Evaluation of metoprolol standard dosing pathway in Chinese patients with acute coronary syndrome:a prospective multicenter single-arm interventional study

OBJECTIVE To evaluate the feasibility and tolerability of metoprolol standard dosing pathway(MSDP)in Chinese patients with acute coronary syndrome(ACS).METHODS In this multicenter,prospective,open label,single-arm and interventional study that was conducted from February 2018 to April 2019 in fifteen Chinese hospitals.A total of 998 hospitalized patients aged≥18 years and diagnosed with ACS were included.The MSDP was applied to all eligible ACS patients based on the standard treatment recommended by international guidelines.The primary endpoint was the percentage of patients achieving the target dose at discharge(V2).The secondary endpoints included the heart rate and blood pressure at V2 and four weeks after discharge(V4),and percentage of patients experiencing bradycardia(heart rate<50 beats/min),hypotension(blood pressure<90/60 mmHg)and transient cardiac dysfunction at V2 and V4.RESULTS Of the 998 patients,29.46%of patients achieved the target dose(≥95 mg/d)at V2.The total population was divided into two groups:target group(patients achieving the target dose at V2)and non-target group(patients not achieving the target dose at V2).There was significant difference in the reduction of heart rate from baseline to discharge in the two groups(-4.97±11.90beats/min vs.-2.70±9.47 beats/min,P=0.034).There was no significant difference in the proportion of bradycardia that occurred in the two groups at V2(0 vs.0,P=1.000)and V4(0.81%vs.0.33%,P=0.715).There was no significant difference in the proportion of hypotension between the two groups at V2(0.004%vs.0.004%,P=1.000)and V4(0 vs.0.005%,P=0.560).No transient cardiac dysfunction occurred in two groups during the study.A total of five adverse events(1.70%)and one serious adverse event(0.34%)were related to the pathway in target group.CONCLUSIONS In Chinese ACS patients,the feasibility and tolerability of the MSDP have been proved to be acceptable.

Anatomical characteristics of patients with symptomatic severe aortic stenosis in China

With accumulating evidence of transcatheter aortic valve replacement(TAVR)worldwide,it is gradually realized that patients being treated are different across different coun-tries,including but not limited to their age,habitus,disease etiology,aortic valve morphology,and sizes of structures.[1]In China,the average age of TAVR patients is around 5 years younger than industrialized countries,[2]making Chinese patients a good predictive sample of what the industrialized countries might see in TAVR screening in the near future due to the expansion of this technique to younger patients,but anatomical features appreciated from multi-slice computed tomography(MSCT)in the Chinese patient population have not been well demonstrated.

F：lole of Jaggedl-Heyl Signal in Angiotensin II-induced Impairment of Myocardial Angiogenesis

Background： Angiotensin II （Ang ll） is a major contributor to the development of heart failure. However, the molecular and cellular mechanisms that underlie this process remain elusive. Inadequate angiogenesis in the myocardium leads to a transition from cardiac hypertrophy to dysfunction, and our previous study showed that Ang II significantly impaired the angiogenesis response. The current study was designed to examine the role of Jaggedl-Notch signaling in the effect of Ang II during impaired angiogenesis and cardiac hypertrophy. Methods： Ang II was subcutaneously infused into 8-week-old male C57BL/6 mice at a dose of 200 ng·kg^-1·min^-1 for 2 weeks using Alzet micro-osmotic pumps. N-[N-（3, 5-difluorophenacetyl）-L-alanyl]-S-phenylglycine tert-butyl ester （DAPT）, a y-secretase inhibitor, was injected subcutaneously during Ang II infusion at a dose of 10.0 mg.kg^-1·d^-1. Forty mice were divided into four groups （n = 10 per group）： control group; Ang 11 group, treated with Ang I1; DAPT group, treated with DAPT; and Ang II ＋ DAPT group, treated with both Ang I1 and DAPT. At the end of experiments, myocardial （left ventricle [LV]） tissue from each experimental group was evaluated using immunohistochemistry, Western blotting, and real-time polymerase chain reaction, Data were analyzed using one-way analysis of variance test followed by the least significant difference method or independent samples t-test. Results： Ang II treatment significantly induced cardiac hypertrophy and impaired the angiogenesis response compared to controls, as shown by hematoxylin and eosin （HE） staining and immunohistochemistry fbr CD31, a vascular marker （P 〈 0.05 for both）. Meanwhile, Jaggedl protein was significantly increased, but gene expression for both Jagl and Heyl was decreased in the LV following Ang II treatment, compared to that in controls （relative ratio for Jag1 gene： 0.45 ± 0.13 vs. 0.84± 0.15; relative ratio for Heyl gene： 0.51 ± 0.08 vs. 0.91 ± 0.09; P 〈 0.05）. All these cellular and molecular effects induced by Ang II in the hearts of mice were reduced by DAPT treatment. Interestingly, Ang II stimulated Heyl, a known Notch target, but did not affect the expression of Hey2, another Notch target gene. Conclusions： A Jaggedl-Heyl signal might mediate the impairment of angiogenesis induced by Ang II during cardiac hypertrophy.