Junjun Quan

Heart failure (HF) represents the clinical end stage of most cardiovascular diseases and remains a major cause of mortality, morbidity, and poor quality of life worldwide. In the present study, we use a mouse model induced by abdominal aortic constriction (AAC) that mimics HF and evaluate the potential therapeutic effects of nootkatone (NKT) on this model. Ejection fraction (EF) and fractional shortening (FS) progressively deteriorated in the AAC mice. The AAC mice were treated with NKT for 8 weeks starting on the eighth day post-AAC. Early NKT treatment prevented cardiac dysfunction in the AAC mice at 8 and 12 weeks after administration, along with thinner left ventricular posterior wall, lower left ventricular mass and ratio of heart weight/tibial length, and fewer cardiomyocyte areas. Furthermore, we found that NKT significantly reduced the expression levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), collagen types Ⅰ and Ⅲ, TGF-β1, Smad3, and the phosphorylation of Smad3. Furthermore, NKT decreased the activation of cardiac fibroblasts and myocardial fibrosis in the AAC mice. Our data suggest that NKT can delay or reverse the progression of HF after AAC and reduce myocardial hypertrophy and fibrosis possibly via inhibition of the TGF-β1/Smad3 signaling pathway.

The effects of anesthetics on liver and kidney functions after infantile living-related liver transplantation (LRLT) are unclear. This study aimed to investigate the effects of propofol-based total intravenous anesthesia (TIVA) or desflurane-based inhalation anesthesia on postoperative liver and kidney functions in infant recipients after LRLT and to evaluate hepatic ischemia–reperfusion injury (HIRI). Seventy-six infants with congenital biliary atresia scheduled for LRLT were randomly divided into two anesthesia maintenance groups: group D with continuous inhalation of desflurane and group P with an infusion of propofol. The primary focus was to assess alterations of liver transaminase and serum creatinine (Scr) levels within the first 7 days after surgery. And the peak aminotransferase level within 72 h post-surgery was used as a surrogate marker for HIRI. There were no differences in preoperative hepatic and renal functions between the two groups. Upon the intensive care unit (ICU) arrival, the levels of aspartate aminotransferase (AST, P = 0.001) and alanine aminotransferase (ALT, P = 0.005) in group P were significantly lower than those in group D. These changes persisted until the fourth and sixth days after surgery. The peak AST and ALT levels within 72 h after surgery were also lower in group P than in group D (856 (552, 1221) vs. 1468 (732, 1969) U/L, P = 0.001 (95% CI: 161–777) and 517 (428, 704) vs. 730 (541, 1100) U/L, P = 0.006, (95% CI: 58–366), respectively). Patients in group P had lower levels of Scr upon the ICU arrival and on the first day after surgery, compared to group D (17.8 (15.2, 22.0) vs. 23.0 (20.8, 30.8) μmol/L, P < 0.001 (95% CI: 3.0–8.7) and 17.1 (14.9, 21.0) vs. 20.5 (16.5, 25.3) μmol/L, P = 0.02 (95% CI: 0.0–5.0) respectively). Moreover, the incidence of severe acute kidney injury was significantly lower in group P compared to that in group D (15.8% vs. 39.5%, P = 0.038). Propofol-based TIVA might improve liver and kidney functions after LRLT in infants and reduce the incidence of serious complications, which may be related to the reduction of HIRI. However, further biomarkers will be necessary to prove these associations.

Genetic defects have been increasingly found in cardiomyopathies, which are often present with mutations in cardiac contractile proteins. These congenital defects involve numerous intracellular pathways and share several critical clinical features, such as systolic or diastolic dysfunction fostering the various cardiomyopathic phenotypes. Hypertrophic cardiomyopathy and restrictive cardiomyopathy (RCM) share a common pathological feature, that is, diastolic dysfunction. Studies have shown that mutations of contractile proteins, especially myosin heavy chain and troponin, are tightly associated with diastolic dysfunction in patients with Cardiomyopathies (CMs), including pediatric patients with CM. Therapeutics, including green tea extract (epigallocatechin gallate) and mavacamten, interact directly with these contractile proteins and have shown promising results. This article will review recent and contemporary research on diastolic dysfunction in CMs, especially hypertrophic cardiomyopathy and RCM, which include their target proteins, mechanisms, clinical diagnosis, and potential therapies.

Cardiomyopathy (CM) is a heterogeneous group of myocardial diseases in children. This study aimed to identify demographic features, clinical presentation and prognosis of children with CM. Clinical characteristics and prognostic factors associated with mortality were evaluated by Cox proportional hazards regression analyses. Genetic testing was also conducted on a portion of patients. Among the 317 patients, 40.1%, 25.2%, 24.6% and 10.1% were diagnosed with dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), left ventricular noncompaction cardiomyopathy (LVNC) and restrictive cardiomyopathy (RCM), respectively. The most common symptom observed was dyspnea (84.2%). Except for HCM, the majority of patients were classified as NYHA/Ross class III or IV. The five-year survival rates were 75.5%, 67.3%, 74.1% and 51.1% in DCM, HCM, LVNC and RCM, respectively. The ten-year survival rates were 60.1%, 56.1%, 57.2% and 41.3% in DCM, HCM, LVNC and RCM, respectively. Survival was inversely related to NYHA/Ross class III or IV in patients with DCM, HCM and RCM. Out of 42 patients, 32 were reported to carry gene mutations.Conclusions: This study demonstrates that CM, especially RCM, is related to a high incidence of death. NYHA/Ross class III or IV is a predictor of mortality in the patients and gene mutations may be a common cause.Trial registration: MR-50-23-011798. What is Known:• Cardiomyopathy (CM) is a heterogeneous group of myocardial diseases and one of the leading causes of heart failure in children due to the lack of effective treatments.• There remains scarce data on Asian pediatric populations though emerging studies have assessed the clinical characteristics and outcomes of CM. What is New:• A retrospective study was conducted and the follow-up records were established to investigate the clinical characteristics, the profile of gene mutations and prognostic outcomes of children with CM in Western China.• CM, especially RCM, is related to a high incidence of death. NYHA/Ross class III or IV is a predictor of mortality in the patients and gene mutations may be a common cause.

Background: Cardiomyopathy (CM) is a heterogeneous group of myocardial diseases in children. This study aimed to identify demographic features, clinical presentation and prognosis of children with CM. Methods: Clinical characteristics and prognostic factors associated with mortality were evaluated by Cox proportional hazards regression analyses. Genetic testing was also conducted on a portion of patients. Results: Among the 317 patients, 40.1%, 25.2%, 24.6%, and 10.1% were diagnosed with dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), left ventricular noncompaction cardiomyopathy (LVNC) and restrictive cardiomyopathy (RCM), respectively. The most common symptom observed was dyspnea (84.2%). Except for HCM, the majority of patients were classified as NYHA/Ross class III or IV. The five- and ten- year survival rates were 75.5% and 60.1%, 67.3% and 56.1%, 74.1% and 57.2%, and 51.1% and 41.3% in DCM, HCM, LVNC, and RCM, respectively. Survival was inversely related to NYHA/Ross class III or IV in patients with DCM, HCM and RCM. Out of 42 patients, 32 were reported to carry gene mutations. Conclusions: This study demonstrates that CM, especially RCM, is related to a high incidence of death. NYHA/Ross class III or IV is a predictor of mortality in the patients and gene mutations may be a common cause.

Cardiomyopathies comprise a group of disorders wherein the primary defect is in cardiac myocytes. The common forms of pediatric cardiomyopathies, classified according to their morphological and functional manifestations, include dilated cardiomyopathy (DCM), restrictive cardiomyopathy (RCM), hypertrophic cardiomyopathy (HCM), and others. Cardiac gene mutations caused abnormal myofibril Ca²⁺ sensitivity may be involved in the underlying molecular mechanisms of cardiomyopathies. Thus far, no effective treatment for cardiomyopathies has been developed, especially for HCM and RCM in which diastolic dysfunction occurs early and followed by diastolic heart failure. Our laboratory is among the first in the field to investigate the mechanisms underlying various cardiomyopathies and search for the treatment for these disorders. In the past, we and other researchers have found that (−)‐epigallocatechin‐3‐gallate (EGCg), the major biomedical polyphenol extracted from green tea, possess multiple therapeutic effects on protecting cardiac function and correcting impaired relaxation. Given its therapeutic effects, EGCg might be a potential drug candidate for administration to patients with cardiomyopathy and heart failure. In this review, we will discuss the molecular mechanisms associated with the pathogenesis of diastolic dysfunction and summarize the pharmacological effects of EGCg on experimental animals and pediatric patients with cardiomyopathies and diastolic dysfunction.