BACKGROUND: Angiotensin receptor neprilysin inhibitors (ARNIs), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers (BBs), and mineralocorticoid receptor antagonists (MRAs) are the cornerstones in treating heart failure with reduced ejection fraction (HFrEF). Sodium-glucose cotransporter 2 inhibitors (SGLT-2is) are included in HFrEF treatment guidelines. However, the effect of SGLT-2i and the five drugs on HFrEF have not yet been systematically evaluated. METHODS: PubMed, Embase, and the Cochrane Library were searched for randomized controlled trials (RCTs) from inception dates to September 23, 2022. Additional trials from previous relevant reviews and references were also included. The primary outcomes were changes in left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter/dimension (LVEDD), left ventricular end-systolic diameter/dimension (LVESD), left ventricular end-diastolic volume (LVEDV), and left ventricular end-systolic volume (LVESV), left ventricular end-systolic volume index (LVESVI), and left ventricular end-diastolic volume index (LVEDVI). Secondary outcomes were New York Heart Association (NYHA) class, 6-min walking distance (6MWD), B-type natriuretic peptide (BNP) level, and N-terminal pro-BNP (NT-proBNP) level. The effect sizes were presented as the mean difference (MD) with 95% confidence interval (CI). RESULTS: We included 68 RCTs involving 16,425 patients. Compared with placebo, ARNI + BB + MRA + SGLT-2i was the most effective combination to improve LVEF (15.63%, 95% CI: 9.91% to 21.68%). ARNI + BB + MRA + SGLT-2i (5.83%, 95% CI: 0.53% to 11.14%) and ARNI + BB + MRA (3.83%, 95% CI: 0.72% to 6.90%) were superior to the traditional golden triangle ACEI + BB + MRA in improving LVEF. ACEI + BB + MRA + SGLT-2i was better than ACEI + BB + MRA (-8.05 mL/m 2 , 95% CI: -14.88 to -1.23 mL/m 2 ) and ACEI + BB + SGLT-2i (-18.94 mL/m 2 , 95% CI: -36.97 to -0.61 mL/m 2 ) in improving LVEDVI. ACEI + BB + MRA + SGLT-2i (-3254.21 pg/mL, 95% CI: -6242.19 to -560.47 pg/mL) was superior to ARB + BB + MRA in reducing NT-proBNP. CONCLUSIONS: Adding SGLT-2i to ARNI/ACEI + BB + MRA is beneficial for reversing cardiac remodeling. The new quadruple drug "ARNI + BB + MRA + SGLT-2i" is superior to the golden triangle "ACEI + BB + MRA" in improving LVEF. REGISTRATION PROSPERO; No. CRD42022354792.
Humans ; Heart Failure/physiopathology* ; Stroke Volume/physiology* ; Angiotensin Receptor Antagonists/therapeutic use* ; Angiotensin-Converting Enzyme Inhibitors/therapeutic use* ; Sodium-Glucose Transporter 2 Inhibitors/therapeutic use* ; Randomized Controlled Trials as Topic ; Mineralocorticoid Receptor Antagonists/therapeutic use* ; Adrenergic beta-Antagonists/therapeutic use*

BACKGROUND: Limited data are available on the changes in the quality of care for ST elevation myocardial infarction (STEMI) during China's health system reform from 2009 to 2020. This study aimed to assess the changes in care processes and outcome for STEMI patients in Henan province of central China between 2011 and 2018. METHODS: We compared the data from the Henan STEMI survey conducted in 2011-2012 ( n = 1548, a cross-sectional study) and the Henan STEMI registry in 2016-2018 ( n = 4748, a multicenter, prospective observational study). Changes in care processes and in-hospital mortality were determined. Process of care measures included reperfusion therapies, aspirin, P2Y12 antagonists, β-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and statins. Therapy use was analyzed among patients who were considered ideal candidates for treatment. RESULTS: STEMI patients in 2016-2018 were younger (median age: 63.1 vs . 63.8 years) with a lower proportion of women (24.4% [1156/4748] vs . 28.2% [437/1548]) than in 2011-2012. The composite use rate for guideline-recommended treatments increased significantly from 2011 to 2018 (60.9% [5424/8901] vs . 82.7% [22,439/27,129], P <0.001). The proportion of patients treated by reperfusion within 12 h increased from 44.1% (546/1237) to 78.4% (2698/3440) ( P <0.001) with a prolonged median onset-to-first medical contact time (from 144 min to 210 min, P <0.001). The use of antiplatelet agents, statins, and β-blockers increased significantly. The risk of in-hospital mortality significantly decreased over time (6.1% [95/1548] vs . 4.2% [198/4748], odds ratio [OR]: 0.67, 95% confidence interval [CI]: 0.50-0.88, P = 0.005) after adjustment. CONCLUSIONS Gradual implementation of the guideline-recommended treatments in STEMI patients from 2011 to 2018 has been associated with decreased in-hospital mortality. However, gaps persist between clinical practice and guideline recommendation. Public awareness, reperfusion strategies, and construction of chest pain centers need to be further underscored in central China.
Humans ; Female ; Middle Aged ; ST Elevation Myocardial Infarction/drug therapy* ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use* ; Cross-Sectional Studies ; Aspirin/therapeutic use* ; Platelet Aggregation Inhibitors/therapeutic use* ; Adrenergic beta-Antagonists/therapeutic use* ; Hospital Mortality ; Registries ; Treatment Outcome ; Percutaneous Coronary Intervention

Objective: To evaluate the consistency on the determination of target heart rate by simple calculation method based on resting heart rate and by anaerobic threshold method in cardiopulmonary exercise test (CPET) for patients with coronary artery disease after percutaneous coronary intervention (PCI). Methods: This study was a diagnostic test. Patients with coronary artery disease who underwent the first PCI in the Department of Cardiology of Peking University People's Hospital from October 2011 to April 2021 were enrolled. Patients were further divided into subgroups according to gender, age (<60 years group and ≥60 years group), with or without myocardial infarction history (myocardial infarction group and angina pectoris group) and whether β blockers were applied. The general clinical data of patients, resting heart rate (RHR) and anaerobic threshold heart rate in CPET were collected through the electronic medical record system. The simple target rate (RHR plus 20 or 30 bpm) and the target rate calculated by anaerobic threshold (anaerobic threshold heart rate minus 10 bpm) were both calculated in each patient. Consistency test of target heart rate derived by above the two methods was shown by intra-class correlation (ICC) and Bland-Altman plots. Results: A total of 439 patients were included, age was (56.2±8.8) years, body mass index was (25.77±2.34) kg/m², there were 382 males (87.0%). The target heart rate determined by anaerobic threshold method was (90.0±11.8)bpm, and the simple target heart rate determined by RHR plus 20 bpm was (91.0±8.4)bpm. There was no significant difference on the target heart rate derived from the two calculation methods (P=0.091). The simple target heart rate determined by RHR plus 30 bpm was (101.0±8.4)bpm, which was significant higher than that determined by anaerobic threshold method (P<0.001). In the following analysis, RHR plus 20 bpm was defined as the simple target heart rate. The ICC value of target heart rate determined by anaerobic threshold and resting rate plus 20 bpm was 0.529(95%CI 0.458-0.593, P<0.001). Bland-Altman plots analysis showed that the ratio of the simple target heart rate and the target heart rate determined by anaerobic threshold method was 1.03±0.11 and the 95% limits of agreement (LOA) were 0.812-1.245. In the subgroup of patients aged<60 years (n=247), the ICC value was 0.492, the ratio by Bland-Altman plots analysis was 1.02±0.11 and LOA was 0.814-1.234; in the subgroup of patients aged ≥60 years (n=192), the ICC value was 0.566, the ratio by Bland-Altman plots analysis was 1.03±0.11 and LOA was 0.810-1.260. In male subgroup(n=382), the ICC value was 0.540, the ratio by Bland-Altman plots analysis was 1.03±0.11 and LOA was 0.813-1.246; in female subgroup(n=57), the ICC value was 0.445, the ratio by Bland-Altman plots analysis was 1.03±0.11 and LOA was 0.810-1.240.In myocardial infarction subgroup (n=186), the ICC value was 0.568, the ratio by Bland-Altman plots analysis was 1.02±0.11 and LOA was 0.810-1.227; in angina pectoris subgroup (n=253), the ICC value was 0.495, the ratio by Bland-Altman plots analysis was 1.04±0.11 and LOA was 0.813-1.260. In the subgroup of patients with β blockers (n=353), the ICC value was 0.520, the ratio by Bland-Altman plots analysis was 1.03±0.11 and LOA was 0.810-1.252; in the subgroup of patients without β blockers (n=86), the ICC value was 0.570, the ratio by Bland-Altman plots analysis was 1.02±0.10 and LOA was 0.821-1.219. Conclusions: The simple target heart rate determined by RHR plus 20 bpm is consistent with the target heart rate determined by anaerobic threshold in patients with coronary artery disease after PCI. But the simple target heart rate determined by RHR plus 20 bpm can't replace the target heart rate determined by anaerobic threshold in this patient cohort.
Adrenergic beta-Antagonists ; Anaerobic Threshold ; Angina Pectoris ; Coronary Artery Disease ; Female ; Heart Rate/physiology* ; Humans ; Male ; Myocardial Infarction ; Percutaneous Coronary Intervention

Objective: To analyze the status of early use of oral β-blocker and its relationship with in-hospital outcomes in eligible patients with acute coronary syndrome (ACS). Methods: The study was based on the Improving Care for Cardiovascular Disease in China (CCC)-ACS project. The data of ACS patients that collected during 2014 to 2019 from 230 collaborating hospitals across China were analyzed. Propensity score matching method and Cox multivariate regression analysis were used to analyze the association between early use of oral β-blocker and in-hospital outcomes within 15 days. Results: A total of 38 663 eligible ACS patients were included in this study. The mean age was (57.0±9.0), and 78.8% of the ACS patients (30 470/38 663) were male. The proportion of early use of oral β-blockers was 64.9% (25 112/38 663), but varied substantially, in the 230 hospitals with a range from 0 to 100%. Compared with the patients no early use of oral β-blocker, the patients receiving early oral β-blocker had significantly lower incidence of major cardiovascular adverse events (MACEs) (3.4% (395/11 536) vs. 2.9%(339/11 536), P=0.036)and less occurrences of heart failure (2.7% (316/11 536) vs. 2.1% (248/11 536), P=0.004). Multivariate Cox regression analyses showed the patients receiving early oral β-blocker had 15.5%, 23.1%, and 35.3% lower risks of MACEs, heart failure and cardiogenic shock respectively than the patients no early oral β-blocker. Conclusions: Compared with the patients no early oral β-blocker, the patients receiving early oral β-blocker had lower risks of MACEs events, heart failure and cardiogenic shock. However, the early use of oral β-blocker in ACS patients was generally insufficient with huge differences among different hospitals in China.
Acute Coronary Syndrome/drug therapy* ; Adrenergic beta-Antagonists/therapeutic use* ; Heart Failure ; Hospitals ; Humans ; Male ; Shock, Cardiogenic

Adrenergic beta-Antagonists ; Heart Failure/etiology* ; Humans ; Pulmonary Disease, Chronic Obstructive/complications*

OBJECTIVE: To study the clinical effect of oral propranolol in the treatment of respiratory hemangioma in infants and young children. METHODS: A retrospective analysis was performed from the chart review data of children with respiratory hemangioma treated by oral propranolol and diagnosed by bronchoscopy and laryngeal plain enhanced CT/MRI from November 2012 to December 2019. RESULTS: A total of 20 children were enrolled. All children had improvement in the symptoms of laryngeal stridor and dyspnea after oral administration of propranolol for 1-2 days. The median treatment time was 10 months (range 6-12 months). The median follow-up time was 10 months (range 3-15 months). Of the 20 children, 19 (95%) achieved regression of tumor, and 1 (5%) experienced an increase in tumor size during reexamination at 6 months after drug withdrawal and had no recurrence after the treatment with an increased dose of propranolol for 6 months. Only 1 child (5%) had adverse reactions, and 1 child (5%) was still under treatment. CONCLUSIONS Oral propranolol can quickly relieve the symptoms such as dyspnea and achieve tumor regression, with few adverse events, and it is therefore an effective method for the treatment of respiratory hemangioma in infants and young children.
Administration, Oral ; Adrenergic beta-Antagonists ; Child ; Child, Preschool ; Hemangioma ; Humans ; Infant ; Neoplasm Recurrence, Local ; Propranolol ; Retrospective Studies ; Treatment Outcome

OBJECTIVE: To study the effect of CYP2D610 (c.100 C>T) on plasma trough concentrations of metoprolol and its metabolite α-hydroxy metoprolol, blood pressure and heart rate in patients with coronary artery disease. METHODS: The patients with coronary artery disease taking metoprolol tablets (=128) and those taking metoprolol sustained-release tablets (=126) were genotyped for CYP2D610 using Taqman real-time quantitative PCR. The trough concentrations of metoprolol and α-hydroxy metoprolol were determined with UPLC-MS/MS, and the dose-normalized concentrations (C/D) were compared among the patients with different CYP2D610 genotypes in both groups. Resting blood pressure and heart rate were recorded in all the patients when the concentration of metoprolol reached the steady state and were compared among the patients with different genotypes. RESULTS: In patients taking metoprolol sustained-release tablets, the plasma trough concentration of α-hydroxy metoprolol was significantly associated with the systolic blood pressure (=0.0204). The CYP2D610 poor metabolizers showed a significant association with the C/D of metoprolol and α-hydroxy metoprolol ( < 0.01) in patients receiving metoprolol in both formulations, and in both groups, the C/D of metoprolol was significantly higher in the patients with a TT genotype than in those with a CC or CT genotype ( < 0.01); compared with those with the CT genotype, the patients with the TT genotype had a significantly lower C/D of α-hydroxy metoprolol ( < 0.01). In patients taking metoprolol sustained-release tablets, those with the CT (=0.0281) and TT (=0.0196) genotypes had lower diastolic blood pressure than patients with the CC genotypes, but the systolic blood pressure or heart rate did not differ significantly among them. CONCLUSIONS CYP2D610T allele mutation can reduce the metabolism of metoprolol, increase the C/D of metoprolol and decrease the C/D of α-metoprolol and diastolic blood pressure in patients with coronary artery disease, but CYP2D610 variation does not significantly affect systolic blood pressure or heart rate in the patients when the concentration of metoprolol reaches a steady state.
Adrenergic beta-Antagonists ; Chromatography, Liquid ; Coronary Artery Disease ; Cytochrome P-450 CYP2D6 ; Genotype ; Humans ; Metoprolol ; Tandem Mass Spectrometry

BackgroundSerum soluble ST2 (sST2) levels are elevated early after acute myocardial infarction and are related to adverse left ventricular (LV) remodeling and cardiovascular outcomes in ST-segment elevation myocardial infarction (STEMI). Beta-blockers (BB) have been shown to improve LV remodeling and survival. However, the relationship between sST2, final therapeutic BB dose, and cardiovascular outcomes in STEMI patients remains unknown.

MethodsA total of 186 STEMI patients were enrolled at the Wuhan Asia Heart Hospital between January 2015 and June 2015. All patients received standard treatment and were followed up for 1 year. Serum sST2 was measured at baseline. Patients were divided into four groups according to their baseline sST2 values (high >56 ng/ml vs. low ≤56 ng/ml) and final therapeutic BB dose (high ≥47.5 mg/d vs. low <47.5 mg/d). Cox regression analyses were performed to determine whether sST2 and BB were independent risk factors for cardiovascular events in STEMI.

ResultsBaseline sST2 levels were positively correlated with heart rate (r = 0.327, P = 0.002), Killip class (r = 0.408, P = 0.000), lg N-terminal prohormone B-type natriuretic peptide (r = 0.467, P = 0.000), lg troponin I (r = 0.331, P = 0.000), and lg C-reactive protein (r = 0.307, P = 0.000) and negatively correlated to systolic blood pressure (r = -0.243, P = 0.009) and LV ejection fraction (r = -0.402, P = 0.000). Patients with higher baseline sST2 concentrations who were not titrated to high-dose BB therapy (P < 0.0001) had worse outcomes. Baseline high sST2 (hazard ratio [HR]: 2.653; 95% confidence interval [CI]: 1.201-8.929; P = 0.041) and final low BB dosage (HR: 1.904; 95% CI, 1.084-3.053; P = 0.035) were independent predictors of cardiovascular events in STEMI.

ConclusionsHigh baseline sST2 levels and final low BB dosage predicted cardiovascular events in STEMI. Hence, sST2 may be a useful biomarker in cardiac pathophysiology.

Adrenergic beta-Antagonists ; administration & dosage ; therapeutic use ; Adult ; Aged ; Biomarkers ; blood ; Female ; Humans ; Interleukin-1 Receptor-Like 1 Protein ; blood ; Male ; Middle Aged ; Prognosis ; Prospective Studies ; ST Elevation Myocardial Infarction ; blood ; drug therapy ; pathology

Even though the relationship between antiarrhythmic drug usage and subsequent prostate cancer (PCa) risk has recently been highlighted, relevant findings in the previous literature are still inconsistent. In addition, very few studies have attempted to investigate the association between sodium channel blockers or potassium channel blockers for arrhythmia and the subsequent PCa risk. Therefore, this cohort study aimed to find the relationship between antiarrhythmic drug usage and the subsequent PCa risk using a population-based dataset. The data used in this study were derived from the Longitudinal Health Insurance Database 2005, Taiwan, China. We respectively identified 9988 sodium channel blocker users, 3663 potassium channel blocker users, 65 966 beta-blocker users, 23 366 calcium channel blockers users, and 7031 digoxin users as the study cohorts. The matched comparison cohorts (one comparison subject for each antiarrhythmic drug user) were selected from the same dataset. Each patient was tracked for a 5-year period to define those who were subsequently diagnosed with PCa. After adjusting for sociodemographic characteristics, comorbidities, and age, Cox proportional hazard regressions found that the hazard ratio (HR) of subsequent PCa for sodium channel blocker users was 1.12 (95% confidence interval [CI]: 0.84-1.50), for potassium channel blocker users was 0.89 (95% CI: 0.59-1.34), for beta-blocker users was 1.08 (95% CI: 0.96-1.22), for calcium channel blocker users was 1.14 (95% CI: 0.95-1.36), and for digoxin users was 0.89 (95% CI: 0.67-1.18), compared to their matched nonusers. We concluded that there were no statistical associations between different types of antiarrhythmic drug usage and subsequent PCa risk.
Adrenergic beta-Antagonists/adverse effects* ; Adult ; Age Factors ; Aged ; Anti-Arrhythmia Agents/adverse effects* ; Calcium Channel Blockers/adverse effects* ; Cohort Studies ; Comorbidity ; Databases, Factual ; Digoxin/adverse effects* ; Humans ; Incidence ; Male ; Middle Aged ; Potassium Channel Blockers/adverse effects* ; Prostatic Neoplasms/epidemiology* ; Retrospective Studies ; Socioeconomic Factors ; Sodium Channel Blockers/adverse effects* ; Taiwan/epidemiology*

OBJECTIVE: The impact of beta blockers (BBs) on survival outcomes in ovarian cancer was investigated. METHODS: By using Korean National Health Insurance Service Data, Cox proportional hazards regression was performed to analyze hazard ratios (HRs) with 95% confidence intervals (CIs) adjusting for confounding factors. RESULTS: Among 866 eligible patients, 206 (23.8%) were BB users and 660 (76.2%) were non-users. Among the 206 BB users, 151 (73.3%) were non-selective beta blocker (NSBB) users and 105 (51.0%) were selective beta blocker (SBB) users. BB use in patients aged ≥60 years, longer duration use (≥1 year), in patients with Charlson Comorbidity Index (CCI) ≥3, and in cardiovascular disease including hypertension was associated with better survival outcome. These findings were observed in both NSBB and SBB. When duration of medication was analyzed based on number of days, NSBB (≥180 days) was associated with improved overall survival (OS) with a relatively shorter period of use compared to SBB (≥720 days). In multivariate Cox proportional hazards model, longer duration of BB medication (≥1 year) was an independent favorable prognostic factor for both OS and disease-specific survival in ovarian cancer patients. CONCLUSION: In our nationwide population-based cohort study, BB use was associated with better survival outcomes in ovarian cancer in cases of long term duration of use, in older patients, and in cardiovascular and/or other underlying disease (CCI ≥3).
Adrenergic beta-Antagonists ; Cardiovascular Diseases ; Cohort Studies* ; Comorbidity ; Humans ; Hypertension ; National Health Programs ; Ovarian Neoplasms* ; Proportional Hazards Models ; Treatment Outcome