Context Paeonol (PAE) is the main phytochemical from Cortex Moutan . Its main pharmacological effects are anti-inflammatory and antioxidant, but its cardioprotective effect is unclear. Objective The study investigates the effects and underlying mechanisms of PAE on transverse aortic constriction (TAC)-induced heart failure (HF) in mice. Materials and methods C57BL/6 mice were randomly divided into five groups: sham, TAC, PAE10 (TAC + PAE 10 mg/kg), PAE20 (TAC + PAE 20 mg/kg) and PAE 50 (TAC + PAE 50 mg/kg). Paeonol was intragastrically administered to mice for 4 weeks. Mice were anaesthetized with pentobarbital sodium and underwent cardiac echocardiography using echocardiography system. Serum levels of atrial natriuretic peptide (ANP), tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay (ELISA). Myocardial apoptosis was detected with terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) staining. Haematoxylin–eosin (H&E) and Masson’s staining were used for histopathological evaluation. Western and quantitative real-time PCR (qRT-PCR) were performed to detect levels of apoptosis and fibrosis-related proteins. Results Echocardiography showed PAE improved cardiac function (LVEF: TAC, 52.3±6.8%; PAE20, 65.8±3.6%; PAE50, 71.4±2.5%) and H&E staining showed PAE alleviated myocardial injury (TAC: 1170.3 ± 134.6 μm 2 ; PAE50: 576.0 ± 53.5 μm 2 ). Western and qRT-PCR results showed that PAE down-regulated the levels of ANP, BNP and α-MHC. In addition, TUNEL and western results showed PAE significantly inhibited apoptosis. Masson and western results showed PAE inhibited cardiac hypertrophy. Western results showed the ERK1/2/JNK pathway could be inhibited by PAE. Discussion and conclusions Paeonol regulates ERK1/2/JNK to improve cardiac function, which provides theoretical support for the extensive clinical treatment of HF.

BackgroundEarly detection of subclinical cardiotoxicity of immune checkpoint inhibitor (ICI) therapy can be challenging.ObjectiveTo evaluate subclinical cardiac dysfunction using two-dimensional speckle tracking imaging (2D-STI) and three-dimensional echocardiography in Chinese patients.MethodsFifty-five consecutive patients with malignant tumors treated by immunotherapy were included. They were examined by echocardiography before immunotherapy and after immunotherapy. Left ventricular ejection fraction (LVEF) was calculated in three-dimensional imaging. Moreover, left ventricular global longitudinal peak systolic strain (LVGLS), left ventricular global circumferential peak systolic strain (LVGCS), right ventricular global longitudinal systolic strain (RVGLS), right ventricular free wall longitudinal peak systolic strain (RVFWLS), and tricuspid annular plane systolic excursion (TAPSE) were evaluated. Clinical and laboratory parameters were recorded. Cardiac toxicity events were defined as the presence of heart failure symptoms, LVEF reduction, and increase in troponin. Subclinical cardiac toxicity was defined as cardiac dysfunction associated with ICI treatment, with absent or delayed ICI-associated cardiotoxicity clinical symptoms.ResultsCompared with baseline, the LVGLS, TAPSE, and RVGLS significantly deteriorated after ICI treatment [(–18.63 ± 2.53)% vs. (–17.35 ± 2.58)%, P = 0.000; 18.29 ± 6.23 vs. 14.57 ± 3.81, P = 0.0001; and (–18.45 ± 4.65)% vs. (–14.98 ± 3.85)%, P = 0.0001, respectively]. LVGLS (–17.35 ± 2.58, P = 0.000), TAPSE (14.57 ± 3.81, P = 0.0001), and RVGLS [(–14.98 ± 3.85)%, P = 0.0001] were decreased after ICI immunotherapy. Kaplan-Meier curve analysis showed that LVGLS was more sensitive than the cardiac toxicity events to assess ICI-related subclinical cardiac dysfunction (log-rank P = 0.205). The ROC curve showed that the cutoff value of ΔLVGLS was -13%.ConclusionSubclinical cardiac dysfunction can be detected using two-dimensional speckle-tracking imaging. LVGLS, RVGLS, and TAPSE are more sensitive indices for detection.Clinical trial registration[https://www.chictr.org.cn/showprojen.aspx?proj=27498], identifier [ChiCTR1800016216].

Objective: Immune checkpoint inhibitors (ICIs) are effective anti-cancer drugs that can improve survival in cancer patients, but their use may be associated with adverse cardiovascular side effects. Therefore, there is a clinical unmet need to identify non-invasive biomarker to detect subclinical cardiac toxicity after ICI treatment. The aim of this study is to examine the plasma levels of biomarkers in cancer survivors who were treated with ICIs.Patients and Methods: In a cohort of 19 cancer patients, biomarkers were evaluated at baseline, 1 month, 3 and 6 months after ICI administration. These biomarkers, hypothesized to be mechanistically relevant to cardiotoxicity, included cardiac troponin I (cTnI), high-sensitivity C-reactive protein (Hs-CRP), N-terminal pro–B-type natriuretic peptide (NT-pro BNP), CK (creatine kinase), CK-MB (creatine kinase-MB), Pentraxin-related protein 3 (PTX3), growth differentiation factor 15 (GDF-15), heart type-fatty acid binding protein (H-FABP) and galectin 3 (Gal-3).Results: H-FABP, but not other biomarkers, were increased at 3 months, which persisted at 6 months (529.28 ± 312.83 vs. 752.33 ± 283.65 vs. 808.00 ± 289.69 pg/ml, p = 0.031 and p = 0.013). Left ventricular ejection fraction (63.00 ± 4.15% vs. 63.74 ± 4.07%, p > 0.05) was not significantly reduced at this time point.Conclusions: H-FABP, but not other biomarkers, were increased in patients who were treated using ICIs. H-FABP might be a more sensitive biomarker to detect ICI-related subclinical myocardial damage than traditional cardiac biomarkers.

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