Sepsis is a life-threatening organ dysfunction caused by the body's dysregulated response to infection. Reversible myocardial dysfunction caused by sepsis is known as septic cardiomyopathy. A thorough understanding of the pathogenesis of septic cardiomyopathy is crucial for early intervention to prevent its progression and improve the success rate of sepsis treatment. At present, the research on the pathogenesis of septic cardiomyopathy mainly focuses on two aspects: the systemic neuroimmune mechanism and the local changes of cardiomyocytes. The former mainly includes the autonomic nervous dysfunction mainly caused by sympathetic overactivation and the inflammatory storm induced by immune response disorder. The latter covers the dysregulation of calcium homeostasis, mitochondrial dysfunction and energy metabolism disorder of cardiomyocytes. Immune dysfunction is one of the key factors that cause the poor prognosis of patients with septic cardiomyopathy. Macrophages are sentinel cells of the body's innate immunity. Cardiac macrophages have been confirmed to be one of the most heterogeneous immune cells in the heart. According to their origin and differentiation, they can be divided into bone marrow-derived tissue infiltrating macrophages and cardiac resident macrophages, which have roles of polarization, phagocytosis, regulation of inflammatory response, and participate in innate and adaptive immunity. In the occurrence and development of septic cardiomyopathy, cardiac macrophages recruited from the blood participate in balancing the inflammation and repair of myocardial tissue through the conversion of pro-inflammatory phenotype and anti-inflammatory phenotype. Cardiac resident macrophages mediate immune phagocytosis to maintain the local homeostasis of cardiomyocytes, and the glycometabolic reprogramming of macrophages regulates the release of inflammatory factors, while macrophage metabolic reprogramming regulates the release of inflammatory factors. A deeper understanding of the biological behavior of macrophages, and regulating the polarization, metabolism and phagocytosis of cardiac macrophages, could serve as new target for the prevention and treatment of septic cardiomyopathy. Therefore, this article reviews the key pathogenesis of septic cardiomyopathy and the role of macrophages of different origins and differentiation, revealing the possibility of developing new strategies for the prevention and treatment of septic cardiomyopathy.
Humans ; Cardiomyopathies/pathology* ; Macrophages/immunology* ; Sepsis/complications* ; Myocytes, Cardiac

OBJECTIVE: Baicalein has been reported to have wide therapeutic effects that act through its anti-inflammatory activity. This study examines the effect and mechanism of baicalein on sepsis-induced cardiomyopathy (SIC). METHODS: A thorough screening of a small library of natural products, comprising 100 diverse compounds, was conducted to identify the most effective drug against lipopolysaccharide (LPS)-treated H9C2 cardiomyocytes. The core target proteins and their associated signaling pathways involved in baicalein's efficacy against LPS-induced myocardial injury were predicted by network pharmacology. RESULTS: Baicalein was identified as the most potent protective agent in LPS-exposed H9C2 cardiomyocytes. It exhibited a dose-dependent inhibitory effect on cell injury and inflammation. In the LPS-induced septic mouse model, baicalein demonstrated a significant capacity to mitigate LPS-triggered myocardial deficits, inflammatory responses, and ferroptosis. Network pharmacological analysis and experimental confirmation suggested that hypoxia-inducible factor 1 subunit α (HIF1-α) is likely to be the crucial factor in mediating the impact of baicalein against LPS-induced myocardial ferroptosis and injury. By combining microRNA (miRNA) screening in LPS-treated myocardium with miRNA prediction targeting HIF1-α, we found that miR-299b-5p may serve as a regulator of HIF1-α. The reduction in miR-299b-5p levels in LPS-treated myocardium, compared to the control group, was reversed by baicalein treatment. The reverse transcription quantitative polymerase chain reaction, Western blotting, and dual-luciferase reporter gene analyses together identified HIF1-α as the target of miR-299b-5p in cardiomyocytes. CONCLUSION Baicalein mitigates SIC at the miRNA level, suggesting the therapeutic potential of it in treating SIC through the regulation of miR-299b-5p/HIF1-α/ferroptosis pathway. Please cite this article as: Zhou WY, Du JK, Liu HH, Deng L, Ma K, Xiao J, Zhang S, Wang CN. Baicalein attenuates lipopolysaccharide-induced myocardial injury by inhibiting ferroptosis via miR-299b-5p/HIF1-α pathway. J Integr Med. 2025; 23(5):560-575.
Flavanones/pharmacology* ; Animals ; MicroRNAs/genetics* ; Lipopolysaccharides ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Ferroptosis/drug effects* ; Mice ; Myocytes, Cardiac/metabolism* ; Signal Transduction/drug effects* ; Rats ; Male ; Mice, Inbred C57BL ; Cardiomyopathies/etiology* ; Cell Line ; Sepsis/complications*

Objective: To review the clinical data of 7 patients with Danon disease and analyze their clinical characteristics. Methods: The medical records of 7 patients with Danon disease, who were hospitalized in Peking Union Medical College Hospital of Chinese Academy of Medical Sciences from April 2008 to July 2021, were reviewed and summarized, of which 6 cases were diagnosed as Danon disease by lysosomal-associated membrane protein-2 (LAMP-2) gene mutation detection and 1 case was diagnosed by clinicopathological features. Clinical manifestations, biochemical indexes, electrocardiogram, echocardiography, skeletal muscle and myocardial biopsy and gene detection results were analyzed, and patients received clinical follow-up after discharge. Results: Six patients were male and average age was (15.4±3.5) years and the average follow-up time was (27.7±17.0) months. The main clinical manifestations were myocardial hypertrophy (6/7), decreased myodynamia (2/7) and poor academic performance (3/7). Electrocardiogram features included pre-excitation syndrome (6/7) and left ventricular hypertrophy (7/7). Echocardiography examination evidenced myocardial hypertrophy (6/7), and left ventricular dilatation and systolic dysfunction during the disease course (1/7). The results of skeletal muscle biopsy in 6 patients were consistent with autophagy vacuolar myopathy. Subendocardial myocardial biopsy was performed in 3 patients, and a large amount of glycogen deposition with autophagosome formation was found in cardiomyocytes. LAMP-2 gene was detected in 6 patients, and missense mutations were found in all these patients. During the follow-up period, implantable cardioverter defibrillator implantation was performed in 1 patient because of high atrioventricular block 4 years after diagnosis, and there was no death or hospitalization for cardiovascular events in the other patients. Conclusion: The main clinical manifestations of Danon disease are cardiomyopathy, myopathy and mental retardation. Pre-excitation syndrome is a common electrocardiographic manifestation. Autophagy vacuoles can be seen in skeletal muscle and myocardial pathological biopsies. LAMP-2 gene mutation analysis is helpful in the diagnose of this disease.
Adolescent ; Child ; Female ; Humans ; Male ; Cardiomyopathies/etiology* ; Glycogen Storage Disease Type IIb/complications* ; Hypertrophy, Left Ventricular/etiology* ; Lysosomal-Associated Membrane Protein 2/genetics* ; Pre-Excitation Syndromes/genetics*

Recent decades have seen the remarkable development of China in medical accessibility and quality index, and the application of a number of new advanced cardiovascular technologies benefits more patients. However, according to the Annual Report on Cardiovascular Health and Diseases in China published in this article, which was organized and summarized by National Center for Cardiovascular Diseases, there is still a huge population living with risk factors of cardiovascular diseases (CVD), and the morbidity and mortality of CVD are increasing. It is estimated that there are around 330 million patients suffering from CVD currently, including 245 million of hypertension, 13 million of stroke, 45.3 million of peripheral artery disease, 11.39 million of coronary heart disease (CHD), 8.9 million of heart failure, 5 million of pulmonary heart disease, 4.87 million of atrial fibrillation, 2.5 million of rheumatic heart disease, and 2 million of congenital heart disease. Tobacco use, diet and nutrition factors, physical activity, overweight and obesity, and psychological factors are what affect cardiovascular health, while hypertension, dyslipidemia, diabetes, chronic kidney disease, metabolic syndrome, and air pollution are the risk factors for CVD. In this article, in addition to risk factors for CVD, we also report the epidemiological trends of CVD, including CHD, cerebrovascular disease, arrhythmias, valvular heart disease, congenital heart disease, cardiomyopathy, heart failure, pulmonary vascular disease and venous thromboembolism, and aortic and peripheral artery diseases, as well as the basic research and medical device development in CVD. In a word, China has entered a new stage of transforming from high-speed development focusing on scale growth to high-quality development emphasizing on strategic and key technological development to curb the trend of increasing incidence and mortality of CVD.
Humans ; Cardiovascular Diseases/etiology* ; Hypertension/complications* ; Risk Factors ; Cardiomyopathies ; Heart Failure/complications* ; Heart Defects, Congenital/complications* ; Coronary Disease ; Atrial Fibrillation/complications*

OBJECTIVE: To investigate the value of maximal rate of left ventricular pressure (dp/dtmax) in evaluating the changes of cardiac function before and after heart rate reduction in patients with sepsis-induced cardiomyopathy (SIC). METHODS: A single-center, prospective randomized controlled study was conducted. Adult patients with sepsis/septic shock admitted to the department of intensive care unit (ICU) of Tianjin Third Central Hospital from April 1, 2020 to February 28, 2022 were enrolled. Speckle tracking echocardiography (STE) and pulse indication continuous cardiac output (PiCCO) monitoring were performed immediately after the completion of the 1 h-Bundle therapy. The patients with heart rate over 100 beats/minutes were selected and randomly divided into esmolol group and regular treatment group, 55 cases in each group. All patients underwent STE and PiCCO monitoring at 6, 24 and 48 hours after admission in ICU and calculated acute physiology and chronic health evaluation II (APACHE II) and sequential organ failure assessment (SOFA). Primary outcome measure: change in dp/dtmax after reducing heart rate by esmolol. Secondary outcome measures: correlation between dp/dtmax and global longitudinal strain (GLS); changes of vasoactive drug dosage, oxygen delivery (DO₂), oxygen consumption (VO₂) and stroke volume (SV) after the administration of esmolol; proportion of heart rate reaching the target after the administration of esmolol; 28-day and 90-day mortality in two groups. RESULTS: Baseline data on age, gender, body mass index, SOFA score, APACHE II score, heart rate, mean arterial pressure, lactic acid, 24-hour fluid balance, sepsis etiology and prior comorbidities were similar between esmolol group and regular treatment group, there were no significant differences between the two groups. All SIC patients achieved the target heart rate after 24 hours of esmolol treatment. Compared with regular treatment group, parameters reflecting myocardial contraction such as GLS, global ejection fraction (GEF) and dp/dtmax were significantly increased in esmolol group [GLS: (-12.55±4.61)% vs. (-10.73±4.82)%, GEF: (27.33±4.62)% vs. (24.18±5.35)%, dp/dtmax (mmHg/s): 1 312.1±312.4 vs. 1 140.9±301.0, all P < 0.05], and N-terminal pro-brain natriuretic peptide (NT-proBNP) significantly decreased [μg/L: 1 364.52 (754.18, 2 389.17) vs. 3 508.85 (1 433.21, 6 988.12), P < 0.05], DO₂ and SV were significantly increased [DO₂ (mL×min^-1×m^-2): 647.69±100.89 vs. 610.31±78.56, SV (mL): 49.97±14.71 vs. 42.79±15.77, both P < 0.05]. The system vascular resistance index (SVRI) in esmolol group was significantly higher than that in regular treatment group (kPa×s×L^-1: 287.71±66.32 vs. 251.17±78.21, P < 0.05), even when the dosage of norepinephrine was similar between the two groups. Pearson correlation analysis showed that dp/dtmax was negatively correlated with GLS in SIC patients at 24 hours and 48 hours after ICU admission (r values were -0.916 and -0.935, respectively, both P < 0.05). Although there was no significant difference in 28-day mortality between esmolol group and regular treatment group [30.9% (17/55) vs. 49.1% (27/55), χ² = 3.788, P = 0.052], the rate of esmolol use in patients who died within 28 days was lower than that in patients who survived [38.6% (17/44) vs. 57.6% (38/66), χ² = 3.788, P = 0.040]. In addition, esmolol has no effect on the 90-day mortality of patients. Logistic regression analysis showed that after adjusting for SOFA score and DO₂ factors, patients who used esmolol had a significantly lower risk of 28-day mortality compared with patients who did not use esmolol [odds ratio (OR) = 2.700, 95% confidence interval (95%CI) was 1.038-7.023, P = 0.042]. CONCLUSIONS dp/dtmax in PiCCO parameter can be used as a bedside indicator to evaluate cardiac function in SIC patients due to its simplicity and ease of operation. Esmolol control of heart rate in SIC patients can improve cardiac function and reduce short-term mortality.
Adult ; Humans ; Prospective Studies ; Ventricular Pressure ; Sepsis/complications* ; Shock, Septic/drug therapy* ; Cardiomyopathies/etiology* ; Prognosis

Objectives: This study sought to describe our institutional experience of repeated percutaneous stellate ganglion blockade (R-SGB) as a treatment option for drug-refractory electrical storm in patients with nonischemic cardiomyopathy (NICM). Methods: This prospective observational study included 8 consecutive NICM patients who had drug-refractory electrical storm and underwent R-SGB between June 1, 2021 and January 31, 2022. Lidocaine (5 ml, 1%) was injected in the vicinity of the left stellate ganglion under the guidance of ultrasound, once per day for 7 days. Data including clinical characteristics, immediate and long-term outcomes, and procedure related complications were collected. Results: The mean age was (51.5±13.6) years. All patients were male. 5 patients were diagnosed as dilated cardiomyopathy, 2 patients as arrhythmogenic right ventricular cardiomyopathy and 1 patient as hypertrophic cardiomyopathy. The left ventricular ejection fraction was 37.8%±6.6%. After the treatment of R-SGB, 6 (75%) patients were free of electrical storm. 24 hours Holter monitoring showed significant reduction in ventricular tachycardia (VT) episodes from 43.0 (13.3, 276.3) to 1.0 (0.3, 34.0) on the first day following R-SGB (P<0.05) and 0.5 (0.0, 19.3) after whole R-SGB process (P<0.05). There were no procedure-related major complications. The mean follow-up was (4.8±1.1) months, and the median time of recurrent VT was 2 months. Conclusion: Minimally invasive R-SGB is a safe and effective method to treat electrical storm in patients with NICM.
Humans ; Male ; Adult ; Middle Aged ; Aged ; Female ; Stroke Volume ; Stellate Ganglion/surgery* ; Ventricular Function, Left ; Cardiomyopathies/complications* ; Tachycardia, Ventricular/therapy* ; Treatment Outcome ; Catheter Ablation

Cardiovascular diseases account for approximately 80% of deaths among individuals with diabetes mellitus, with diabetic cardiomyopathy as the major diabetic cardiovascular complication. Hyperglycemia is a symptom that abnormally activates multiple downstream pathways and contributes to cardiac hypertrophy, fibrosis, apoptosis, and other pathophysiological changes. Although glycemic control has long been at the center of diabetes therapy, multicenter randomized clinical studies have revealed that intensive glycemic control fails to reduce heart failure-associated hospitalization and mortality in patients with diabetes. This finding indicates that hyperglycemic stress persists in the cardiovascular system of patients with diabetes even if blood glucose level is tightly controlled to the normal level. This process is now referred to as hyperglycemic memory (HGM) phenomenon. We briefly reviewed herein the current advances that have been achieved in research on the underlying mechanisms of HGM in diabetic cardiomyopathy.
Cardiovascular Diseases ; Diabetes Complications ; Diabetes Mellitus ; Diabetic Cardiomyopathies/etiology* ; Humans ; Hyperglycemia/metabolism* ; Multicenter Studies as Topic

OBJECTIVE: To investigate the inhibitory effect of Zhenwu Decoction on ventricular hypertrophy in rats with uremic cardiomyopathy and explore the mechanism. METHODS: Cardiocytes isolated from suckling rats were divided into control group and indoxyl sulfate (IS) group, and the protein synthesis was assayed with [H]- leucine incorporation and cellular protein expressions were detected using Western blotting. Fifty SD rats were randomly divided into sham operation group, model group, and low- and high-dose Zhenwu Decoction treatment groups, and except for those in the sham operation group, all the rats underwent 5/6 nephrectomy. Four weeks after the operation, the rats in low- and high-dose treatment groups were given Zhenwu Decoction gavage at the dose of 4.5 g/kg and 13.5 g/kg, respectively; the rats in the sham-operated and model groups were given an equal volume of distilled water. After 4 weeks of treatment, serum levels of IS were determined, and cardiac and ventricular mass indexes were measured in the rats; cardiac ultrasound was performed and Western blotting was used to measure the expressions of BNP, p-ERK1/2, p-p38 and p-JNK in the myocardium. RESULTS: Rat cardiomyocytes treated with IS showed significantly enhanced protein synthesis and increased expression levels of BNP, p-erk1/2, and p-p38 as compared with the control cells ( < 0.01), but the expression of p-jnk was comparable between the two groups. In the animal experiment, the rats in the model group showed significantly increased serum creatinine (SCr) and urea nitrogen (BUN) levels, 24-h urine protein (24 hUpro), plasma IS level, left ventricular mass index (LVMI) and whole heart mass index (HMI) compared with those in the sham group ( < 0.01); Both LVESD and LVEDD were significantly reduced and LVAWS, LVAWD, LVPWS and LVPWD were significantly increased in the model rat, which also presented with obvious cardiomyocyte hypertrophy and increased myocardial expressions of BNP, p-ERK1/2, p-p38 and p-jnk ( < 0.01). Compared with the rats in the model group, the rats treated with low-dose and high-dose Zhenwu Decoction had significantly lowered levels of SCr, BUN, 24 hUpro and IS ( < 0.05) and decreased LVMI and HMI; LVESD, LVEDD, LVPWS, LVAWS, and LVAWD were improved more obviously in the high-dose group, and the myocardial expressions of BNP, p-ERK1/2, p-p38 and p-JNK was significantly downregulated after the treatment. CONCLUSIONS Zhenwu Decoctin can reduce plasma IS levels and inhibit ventricular hypertrophy to delay ventricular remodeling in rats with uremic cardiomyopathy.
Animals ; Blood Urea Nitrogen ; Cardiomegaly ; prevention & control ; Cardiomyopathies ; complications ; Creatinine ; blood ; Drugs, Chinese Herbal ; pharmacology ; Heart Ventricles ; Indican ; blood ; pharmacology ; Myocytes, Cardiac ; drug effects ; metabolism ; Nephrectomy ; Random Allocation ; Rats ; Rats, Sprague-Dawley

There is a close relationship between diabetes mellitus and heart failure, both of which are known to increase morbidity and mortality. Diabetes can cause or aggravate heart failure, and heart failure can precipitate diabetes. Diabetes mellitus causes structural and functional changes in the heart, such as fibrosis of the myocardium and left ventricular dysfunction. The mechanisms of diabetic cardiomyopathy are metabolic disturbance, myocardial fibrosis, microvascular disease, and autonomic dysfunction. Improper blood glucose control leads to deterioration of heart failure, but the role of strict glycemic control in reducing heart failure is unclear. The role of SGLT2 inhibitors in reducing the incidence of heart failure is of great importance in the treatment of diabetic patients. However, further long-term follow-up and safety studies are needed.
Blood Glucose ; Diabetes Complications ; Diabetes Mellitus ; Diabetic Cardiomyopathies ; Fibrosis ; Follow-Up Studies ; Heart Failure ; Heart ; Humans ; Incidence ; Mortality ; Myocardium ; Ventricular Dysfunction, Left

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. The early mortality of patients with sepsis-induced myocardial dysfunction (SMD) is higher than those with normal cardiac function, and the long-term prognosis is worse. Therefore, early detection of SMD and timely intervention can reduce mortality and improve prognosis. This review focused on the progress in evaluation and treatment of SMD, with a view to provide some ideas for the diagnosis and treatment of SMD.
Cardiomyopathies/therapy* ; Humans ; Sepsis/complications*