Lin Liu

Background: Patients with hypertrophic cardiomyopathy (HCM) may develop heart failure symptoms despite preserved left ventricular ejection fraction, while conventional indices may incompletely capture right-heart reserve. This study evaluated the prognostic value of right atrial reservoir strain in patients with HCM meeting criteria for heart failure with preserved ejection fraction (HFpEF).Methods:This retrospective cohort included 103 patients with HCM meeting HFpEF criteria. Right atrial reservoir strain was measured using speckle-tracking echocardiography. The primary endpoint was a composite of heart failure–related events or cardiovascular death. Associations with right ventricular function, clinical outcomes, and incremental prognostic value were evaluated.Results:During a median follow-up of 24.0 months, 39 patients experienced the primary endpoint. Right atrial reservoir strain correlated with absolute right ventricular global longitudinal strain, absolute right ventricular free-wall longitudinal strain, and tricuspid annular plane systolic excursion (r = 0.482-0.517, all P < 0.001). Right atrial reservoir strain discriminated the primary endpoint with an area under the curve of 0.797 (95% CI, 0.706-0.876). In the fully adjusted Cox model, each 1% increase in right atrial reservoir strain was associated with a lower risk of the primary endpoint (hazard ratio, 0.89; 95% CI, 0.85-0.93; P < 0.001). Adding right atrial reservoir strain to the clinical model increased the C-index from 0.565 to 0.759 and AUC from 0.597 to 0.814.Conclusions:Among patients with HCM meeting HFpEF criteria, right atrial reservoir strain was independently associated with adverse outcomes and may provide complementary prognostic information. External validation in larger cohorts is warranted.

Background: Risk prediction in dilated cardiomyopathy (DCM) remains suboptimal, and there is uncertainty about how newer machine-learning (ML) methods compare with conventional regression for clinically useful prognostic modelling. Advanced three-dimensional (3D) echocardiographic measures, particularly of right ventricular function, may improve model performance when combined with routinely collected clinical data. We aimed to compare conventional Cox regression, penalised Cox regression, and ML approaches for prognostic modelling in DCM and to identify models that offer the best balance of discrimination, calibration, and interpretability for risk stratification. Methods: We conducted a retrospective cohort study including 196 adults with DCM attending a tertiary cardiology centre between 2021 and 2023. Participants were followed for a composite outcome of all-cause mortality, heart failure rehospitalisation, or left ventricular assist device (LVAD) implantation. We considered 41 candidate predictors, including demographic and clinical variables and 3D echocardiographic parameters (e.g. 4D right ventricular ejection fraction [4D-RVEF], tricuspid annular plane systolic excursion [TAPSE], right ventricular global longitudinal strain [RVGLS], left atrial volume index [LAVI], and pulmonary artery systolic pressure [PASP]). Twelve prognostic models were developed including conventional Cox regression, penalised Cox regression (Lasso-Cox), and several ML models—and evaluated using internal and performance assessment at different prediction horizons (up to 24 months). Performance was assessed using area under the receiver operating characteristic curve (AUC), calibration plots, and SHAP-based feature importance. Results: At 12 months, he best-performing ML model achieved the highest discrimination (AUC 0.990),followed by GBDT and Lasso-Cox (AUC 0.825). Model discrimination attenuated at longer prediction horizons, with the Lasso-Cox model maintaining acceptable performance at 24 months (AUC 0.729). Although RF and GBDT demonstrated excellent discrimination, calibration analyses revealed systematic under- and over-prediction at the extremes of risk. By contrast, Lasso-Cox showed more stable and favourable calibration across risk deciles. Across models, key predictors consistently included 4D-RVEF, LAVI, PASP, and TAPSE. Conclusions: In this DCM cohort, ML models, particularly RF, maximised discrimination but exhibited calibration issues. A penalised regression model (Lasso-Cox) provided the best overall trade-off between discrimination, calibration, and interpretability, and is therefore recommended as the preferred approach for clinical risk stratification and future public health–oriented implementation studies in DCM.

The most severe side effect of chemotherapy is cardiotoxicity, frequently causing myocardial injury characterized by excessive oxidative stress and fibrosis for which effective treatments are lacking. To address this, a hydrogen delivery system, hydrogen nanobubbles (HNBs), was constructed, leveraging hydrogen's selective antioxidant and antifibrotic properties to counteract doxorubicin (Dox)-induced myocardial injury and explore its mechanism. HNBs were constructed via polymer self-assembly. Nanoparticle tracking analysis indicated a size of 265.1 ± 26 nm. The average hydrogen content of HNBs measured by chemical titration was about 1.9 mg/L. TEM revealed spherical HNBs with a dense outer lipid polymer layer encapsulating hydrogen. CCK-8 assays confirmed over 90% cell viability, demonstrating good biosafety. ROS fluorescence staining and flow cytometry showed that HNBs significantly reduced Dox-induced ROS increases. RT-qPCR revealed the upregulation of antioxidant genes (NRF2, SOD2, and GPX-1). Flow cytometry and JC-1 staining indicated that HNBs mitigated apoptosis and restored mitochondrial membrane potential. TEM displayed reduced mitochondrial damage and intracellular vacuolation. In a Dox-induced cardiomyopathy mouse model, HNBs improved cardiac function, normalized echocardiographic parameters (EF, FS, LVIDs, and LVIDd), and lowered myocardial ROS levels. Ultrasonic enhanced images showed that HNBs have good myocardial differential targeting. In vivo fluorescence imaging of mice showed that HNBs could accumulate in the myocardium in large quantities at 1 h. mRNA-seq and network pharmacology suggested that HNBs inhibit myocardial fibrosis. Masson staining results showed that HNBs could improve Dox-induced myocardial fibrosis. RT-qPCR and Western blotting confirmed the reduced expression of fibrosis markers (ACTA2, COL1, and FN1), preliminarily linking the mechanism to suppression of both PI3K/AKT and TGF-β/SMAD pathways. In summary, HNBs inhibit oxidative stress and myocardial fibrosis, reversing Dox-induced cardiac injury primarily through the dual suppression of the PI3K/AKT and TGF-β/SMAD pathways.

Pathological cardiac hypertrophy, often triggered by the excessive production and accumulation of reactive oxygen and nitrogen species (RONS), may ultimately lead to heart failure. The treatment of myocardial hypertrophy often involves antioxidant stress therapy. In this study, by coordinating curcumin with ferric ions during the synthesis of Prussian blue nanoparticles, a Prussian blue‐curcumin (PB‐Cur) nanozyme is successfully engineered with exceptional reactive oxygen and nitrogen species (RONS) elimination capabilities. Following PVP modification, the PB‐Cur nanozyme exhibited favorable biocompatibility and stability in aqueous solutions. Furthermore, the PB‐Cur nanozyme shows remarkable reversible treatment efficacy against myocardial hypertrophy in both in vitro and in vivo models. After one week of treatment, the PB‐Cur group in the transverse aortic constriction (TAC)‐induced cardiac hypertrophy models displayed a notable decrease in myocardial hypertrophy and fibrosis. Echocardiographic findings also revealed a substantial improvement in cardiac function among TAC mice following PB‐Cur administration. Mechanistically, through reactive oxygen species (ROS) elimination, the PB‐Cur effectively downregulated oxidative stress‐related pathways, including MAPK and PI3K‐Akt, which hold promise for treating oxidative stress‐related cardiac diseases.

Background: Type 2 diabetes mellitus (T2DM) and hypertension (HT) often coexist and contribute to left atrial (LA) functional abnormalities. The aim of the present study was to explore whether there is a potential interaction effect between T2DM and HT on LA function. Methods: A total of 135 patients (45 with T2DM only, 45 with HT only, and 45 with both T2DM and HT) were enrolled and compared to 45 age- and sex-matched controls. LA volume fraction, including LA ejection fraction (LAEF), LA expansion index (LAEI), LA passive emptying fraction (LAPEF), and LA active emptying fraction (LAAEF), and strain parameters, including LA reservoir longitudinal strain (LASr), LA conduit longitudinal strain (LAScd), and LA contraction longitudinal strain (LASct), were obtained using three-dimensional echocardiography (3DE). Results: Patients with T2DM had significantly more impaired LA reservoir and conduit functions compared to those without T2DM (PT2DM + HT =0.002) and LAScd (P_{T2DM + HT} =0.001). Generalized linear model demonstrated that T2DM + HT had a greater relative contribution than either T2DM or HT alone to the LA strain indexes, even after adjustment for other confounders (LASr, β_{T2DM + HT} =−3.931, 95% CI: −6.237 to −1.624, P=0.001; LAScd, β_{T2DM + HT}=−3.781, 95% CI: −5.653 to −1.908, PConclusions: Both T2DM and HT had an adverse effect on LA function. The coexistence of both conditions further impaired LA performance in an additive interaction fashion.

Original Article Interaction effect of hypertension and obesity on left atrial phasic function: a three-dimensional echocardiography study Rui Zhang, Cunying Cui, Shuojing Wang, Ying Wang, Ruijie Liu, Lin Liu