Search Results (184)

Background: Arteriovenous fistulas (AVFs) may contribute to cardiac remodeling and consequently to an increased risk of heart failure and cardiovascular mortality in patients with end-stage kidney disease (ESKD). We aimed to assess cardiac changes following AVF creation and identify potential parameters associated with cardiac remodeling. Methods: In our prospective, single-center study, ESKD patients without significant pre-existing cardiac disease underwent 2D and 3D echocardiographic evaluation before and after AVF creation, along with AVF flow measurement. Cardiac remodeling was assessed using 3D indexed left and right ventricular end-diastolic volumes (LVEDVi, RVEDVi), while systolic function was assessed using longitudinal strain and 3D ejection fraction. Results: We included 20 patients (18 men; median age 73.5 years [IQR: 67–77]) with a mean AVF flow of 1140 ± 345 mL/min. At a median of 8.2 months (IQR: 7.3–9.3) following AVF creation, significant biventricular dilatation was observed: LVEDVi increased from 89 ± 14 to 97 ± 21 mL/m² (p < 0.05) and RVEDVi from 80 ± 15 to 91 ± 18 mL/m² (p < 0.05), while the systolic function of both ventricles did not change significantly. The right ventricle showed the most pronounced remodeling and it was independently associated with volume overload (p = 0.003) and elevated left ventricular filling pressure (p = 0.030), but not with AVF flow. Conclusions: Moderate AVF flow was associated with cardiac remodeling, primarily affecting the right ventricle. Fluid overload and left ventricular filling pressure were key factors associated with right ventricular remodeling, underscoring the need for careful fluid management and vascular access planning in ESKD patients. Full article

Pulmonary hypertension (PH) is a serious pulmonary vascular disease. Vascular remodeling, metabolic reprogramming, inflammation, and fibrosis are all major pathogenic mechanisms in PH. MicroRNAs (miRNAs) are small RNAs, about 20–24 nucleotides long, that play important regulatory roles in biological processes, and in recent years, miRNAs have been found to potentially play a regulatory role in the pathogenesis of PH, and also serve as biomarkers and therapeutic agents for PH. However, there is still a long way to go from these experimental findings to their implementation in clinical practice. This study reviews the potential role of miRNAs in the pathogenesis of PH and suggests future applications of miRNAs in PH. Full article

Pulmonary arterial hypertension (PAH) is a rare, progressive, and incurable disease characterized by an elevated pulmonary blood pressure, extensive remodeling of the pulmonary vasculature, increased pulmonary vascular resistance, and culminating in right ventricular failure. Mitochondrial dysfunction has a major role in the pathogenesis of PAH and secondary right ventricular failure, and its targeting may offer therapeutic benefit. In this study, we provide proof-of-concept for the use of the mitochondrially active drug SUL-150 to treat PAH. PAH was induced in rats by monocrotaline, followed by the placement of an aortocaval shunt one week later. The mitoprotective compound SUL-150 (~6 mg·kg⁻¹·day⁻¹) or vehicle was administered intraperitoneally via osmotic minipump for 28 days, implanted at the time of aortocaval shunt placement. Vehicle-treated PAH rats had dyspnea and showed pulmonary artery remodeling with increased responsiveness to phenylephrine, in addition to remodeling of the intrapulmonary arterioles. SUL-150 administration mitigated the dyspnea and the remodeling responses. Vehicle-treated PAH rats developed right ventricular hypertrophy, fibrosis, and failure. SUL-150 administration precluded cardiomyocyte hypertrophy and inhibited ventricular fibrogenesis. Right ventricular failure in vehicle-treated PAH rats induced mitochondrial loss and dysfunction associated with a decrease in mitophagy. SUL-150 was unable to prevent the mitochondrial loss but improved mitochondrial health in the right ventricle, which culminated in the preservation of right ventricular function. We conclude that SUL-150 improves PAH-associated morbidity by the amelioration of pulmonary vascular remodeling and right ventricular failure and may be considered a promising therapeutic candidate to slow disease progression in pulmonary arterial hypertension and secondary right ventricular failure. Full article

Background: Well-designed endurance training leads to improved cardiovascular fitness and sports performance in prolonged exercise tasks, with the adaptations depending on multiple factors, including the training modality and the population in question. It is still disputable how the type of training affects myocardial remodeling, and the information on myocardial remodeling by high-intensity interval training (HIIT) is particularly scarce. Methods: The current study investigated changes in cardiac structure after volume-progressive HIIT in running mode. As part of their conditioning program, amateur athletes (mean ± SD age of 18.2 ± 1.0 years) exclusively conducted HIIT in a volume-progressive fashion over 7 weeks (a total of 21 sessions). Peak oxygen uptake as well as 200 m and 2000 m running performance were measured, and transthoracic two-dimensional echocardiography was conducted before and after the intervention. Results: Training improved running performance, increased the peak oxygen uptake and left atrium diameter (from 32.0 ± 2.5 to 33.5 ± 2.3 mm; p = 0.01), and induced ~11% thickening of the left-ventricular posterior wall (7.5 ± 0.7 to 8.2 ± 0.4 mm; p = 0.01) and interventricular septum (7.6 ± 0.7 to 8.6 ± 0.9 mm; p = 0.02), but not the dilation of left-ventricular, right-ventricular, or right atrium chambers. Conclusions: HIIT of just 127 km of running per 8.5 h during 7 weeks was sufficient to improve aerobic capacity and running performance, and induce left-ventricular wall hypertrophy and left atrium dilation, in young healthy athletes. Full article

Background: Transthoracic echocardiography (TTE) is the primary imaging modality to assess cardiac morphology and function. In athletes, distinguishing physiological adaptations from pathological changes is essential. This study aimed to evaluate long-term cardiac structural and functional changes in professional soccer players. Methods: This retrospective study included 20 healthy male professional soccer players (mean age 21.2 ± 3.4 years) from the German first division, examined annually from 2016 to 2024 (mean follow-up 5.6 ± 2.0 years). TTE parameters associated with the “athlete’s heart” were assessed, including left ventricular end-diastolic diameter (LVEDD), interventricular septal thickness (IVSD), relative wall thickness (RWT), indexed LV mass (LVMi), and left atrial volume index (LAVi), along with 3D-derived LV and RV volumes. Advanced deformation imaging included global longitudinal strain (GLS), right ventricular strain (RVS), and left/right atrial reservoir strain (LASr and RASr, respectively). Baseline and final follow-up values were compared. Results: No significant changes were observed over time in conventional or advanced echocardiographic parameters (e.g., LVEDD: 54.5 ± 3.1 mm vs. 54.6 ± 3.9 mm; p = 0.868; GLS: −18.7% ± 2.2% vs. −18.4% ± 1.9%; p = 0.670). Ventricular volumes and strain values also remained stable throughout follow-up. Conclusions: Over a mean follow-up of more than five years, professional soccer players showed stable cardiac morphology and function without evidence of pathological remodeling. These findings support the concept that long-term high-level training in mixed-discipline sports leads to balanced, physiological cardiac adaptation. Full article

Right heart failure (RHF) is a major cause of morbidity and mortality, often resulting from pulmonary arterial hypertension and characterized by impaired calcium (Ca²⁺) handling and maladaptive remodeling. Phosphodiesterase 9A (PDE9A), a cGMP-specific phosphodiesterase, has been proposed as a potential contributor to RHF pathogenesis by suppressing the cardioprotective cGMP–PKG signaling pathway—a conclusion largely extrapolated from left-sided heart failure models. This review examines existing evidence regarding PDE9A’s role in RHF, focusing on its effects on intracellular calcium cycling, fibrosis, hypertrophy, and contractile dysfunction. Data from preclinical models demonstrate that pathological stress upregulates PDE9A expression in cardiomyocytes, leading to diminished PKG activation, impaired SERCA2a function, RyR2 instability, and increased arrhythmogenic Ca²⁺ leak. Pharmacological or genetic inhibition of PDE9A restores cGMP signaling, improves calcium handling, attenuates hypertrophic and fibrotic remodeling, and enhances ventricular compliance. Early-phase clinical studies in heart failure populations suggest that PDE9A inhibitors are well tolerated and effectively augment cGMP levels, although dedicated trials in RHF are still needed. Overall, these findings indicate that targeting PDE9A may represent a promising therapeutic strategy to improve outcomes in RHF by directly addressing the molecular mechanisms underlying calcium mishandling and myocardial remodeling. Full article

Tricuspid regurgitation (TR) represents a significant, often silently progressing, valvular heart disease with historically suboptimal management due to perceived high surgical risks. Transcatheter tricuspid valve interventions (TTVI) offer a promising, less invasive therapeutic avenue. Central to the success of TTVI is Right Ventricular Reverse Remodelling (RVRR), defined as an improvement in RV structure and function, which strongly correlates with enhanced patient survival. The right ventricle (RV) undergoes complex multi-scale biomechanical maladaptations, progressing from adaptive concentric to maladaptive eccentric hypertrophy, coupled with increased stiffness and fibrosis. Molecular drivers of this pathology include early failure of antioxidant defenses, metabolic shifts towards glycolysis, and dysregulation of microRNAs. Accurate RV function assessment necessitates advanced imaging modalities like 3D echocardiography, Cardiac Magnetic Resonance Imaging (CMR), and Computed Tomography (CT), along with strain analysis. Following TTVI, RVRR typically manifests as a biphasic reduction in RV volume overload, improved myocardial strain, and enhanced RV-pulmonary arterial coupling. Emerging molecular biomarkers alongside advanced imaging-derived biomechanical markers like CT-based 3D-TAPSE and RV longitudinal strain, are proving valuable. Artificial intelligence (AI) and machine learning (ML) are transforming prognostication by integrating diverse clinical, laboratory, and multi-modal imaging data, enabling unprecedented precision in risk stratification and optimizing TTVI strategies. Full article

Background: Patients with single right ventricular morphology (SRV) may exhibit impaired function with increased morbidity, mortality, and need for cardiac transplant due to progressive SRV failure after the Fontan procedure. The aim of the study was to longitudinally characterize the cardiac mechanics and trajectory of disease evolution of SRV failure in Fontan patients. Methods: We performed a case-controlled longitudinal study of 52 patients who underwent extracardiac Fontan palliation for SRV between 1994 and 2015 and compared echocardiographic measures of right ventricular (RV) function, RV-systemic vascular coupling and ventricular remodeling between patients who required heart transplants due to SRV failure (study group, n = 26) and those who did not (control group, n = 26). To define the trajectory, measurements were obtained at four matching time points equivalent in duration from Fontan. Results: RV circumferential shortening function declined in both groups over the time period, but was significantly lower (p < 0.01) in the study group farther from the Fontan. RV-systemic vascular coupling, assessed by systolic time interval measures and RV work, was preserved in the control group, but significantly altered (p < 0.001) in the study group. Relative wall thickness decreased, and the minor/major-axis ratio, as an index of ventricular geometry, increased in the study group, but both remained stable in the control group. Conclusions: This study suggests that positive ventricular remodeling with enhanced circumferential systolic function, and preserved RV-vascular coupling, appear to be adaptive and protective mechanisms against RV failure in Fontan with SRV. These indices of cardiac mechanics may serve as clinically relevant quantifiable markers of disease evolution, and early indicators for therapeutic intervention. Full article

Transcatheter aortic valve replacement (TAVR) is now established as a safe and effective treatment for severe aortic stenosis across all surgical risk categories. Nevertheless, periprocedural conduction disturbances—including new-onset left bundle branch block (LBBB), right bundle branch block (RBBB), and other intraventricular blocks—remain among the most frequent complications, often resulting in permanent pacemaker (PPM) implantation and impacting left ventricular remodeling. A review was conducted using the PubMed/MEDLINE database. Relevant clinical trials, observational studies, and meta-analyses addressing post-TAVR LBBB were included and analysed with a focus on frequency, risk factors, and association with adverse outcomes. We describe the incidence of post-TAVR conduction disturbances and identify key predictors: pre-existing RBBB, membranous septum length, valve oversizing, implantation depth, infra-annular leaflet extension, compression ratio, and valve type/generation. New-onset LBBB is a frequent complication after TAVR and may negatively affect patient outcomes. Accurate risk stratification and standardised post-procedural monitoring protocols are essential. Further prospective studies are needed to better define management strategies for patients developing LBBB after TAVR. Full article

Objectives: We compared changes in hepatic and cardiac iron levels, left ventricular (LV) and right ventricular (RV) dimensions and function, and bi-atrial areas, all assessed through magnetic resonance imaging (MRI), between patients with non-transfusion-dependent thalassemia (NTDT) and those with neo-transfusion-dependent thalassemia (neo-TDT) over an 18-month follow-up period. Methods: We included 32 NTDT patients (42.78 ± 12.62 years, 53.1% females) and 58 neo-TDT (>4 transfusions per year) patients (44.08 ± 14.13 years, 46.6% females), consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia project. Iron overload was quantified by T2* technique, biventricular function and atrial areas by cine images. Macroscopic myocardial fibrosis was detected by the late gadolinium enhancement technique. Results: Changes in cardiac and hepatic iron levels, in biventricular ejection fractions, in LV mass index, and bi-atrial areas were comparable between the two groups. A trend of worsening biventricular dimensions was observed in the NTDT group, while the neo-TDT group showed an improvement (decrease) in biventricular size (LV stroke volume index: p = 0.036; LV cardiac index: p = 0.031; RV end-diastolic volume index: p = 0.034; RV stroke volume index: p = 0.033). The inter-group comparison showed significant differences in the changes of biventricular end-diastolic volume indexes (LV: p = 0.011 and RV: p = 0.034) and stroke volume indexes (LV: p = 0.036 and RV: p = 0.033) and in the cardiac index (p < 0.0001). At both MRI scans, the frequency of replacement myocardial fibrosis was comparable between the two groups. Conclusions: Our 18-month longitudinal data revealed distinct patterns of cardiac remodeling in NTDT and neo-TDT patients. The progressive ventricular dilation observed in NTDT patients highlights the need for careful MRI monitoring and potential interventions to address the long-term cardiac consequences of anemia. Full article

Pulmonary arterial hypertension (PAH) is a lethal condition marked by the proliferation and remodeling of small pulmonary arteries, ultimately leading to right ventricular hypertrophy and right heart failure. PAH secondary to connective tissue diseases (CTDs) is a progressive complication with a complex pathogenesis that results in the reduced efficacy of vasodilation-based therapies and poor clinical outcomes. Systemic sclerosis is the most commonly associated CTD with PAH in Western countries and has been most extensively investigated. Systemic lupus erythematosus and other CTDs may also be associated with PAH; however, they are less studied. In this review, we explore the general pathobiology of PAH, with a particular emphasis on recent advances in the molecular pathogenesis of CTD-PAH, including endothelial cell dysfunction, dysregulated cell proliferation and vascular remodeling, extracellular matrix remodeling, in situ thrombosis, right ventricular dysfunction, genetic aberrations, and immune dysregulation. We also conduct a thorough investigation into the potential serum biomarkers and immune dysregulation associated with CTD-PAH, summarizing the associated autoantibodies, cytokines, and chemokines. Furthermore, relevant animal models that may help unravel the pathogenesis and contribute to the development of new treatments are also reviewed. Full article

Background/Objectives: This study aims to investigate the potential etiopathogenesis of HFpEF development and identify possible different phenotypes of HFpEF in patients with chronic obstructive pulmonary disease (COPD) and systemic sclerosis-associated interstitial lung diseases (SS-ILDs). It could help clinicians improve early HFpEF personalized detection and management. Methods: This study included 150 patients with chronic lung diseases (CLDs), such as COPD and SS-ILD, who were outside of exacerbation, had no history of chronic heart failure (CHF), and had a left ventricular ejection fraction (LV EF) of ≥50%. The functional status of the lungs, heart, endothelial dysfunction, and acid–base balance was assessed. The results obtained were compared in groups of patients with CLD depending on the presence or absence of HF with preserved ejection fraction (HFpEF). The diagnosis of HFpEF was established based on the HFA-PEFF Score classification. Nonparametric statistical methods were used. Results: In patients with CLD, indicators such as age, longitudinal size of the right atrium, mid-regional pro-atrial natriuretic peptide (MR-proANP), and highly sensitive cardiac troponin T (hsTnT) were higher than in the group of patients without HFpEF. In patients with COPD and HFpEF, statistically significant changes were found in the volume of the left atrium. In patients with SS-ILD and HFpEF, statistically significant differenceswere found in SBP before and after the 6 min walk test (6MWT), the Borg scale before 6MWT, MR-proANP, and the longitudinal dimension of the right atrium. Conclusions: The results of our study allow us to identify two different mechanisms of HFpEF development: In patients with COPD, the predominant factor in the development of HFpEF was hypoxia, while in patients with SS-ILD, myocardial dysfunction with remodeling developed against the background of secondary pulmonary hypertension, highlighting the importance of phenotype-specific evaluation. These findings suggest potential approaches for personalized risk stratification and the development of targeted management strategies for patients with HFpEF. Full article

Nitric oxide (NO), an endogenous vasodilator, has been proposed as a biomarker for pulmonary hypertension (PH) in humans. NO is synthesized by endothelial nitric oxide synthase (eNOS). Alterations in NO/eNOS have not been studied in dogs with PH. We assessed alterations in NO and eNOS in the blood of dogs with PH (n = 17) and healthy dogs (n = 10) and analyzed their correlations with echocardiographic parameters. The results showed significantly higher plasma NO and serum eNOS levels in dogs with PH compared with healthy dogs. Dogs with PH and ascites (n = 11) had significantly lower plasma NO levels than those without ascites (n = 6) and presented a decreasing eNOS trend. In dogs with PH, plasma NO was positively correlated with left ventricular hemodynamics, right ventricular compliance, and pulmonary distensibility, but was negatively correlated with pulmonary vascular resistance and right cardiac remodeling. Serum eNOS was positively correlated with the main pulmonary artery diameter. Increments in NO/eNOS reflected compensatory responses to cardiovascular changes in PH. These compensations were downward in the advanced stages. Other factors may also impact NO/eNOS compensation. Although the role of NO/eNOS as biomarkers for PH in dogs remains equivocal, they may indicate compensatory consequences of cardiovascular alterations. Full article

Background/Objectives: In patients with transthyretin amyloid cardiomyopathy (ATTR-CM), the effect of tafamidis on right ventricular (RV) dysfunction has been poorly investigated. The purpose of this study was to evaluate the effect of tafamidis on RV free wall global longitudinal strain (RV FW-GLS) and right ventricular and pulmonary artery (RV-PA) coupling over 12 months of treatment. Methods: Ninety-three patients with ATTR-CM treated with 61 mg of tafamidis daily who underwent multimodality imaging evaluation at baseline by cardiovascular magnetic resonance (CMR) and speckle-tracking echocardiography were retrospectively studied. The 12-month follow-up included an echocardiographic assessment of RV FW-GLS and RV-PA coupling. RV reverse remodeling was defined as a >10% improvement in RV FW-GLS and/or in RV-PA coupling from baseline. RV-PA coupling was assessed using the tricuspid annular plane systolic excursion/ pulmonary artery systolic pressure (TAPSE/PASP) ratio. Results: Over 12 months of tafamidis treatment, RV reverse remodeling was documented in 22.6% of patients. In these patients, RV FW-GLS improved significantly from 14.5 ± 2.1% to 17.3 ± 2%, p < 0.001, whereas the TAPSE/PASP ratio improved from 0.42 ± 0.05 mm/mmHg to 0.54 ± 0.07 mm/mmHg, p = 0.001. Patients who experienced RV reverse remodeling were at an earlier stage of disease prior to tafamidis treatment with less dilated RV and less severe RV-PA uncoupling (TAPSE/PASP ratio: 0.43 ± 0.06 mm/mmHg vs. 0.39 ± 0.06 mm/mmHg, p = 0.040). CMR-derived baseline RV end-systolic volume (HR 0.83, 95% CI 0.73–0.94, p = 0.005) and NT-proBNP (HR 0.989, 95% CI 0.988–0.999, p = 0.024) were the strongest independent predictors of RV reverse remodeling, followed by PASP (HR 0.82, 95% CI 0.69–0.98, p = 0.030). Conclusions: Patients with ATTR-CM treated with tafamidis at an earlier stage of the disease experienced RV reverse remodeling with significant improvement in RV FW-GLS and RV-PA coupling. Full article

Accurate prognostic stratification in patients with chronic heart failure and reduced ejection fraction (HFrEF) remains a significant clinical challenge. Many different parameters, including left ventricular (LV) and right ventricular (RV) function and cardiopulmonary exercise testing (CPET) parameters, are available in the literature. LV ejection fraction (LVEF) is the most used parameter in clinical practice. This study aimed to analyze CPET and echocardiographic data in patients under evaluation for heart transplantation (HTx) to identify the parameter that best correlates with cardiac events. Methods and Results. Echocardiography and CPET were performed in patients with HFrEF under evaluation for HTx. The population comprised 170 patients (mean age: 55 ± 9 years; 88% male; non-ischemic etiology: 63%). LVEF was 30.4 ± 7.6%, peak oxygen uptake (Vo_2peak) was 17.08 ± 4.6 mL/Kg/min; minute ventilation (VE)/carbon dioxide production (Vco₂) slope was 34.8 ± 8.7. During a follow-up of 4 ± 1 years, 37 hospitalizations, 4 deaths, 14 HTx, and 5 LV assist device implantation occurred. Patients who experienced major events had a lower Vo_2peak (p < 0.005), higher VE/Vco₂ slope (p < 0.005), greater LV end-systolic diameter (p < 0.005), and RV end-diastolic diameter (p < 0.005) than patients without events. Conversely, LVEF did not differ between these two groups. VE/Vco₂ slope and RV dimensions significantly correlated with hard cardiac events (p = 0.019 and p = 0.008, respectively). Conclusions. In patients with HFrEF, parameters quantifying the system reserve (i.e., Vo_2peak and VE/Vco₂ slope) and those demonstrating advanced biventricular remodeling may help stratify the risk of cardiac events. Conversely, LVEF showed a limited prognostic value in this setting. Full article