BACKGROUND: Postural tachycardia syndrome (POTS) is a common childhood disease that seriously affects the patient's physical and mental health. This study aimed to investigate whether pre-treatment baseline left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) values were associated with symptom improvement after metoprolol therapy for children and adolescents with POTS. METHODS: This retrospective study evaluated 51 children and adolescents with POTS who received metoprolol therapy at the Peking University First Hospital between November 2010 and July 2019. All patients had completed a standing test or basic head-up tilt test and cardiac echocardiography before treatment. Treatment response was evaluated 3 months after starting metoprolol therapy. The pre-treatment baseline LVEF and LVFS values were evaluated for correlations with decreases in the symptom score after treatment (ΔSS). Multivariable analysis was performed using factors with a P value of <0.100 in the univariate analyses and the demographic characteristics. RESULTS: A comparison of responders and non-responders revealed no significant differences in demographic, hemodynamic characteristics, and urine specific gravity (all P > 0.050). However, responders had significantly higher baseline LVEF (71.09% ± 4.44% vs. 67.17% ± 4.88%, t = -2.789, P = 0.008) and LVFS values (40.00 [38.00, 42.00]% vs. 36.79% ± 4.11%, Z = -2.542, P = 0.010) than the non-responders. The baseline LVEF and LVFS were positively correlated with ΔSS (r = 0.378, P = 0.006; r = 0.363, P = 0.009), respectively. Logistic regression analysis revealed that LVEF was independently associated with the response to metoprolol therapy in children and adolescents with POTS (odds ratio: 1.201, 95% confidence interval: 1.039-1.387, P = 0.013). CONCLUSIONS Pre-treatment baseline LVEF was associated with symptom improvement after metoprolol treatment for children and adolescents with POTS.
Adolescent ; Child ; Humans ; Metoprolol/therapeutic use* ; Postural Orthostatic Tachycardia Syndrome/drug therapy* ; Retrospective Studies ; Stroke Volume ; Ventricular Function, Left

BACKGROUNDOrthostatic intolerance (OI) is a common disease at pediatric period which has a serious impact on physical and mental health of children. The purpose of this study was to investigate the effect of related factors on the prognosis of children with OI.

METHODSThe subjects were 170 children with OI, including 71 males (41.8%) and 99 females (58.2%) with age from 6 to 17 (12.0±2.6) years. The effect of related factors on the prognosis of children was studied by using univariate analysis. Then, the impact of children's age, symptom score, duration, disease subtype, and treatment on patient's prognosis was studied via analysis of COX proportional conversion model.

RESULTSAmong 170 cases, 48 were diagnosed with vasovagal syncope, including 28 cases of vasoinhibitory type, 16 cases of mixed type, and 4 cases of cardioinhibitory type; 115 cases were diagnosed with postural tachycardia syndrome and 7 cases with orthostatic hypotension. By using univariate analysis of Cox regression, the results showed that symptom score had a marked impact on the time of symptoms improvement of children after taking medication (P < 0.05), while other univariates had no impact (P > 0.05). Multivariate analysis using Cox proportional hazards regression model showed that the symptom score at diagnosis had a significant effect on holding time of symptoms improvement of children after taking medication (P < 0.05). Kaplan-Meier curve showed that symptom-free survival was higher in children with symptom score equal to 1 than children with symptom score equal to or greater than 2 during follow-up (P < 0.05).

CONCLUSIONSymptom score is an important factor affecting the time of symptom improvement after treatment for children with OI.

Adolescent ; Child ; Female ; Humans ; Male ; Metoprolol ; therapeutic use ; Midodrine ; therapeutic use ; Orthostatic Intolerance ; diagnosis ; drug therapy ; mortality ; pathology ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Saline Waters ; therapeutic use ; Syncope, Vasovagal ; diagnosis ; drug therapy ; mortality ; pathology

BACKGROUNDStudies have confirmed that angiotensin II receptor blocker (ARB) and angiotensin converting enzyme inhibitors (ACEI) in the treatment of diabetic nephropathy (DN) has special advantages. We observed the effects of valsartan and metoprolol tartrate hydrchloride in treatment of DN patients with positive β1-adrenergic and anti-angiotensin II type 1 (AT1) receptor antibody.

METHODSThe epitopes of the second extracellular loop of β1 receptor (197 - 222) and AT1 receptor (165 - 191), were synthesized and used respectively to screen serum autoantibodies from patients with DN (n = 371, group A), diabetes mellitus (DM) without renal failure (n = 107, group B) and healthy blood donors (n = 47, control, group C) by enzyme-linked immunosorbent assay (ELISA). Metoprolol tartrate 25 - 50 mg, three times per day, valsartan 160 mg, once a day, aspirin 100 mg, once a day, and nitrendipine 10 - 20 mg, three times per day, were given to DN patients with positive or negative autoantibodies. The cystatin C level and 24-hour urinary protein were measured before and after treatment.

RESULTSIn DN patients, the positive rate of the autoantibodies against β1 receptors and AT1 receptor was 47.7% and 51.5%, respectively, which were significantly higher than those in DM patients and healthy controls (all P < 0.01). Patients with anormalous cystatin C had higher positive rates of the autoantibodies than patients with normal cystatin C. Valsartan and metoprolol tartrate reduced proteinuria significantly (P < 0.01) in DN patients with positive autoantibodies.

CONCLUSIONSThe findings suggest that these autoantibodies against β1 and AT1-receptor may play important roles in the pathogenesis of DN. Valsartan and metoprolol tartrate are effective and safe in the treatment of DN.

Aged ; Autoantibodies ; immunology ; Diabetic Nephropathies ; drug therapy ; immunology ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Male ; Metoprolol ; therapeutic use ; Receptor, Angiotensin, Type 1 ; immunology ; Receptors, Adrenergic, beta-1 ; immunology ; Tetrazoles ; therapeutic use ; Valine ; analogs & derivatives ; therapeutic use ; Valsartan

BACKGROUNDStudies have shown that β-blockers can improve cardiac performance in heart failure (HF) by reversing protein kinase A (PKA)-mediated sarcoplasmic reticulum (SR) Ca2+ leak. However, it is being strongly questioned as to whether the PKA-mediated ryanodine receptor (RyR2) hyper-phosphorylation is a critical regulator of SR Ca2+ leak. In this study, we used a rabbit HF model to investigate whether β-blockers affect SR Ca2+ leak by other potential mechanisms.

METHODSNew Zealand white rabbits were randomly divided in three groups (n=7 in each group): normal group, metoprolol-untreated group and metoprolol-treated group. Cardiac function was determined by echocardiography and hemodynamic assays. The SR Ca2+ leak was measured by a calcium-imaging device, and the expression and activities of related proteins were evaluated by Western blotting and auto-phosphorylation.

RESULTSIn the metoprolol-untreated group, there was significantly increased ventricular cavity size, reduced systolic function, increased SR Ca2+ leak, reduced associated amount of FK506 binding protein 12.6 (FKBP12.6), increased expression and activity of PKA and Ca2+/calmodulin-dependent protein kinase II (CaMKII), and increased phosphorylated RyR2 phosphorylation sites (with unchanged RyR2-P2030). In the treated group, there was partly increased ventricular cavity size with preserved systolic function, but no prominent Ca2+ leak, with unchanged expression and activity of PKA, CaMKII and their RyR2 phosphorylation sites.

CONCLUSIONChronic administration of metoprolol prevented the SR Ca2+ leak by restoring not only PKA-dependent but also CaMKII-dependent hyper-phosphorylation of RyR2, which may be one of the potential mechanisms by which β-blockers improve cardiac function and reduce the incidence of fatal arrhythmia in HF.

Animals ; Calcium ; metabolism ; Calcium-Calmodulin-Dependent Protein Kinase Type 2 ; metabolism ; Cyclic AMP-Dependent Protein Kinases ; metabolism ; Echocardiography ; Heart Failure ; drug therapy ; metabolism ; Hemodynamics ; drug effects ; Metoprolol ; therapeutic use ; Rats ; Sarcoplasmic Reticulum ; drug effects ; metabolism

OBJECTIVEThis study was designed to compare the short-term and long-term effects of oral rehydration salts, oral rehydration salts plus metoprolol or oral rehydration salts plus midodrine hydrochloride on the treatment of postural tachycardia syndrome (POTS) in children.

METHODA total of 118 children with POTS were divided into oral rehydration salts group (n = 39), metoprolol group (oral rehydration salts plus metoprolol, n = 10) or midodrine hydrochloride group (oral rehydration salts plus midodrine hydrochloride, n = 69). The patients were followed up in clinics or over telephone for 3 - 18 months, with a mean of (11.7 ± 4.1) months. The symptom scores were recorded before treatment, after 3 months and at the end of the follow-up. Reduction of the score by 2 points or more was considered that the treatment was effective. The effective rate in 3 months was applied to evaluate short-term effects of 3 different therapies by chi-square test. Taking futility as events, Kaplan-Meier curves were drawn to compare long-term effects of the 3 different therapies in treating POTS in children.

RESULTNo significant differences among the 3 groups were found in sex, age, body height, weight, the symptom scores before treatment or hemodynamic variables. Oral rehydration salts, metoprolol and midodrine hydrochloride improved clinical symptoms after 3 months. The symptom scores of the 3 groups before treatment and after 3 months were 2.4 ± 3.2 vs. 5.5 ± 2.9, 2.2 ± 3.0 vs. 6.1 ± 3.0 and 1.9 ± 1.6 vs. 5.9 ± 2.7, respectively. The difference was significant (P < 0.05). Descending order of the short-term effective rate was 91.3% in midodrine hydrochloride group, 80.0% in metoprolol group and 74.4% in oral rehydration salts group. The difference was significant (χ(2) = 5.85, P < 0.05). All the 3 different therapies improved clinical symptoms at the end of follow-up. The symptom scores were 2.6 ± 3.2 vs. 5.6 ± 2.9, 2.5 ± 3.1 vs. 6.1 ± 3.0 and 2.2 ± 2.1 vs. 6.0 ± 2.7, respectively. (P < 0.05). The result of the Kaplan-Meier curves showed that the long-term effect of midodrine hydrochloride was significantly superior to metoprolol group and oral rehydration salts group (P < 0.05). There was no significant difference between the latter two groups.

CONCLUSIONOral rehydration salts plus midodrine hydrochloride or plus metoprolol improved the efficacy of drugs in children with POTS. And the efficacy of midodrine hydrochloride was superior to that of metoprolol.

Adolescent ; Child ; Female ; Humans ; Male ; Metoprolol ; therapeutic use ; Midodrine ; therapeutic use ; Postural Orthostatic Tachycardia Syndrome ; drug therapy ; Prospective Studies ; Treatment Outcome ; Young Adult

OBJECTIVETo evaluate the efficacy and safety of amiodarone and metoprolol in the treatment of ventricular premature beats.

METHODSControlled randomized clinical trials from 1999 through 2009 were retrieved in China HowNet, VIP Web, Pubmed home. Using Rev Man4.2 software provided by Cochrane Collaboration, Meta-analysis was conducted of 30 articles meeting the inclusion criteria involving a total of 1188 patients.

RESULTSMerged analysis of amiodarone and metoprolol in the treatment of premature ventricular merge showed a comprehensive test results of Z=1.25, P=0.21, OR=1.18, 95%CI: 0.91-1.54; funnel plot analysis suggested the possible presence of publication bias. The comprehensive test of the incidence of adverse reactions in relation to the two drugs resulted in an OR of 1.96 (95%CI: 1.39-2.77), and funnel plot analysis also indicated publication bias.

CONCLUSIONSThe total response rate of amiodarone does not seem to be superior to metoprolol in the treatment of premature ventricular contractions, and amiodarone is associated with higher incidence of adverse reactions.

Amiodarone ; adverse effects ; therapeutic use ; Drug Therapy, Combination ; Humans ; Metoprolol ; adverse effects ; therapeutic use ; Treatment Outcome ; Ventricular Premature Complexes ; drug therapy

BACKGROUNDGlucocorticoid signaling exerts major roles in inflammation, metabolism and depression, which are three crucial factors accompanying or underlying coronary heart disease. Although accumulating evidence indicates the influence of glucocorticoids on the pathology and treatment of coronary heart disease, there is still a dearth of pharmaceutical mechanisms for this relationship. This study aimed to investigate the influence of drug treatment on glucocorticoid receptor levels in coronary heart disease.

METHODSEighty hospitalized patients (average age (59.0 +/- 7.5) years, 46 male and 34 female) with coronary heart disease were categorized into four groups with 20 members in each according to one of the four drugs they were treated with. The four drugs were: nitrated derivative isosorbide dinitrate, the beta-adrenergic receptor blocker metoprolol, the calcium antagonist nifedipine, and the HMG-CoA reductase inhibitor lovastatin. Glucocorticoid receptor protein levels of peripheral blood lymphocytes were tested using immunoblotting analysis before and after one month of treatment.

RESULTSImmunoblotting analysis showed increased glucocorticoid receptor levels after treatment with metoprolol and nifedipine. There were no statistically significant changes of glucocorticoid receptor levels after treatment with isosorbide dinitrate or lovastatin, although there were trends of up-regulation of glucocorticoid receptor expression after both treatments.

CONCLUSIONSBoth the beta-blocker and the calcium blocker can increase glucocorticoid receptor levels after chronic administration. This effect suggests a mechanism for their anti-inflammatory and other therapeutic roles for coronary heart disease and comorbid disorders.

Aged ; Blotting, Western ; Coronary Disease ; drug therapy ; metabolism ; Female ; Humans ; Isosorbide Dinitrate ; therapeutic use ; Lovastatin ; therapeutic use ; Male ; Metoprolol ; therapeutic use ; Middle Aged ; Nifedipine ; therapeutic use ; Receptors, Glucocorticoid ; metabolism

BACKGROUNDGenetic factors can influence antihypertensive response to metoprolol, and many studies focused on the relationship between the genotype in beta1-adrenergic receptor and blood pressure (BP), little was known about the association of angiotensin-converting enzyme (ACE) genotype with the therapeutic result of metoprolol. The present study aimed to investigate whether the ACE gene insertion (I)/deletion (D) polymorphism is related to the response to metoprolol in Chinese Han hypertensive patients.

METHODSNinety-six patients with essential hypertension received metoprolol (100 mg once daily) as monotherapy for 8 weeks. Twenty-four hours ambulatory blood pressure monitoring and dynamic electrocardiogram were performed before and after treatment. Genotyping analysis was performed using PCR. The association of the ACE gene I/D polymorphism with variations in BP and heart rate (HR) was observed after the 8-week treatment.

RESULTSThe patients with ACE gene II polymorphism showed greater reduction in 24-hour average HR than those with ID or DD polymorphisms (P = 0.045), no effect of this genotype on the reduction in seating HR or in BP was observed. After adjusting for age, gender, body mass index, BP and HR at baseline, the ACE gene I/D polymorphism was still an independent predictor for variations in 24-hour average HR.

CONCLUSIONSThe II polymorphism in ACE gene could be a candidate predictor for greater reduction in 24-hour average HR in Chinese Han hypertensive patients treated by metoprolol. Greater benefits would be obtained by patients with II polymorphism from the treatment with metoprolol. Larger studies are warranted to validate this finding.

Adult ; Aged ; Antihypertensive Agents ; therapeutic use ; Female ; Genotype ; Heart Rate ; drug effects ; genetics ; Humans ; Hypertension ; drug therapy ; genetics ; Male ; Metoprolol ; therapeutic use ; Middle Aged ; Peptidyl-Dipeptidase A ; genetics ; Polymorphism, Genetic ; genetics

OBJECTIVETo investigate the effect of metoprolol succinate sustained-release tablets on cardiac function, serum vascular endothelial growth factor (VEGF) and C-reactive protein (CRP) in elderly hypertensive patients and its relation with pulse pressure (PP).

METHODSA total of 330 elderly hypertensive patients with chronic heart failure receiving basic therapy were included. Before initiation and 3 months after the maximal tolerated dose of metoprolol succinate sustained-release tablets, the parameters of blood pressure, clinical features, radionuclide ventriculographic and laboratory findings of the patients were analyzed.

RESULTSAs the PP was elevated, the serum levels of VEGF, hs-CRP and BNP increased and the cardiac systolic and diastolic functions decreased. In patients with PP of 59-68 mmHg and > 68 mmHg, 3 months of treatment with the tablets caused significantly increased LVEF by (3.32 ± 2.35)% and (4.12 ± 3.05)% and LVPER by 0.37 ± 0.26 and 0.53 ± 0.37, respectively; PP were decreased by 8.2 ± 3.1 mmHg and 9.4 ± 4.3 mmHg and VEGF by 18.39 ± 8.43 pg/ml and 26.79 ± 14.32 pg/ml, respectively. The treatment also resulted in lowered hs-CRP and BNP in these patients by 0.26 ± 0.13 mg/L and 0.33 ± 0.16 mg/L and by 140.36 ± 68.62 ng/L and 155.39 ± 73.58 ng/L, respectively.

CONCLUSIONObvious elevation of PP is associated with a better response to metoprolol succinate sustained-release tablets in elderly hypertensive patients with chronic heart failure, and 3 months of treatment with the tablets can significantly improve the cardiac function and lower the levels of VEGF, hs-CRP and BNP in these patients.

Adrenergic beta-Antagonists ; administration & dosage ; therapeutic use ; Aged ; Aged, 80 and over ; Blood Pressure ; C-Reactive Protein ; metabolism ; Chronic Disease ; Delayed-Action Preparations ; Female ; Heart Failure ; blood ; drug therapy ; etiology ; Humans ; Hypertension ; blood ; complications ; drug therapy ; Male ; Metoprolol ; administration & dosage ; analogs & derivatives ; therapeutic use ; Middle Aged ; Natriuretic Peptide, Brain ; blood ; Vascular Endothelial Growth Factor A ; blood

OBJECTIVETo explore the therapeutic effects of amiodarone and metoprolol, either alone or in combination, on chronic heart failure (CHF) complicated by ventricular arrhythmia.

METHODSA total of 110 NYHA class II-III patients with CHF complicated by ventricular arrhythmia were randomly divided into amiodarone group, metoprolol group and amiodarone + metoprolol group. The therapeutic effects was evaluated at the end of the 1-year follow-up.

RESULTSAmiodarone, metoprolol and their combination produced statistically different therapeutic effects (P<0.05). Compared with amiodarone and metoprolol used alone, amiodarone combined with metoprolol resulted in significant cardiac function improvement (P<0.05) and ventricular arrhythmia control (P<0.01). During the 1-year follow-up, the readmission rate and cardiac event rate in the amiodarone + metoprolol group were significantly lower than those in amiodarone group (P<0.01) and metoprolol group (P<0.05). The adverse reaction rates in the 3 groups were similar (P>0.05).

CONCLUSIONThe combination of amiodarone and metoprolol produces better effect than amiodarone or metoprolol alone in the treatment of CHF complicated by ventricular arrhythmia.

Adrenergic beta-Antagonists ; therapeutic use ; Adult ; Amiodarone ; therapeutic use ; Anti-Arrhythmia Agents ; therapeutic use ; Chronic Disease ; Drug Therapy, Combination ; Female ; Heart Failure ; complications ; drug therapy ; physiopathology ; Humans ; Male ; Metoprolol ; therapeutic use ; Tachycardia, Ventricular ; drug therapy ; etiology ; physiopathology ; Treatment Outcome ; Ventricular Premature Complexes ; drug therapy ; etiology