3.The role of inflammation in heart failure with preserved ejection fraction.
Qi ZHANG ; Yun-Er CHEN ; Xin-Xin ZHU ; Xia WANG ; Ai-Juan QU
Acta Physiologica Sinica 2023;75(3):390-402
Heart failure with preserved ejection fraction (HFpEF) is a type of heart failure characterized by left ventricular diastolic dysfunction with preserved ejection fraction. With the aging of the population and the increasing prevalence of metabolic diseases, such as hypertension, obesity and diabetes, the prevalence of HFpEF is increasing. Compared with heart failure with reduced ejection fraction (HFrEF), conventional anti-heart failure drugs failed to reduce the mortality in HFpEF due to the complex pathophysiological mechanism and multiple comorbidities of HFpEF. It is known that the main changes of cardiac structure of in HFpEF are cardiac hypertrophy, myocardial fibrosis and left ventricular hypertrophy, and HFpEF is commonly associated with obesity, diabetes, hypertension, renal dysfunction and other diseases, but how these comorbidities cause structural and functional damage to the heart is not completely clear. Recent studies have shown that immune inflammatory response plays a vital role in the progression of HFpEF. This review focuses on the latest research progress in the role of inflammation in the process of HFpEF and the potential application of anti-inflammatory therapy in HFpEF, hoping to provide new research ideas and theoretical basis for the clinical prevention and treatment in HFpEF.
Humans
;
Heart Failure
;
Stroke Volume/physiology*
;
Hypertrophy, Left Ventricular/metabolism*
;
Ventricular Dysfunction, Left/metabolism*
;
Inflammation/complications*
;
Obesity
;
Hypertension
4.Clinical characteristics of Danon disease.
Wu Wan WANG ; Yuan Yuan ZHU ; Wei WU ; Da Chun ZHAO ; Xue LIN ; Li Gang FANG ; Shu Yang ZHANG
Chinese Journal of Cardiology 2023;51(1):51-57
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*
5.Clinical features and risk factors of left ventricular hypertrophy in children with primary hypertension.
Yang LIU ; Lin SHI ; Yao LIN ; Ya Qi LI ; Yan Yan LIU ; Hong Wei ZHANG
Chinese Journal of Pediatrics 2023;61(11):1031-1037
Objective: To assess the clinical features and relative factors of left ventricular hypertrophy (LVH) in children with primary hypertension. Methods: In this retrospective cohort study, 430 children diagnosed with primary hypertension in Children's Hospital, Capital Institute of Pediatrics from January 2019 to September 2022 were enrolled. Their clinical data was analyzed and LVH was assessed by echocardiography. According to left ventricular geometry, these children were assigned to the LVH group and normal geometry group. General conditions, laboratory indicators and ambulatory blood pressure parameters between two groups were compared by independent sample t-test or Mann-Whitney U test. Spearman correlation coefficient was used to analyze the correlation between LVH and clinical indicators including blood pressure, biochemical and metabolic indicators. The independent risk factors of LVH were analyzed by multivariable logistic regression. The receiver operating characteristic (ROC) curve was used to explore the value of risk factors in the diagnosis of LVH. Results: Among the 430 children with primary hypertension, 342 (79.5%) were males and 88 (20.5%) females. Their age was (12.6±2.3) years, and 123 children (28.6%) of them had LVH. Body mass index (BMI) ((30.0±5.2) vs. (26.2±4.3) kg/m2), ratio of stage 2 hypertension (75.6% (93/123) vs. 59.6% (183/307)), 24-hour systolic blood pressure (24 h SBP)((131±10) vs. (128±10) mmHg,1 mmHg=0.133 kPa), daytime systolic blood pressure (SBP) ((135±11) vs. (131±11) mmHg), nighttime SBP ((128±11) vs. (123±10) mmHg), cholesterol level ((4.0±0.7) vs. (3.9±0.7) mmol/L), serum uric acid level ((447±81) vs. (426±91) μmol/L) and incidence of hyperinsulinemia (69.9% (86/123) vs.59.0% (181/307)) were significantly elevated in the LVH group compared with those in the normal geometry group (all P<0.05). There were more patients with a disease course over 5 years in the LVH group than in the normal geometry group, with a statistically significant difference (χ2=8.90,P=0.031). Spearman correlation analysis showed that BMI, 24 h SBP, daytime SBP, nighttime SBP, triglyceride, uric acid, and serum sodium level were positively correlated with LVMI (r=0.43, 0.20, 0.18, 0.18, 0.18, 0.16, and 0.12, all P<0.05). BMI, hyperinsulinemia, and cholesterol level were positively correlated with relative wall thickness (RWT) (r=0.22, 0.12, and 0.16, all P<0.05). The multivariate logistic regression analysis showed that BMI (OR=1.17, 95%CI 1.10-1.25) and 24 h SBP (OR=1.04, 95%CI 1.01-1.08) were the independent risk factors for LVH (both P<0.05). The area under the receiver operator characteristic curve, combined with BMI and 24 h SBP, was 0.72 (95%CI 0.67-0.77, P<0.05), with a sensitivity and specificity of 71.5% and 64.8%, respectively. Conclusions: BMI and 24 h SBP are the independent risk factors for LVH in children with primary hypertension, and the combination of BMI and 24 h SBP has an acceptable diagnostic value for LVH. Early monitoring of these indexes is necessary to predict preclinical cardiac damage.
Male
;
Female
;
Humans
;
Child
;
Adolescent
;
Hypertension/diagnosis*
;
Hypertrophy, Left Ventricular/etiology*
;
Uric Acid
;
Blood Pressure Monitoring, Ambulatory
;
Retrospective Studies
;
Blood Pressure/physiology*
;
Risk Factors
;
Essential Hypertension
;
Hyperinsulinism
;
Cholesterol
6.Analysis of etiology and complications in children with stage 5 chronic kidney disease.
Cheng ZHONG ; Ya Ling CHEN ; Xi Xi YU ; Qin YANG ; Yong Qi SHI ; Li Wen TAN ; An Shuo WANG ; Dao Qi WU ; Gao Fu ZHANG ; Hai Ping YANG ; Qiu LI ; Mo WANG
Chinese Journal of Pediatrics 2023;61(12):1109-1117
Objective: To investigate the etiology, complications, and prognostic factors of stage 5 chronic kidney disease (CKD5) in children. Methods: A case series study was conducted to retrospectively analyze the general situation, clinical manifestations, laboratory tests, genetic testing, and follow-up data (until October 2022) of 174 children with CKD5 who were diagnosed and hospitalized at the Children's Hospital of Chongqing Medical University from April 2012 to April 2021. The characteristics of complications in the children were compared based on age, gender, and etiology. Based on the presence or absence of left ventricular hypertrophy (LVH), patients were divided into LVH group and non LVH group for analyzing the influencing factors of cardiovascular disease. Patients were also divided into death group and survival group, peritoneal dialysis group and hemodialysis group based on the follow-up data for analyzing the prognostic factors. The chi-square test, independent sample t-test, Fisher exact probability test, Mann-Whitney U test and Kruskal Wallis test were used to analyze data among different groups. Multivariate Logistic regression analysis was used to identify the prognostic factors. Results: A total of 174 children with CKD5 were enrolled in the study (96 boys and 78 girls), aged 11.2 (8.2, 13.0) years. Congenital kidney and urinary tract malformations (CAKUT) were the most common causes of the CKD5 (84 cases, 48.3%), followed by glomerular diseases (83 cases, 47.7%), and among which 28 cases (16.1%) were hereditary glomerular diseases. The common complications of CKD5 included anemia (98.2%, 165/168), mineral and bone disorder in chronic kidney disease (CKD-MBD) (97.7%, 170/174), lipid metabolism disorders (87.5%, 63/72), hypertension (81.4%, 127/156) and LVH (57.6%,57/99). The incidences of hypertension in primary glomerular disease were higher than that in CAKUT(93.8%(30/32) vs.73.7%(56/76),χ2=5.59,P<0.05). The incidences of hypertension in secondary glomerular disease were higher than that in CAKUT and that in hereditary kidney disease (100.0%(20/20) vs. 73.7%(56/76), 68.2%(15/22), both P<0.05). The incidence of hypocalcemia in CAKUT, primary glomerular disease, and hereditary kidney disease was higher than that in secondary glomerular disease (82.1%(69/84), 88.2%(30/34), 89.3%(25/28) vs. 47.6%(10/21), χ2=10.21, 10.75, 10.80, all P=0.001); the incidence of secondary hyperparathyroidism in women was higher than that in men (80.0%(64/80) vs. 95.0%(57/60), χ2=6.58, P=0.010). The incidence of LVH in children aged 6-<12 was higher than that in children aged 12-18 (73.5%(25/34) vs. 43.1%(22/51), χ2=7.62, P=0.006). Among 113 follow-up children, the mortality rate was 39.8% (45/113). Compared to the survival group, the children in the death group had lower hemoglobin, higher blood pressure, lower albumin, lower alkaline phosphatase and higher left ventricular mass index ((67±19) vs. (75±20) g/L, 142 (126, 154) vs. 128(113, 145) mmHg(1 mmHg=0.133 kPa), (91±21) vs. (82±22) mmHg, 32 (26, 41) vs. 40 (31, 43) g/L, 151 (82, 214) vs. 215 (129, 37) U/L, 48 (38, 66) vs. 38(32, 50) g/m2.7,t=2.03, Z=2.89, t=2.70, Z=2.49, 2.79, 2.29,all P<0.05), but no independent risk factors were identified (all P>0.05). The peritoneal dialysis group had better alleviation for anemia, low calcium, and high phosphorus than the hemodialysis group ((87±22) vs. (72±16) g/L, (1.9±0.5) vs. (1.7±0.4) mmol/L, (2.2±0.7) vs. (2.8±0.9) mmol/L, t=2.92, 2.29, 2.82, all P<0.05), and the survival rate of the peritoneal dialysis group was significantly higher than that of the hemodialysis group (77.8% (28/36) vs. 48.4% (30/62), χ2=8.14, P=0.004). Conclusions: CAKUT is the most common etiology in children with CKD 5, and anemia is the most common complication. The incidence of complications in children with CKD 5 varies with age, gender and etiology. Anemia, hypertension, hypoalbuminemia, reduced alkaline phosphatase and elevated LVMI may be the prognostic factors in children with CKD5. Peritoneal dialysis may be more beneficial for improving the long-term survival rate.
Male
;
Humans
;
Child
;
Female
;
Retrospective Studies
;
Alkaline Phosphatase
;
Kidney Failure, Chronic/therapy*
;
Renal Insufficiency, Chronic/therapy*
;
Hypertension
;
Risk Factors
;
Hypertrophy, Left Ventricular/etiology*
;
Anemia/etiology*
7.Effect and mechanism of leonurine on pressure overload-induced cardiac hypertrophy in rats.
Xiao-Li DING ; Qing-Qing YUAN ; Ding-Jia XUE ; Fu-Ming YANG ; Yi-Zhun ZHU ; Hai-Bing QIAN
China Journal of Chinese Materia Medica 2022;47(2):461-468
To investigate the effects of leonurine(Leo) on abdominal aortic constriction(AAC)-induced cardiac hypertrophy in rats and its mechanism. A rat model of pressure overload-induced cardiac hypertrophy was established by AAC method. After 27-d intervention with high-dose(30 mg·kg~(-1)) and low-dose(15 mg·kg~(-1)) Leo or positive control drug losartan(5 mg·kg~(-1)), the cardiac function was evaluated by hemodynamic method, followed by the recording of left ventricular systolic pressure(LVSP), left ventricular end-diastolic pressure(LVESP), as well as the maximum rate of increase and decrease in left ventricular pressure(±dp/dt_(max)). The degree of left ventricular hypertrophy was assessed based on heart weight index(HWI) and left ventricular mass index(LVWI). Myocardial tissue changes and the myocardial cell diameter(MD) were measured after hematoxylin-eosin(HE) staining. The contents of angiotensin Ⅱ(AngⅡ) and angiotensin Ⅱ type 1 receptor(AT1 R) in myocardial tissue were detected by ELISA. The level of Ca~(2+) in myocardial tissue was determined by colorimetry. The protein expression levels of phospholipase C(PLC), inositol triphosphate(IP3), AngⅡ, and AT1 R were assayed by Western blot. Real-time quantitative PCR(qRT-PCR) was employed to determine the mRNA expression levels of β-myosin heavy chain(β-MHC), atrial natriuretic factor(ANF), AngⅡ, and AT1 R. Compared with the model group, Leo decreased the LVSP, LVEDP, HWI, LVWI and MD values, but increased ±dp/dt_(max) of the left ventricle. Meanwhile, it improved the pathological morphology of myocardial tissue, reduced cardiac hypertrophy, edema, and inflammatory cell infiltration, decreased the protein expression levels of PLC, IP3, AngⅡ, AT1 R, as well as the mRNA expression levels of β-MHC, ANF, AngⅡ, AT1 R, c-fos, and c-Myc in myocardial tissue. Leo inhibited AAC-induced cardiac hypertrophy possibly by influencing the RAS system.
Angiotensin II/metabolism*
;
Animals
;
Cardiomegaly/genetics*
;
Gallic Acid/analogs & derivatives*
;
Hypertrophy, Left Ventricular/pathology*
;
Myocardium/pathology*
;
Rats
8.Network Meta-analysis of oral blood-activating and stasis-removing Chinese patent medicines in treatment of hypertensive left ventricular hypertrophy.
Ya-Wei ZHENG ; Jie LI ; Wen-Qiang YAO ; Ming-Yao PAN ; Yuan FANG
China Journal of Chinese Materia Medica 2022;47(5):1383-1391
This study was designed to assess the clinical efficacy of oral blood-activating and stasis-removing Chinese patent medicines in treating hypertensive left ventricular hypertrophy(LVH) based on network Meta-analysis. The clinical randomized controlled trials(RCTs) concerning the treatment of hypertensive LVH with oral blood-activating and stasis-removing Chinese patent medicines were retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, Web of Science, and Cochrane Library from their inception to September 2021. Two researchers independently completed the literature screening, data extraction, and quality evaluation. The data were then analyzed by RevMan 5.3, Stata 15.1, and ADDIS 1.16.8. Finally, a total of 31 RCTs were included, involving 3 001 patients and four oral blood-activating and stasis-removing Chinese patent medicines. In terms of the alleviation of heart damage, the Chinese patent medicines combined with conventional western medicine groups were superior to the conventional western medicine groups in lo-wering the left ventricular mass index(LVMI). There was no significant difference in LVMI, left ventricular ejection fraction(LVEF), or the ratio of early diastolic peak flow velocity to late diastolic peak flow velocity(E/A) between different Chinese patent medicines combined with conventional western medicine groups. Xinnao Shutong Capsules/Tablets combined with conventional western medicine had the best efficacy in reducing LVMI and elevating LVEF, while Xinkeshu Capsules/Tablets combined with conventional western medicine had the best effect in improving E/A. In the control of blood pressure, when all Chinese patent medicines except for Xinnao Shutong Capsules/Tablets were combined with conventional western medicine, the resulting systolic blood pressure(SBP) and diastolic blood pressure(DBP) were significantly lower than those in the conventional western medicine group. Xinkeshu Capsules/Tablets combined with conventional western medicine produced the best effect in reducing SBP and DBP, followed by Xinnao Shutong Capsules/Tablets. In terms of safety, no serious adverse reactions occurred in all trials. The four oral blood-activating and stasis-removing Chinese patent medicines included in this study exhibited obvious advantages in the treatment of hypertensive LVH when they were combined with conventional western medicine, with the best effects observed in the Xinnao Shutong Capsules/Tablets combined with conventional western medicine group. However, due to the limitation of the quantity and quality of the included articles, the conclusion of this study still needs to be verified by more high-quality, multi-center, and large-sample RCTs.
China
;
Humans
;
Hypertrophy, Left Ventricular/drug therapy*
;
Medicine, Chinese Traditional
;
Network Meta-Analysis
;
Nonprescription Drugs
;
Stroke Volume
;
Ventricular Function, Left
9.Meta-analysis of clinical efficacy and safety of Compound Danshen Dripping Pills combined with conventional antihypertensive drugs in treatment of hypertensive left ventricular hypertrophy.
Zhe CHEN ; Ying-Ying PENG ; Feng-Wen YANG ; Hai-Yin HU ; Chun-Xiang LIU ; Jun-Hua ZHANG
China Journal of Chinese Materia Medica 2021;46(10):2578-2587
To systematically evaluate the clinical efficacy and safety of Compound Danshen Dripping Pills combined with conventional antihypertensive drugs in the treatment of hypertensive left ventricular hypertrophy. China National Knowledge Infrastructure(CNKI), Wanfang, VIP, PubMed, EMbase, Cochrane Library, Ovid and Web of Science databases were searched by computer to retrieve the randomized controlled trials(RCTs) of Compound Danshen Dripping Pills combined with conventional antihypertensive drugs in the treatment of hypertensive left ventricular hypertrophy from the establishment of databases to July 2020. After two researchers performed data retrieval, data extraction, and risk assessment of bias, they used RevMan 5.3 software for Meta-analysis. A total of 10 RCTs were included, with a total of 979 patients. Meta-analysis results showed that in terms of interventricular septal thickness(MD=-0.70, 95%CI[-1.15,-0.24], P=0.003), left ventricular posterior wall thickness(MD=-0.81, 95%CI[-1.41,-0.21], P=0.008), left ventricular mass index(MD=-8.75, 95%CI[-17.40,-0.10], P=0.05), systolic blood pressure(MD=-8.97, 95%CI[-13.46,-4.48], P<0.000 1), diastolic blood pressure(MD=-5.87, 95%CI[-8.39,-3.34], P<0.000 01) and left ventricular end-diastolic diameter(MD=-1.73, 95%CI[-2.38,-1.08], P<0.000 01), Compound Danshen Dripping Pills combined with conventional antihypertensive drugs was superior to conventional antihypertensive drugs. In terms of left ventricular ejection fraction(MD=0.41, 95%CI[-0.74, 1.55], P=0.49), there was no statistical difference in treatment between the two groups. Because of the small amount of literatures included in the safety aspect, it is impossible to give an accurate conclusion. The GRADE score showed that the level of evidence was low and extremely low. The results show that the Compound Danshen Dripping Pills combined with conventional antihypertensive drugs may effectively improve the clinical efficacy for hypertensive ventricular hypertrophy, and the safety needs to be further explored. Due to the low quality of the included literatures, more high-quality RCTs are needed for verification.
Antihypertensive Agents/adverse effects*
;
China
;
Drugs, Chinese Herbal/adverse effects*
;
Humans
;
Hypertrophy, Left Ventricular/drug therapy*
;
Stroke Volume
;
Treatment Outcome
;
Ventricular Function, Left
10.Association between serum uric acid and subclinical cardiac damage in children with primary hypertension.
Miao HOU ; Ling SUN ; Wan-Ping ZHOU ; Yue-Yue DING ; Qiu-Qin XU ; Lei CAO ; Jie SHEN ; Dao-Ping YANG ; Hai-Tao LYU
Chinese Journal of Contemporary Pediatrics 2021;23(2):174-179
OBJECTIVE:
To evaluate the condition of subclinical cardiac damage in children with primary hypertension and the association between serum uric acid and subclinical cardiac damage.
METHODS:
A retrospective analysis was performed on the medical data of 55 children who were hospitalized and diagnosed with primary hypertension in the Department of Cardiology, Children's Hospital of Soochow University from January 2015 to June 2020. Forty-five healthy children, matched for age and sex, were enrolled as the control group. The two groups were compared in terms of clinical features, laboratory examination, and parameters for left ventricular structure, systolic function, and diastolic function. The correlation of serum uric acid with the parameters for left ventricular structure, systolic function, and diastolic function in children with primary hypertension was analyzed.
RESULTS:
Compared with the control group, the hypertension group had significantly higher left ventricular mass (LVM), left ventricular mass index (LVMI), and relative wall thickness (RWT) (
CONCLUSIONS
Children with primary hypertension may have subclinical cardiac damage such as left ventricular hypertrophy, left ventricular diastolic dysfunction, left atrial enlargement, and proximal aortic dilation. Elevated serum uric acid is significantly associated with cardiac damage in children with primary hypertension.
Blood Pressure
;
Child
;
Humans
;
Hypertension/complications*
;
Hypertrophy, Left Ventricular/etiology*
;
Retrospective Studies
;
Uric Acid

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