Several groups have demonstrated that PERM1 is a positive regulator of mitochondrial bioenergetics in the heart. However, conflicting results have emerged regarding whether PERM1 loss of function affects cardiac contractility. Here, we present data from a retrospective study compiling echocardiography data from all Perm1-knockout (Perm1-KO) mice and their wild-type (WT) littermates used for various molecular biology experiments in our laboratory between April 2022 and September 2023. This yielded an atypically large number of subjects per group-84 WT mice and 88 Perm1-KO mice. We analyzed echocardiography-derived parameters of left ventricular (LV) systolic function. The ejection fraction (EF) was 65.43 ± 7.13% in WT vs. 53.98 ± 8.80% in Perm1-KO mice (p = 5.21E-17, unpaired t-test). Other parameters showing statistically significant differences between WT and Perm1-KO (p < 0.05) included LV fractional shortening, LV diastolic and systolic diameters, LV anterior and posterior systolic wall thickness, LV posterior wall systolic thickening, stroke volume, and cardiac output. Importantly, this large cohort of echocardiography analyses revealed a broad range of cardiac contractile function among WT mice, and this degree of variability persisted in Perm1 KO; however, the entire distribution was shifted downward, suggesting that Perm1 deficiency reduces mean cardiac performance without altering intrinsic variability. Overall, our study indicates that constitutive Perm1 deletion leads to reduced contractility partially compensated by increased LV circumference. This study provides strong evidence that Perm1-KO causes specific remodeling of cardiac contractile function and provides a retrospective power analysis to guide future prospective studies.

Right ventricular (RV) hypertrophy is the principal adaptive response to increased afterload. This response can be appropriate, preserving RV systolic function and RV-pulmonary artery coupling, or maladaptive, leading to RV dilatation and failure. While pure pressure overload typically induces adaptive hypertrophy, concomitant myocardial injury and ischemia often drive maladaptive changes. Multimodality imaging plays a crucial role in distinguishing these states by characterizing the relationship between RV mass, volume, and function. Cardiac magnetic resonance imaging, in particular, provides the reference standard for quantifying these parameters and offers unique insights through myocardial tissue characterization. This narrative review outlines the pathophysiology of RV hypertrophy and the application of cardiovascular imaging for its clinical assessment. We conclude by highlighting the critical clinical utility of evaluating RV hypertrophy for screening for pulmonary hypertension, risk stratification, and as a potential therapeutic target.

Objective Astragaloside IV (AsIV) has been reported to alleviate diabetes-induced endothelial dysfunction by inhibiting calpain-1. This study aimed to determine whether the same mechanism underlies its protective effect against diabetic cardiomyopathy (DCM). Methods At the in vivo level, calpain-1 knockout mice with the genotype Capn1 EK684−/− (Capn1 EK684 knockout mice) were used to establish a type 2 diabetic cardiomyopathy model. At the in vitro level, H9c2 cells and cardiac fibroblasts were stimulated with high glucose to construct corresponding models. Meanwhile, a calpain-1 overexpression lentivirus was constructed to assess the effect of calpain-1 on myocardial cell injury. Different doses of AsIV were then used to intervene in diabetic mice and H9c2 cells. Body weight, blood glucose, myocardial hypertrophy, myocardial fibrosis, cardiac function, Ca 2+ overload and its regulation, myocardial cell apoptosis and oxidative stress were evaluated in the current study. Results AsIV could not completely normalize blood glucose in mice, but could significantly improve cardiac systolic and diastolic function, myocardial hypertrophy and fibrosis. The beneficial effect of calpain-1 gene knockout on diabetic cardiomyopathy was similar to that of AsIV, and calpain-1 knockout did not further enhance the beneficial effect of AsIV. Calpain-1 overexpression abolished the beneficial effect of AsIV on high glucose induced H9c2 cell injury and fibroblast proliferation. In addition, the intracellular Ca 2+ overload, abnormal levels of sarco/endoplasmic reticulum Ca 2+ -ATPase 2a (SERCA2a), phosphorylation of phospholamban (p-PLN) and ryanodine receptor 2 (p-RyR2), apoptosis and oxidative stress associated with DCM were also improved by AsIV or calpain-1 knockout, and AsIV has the capacity to suppress the overactivation of calpain-1 and calcium/calmodulin-dependent protein kinase Ⅱ (CaMKII). Conclusions AsIV could ameliorate intracellular Ca 2+ overload, apoptosis, and oxidative stress by regulating the calpain-1/CaMKII pathway, thereby improving myocardial hypertrophy and fibrosis caused by diabetes mellitus.

This study aimed to evaluate patients with beta thalassaemia major using the cardiac electrophysiological index of balance, a new electrocardiography parameter, and to predict ventricular arrhythmias. In this study, 60 beta thalassaemia major and 60 healthy children were included. All patients were evaluated with echocardiography. P-wave dispersion, repolarisation times, repolarisation dispersion times, and cardiac electrophysiological balance index were measured using 12-lead electrocardiography. Heart rate variability parameters were evaluated with a 24-hour Holter electrocardiography. Left ventricular functions were similar between the groups. Although repolarisation times (QT, JT, and JTp) were significantly lower in the beta thalassaemia major group, heart rate-corrected repolarisation times were similar. Except for Tpe/QT, which is one of the repolarisation dispersion parameters, the other parameters were similar. The heart rate-corrected cardiac electrophysiological index of balance ratio was significantly higher in the beta thalassaemia major group. QRS duration and QRS-dispersion duration (QRS-d) were similar between the groups. There was a correlation between blood ferritin levels and LVmass-i, Tpe/QT, Tpe/QTc, QTc/QRS ratio, and QT, JT, and JTp values. Patients with beta thalassaemia major are at high risk for ventricular arrhythmia due to a high QTc/QRS ratio, despite normal left ventricular systolic, diastolic, and autonomic function in the early period. We believe that there is a moderate correlation between blood ferritin levels and the QTc/QRS ratio and that the QTc/QRS ratio can provide important information for the follow-up and evaluation of patients with beta thalassaemia major. Despite normal early ventricular function in the beta thalassaemia major group, they were at high risk of ventricular arrhythmias.

The interplay between systolic and diastolic dysfunction in heart failure with preserved ejection fraction (HFpEF) progression is unclear. First-phase ejection fraction (EF1), a sensitive marker of early systolic function, aids in assessing systolic-diastolic relationships in human hypertension and aortic stenosis. This study examines temporal changes in these relationships in mouse models of HFpEF and elevated afterload. Mouse models of abdominal aortic banding (AAB) and HFpEF (induced by hypertension and high fat feeding) underwent comprehensive serial echocardiography. In AAB, EF1 significantly decreased at week 1 post-surgery (18.8 ± 1.2 vs 24.3 ± 0.8%, p<0.001) compared to controls, with further reduction at week 3 (16.8 ± 0.6%) and week 6 (13.9 ± 0.9%, both p<0.001). EF, global longitudinal strain (GLS) and longitudinal strain rate (LSR) remained unchanged until week 3. Isovolumic relaxation time (IVRT) was the only abnormal index of diastolic function at week 1. In the HFpEF model, EF1 significantly decreased at week 2 (19.1 ± 1.1 vs 25.8 ± 1.0%, p<0.001) compared to controls, while EF, GLS, and LSR were unaltered. At week 3, EF1 decreased further (18.1 ± 0.7%) alongside a significant reduction in GLS (p<0.01), while EF and LSR remained unchanged. IVRT increased early in the HFpEF model, followed by later left atrial (LA) enlargement. EF1, an early marker of systolic impairment, decreases early in HFpEF and afterload-induced dysfunction, accompanied by IVRT prolongation. LA dilatation appears later. These findings highlight the interplay between systolic and diastolic dysfunction in HFpEF progression.

Neuregulin-1β (NRG1) improves cardiac output in heart failure patients, yet concerns remain that ErbB activation may promote maladaptive hypertrophy, particularly during hemodynamic stress. We investigated how NRG1 influences structural, functional, and molecular remodeling during pressure overload. Male and female C57BL/6NRj mice underwent transverse aortic constriction (TAC) or sham surgery and received saline or recombinant NRG1 via osmotic minipumps or daily injection. In male mice, NRG1 increased ejection fraction at 1 and 4 weeks after TAC. NRG1 accentuated TAC-induced concentric remodeling without increasing left ventricular weight or cardiomyocyte cross-sectional area. It markedly reduced fibrosis and macrophage infiltration and prevented progression toward early cardiac decompensation. NRG1 amplified TAC-induced Myh7 and Nppa expression and also shifted Glut1/Glut4 toward their fetal profile. Transcriptomic analysis identified two novel NRG1-regulated genes: NRG1 reversed TAC-induced upregulation of the skeletal muscle gene Mybpc2 and induced the expression of Popdc2. Furthermore, NRG1 increased expression of Gja1 and localization of connexin 43 at the intercalated disc, consistent with enhanced electrical coupling. In female mice, NRG1 increased systolic function and regulated similar molecular targets yet did not reduce the modest increase in fibrosis that was observed. In conclusion, our findings show that NRG1 promotes adaptive molecular and structural remodeling under pressure overload and enhances contractile performance without exacerbating hypertrophy. The identification of NRG1-responsive genes linked to contraction and conduction highlights potential mechanisms and supports further exploration of NRG1-based strategies for cardiac disease.

Pediatric epilepsy may adversely affect cardiac function. This study examined cardiac outcomes in children with controlled and drug-resistant epilepsy (DRE). Sixty children with epilepsy (30 DRE, 30 drug-responsive) and 30 healthy controls underwent 12-lead ECG, M-mode echocardiography, and speckle tracking echocardiography (STE) to assess cardiac electrical activity, left ventricular (LV) volumes, ejection fraction (EF), fractional shortening (FS), and global longitudinal strain (GLS). ECG findings were comparable among the three groups. LV end-diastolic (LVEDV) and end-systolic volumes (LVESV), FS, and EF were significantly lower in DRE vs. controls (p < 0.05). LVEDV and EF were significantly lower in DRE vs. drug-responsive epilepsy (p < 0.05), while drug-responsive cases had lower LVEDV vs. controls (p = 0.015). LV GLS was significantly lower in DRE (-19.34 ± 1.80) vs. drug-responsive epilepsy (-20.33 ± 1.45) (p = 0.023) and controls (-20.58 ± 0.91) (p = 0.003). LV GLS correlated positively with time since last seizure (p = 0.007) and negatively with the number of antiseizure medications (p = 0.007). Children with DRE exhibit significant cardiac dysfunction. STE enables early detection of subclinical cardiac abnormalities in DRE, advocating for its integration into routine monitoring. Compares cardiac function in pediatric drug-resistant epilepsy (DRE) and drug-responsive epilepsy, identifying impaired systolic function and global longitudinal strain (GLS) in DRE. Correlates GLS abnormalities with antiseizure medication burden and time since last seizure, linking cardiac dysfunction to treatment intensity and epilepsy disease course. Advocates STE for early cardiac monitoring in DRE and urges longitudinal studies to disentangle epilepsy-related cardiovascular risks from drug-driven effects.

Folate receptor ß (FR-ß) is expressed on activated macrophages in inflammatory conditions. In order to study FR-ß in inflammatory response following myocardial infarction (MI), we evaluated FR-ß-targeted PET imaging using aluminum fluoride-18-labeled NOTA-folate ([18F]FOL) in a rat model of MI. Rats underwent [18F]FOL PET imaging on 3, 7, 15, and 90 days after induction of MI by permanent coronary artery ligation or sham-operation. [18F]FDG PET was performed a day before [18F]FOL scan to localize the infarct area. A subset of rats underwent [18F]FOL PET on day 7 and serial echocardiography until 90 days post-surgery. The [18F]FOL uptake was significantly higher in infarct area than in the myocardium of sham-operated rats on day 3 (SUV 1.97 ± 0.17 vs. 0.74 ± 0.13), and remained higher on day 7 (SUV 1.35 ± 0.33 vs. 0.70 ± 0.16), day 15 (SUV 1.24 ± 0.20 vs. 0.59 ± 0.07), and day 90 (SUV 1.39 ± 0.25 vs. 0.69 ± 0.11). Autoradiography of tissue sections confirmed tracer uptake in the infarct area, where immunofluorescence showed FR-ß in CD68-positive macrophages. Uptake of [18F]FOL correlated with CD68-positive macrophage density (r = 0.669, p < 0.001) and was associated with decline in left ventricular ejection fraction between days 7 and 90 post-MI (r = -0.665, p = 0.007). [18F]FOL PET detects expression of FR-β, a marker of activated macrophages after MI. FR-β expression peaks early and remains elevated up to 3 months post-MI. Early FR-β expression is associated with worsening of left ventricular systolic function.

Cumulative effect of hyperglycemia and insulin resistance on cardiac dysfunction: The coronary artery risk development in young adults (CARDIA) study.

Objective The long-term effects of childhood asthma on cardiac functions remain unclear. This study evaluates the relationship between asthma severity and cardiac function in pediatric asthma patients. Methods Children aged 10–18 years with at least five years of asthma follow-up and no known cardiac disease were included. A control group of healthy children with no chronic diseases participated. Both groups underwent electrocardiography, conventional echocardiography, tissue Doppler examination (TDI), and 2D speckle tracking echocardiography (2D-STE). Results A total of 113 asthma patients (59 mild, 54 moderate-severe) and 59 controls were assessed. Compared to controls, the asthma group had increased right ventricular area (RVA) (p = 0.04), while interventricular septal and left ventricular S’ velocity (IVSS’, LVS’) and right ventricular late diastolic velocity (RVA’) were lower (p = 0.04, p = 0.04, p = 0.02, respectively). Conventional and TDI parameters showed no other significant differences. In 2D-STE measurements, left ventricular global longitudinal and circumferential strain (LVGLS, LVGCS), right ventricular global longitudinal strain (RVGLS), and right atrial reservoir strain (RARS) were lower (p = 0.01, p = 0.03, p = 0.01, p = 0.01, respectively), while left ventricular global longitudinal and circumferential strain rate (LVGLSR, LVGCSR), right ventricular global longitudinal strain rate (RVGLSR), and right atrial reservoir strain rate (RARSR) were higher (p = 0.04, p = 0.04, p = 0.03, p = 0.04, respectively) in the asthma group, with more pronounced differences in the moderate-severe asthma group. Conclusion Our study shows a decrease in both systolic and diastolic functions in both ventricles and right atrium in relation to the severity of childhood asthma, and 2D-STE can be useful in identifying early changes.

Myocardial work indexes in elite athletes: An emerging echocardiographic tool to confirm physiologic cardiac remodeling in elite athletes with mildly reduced systolic function.

Outcomes of cardiac pacing in adults with congenitally corrected transposition of great arteries.

Abstract Background Anthracyclines are very efficient in acute lymphoblastic leukemia (ALL) treatment resulting in promising survival rates. Anthracycline related cardiotoxicity has been detected by the diastolic and systolic cardiac impairment in the follow-up of adult oncological patients and childhood cancer survivors. The data for children on echocardiographic detection of early anthracycline induced diastolic dysfunction is lacking. Purpose We aim to present preliminary results of the study on left ventricle diastolic function evaluation among children treated for acute lymphoblastic leukemia before initiation of anthracycline treatment and after induction and intensification of the therapy. Methods For this prospective study, consecutive pediatric patients diagnosed with ALL were enrolled. Transthoracic echocardiography was conducted following diagnosis and prior to the initiation of anthracycline therapy (first assessment), and after the completion of induction and intensification therapy (second assessment)(fig 1). All studies were performed on the same echocardiographic machine and were obtained from at least 2 cardiac cycles. The echocardiography included conventional 2D diastolic function assessment with tissue doppler imaging and the left atrial (LA) strain. Interobserver reliability of the data was assessed by two echocardiographers. Results The preliminary study group included 25 children (13 females, 12 males) aged between 1-16 years (mean age 5,8±3,7years). All of the children were diagnosed with ALL type C and were treated with the same treatment protocol. Mean dosage of anthracycline equivalent was 107,4±45 mg/m2(min. 26.4 - max 216.0 mg/m2), 7 children received &amp;gt;120 mg/m2 and 1 child &amp;gt;200mg/m2 of anthracycline equivalent. Mean time between the first and second assessment was 214±42 days(~7 months). Diastolic left ventricle function assessed by the E/A ratio, deceleration time, tissue Doppler and left atrial volume index (LAVI) was not significantly different between the first and the second assessment (table 1). However, the LA conduit strain at end diastole (LAScd ED)(-36.6 ± 16.0 vs -25.8 ± 12.0, p=0.028) as well as at atrial contraction(LAScd AC)(-33.4 ± 14.1 vs -23.1 ± 10.9, p=0.016) were significantly reduced after the anthracycline therapy. Other left atrial strain parameters including LA strain during reservoir at end diastole(LASr ED) and at atrial contraction(LASr AC), in the contraction phase at end diastole(LASct ED) and at atrial contraction(LASct AC) did not differ significantly between the assessments. The systolic function of the left ventricle were within norms at both measurements(table 1). Conclusions Early anthracycline induced LV diastolic dysfunction may not be detectable by the conventional echocardiographic methods in children treated for ALL. Subclinical dysfunction may be identified by close echocardiographic monitoring with the left atrial strain.

Abstract Background Aortic stenosis (AS) is the most common valvular heart disease in the elderly and often associated with atrial fibrillation (AF). The impact of AF on mortality is controversial in patients with preserved ejection fraction (EF) after transcatheter aortic valve replacement (TAVR). Aims Our aim was to assess the impact of AF on survival in patients after TAVR with preserved EF in comparison with patients with sinus rhythm (SR), and to evaluate prognostic factors in AF patients. Methods In our retrospective study we enrolled patients with preserved EF ( ≥ 50%) who underwent TAVR in our tertiary cardiovascular center between 01.01.2020-01.09.2024. All-cause mortality was assessed, with a median follow-up of 17.5 months (IQR: 7.5 - 30.2 months). Results During the observed period 1511 patients underwent TAVR, of whom 947 had preserved EF. In the AF group (n= 348) patients were older (80.4±5.5 yrs vs 79.63±5.6 yrs, p=0.03) but the proportion of male sex (43% vs 39%; p=0.27) did not differ from patients with SR (n=599). There was no difference in EF (63.3±7.6% vs 64.1±7.7%, p=0.11), but the rate of paradoxical low-flow (SVi &amp;lt;35 ml/m2) and low-gradient (mean gradient &amp;lt;40 mmHg) AS was more prevalent in patients with AF (49% vs 36%; p&amp;lt;0.0001), and Doppler index (DI) was significantly lower (0.19±0.05 vs 0.21 ± 0.05; p=0.001) compared to patients with SR. Patients with AF had larger right atrium (RAVi: 35.9 ± 26.2 ml/m2 vs 23.3 ± 10.4 ml/m2; p&amp;lt;0.001) and right ventricle (RV mid diameter: 33.0 ± 6.5 mm vs 30.6 vs 5.2 mm; p&amp;lt;0.001), and worse right ventricular systolic function (TAPSE: 20.9±12.8 mm vs 22.6±4.3 mm; p&amp;lt;0.01; RV S’: 11.4±2.5 cm/s vs 12.4±2.8 cm/s; p&amp;lt;0.001). Kaplan-Meier analysis showed better survival in patients with SR than in patients with AF (79.6% vs. 65.2%, log-rank &amp;lt;0.001). Considering the whole group in univariate Cox proportional hazard model EF, aortic Vmax, aortic mean gradient, AVA had no effect on survival, while age (HR: 1.030 [CI: 1.007-1.054], p=0.01), male sex (HR: 1.317 [CI: 1.023-1.695], p=0.03), AF (HR: 1.705 [CI: 1.325-2.193], p&amp;lt;0.001), SVi (HR: 0.984 [CI: 0.970-0.998], p=0.023), and DI (HR: 0.036 [CI: 0.002-0.540], p=0.016) were significant predictors, of which only age (HR: 1.026 [CI: 1.003-1-050], p=0.025) male sex (HR: 1.140 [CI: 1.005-1.294], p=0.041), and AF (HR: 1.611 [CI: 1.248-2.080], p&amp;lt;0.001) remained independent predictors in a multivariate model. Subgroup analysis of patients with AF showed that only male sex (HR: 1.443 [CI: 1.006-2.075], p&amp;lt;0.05) and SVi (HR: 0.974 [CI: 0.951-0.997], p&amp;lt;0.05) was an independent predictor for outcome. Conclusions Patients after TAVR with preserved ejection fraction and atrial fibrillation had worse outcome than those in sinus rhythm. Atrial fibrillation, stroke voulume index and male sex was found to be an independent predictor of mortality.Kaplan-Meier survival curve

Abstract Heart failure with preserved ejection fraction (HFpEF) is a complex syndrome associated with diastolic dysfunction, left atrial (LA) impairment, and atrial remodeling (1). Despite the preserved systolic function, HFpEF patients often experience elevated left ventricular (LV) filling pressures, myocardial fibrosis, and altered atrial mechanics, all contributing to worsening outcomes (2). Sodium-glucose cotransporter 2 (SGLT2) inhibitors, originally developed for glycemic control in diabetes mellitus, have recently emerged as promising therapeutic agents in HFpEF due to their pleiotropic cardiovascular effects (3). The primary aim of this study is to evaluate the impact of SGLT2 inhibitors on diastolic function, left atrial function, and atrial remodeling in HFpEF patients using echocardiography and cardiac magnetic resonance (CMR) imaging. Additionally, the study seeks to contribute to understanding HFpEF pathophysiology by analyzing circulating biomarkers (galectin-3 and heart-type fatty acid-binding protein (H-FABP)) which reflect myocardial fibrosis and injury, respectively. A total of 26 patients with HFpEF and type 2 diabetes mellitus who were followed at our Hospital between May 29, 2023, and May 28, 2024, were included in the study. Echocardiographic and CMR imaging assessments were performed before and after treatment with SGLT2 inhibitors. Blood samples were collected at both time points for biomarker evaluation. Post-treatment imaging showed significant reductions in LA volüme index (from 40,6±12,9 mL to 36,9±13,8 ml/m², p&amp;lt;0.028) and improvements in LA reservoir strain (from 22.3±9.4% to 23.0±8.3%, p=0.010). LV volumes and mass also decreased significantly, including a reduction in LV end-diastolic volume index (152.27±28.92 mL to 139.08±28.28 mL, p&amp;lt;0.001) and LV mass index (52.67±10.15 g/m² to 49.27±8.99 g/m², p&amp;lt;0.001). TAPSE values increased (18.3±4.65 mm to 20.54±4.22 mm, p=0.001), indicating improved RV function (Table 1). Diastolic parameters improved, such as lateral e' velocity (6.77±1.66 to 8.17±1.98 cm/s, p=0.010) and E/A ratio (0.83±0.38 to 0.85±0.27, p=0.002) (Table 2). A significant decline in galectin-3 levels was observed (773.99±885.55 ng/mL to 502.05±535.90 ng/mL, p=0.028), while H-FABP levels remained unchanged. In conclusion, SGLT2 inhibitors demonstrated beneficial effects on structural and functional cardiac parameters in patients with HFpEF, particularly in improving left atrial mechanics and reducing fibrosis. These findings support their role in HFpEF management, although further studies with larger cohorts and longer follow-up are needed to validate and expand upon these results.Comparison of cardiac MRI findings in pa Comparison of echocardiographic paramete

Abstract Background The progression of mitral valve (MV) remodeling in atrial fibrillation (AF) patients without significant mitral regurgitation (MR) remains poorly characterized. This study investigates the differential impact of AF burden (paroxysmal vs. persistent) on early MV structural and functional changes using 3D transesophageal echocardiography. Methods In this prospective cohort, 46 AF patients without significant MR (paroxysmal AF: n=18; persistent AF: n=28) underwent comprehensive 3D transesophageal echocardiography. Annular dimensions, geometry, shape, leaflet morphology, and functional parameters were quantified and statistically compared between groups.. Results Patients with persistent AF exhibited significant early mitral annular remodeling compared to paroxysmal AF, despite comparable baseline age, BMI, and BSA. The persistent AF group had significantly larger left atrial diameter (45.4 ± 7.13 mm vs. 40.3 ± 6.26 mm, p=0.05), lower left ventricular ejection fraction (45.5 ± 15.4 vs. 56.5 ± 15.2, p=0.042), and larger LV end-systolic dimension (41.3 ± 9.65 mm vs. 33.1 ± 9.35 mm, p=0.018). Quantitative 3D analysis revealed persistent AF was associated with significantly larger annular dimensions, including anteroposterior diameter (3.92 ± 0.53 mm vs. 3.60 ± 0.47 mm; p=0.042), AL-PM diameter (3.74 ± 0.50 mm vs. 3.49 ± 0.34 mm; p=0.048), 3D saddle-shaped annulus area (11.98 ± 3.19 cm² vs. 10.34 ± 2.05 cm²; p=0.038), and 2D D-shaped annulus area (9.78 ± 2.83 cm² vs. 8.27 ± 1.87 cm²; p=0.035). Perimeter measurements for both 3D saddle-shaped (12.74 ± 1.56 mm vs. 11.94 ± 1.14 mm; p=0.05) and 2D D-shaped (11.51 ± 1.47 mm vs. 10.69 ± 1.15 mm; p=0.042) annuli were also significantly larger. Leaflet morphology changes included significantly larger anterior leaflet area (8.93 ± 2.07 cm² vs. 7.60 ± 2.02 cm²; p=0.036) and smaller distal anterior leaflet angle (16.97 ± 5.03° vs. 20.76 ± 6.40°; p=0.042) in persistent AF. Functional parameters (tenting volume/area, coaptation depth) and dynamic annular motion showed no statistically significant differences. Conclusion Persistent AF is associated with adverse early mitral annular and leaflet remodeling, independent of significant MR and alongside worse LV systolic function and larger LA size. This remodeling may predispose to future MR progression, underscoring the importance of rhythm control strategies to mitigate structural changes in high-burden AF populations.

Abstract Background Right ventricular (RV) - pulmonary artery (PA) coupling reflects the capacity of the RV to adapt to afterload and is increasingly recognized as a functional and prognostic marker in mitral valve disease. Noninvasive indices such as TAPSE/SPAP, RV S′/SPAP, and RV free wall strain (FWS)/SPAP seem promising, but their role across different grades of mitral regurgitation (MR) is not well defined. Aim To assess whether RV-PA coupling indices can differentiate between moderate and severe organic MR using transthoracic echocardiography. Methods This retrospective, single-center study included patients with echocardiographically confirmed organic MR evaluated between July 2020 and January 2025 in the echocardiography laboratory of a tertiary hospital. Patients with inadequate image quality, coexistent significant valvular disease, ischemic heart disease, or chronic atrial fibrillation were excluded. RV–PA coupling was assessed using TAPSE/SPAP, RV S′/SPAP, and RV FWS/SPAP. Non-parametric comparisons were performed using the Mann–Whitney U test. Results A total of 71 patients were included: 44 (62%) with severe MR and 27 (38%) with moderate MR. Median age was 71 years in the severe MR group and 67 years in the moderate group. In the severe MR group, 59.1% were male and 40.9% female; in the moderate MR group, 40.7% were male and 59.3% female. RV–PA coupling indices were significantly lower in the severe MR group. TAPSE/SPAP was reduced to a median of 0.39 (interquartile range [IQR] 0.30–0.52) compared to 0.49 (IQR 0.38–0.64) in moderate MR (p = 0.011). Similarly, RV S′/SPAP was lower in severe MR (median 0.26, IQR 0.20–0.34) than in moderate MR (0.33, IQR 0.26–0.41; p = 0.018). RV FWS/SPAP also decreased with MR severity (0.65 [IQR 0.49–0.83] vs. 0.80 [IQR 0.64–1.00]; p = 0.028). Conclusion Echocardiographic indices of RV–PA coupling—TAPSE/SPAP, RV S′/SPAP, and RV FWS/SPAP—were significantly impaired in patients with severe organic MR, even in the presence of similar biventricular systolic function. These indices may enhance early identification of RV–PA uncoupling and support their inclusion in routine MR assessment to refine timing of intervention.

Abstract Background Accurate prediction of atrial fibrillation recurrence remains challenging despite rhythm control strategies. Echocardiographic markers such as left atrial (LA) strain components have shown predictive value, but their utility may be affected by technical and clinical factors. Indices reflecting atrioventricular (A-V), ventriculo-atrial (V-A), and right atrial-right ventricular (RA-RV) coupling remain underexplored and may offer additional prognostic insight. Purpose To assess the prognostic significance of established echocardiographic markers and coupling indices for AF recurrence in a homogeneous cohort of patients with paroxysmal AF (PAF). Methods We prospectively studied 73 patients (mean age 59.6±11.6 years; 52% female) with PAF in sinus rhythm at baseline. All underwent comprehensive transthoracic echocardiography including strain and volumetric analysis. AF recurrence was documented over 12 months via ECG, Holter monitoring, or clinical documentation of symptomatic episodes. Variables and coupling indices, including LA volume index (LAVI), LA strain components, E/e’, LA coupling index (LACI), right ventricular fractional area change (RV FAC)/right atrial (RA) volume, tricuspid annular plane systolic excursion (TAPSE)/pulmonary arterial systolic pressure (PASP), were assessed using univariable logistic regression. Significant predictors were entered into multivariable analysis. Results At baseline, recurrence (n=31) and non-recurrence (n=42) groups were similar in age, sex, cardiovascular risk factors, and medication use (all p&amp;gt;0.05), confirming group homogeneity. Most conventional markers, including LAVI, LAEF, E/e’, and LA reservoir or conduit strain, were not associated with recurrence. Coupling indices across the left and right heart also lacked predictive value (all p&amp;gt;0.05). Univariable analysis identified 3 significant predictors: lower RV FAC (OR=0.918 per 1% increase; 95% CI: 0.854–0.987; p=0.020), reduced LA contraction strain (OR=0.886, 95% CI: 0.790–0.994, p=0.039), and a higher LA contraction strain/LAVI ratio (OR=12.238; 95% CI: 1.294–115.775; p=0.029), possibly reflecting mechanical-structural mismatch. In multivariable analysis, RV FAC remained independently predictive (OR=0.921; p=0.034), while the LA contraction strain/LAVI ratio showed a borderline association (OR=14.769, 95% CI: 0.806–84.792, p=0.076) (Table 1). LA contraction strain alone lost significance. Our findings are illustrated in Figure 1, showing measurement of LA contraction strain and RV FAC, two key predictors of AF recurrence in this cohort. Conclusions In this homogeneous PAF cohort, conventional left heart indices and coupling markers were not predictive of recurrence. Instead, impaired RV systolic function and reduced atrial contractile efficiency indexed to atrial size emerged as more relevant predictors. These findings highlight the underrecognized importance of RV function and LA mechanical–structural mismatch in AF risk stratification.

Abstract Background and purpose Dilated cardiomyopathy (DCM), characterised by left ventricular (LV) dilation with impaired systolic function, is also associated with diastolic abnormalities, which contribute significantly to symptoms, disease progression and prognosis. Myocardial remodelling includes fibrosis and increased chamber stiffness, which impair LV relaxation and elevate filling pressures. We aimed to assess LV stiffness non-invasively using 3D echocardiography and to evaluate its prognostic role in a cohort of patients with DCM. Methods 121 consecutive patients with non-ischemic DCM underwent comprehensive 2D and 3D echocardiographic assessment, using dedicated software for 3D LV analysis. LV stiffness was defined as 100 * the mitral E/ lateral annular e' ratio divided by 3D LV end-diastolic volume. Patients were prospectively followed for 19±11 months for a composite endpoint of death or heart failure decompensation requiring hospitalisation. Results Mean age in the study group was 59±14 years and the majority (74%) were men. 55 patients reached the endoint: there were 26 deaths and 29 hospitalisations for heart failure. LV systolic dysfunction was similar between patients with and without events, with no significant differences in terms of LV stroke volume (p=0.88), LV ejection fraction (LVEF) (p=0.08) or LV global longitudinal strain (p=0.09). There were no differences in 3D LV end-diastolic volume (p=0.11), end-systolic volume (p=0.09) or 3D LVEF (p=0.22) between patients reaching and not reaching the endpoint. On the other hand, diastolic dysfunction was greater in patients with events: 1.7±0.8 vs. 1.2±0.7, p&amp;lt;0.001 for mitral E/A ratio, 118±51 ml vs. 88±45 ml, p=0.001 for LA volume. LVSI was higher in patients reaching the endpoint (7.5±4.3 vs. 6.0±2.6, p=0.02), reflecting greater LV stiffness. In Cox regression analysis, LVSI predicted adverse outcome (HR=1.11 [95% CI, 1.04–1.19], p=0.003), while LVEF did not (p=0.08). LVSI remained a independent predictor of events after adjusting for age, NYHA class, mitral regurgitation severity and pulmonary artery systolic pressure (HR=1.10 [95% CI, 1.02–1.18], p=0.01). Conclusions LV stiffness was greater in patients with DCM and adverse events, reflecting a more impaired diastolic dysfunction. LVSI was an independent outcome predictor in survival analysis, while LV systolic dysfunction was not.

Abstract Background Peripartum cardiomyopathy (PPCM) is a rare complication occurring in the last weeks of pregnancy and in the peripartum period characterized by sign and symptoms of heart failure and left ventricular (LV) systolic dysfunction. While recovery is observed in about 50% of women, this condition is still associated with high morbidity and mortality. To date, little is known about clinical and echocardiographic factors related to LV function recovery, and no data are available on myocardial mechanics and performance. Methods We retrospectively selected 17 consecutive women (mean age 39.2 ±9.0 years) with confirmed diagnosis of PPCM enrolled in the Italian multicenter, observational registry of PPCM coordinated by our hospital. Demographics were collected and myocardial mechanics were assessed using speckle tracking-derived global longitudinal strain (GLS), global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE). Patients were categorized according to the subsequent LV ejection fraction (LVEF): group A, LVEF≤35%; group B, 35%&amp;lt;LVEF&amp;lt;50%;&amp;gt; Results LV recovery was observed in 8 women (47%, group C), with a mean LVEF of 55±2%. In 6 patients (35%) mild dysfunction was still observed (mean LVEF 44±3%, group B), while 3 patients had persistent severe LV dysfunction (mean LVEF 26±7%), requiring ICD implantation (group A). The three groups significantly differed for LV end-diastolic diameter (62.7 ± 9.5 vs 54.7 ± 5.0 vs 48.5 ±2.6 mm respectively in group A vs group B vs group C, p=0.002), LV volume (209.7 ± 110.6 vs 147.3 ±37.1 vs 101.1 ± 19.8 ml respectively, p=0.017), TAPSE (15.3 ± 5.8 vs 23.3 ± 1.9 vs 22.9 ± 2.3 mm respectively, p=). Speckle tracking analysis revealed a significant improvement in myocardial performance from group A to C: GLS (9.7 ±5.4 vs 14.6 ±3.2% vs 19.9 ±0.9% respectively, p&amp;lt;0.001), GWI (854±674 vs 1231±476 vs 1914±511mmHg%, p=0.021), GCW(1123±699 vs 1695±536 vs 2239 ± 540 mmHg%, p=0.032), GWW (166±81 vs 261±78 vs 104±34 mmHg%, p=0.002), GWE (84±10 vs 86±4 vs 95±2%, p=0.005). Also atrial strain improved across the different groups (17±11 vs 29±9 vs 42±4%, p=0.001), with no significant difference in left atrial volume. Also in patients with recovered LV systolic function, GLS was significantly reduced compared to controls (19.9 ±9 vs 21.7±1.3% respectively, p=0.007). Conclusion in patients with history of PPCM, GLS and myocardial work provide a better definition of myocardial performance in those with partially o complete systolic recovery. GLS remains impaired also in women with normalized LVEF suggesting that GLS is a more sensitive marker of continued LV dysfunction in recovered PPCM.LVEF&amp;lt;50%;&amp;gt;