孙慧
中国医学科学院阜外医院 心血管内科
Nifekalant hydrochloride is a class III antiarrhythmic agent which could increase the duration of the action potential and the effective refractory period of ventricular and atrial myocytes by blocking the K+ current. Nifekalant is used to prevent ventricular tachycardia/ventricular fibrillation. QT interval prolongation is the main measurable drug effect. However, due to the complicated dosing plan in clinic, the relationship among dosage, time, drug concentration and efficacy is not fully understood. In this study, a single-center, randomized, blind, dose-ascending, placebo-controlled study was conducted to explore the intrinsic characteristics of nifekalant injection in healthy Chinese volunteers by a population pharmacokinetic (PK)-pharmacodynamic (PD) model approach. 42 subjects were enrolled in this study and received one of three dose plans (loading dose on Day 1 (0.15, 0.3 or 0.5 mg/kg), loading dose followed by maintenance dose (0.2, 0.4 or 0.8 mg/kg/h) on Day 4) or vehicle. Blood samples were drawn for PK evaluation, and ECGs were recorded for QTc calculation at the designed timepoints. No Torsades de Pointes occurred during the study. The popPK model of nifekalant injection could be described by a two-compartment model with first-order elimination. The population mean clearance (CL) was 53.8 L/h. The population mean distribution volume of the central (Vc) and peripheral (Vp) compartments was 8.27 L and 45.6 L, respectively. A nonlinear dose-response (Emax) model well described the pharmacodynamic effect (QTc interval prolongation) of nifekalant. The Emax and EC50 from current study were 101 ms and 342 ng/mL, respectively.
Journal of pharmacokinetics and pharmacodynamics 2024
OBJECTIVES:The risk of adverse events and prognostic factors are changing in different time phases after acute myocardial infarction (AMI). The incidence of adverse events is considerable in the early period after AMI hospitalisation. Therefore, dynamic risk prediction is needed to guide postdischarge management of AMI. This study aimed to develop a dynamic risk prediction instrument for patients following AMI.DESIGN:A retrospective analysis of a prospective cohort.SETTING:108 hospitals in China.PARTICIPANTS:A total of 23 887 patients after AMI in the China Acute Myocardial Infarction Registry were included in this analysis.PRIMARY OUTCOME MEASURES:All-cause mortality.RESULTS:In multivariable analyses, age, prior stroke, heart rate, Killip class, left ventricular ejection fraction (LVEF), in-hospital percutaneous coronary intervention (PCI), recurrent myocardial ischaemia, recurrent myocardial infarction, heart failure (HF) during hospitalisation, antiplatelet therapy and statins at discharge were independently associated with 30-day mortality. Variables related to mortality between 30 days and 2 years included age, prior renal dysfunction, history of HF, AMI classification, heart rate, Killip class, haemoglobin, LVEF, in-hospital PCI, HF during hospitalisation, HF worsening within 30 days after discharge, antiplatelet therapy, β blocker and statin use within 30 days after discharge. The inclusion of adverse events and medications significantly improved the predictive performance of models without these indexes (likelihood ratio test p<0.0001). These two sets of predictors were used to establish dynamic prognostic nomograms for predicting mortality in patients with AMI. The C indexes of 30-day and 2-year prognostic nomograms were 0.85 (95% CI 0.83-0.88) and 0.83 (95% CI 0.81-0.84) in derivation cohort, and 0.79 (95% CI 0.71-0.86) and 0.81 (95% CI 0.79-0.84) in validation cohort, with satisfactory calibration.CONCLUSIONS:We established dynamic risk prediction models incorporating adverse event and medications. The nomograms may be useful instruments to help prospective risk assessment and management of AMI.TRIAL REGISTRATION NUMBER:NCT01874691.
BMJ open 2023
BACKGROUND:Recent publications reported a paradoxical finding that there was an inverse association between the number of standard modifiable risk factors (SMuRFs; smoking, hypertension, diabetes, and hyperlipidemia) and mortality in patients with myocardial infarction. However, the current evidence is only limited to those highly developed countries with advanced medical management systems.METHODS:The China Acute Myocardial Infarction registry is a prospective observational study including patients with acute myocardial infarction from three-level hospitals across 31 administrative regions throughout mainland China. A total of 16,228 patients with first-presentation ST-elevation myocardial infarction (STEMI) admitted to hospitals from January 2013 to September 2014 were enrolled in the current analysis. Cox proportional hazard models adjusting for baseline characteristics, clinical profiles at presentation, and in-hospital treatments were used to assess the association of the number of SMuRFs with all-cause mortality at 30 days after STEMI presentation.RESULTS:A total of 1918 (11.8%), 11,503 (70.9%), and 2807 (17.3%) patients had 0, 1-2, and 3-4 SMuRFs at presentation, respectively. Patients with fewer SMuRFs were older and more likely to be females, experienced longer pre-hospital delays, and were less likely to receive primary percutaneous coronary intervention and evidence-based medications. Compared with those without any SMuRF, patients with 1-2 SMuRFs and 3-4 SMuRFs were associated with an HR of 0.74 (95% CI, 0.63-0.87) and 0.63 (0.51-0.77) for all-cause mortality up to 30 days in the unadjusted model (Ptrend < 0.0001). However, after multivariate adjustment, the number of SMuRFs was positively associated with increased mortality risk (HR for 1-2 SMuRFs, 1.15 [0.95-1.39]; HR for 3-4 SMuRFs, 1.31 [1.02-1.68]; Ptrend = 0.03), and the association was only significant among patients admitted to hospitals beyond 12 h from onset (HR for 1-2 SMuRFs, 1.39 [1.03-1.87]; HR for 3-4 SMuRFs, 2.06 [1.41-3.01]) but not their counterparts (Pinteraction = 0.01).CONCLUSIONS:The increased crude mortality risk among patients without SMuRFs is explained by confounding factors related to their poor risk profiles (old age, longer pre-hospital delays, and poor clinical management). After multivariate adjustment, a higher risk-factor burden was associated with poor prognosis among patients with STEMI.
BMC medicine 2022
Background: Young people hold a stable or increasing percentage of patients with acute myocardial infarction (AMI) in many countries. However, data on clinical characteristics and outcomes of young AMI patients were insufficient. This study aimed to analyze clinical characteristics, prognosis, and gender disparities in patients aged ≤45 years with AMI. Methods: A total of 24,125 patients from China Acute Myocardial Infarction registry were included in this study. Clinical characteristics, managements, and in-hospital and 2-year outcomes were compared between patients aged ≤45 years and those aged >45 years. Predictors of all-cause death were obtained using multivariate regression models. Gender disparities of AMI were analyzed among young patients. Results: Of 24,125 patients, 2,042 (8.5%, 116 female) were aged ≤45 years. Compared with patients aged >45 years, young patients were more often male, current smokers, and more likely to have medical history of hyperlipidemia. Smoking (72.1%) was the major modifiable risk factor in patients aged ≤45 years. Young patients received more evidence-based medications and had significantly lower risk of both in-hospital and 2-year adverse events than older patients. Education level and left ventricular ejection fraction were independent predictors of 2-year mortality in young patients. Moreover, symptom onset to admission time of young women was significantly longer than that of young men. Young women were less likely to receive percutaneous coronary intervention and suffered higher risk of in-hospital adverse events than young men (adjusted odds ratio for death: 5.767, 95% confidence interval 1.580-21.049, p = 0.0080; adjusted odds ratio for the composite of death, re-infarction, and stroke: 3.981, 95% confidence interval 1.150-13.784, p = 0.0292). Young women who survived at discharge had a higher 2-year cumulative incidence of death (3.8 vs 1.4%, p log-rank = 0.0412). Conclusions: Patients aged ≤45 years constituted a non-negligible proportion of AMI patients, with higher prevalence of smoking and hyperlipidemia but better care and prognosis compared with older patients. There were significant gender disparities of managements and outcomes in young patients. More efforts to improve quality of care in young women are needed.
Frontiers in cardiovascular medicine 2021
BACKGROUND:With the growing burden of non-ST-elevation myocardial infarction (NSTEMI), developing countries face great challenges in providing equitable treatment nationwide. However, little is known about hospital-level disparities in the quality of NSTEMI care in China. We aimed to investigate the variations in NSTEMI care and patient outcomes across the three hospital levels (province-, prefecture- and county-level, with decreasing scale) in China.METHODS:Data were derived from the China Acute Myocardial Infarction Registry on patients with NSTEMI consecutively registered between January 2013 and November 2016 from 31 provinces and municipalities throughout mainland China. Patients were categorized according to the hospital level they were admitted to. Multilevel generalized mixed models were fitted to examine the relationship between the hospital level and in-hospital mortality risk.RESULTS:In total, 8,054 patients with NSTEMI were included (province-level: 1,698 patients; prefecture-level: 5,240 patients; county-level: 1,116 patients). Patients in the prefecture- and county-level hospitals were older, more likely to be female, and presented worse cardiac function than those in the province-level hospitals (P <0.05). Compared with the province-level hospitals, the rate of invasive strategies was significantly lower in the prefecture- and county-level hospitals (65.3, 43.3, and 15.4%, respectively, P <0.001). Invasive strategies were performed within the guideline-recommended timeframe in 25.4, 9.7, and 1.7% of very-high-risk patients, and 16.4, 7.4, and 2.4% of high-risk patients in province-, prefecture- and county-level hospitals, respectively (both P <0.001). The use of dual antiplatelet therapy in the county-level hospitals (87.2%) remained inadequate compared to the province- (94.5%, P <0.001) and prefecture-level hospitals (94.5%, P <0.001). There was an incremental trend of in-hospital mortality from province- to prefecture- to county-level hospitals (3.0, 4.4, and 6.9%, respectively, P-trend <0.001). After stepwise adjustment for patient characteristics, presentation, hospital facilities and in-hospital treatments, the hospital-level gap in mortality risk gradually narrowed and lost statistical significance in the fully adjusted model [Odds ratio: province-level vs. prefecture-level: 1.23 (0.73-2.05), P = 0.441; province-level vs. county-level: 1.61 (0.80-3.26), P = 0.182; P-trend = 0.246].CONCLUSIONS:There were significant variations in NSTEMI presentation and treatment patterns across the three hospital levels in China, which may largely explain the hospital-level disparity in in-hospital mortality. Quality improvement initiatives are warranted, especially among lower-level hospitals.
Frontiers in cardiovascular medicine 2021
BACKGROUND:Length of stay (LOS) in patients with ST-segment elevation myocardial infarction (STEMI) is directly associated with financial pressure and medical efficiency. This study aimed to determine impact of LOS on short-term outcomes and associated factors of LOS in patients with ST-segment elevation myocardial infarction (STEMI) after primary percutaneous coronary intervention (PPCI).METHODS:A total of 3615 patients with STEMI after PPCI in the China Acute Myocardial Infarction registry were included in the analysis. Predictors of prolonged LOS were analyzed by multivariate logistic regression model with generalized estimating equation. The impact of LOS on 30-day clinical outcomes was assessed.RESULTS:The median LOS was 9 (7, 12) days. Patients with a longer LOS (>7 days) were older, more often in lower-level hospitals, had more periprocedural complications and hospitalization expense. Fourteen variables, such as weekend admission and lower-level hospitals, were identified as independent associated factors of prolonged LOS. There were no significant difference in 30-day major adverse cardiac and cerebrovascular events (MACCE), readmission, and functional status between patients with LOS≤7d and LOS>7d after multivariate adjustment and propensity score matching. However, patients who discharged over one week had better medication adherence (adjusted odds ratio: 0.817, 95% confidence interval: 0.687-0.971, P=0.022). Significant interaction was observed in medication use between gender and LOS (Pinteraction=0.038).CONCLUSION:Patients with STEMI undergoing PPCI experienced a relatively long LOS in China, which resulted in more medical expenses but no improvement on 30-day MACCE, readmission, and functional recovery. Poor 30-day medication adherence with short LOS reflects unsatisfying transition of management from hospital to community. More efforts are needed to reduce LOS safely and improve the efficiency of medical care.
International journal of general medicine 2021
Objective: To understand gender differences of cardiovascular risk factors in patients with acute myocardial infarction (AMI) in China. Methods: A total of 26 592 patients with AMI from 107 hospitals in 31 provinces in China from January 1, 2013 to September 30, 2014 were included. Self-designed questionnaire was used to collect patients' age, gender, height, weight, type of AMI, medical history of cardiovascular and cerebrovascular diseases, medication history, lifestyle and AMI risk factors, including high blood pressure, diabetes, dyslipidemia, overweight and/or obesity, smoking history and family history of early onset coronary artery disease. A total of 24 394 patients with complete clinical data were included in the analysis, and gender differences in cardiovascular risk factors were analyzed in all and subgroups with different characteristics. Results: The patients were (62.2±13.8) years old, including 18 162 (74.5%) males and 18 209 (74.6%) ST-segment elevation myocardial infarction (STEMI). The age of male patients was (60.2±13.7) years, which was younger than that of female patients [(68.2±12.3) years]. The body mass index of male patients was (24.2±3.0) kg/m2, which was higher than that of female patients [(23.8±3.4) kg/m2]. The proportions of patients with overweight and/or obesity, smoking history, dyslipidemia, family history of early onset coronary heart disease, fatty diet and history of AMI were 51.8%, 55.2%, 7.2%, 3.8%, 80.4% and 7.7%, which were higher than those of females (45.9%, 9.9%, 5.8%, 2.3%, 65.0% and 5.9%, respectively]. The proportions of hypertension, diabetes, physical inactivity and stroke history were 46.5%, 17.2%, 77.8% and 8.5%, respectively, which were lower than those in female patients [61.4% (3 829 cases), 24.8%, 81.7% and 11.1%, respectively] (all P values<0.05).The proportions of peripheral vascular diseases history in male and female patients were 0.6% and 0.7%, respectively, with no statistical significance in difference (P>0.05). Subgroup analysis showed inconsistent results comparing to analysis of all patients: there were no statistical significance in gender differences as for the proportion of dyslipidemia in the non-ST-segment elevation MI group, the proportion of family history of early onset coronary heart disease in the young and middle aged groups, the proportion of overweight and/or obesity, and the proportion of physical inactivity in the elderly group (all P values>0.05). Conclusions: There are gender differences in cardiovascular risk factors among Chinese patients with acute myocardial infarction. Hypertension and diabetes are more common in women, and overweight and/or obesity, fatty diet and smoking are more common in men.
Zhonghua yi xue za zhi 2021
Importance:The incidence of acute myocardial infarction has increased over the past decades in China, and management challenges include an unbalanced economy, disparate resources, and variable access to medical care across the nation.Objective:To examine the variations in care and outcomes of patients with ST-segment elevation myocardial infarction among 3 levels of hospitals in the typical Chinese public hospital model.Design, Setting, and Participants:This cross-sectional study used data from the China Acute Myocardial Infarction Registry to compare the differences in care and outcomes among patients at 108 hospitals from 31 provinces and municipalities throughout mainland China. Participants included patients with ST-segment elevation myocardial infarction directly admitted to hospitals between January 2013 and September 2014. Data analyses were performed from June 2015 to June 2019.Exposures:Care in province-level, prefecture-level, or county-level hospitals in China.Main Outcomes and Measures:The primary outcome was in-hospital mortality. Secondary outcomes included presentation, treatments, and major complications.Results:A total of 12 695 patients (9593 men [75.6%]; median [interquartile range] age, 63 [54-72] years) were included; 3985 were at province-level hospitals, 6731 were at prefecture-level hospitals, and 1979 were at county-level hospitals. Compared with patients admitted to province-level hospitals, those admitted to prefecture-level and county-level hospitals were older (median [interquartile range] age, 61 [52-70] years vs 63 [54-72] years and 65 [57-75] years) and more likely to be women (815 women [20.5%] vs 1620 women [24.1%] and 667 women [33.7%]). Patients in prefecture-level and county-level hospitals were less likely to use ambulances compared with patients at province-level hospitals (11.6% [95% CI, 10.8%-12.4%] and 12.0% [95% CI, 10.6%-13.5%] vs 19.4% [95% CI, 18.1%-20.7%]; P < .001) and were less likely to experience early presentation, with onset-to-arrival times less than 12 hours for 75.3% (95% CI, 73.9%-76.6%) of patients at province-level hospitals, 70.8% (95% CI, 69.7%-71.9%) of patients at prefecture-level hospitals, and 69.8% (95% CI, 67.7%-71.8%) of patients at county-level hospitals (P < .001). The rates of reperfusion therapy were significantly lower in low-level hospitals (54.3% [95% CI, 53.1%-55.5%] for prefecture-level hospitals and 45.8% [95% CI, 43.6%-48.1%] for county-level hospitals) compared with province-level hospitals (69.4% [95% CI, 67.9%-70.8%]; P < .001). There was a progressively higher rate of in-hospital mortality at the 3 levels of hospitals: 3.1% (95% CI, 2.6%-3.7%) for province-level hospitals, 5.3% (95% CI, 4.8%-5.9%) for prefecture-level hospitals, and 10.2% (95% CI, 8.9%-11.7%) for county-level hospitals (P for trend < .001). After adjustment for patient characteristics, presentation, hospital facility, and treatments, the odds of death remained higher in prefecture-level (odds ratio, 1.39 [95% CI, 1.06-1.84]) and county-level (odds ratio, 1.43 [95% CI, 0.97-2.11]) hospitals compared with province-level hospitals (P for trend = .04).Conclusions and Relevance:These findings suggest that there are significant variations in care and outcomes of patients among the 3 levels of hospitals in China. More efforts should be made to address the identified gaps, particularly in the prefecture-level and county-level hospitals. This work can inform national quality improvements efforts in China and in other developing countries.
JAMA network open 2020
OBJECTIVE:To investigate the medical care resources of acute myocardial infarction (AMI) in Chinese hospitals of different regions and levels.METHODS:We selected 115 hospitals in China, including 61 northern hospitals, 54 southern hospitals, 52 eastern hospitals, 26 central hospitals, 37 western hospitals, 79 tertiary hospitals, 36 secondary hospitals, 34 pro vincial-level hospitals, 46 prefectural-level hospitals and 35 county hospitals. From November 2012 to August 2013, we sent questionnaire to the cardiologists in each hospital, to collect related information.RESULTS:(1) The number of AMI admitted each year of northern hospital was more than the number of southern hospital (220 (120, 400) cases vs. 220 (80, 350) cases, P=0.033), while number of coronary care unit (CCU), thrombolytic therapy, percutaneous coronary intervention (PCI), primary PCI and coronary artery bypass grafting (CABG) were similar (all P> 0.05). (2) The number of AMI admitted each year of eastern, central and western hospital was 295(150, 501) cases, 175(75, 300) cases and 170(50, 250) cases respectively(P=0.007), with no significant difference among them for setting CCU, carrying out thrombolytic therapy, PCI, primary PCI and CABG (all P>0.05). (3) The total number of the in-patient beds and AMI admitted each year of tertiary hospitals were significantly higher than that in the secondary hospitals(104(70, 152)vs. 47(30, 52), P<0.001) and (300(200, 460)cases vs.80(47, 135)cases, P<0.001) respectively. There was a significant difference between tertiary and secondary hospitals for the number of CCU (97.5% (77/79)and 75.0%(27/36)), PCI (98.7%(78/79)and 27.8%(10/36)), primary PCI (96.2%(76/79)and 22.2%(8/36)), CABG (81.0%(64/79)and 11.1%(4/36)), intra-aortic balloon pump (IABP) (91.1%(72/79) and 13.9%(5/36)) respectively (all P<0.001). (4) There were obvious differences among provincial-level, prefectural-level and country-level hospitals for the admitted AMI patient numbers annually which was 400(250, 600), 232(100, 380)and 80(50, 162)cases, CCU proportion which was 100 %(34/34), 95.7%(44/46) and 74.3%(26/35), thrombolytic therapy proportion which was 88.2%(30/34), 100%(46/46)and 91.4%(32/35), PCI proportion which was 100%(34/34), 89.1%(41/46)and 37.1%(13/35), primary PCI proportion which was 100%(34/34), 84.8%(39/46)and 31.4%(11/35), CABG proportion which was 97.1%(33/34), 67.4%(31/46) and 11.4%(4/35)respectively (P<0.01 or 0.05) .CONCLUSIONS:Different regional hospitals have no significant difference in number of CCU and reperfusion therapies, while there is a big difference on medical care resources of AMI between different-level hospitals, which may affect the diagnosis and treatment effect of patients with AMI. Clinical Trail Registry: National Institutes of Health, NCT01874691.
Zhonghua xin xue guan bing za zhi 2016
OBJECTIVE:To review the experience of correction of congenital cardiac defects through a right minithoracotomy.METHOD:319 patients underwent correction of congenital heart malformations through right lateral thoracotomy under cardiopulmonary bypass. The average age was 3.44 +/- 1.59 years (range, 5 months-8 years). The average body weight was 13.66 - 3.98 kg (range, 6 - 26 kg). Cardiac defects repaired included atrial septal defect in 87 patients (1 patient associated with left superior vena cava (LSVC), 6 pulmonary stenosis, 5 partial anomalous pulmonary venous connection), ventricular septal defect in 200 (7 patients with coexisting patent ductus arteriosus, 7 mitral insufficiency, 3 LSVC, 11 right ventricular outflow tract obstruction), Fallot's Tetralogy in 19 (3 patients associated with LSVC, 1 single coronary malformation), partial endocardial cushion defect in 2 and other defects in 11. The mean cardiopulmonary bypass time was 56.07 +/- 24.90 min (range, 20 - 176 min) and the mean aortic crossclamping time was 32.97 +/- 20.38 min (range, 6 - 140 min). The average mechanical ventilation time after operation was 18.75 +/- 24.57 hr (range, 2 - 140.72 hr), and the mean postoperative hospital stay was 7.08 +/- 0.69 days (range, 7 - 17 days).RESULT:No operative mortality and severe postoperative complications were noted.CONCLUSION:The right lateral thoracotomy is a safe and effective alternative to a median sternotomy for correction of cardiac defects. Advantages of this approach include less injury, maintaining the continuity and the integrity of the bony thorax, and preventing postoperative pigeon breast. The cosmetic result is superior to that of median sternotomy or bilateral submammary incision.
Zhonghua wai ke za zhi [Chinese journal of surgery] 1998
