difficult to manage with traditional single-access techniques. METHODS:We present a case of a patient with a mechanical mitral prosthesis and two clinically significant mitral PVLs-one anterior and one posterolateral. The patient presented with symptoms of heart failure and was experiencing transfusion-dependent hemolytic anemia. To address the PVLs, we employed a dual-access strategy. We used a standard transseptal anterograde approach to close the anterior PVL and a retrograde transfemoral arterial approach to close the larger posterolateral defect. Two dedicated PVLs occlude devices were successfully implanted without impacting the motion of the prosthetic leaflets. The total procedural time was 95 min, comprising 38 min of fluoroscopy and a total iodinated contrast volume of 120 mL. Fortunately, no periprocedural complications occurred. Upon follow-up, the patient demonstrated sustained clinical improvement, with resolution of hemolysis and only a trivial residual mitral PVL observed on echocardiography. RESULTS:The DASH approach combines two access routes to overcome the limitations of traditional single-access methods. By using the Venturi effect, we simplify the procedure, improve device maneuverability, and increase success rates, even in complex cases. CONCLUSION:In selected patients with multiple, anatomically complex mitral PVLs-particularly when catheter alignment, stability, or prosthetic leaflet interaction limits a single-access approach, a planned dual-access strategy may represent a complementary technical option to facilitate safe device delivery. Larger series and longer follow-up are needed to define the indications, safety profile, and durability of the DASH approach.

Background Loop diuretics are used to solve congestion in acute heart failure. However, a clear indication about the best infusion modality, dose, and duration of the treatment has not yet been established. In this analysis of the DIUR-AHF (Different Loop Diuretic Dosing and Administration in Acute Heart Failure) study, we aimed to investigate the effects of different diuretic administration modalities (ie, intermittent versus continuous furosemide infusion) and dose (high dose [HD] versus low dose) on congestion, renal function, and outcome. Methods Patients received intermittent or continuous intravenous loop diuretics infusion combined as a 1:1 ratio for a period of 72 to 120 hours. HD was defined as a high loop diuretic dose >120 mg/d. Clinical outcome was evaluated in terms of death or heart failure rehospitalization over a 6-month follow-up period. Results A total of 370 patients with AHF were included in this analysis, 189 treated with continuous intravenous loop diuretics infusion and 181 with intermittent intravenous loop diuretics infusion. At baseline, the continuous intravenous loop diuretic infusion group showed increased median values of blood urea (P=0.010) and creatinine (P=0.017). Dividing our sample according to loop diuretic dosage, the HD group revealed similar congestion and weight loss compared with the low-dose group; however, the HD group showed a reduced diuretic efficiency (-0.13 [-0.22 to -0.07] versus -0.32 [-0.59 to -0.20] kg/d; P<0.001) and an increased rate of adverse event occurrence (55% versus 20%; P<0.001). Multivariable analysis showed the association between HD treatment and poor postdischarge outcome (hazard ratio, 1.95 [95% CI, 1.23-3.10]; P=0.005). Conclusions An HD of loop diuretics infusion revealed an increased risk for adverse events together with reduced diuretic response. Our results extend previous findings revealing the association between HD diuretics and prognosis in patients with chronic HF. Additional studies may confer loop diuretic response in relation to the other decongestive treatments.

An increased production of reactive oxygen species and elevated levels of free fatty acids are linked to inflammation and vascular endothelial dysfunction. Here, we investigated the effects of two pharmacological inhibitors of the NLRP3 inflammasome, INF150 and INF195, on Human Coronary Artery Endothelial Cells (HCAECs) exposed to hydrogen peroxide (H2O2) and palmitic acid (PA), to mimic the oxidative and lipotoxic stress underlying endothelial dysfunction. HCAECs were pre-treated for 15 min with either INF150 or INF195, followed by exposure to increasing concentrations of H2O2 or PA staring from doses that induce endothelial dysfunction without causing cell death. Cell viability was assessed by MTT assay, while in vitro angiogenesis was evaluated through pseudo-capillary formation. NLRP3, caspase-1, and IL-1β levels were quantified by ELISA and pyroptosis by LDH release and gasdermin D cleavage. Additionally, we evaluated the protective effects of the two inhibitors in HCAECs primed with TNF-α and subsequently challenged with PA. Both inhibitors preserved cell viability under oxidative stress conditions, with INF195 showing greater efficacy. Notably, only INF195 significantly protected HCAECs from both PA and TNF-α + PA-induced injury. Exposure to PA, with or without TNF-α, markedly increased caspase-1 expression and pyroptosis which were rescued by INF195. Furthermore, H2O2 and PA significantly impaired in vitro pseudocapillary formation by HCAECs and HUVECs, considered the gold standard for in vitro angiogenesis assays, an effect counteracted by INF195. These findings suggest that, under oxidative and lipotoxic stress, NLRP3 inflammasome inhibition -particularly via INF195 - supports the maintenance of vascular endothelial homeostasis by preserving cell viability and angiogenic function.

Coronary microvascular dysfunction (CMD) is a major contributor to ischemic heart disease (IHD), acting both independently and together with atherosclerosis. CMD encompasses structural and functional microcirculatory changes that result in dysregulated coronary blood flow. Structural abnormalities include microvascular remodeling, resulting in arteriolar and capillary narrowing, perivascular fibrosis and capillary rarefaction. Endothelial dysfunction and smooth muscle cell hyperactivity further impair microcirculation. Genetic factors may play a crucial role in the pathophysiology of CMD, mainly due to single nucleotide polymorphisms (SNPs) in genes that regulate coronary blood flow and microcirculation structural modifications. This manuscript aims to review the genetic determinants of CMD, with particular focus on ion channels, microRNAs (miRNAs), and proteins involved in the endothelial environment. The improving knowledge about genetic aspects of CMD opens the possibility to have new biomarkers, improving diagnosis and the development of targeted treatments in light of an even more patient-tailored approach.

: Heart failure with preserved ejection fraction (HFpEF) accounts for approximately 50% of heart failure cases and is primarily characterized by impaired diastolic function, leading to increased ventricular filling pressures and symptoms like dyspnea and reduced exercise tolerance. Significant gender-specific differences are observed, with women, particularly post-menopausal, experiencing higher prevalence and distinct clinical profiles compared to men. Diastolic dysfunction in HFpEF involves altered cellular mechanisms such as reduced SERCA2a expression, impacting calcium handling and myocardial relaxation. Diagnostic strategies mainly employ echocardiography, including Doppler imaging, tissue Doppler imaging, and strain imaging, to assess ventricular relaxation and stiffness. However, early identification remains challenging, necessitating advanced tools like cardiac magnetic resonance and exercise stress testing for accurate diagnosis, especially in women who often present with subtle symptoms. Treatment options for HFpEF have traditionally been limited, but recent trials, notably EMPEROR-PRESERVED and DELIVER, demonstrated significant cardiovascular benefits using sodium–glucose cotransporter-2 (SGLT2) inhibitors. Additionally, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown promising results, particularly in obese patients. Despite these advances, gender differences in therapeutic response necessitate further research for personalized management strategies. Understanding sex-specific pathophysiological mechanisms and optimizing diagnostic criteria remain essential to improving prognosis and quality of life in HFpEF patients.

Purpose: The management of acute heart failure (AHF) is crucial and challenging. Regarding the use of inotropes, correct patient selection and time of administration are of the essence. We hypothesize that the early use of Levosimendan favouring hemodynamic stabilization and enables rapid optimization of guideline-directed medical treatment (GDMT) in patients with HF, eventually impacting the patient’s prognosis during the vulnerable phase. Methods: This prospective, observational study enrolled consecutive patients admitted due to AHF. Propensity score matching (PSM) analysis has been used to homogenize differences between groups. In group 1 (G1), patients were treated with early 24-h Levosimendan infusion followed by in-hospital introduction/up-titration of GDMT. In group 2 (G2), patients were treated with alternative inotropes/ vasopressors followed by in-hospital introduction/up-titration of GDMT. The comparison between the two groups has been performed at the 6-month follow-up in terms of cardiovascular (CV) mortality and HF hospitalizations (HFH). Results: 233 patients were included in the present study, and after propensity match adjustments, 176 patients were analysed, 88 patients for each group. No differences in the baseline characteristics have been reported between the groups. At 6 months follow-up, no statistically significant differences were shown in terms of the composite endpoint of CV death and HFH (p= 0.445) and CV death (p=0.62). Statistically significant differences between the two groups were reported in terms of HFH (p= 0.02). The Kaplan-Meier survival analysis showed that patients in G1 were significantly less hospitalized compared to G2 during the 6 months after the index hospitalization (log-rank p= 0.03). Conclusions: Early 24-hour infusion of Levosimendan followed by rapid optimization of HF diseasemodifying therapies results in a significant reduction of HFH in the vulnerable post-discharge phase.

Background Although Loop diuretics (LD) represent the milestone treatment in acute heart failure (AHF), relevant concerns exist about the best administration modality. We aim to investigate the effects of different LD regimen and dosage in patients with AHF. Methods In this multicenter prospective observational open-label study, patients were assigned to receive twice-daily intravenous injections (Bolus infusion, BiV) or continuous intravenous infusion (CiV) of furosemide for a period of 72-120 hours. High dose (HD) was defined as furosemide dose >120 mg/day. Patients were eligible if they showed clinical signs of congestion associated with N-terminal pro-B-type natriuretic peptide (NT-proBNP) >500 pg/ml. Combined of rehospitalisation or death for cardiovascular causes were evaluated as primary endpoint during a 6-months follow-up. Results 402 AHF patients were included, 197 treated with CiV and 205 with BiV. CiV showed higher rate of NTproBNP decrease >30 % (63 % vs 45 %, p < 0.001), associated with significantly weight loss (-4.3 ± 2.6 vs -3.2 ± 2.4 Kg, <0.001) and daily mean urine output (2181 ± 845 ml vs 2019 ± 696 ml, p = 0.036) compared to BiV. Conversely, BiV patients experienced a shorter hospital stay (11.5 ± 4.5 vs 12.7 ± 4.5 days, p = 0.006) and lower adverse events rate (29 % vs 45 %, p = 0.001). HD administration was associated with prolonged hospital stay and poor outcome (55 % vs 18 %). Multivariable analysis confirmed CiV (HR 1.51, 1.02-2.23) and HD infusion (HR 2.50,1.64-3.83) were both associated with the primary endpoints. Conclusions CiV was associated with higher NTproBNP decrease and weight loss but it demonstrates a poorer outcome. Similarly, HD was associated with an increased risk.

Adherence to exercise and rehabilitation programs is crucial for effectively managing and preventing cardiovascular disease (CVD). While cardiac rehabilitation (CR) offers clear benefits, patient engagement can be suboptimal, with noticeable gender gaps affecting program success and outcomes. This review examines adherence patterns to exercise and rehab in individuals with CVD, focusing on gender differences, barriers to participation, and potential improvement strategies. we integrate diverse findings into a practical, gender-aware model for CR delivery that can be adopted and evaluated across settings. Optimal adherence to CR programs leads to a 27% decrease in all-cause mortality, a 31% reduction in cardiac-related deaths, lower rates of rehospitalization, and improvements in functional capacity and quality of life. On the other hand, non-adherence is associated with decreased functional abilities, higher risk of re-injury, and poorer long-term outcomes. Women, in particular, may benefit significantly from participation in CR but are often undertreated or underrepresented. Consistent adherence to exercise and CR poses a significant challenge in cardiovascular care, with evident gender disparities necessitating tailored solutions. Women face various barriers, biological, psychological and social, that require gender-specific approaches to rehab program design and delivery. Promising strategies include technology-enabled interventions, home-based programs, multidisciplinary team care, and a family-centered model that considers individual patient needs. Moving forward, efforts should focus on program delivery and ongoing support systems to maximize adherence and fully realize the benefits of CR for all patients.

Background:Vitamin D plays several roles beyond bone metabolism, potentially protecting the cardiovascular system. Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis and vascular dysfunction, carrying a high cardiovascular risk. However, the relationship between vitamin D insufficiency and cardiovascular involvement in SSc patients remains unclear. This study aims to assess the association between low vitamin D levels, echocardiographic parameters indicative of ventricular dysfunction, and cardiovascular risk factors in SSc patients. Methods:A retrospective observational study involved 160 SSc patients undergoing echocardiography and serum 25-hydroxyvitamin D measurement. Patients were categorized into two groups: vitamin D insufficiency (<30 ng/mL) and normal levels (≥30 ng/mL). Echocardiographic parameters and cardiovascular risk factors were evaluated. Results:Vitamin D insufficiency was detected in 68.9 % of patients. Patients with insufficient vitamin D had higher systolic pulmonary arterial pressure (PAPs; 37.68 ± 7.56 mmHg vs. 33.12 ± 6.17 mmHg; p = 0.004), reduced TAPSE/PAPs ratio (0.65 ± 0.13 vs. 0.72 ± 0.14; p = 0.021), increased interventricular septal thickness (8.17 ± 1.28 mm vs. 7.69 ± 1.18 mm; p = 0.028), and greater left ventricular end-diastolic diameter (44.06 ± 4.28 mm vs. 42.67 ± 3.44 mm; p = 0.037), indicating ventricular dysfunction. Vitamin D insufficiency significantly correlated with hypertension (OR = 2.31; p = 0.032), dyslipidemia (OR = 2.45; p = 0.015), and overweight/obesity (OR = 4.73; p = 0.002), but not with diabetes or smoking. Conclusions:Vitamin D insufficiency may contribute to cardiovascular dysfunction in SSc patients. Monitoring vitamin D levels might improve cardiovascular risk stratification. Further studies are necessary to determine if supplementation could enhance cardiac outcomes.

Adherence to exercise-based cardiac rehabilitation (CR) is essential for preventing and managing cardiovascular disease (CVD). Participation in CR reduces all-cause mortality by 27% and cardiac deaths by 31% and lowers rehospitalization rates while also improving functional capacity and quality of life. However, many patients do not start, complete, or maintain CR, resulting in reduced functional abilities, a higher risk of recurring events, and poorer long-term outcomes. This narrative review summarizes patterns of adherence to exercise and CR in CVD, with a specific focus on sex- and gender-related differences in referral, participation, and completion. We synthesize evidence on biological, psychological, and social barriers that limit engagement and describe emerging strategies, such as technology-enabled and home-based programs, multidisciplinary care, and family-centered models, to enhance adherence. Finally, we propose a practical, gender-aware framework for CR design and delivery that can be adjusted and evaluated across diverse healthcare settings to guide clinical practice and future research.

Women remain severely underrepresented in clinical trials, leading to a significant disparity in clinical care and outcome among male vs female patients with advanced heart failure (HF). Sex-specific disparities regarding the etiology of HF, time to diagnosis, severity of disease at time of index hospitalization, response to treatment, and treatment options, including use of temporary or durable mechanical circulatory support devices, may affect women unfavourably. Lack of knowledge regarding sex-specific complications has had an impact on the overall higher mortality level in women vs men. Increasing the awareness regarding this sex-specific imbalance is imperative. The inclusion of women in clinical mechanical circulatory support trials is critical, to improve female patient outcomes in stage D HF with reduced ejection fraction.