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 ± 11.90 beats/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.

Efficacy and safety profile of angiotensin receptor neprilysin inhibitors in the management of heart failure: a systematic review and meta-analysis of randomized controlled trials.

Several guidelines have recommended the use of angiotensin receptor neprilysin inhibitors (ARNIs) as replacement for angiotensin-converting enzyme inhibitors in the management of heart failure. Till date, there are no reviews done that comprehensively cover different aspects of efficacy and safety parameters. Hence, we have performed a comprehensive systematic review and meta-analysis on role of ARNIs for the management of heart failure patients. Searches were done in Embase, Scopus, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, PubMed Central, Cochrane Library, MEDLINE, Google Scholar, ScienceDirect and Clinicaltrials.gov until June 2022. Risk of bias assessment was done with Cochrane's risk of bias tool. Meta-analysis was carried out using random-effects model. Pooled standardized mean difference (SMD)/mean difference (MD) and/or risk ratio (RR) with 95% confidence intervals (CIs) was reported. In total, we analysed 34 studies, with almost all of them had a high risk of bias. Pooled RR was 0.88 (95% CI: 0.82-0.95) for all-cause mortality, 0.84 (95% CI: 0.77-0.92) for cardiovascular mortality and 0.78 (95% CI: 0.70-0.87) for hospitalization. Pooled MD was 3.74 (95% CI: 1.93-5.55) for left ventricular ejection fraction, -2.16 (95% CI: -3.58 to -0.74) for left atrial volume index, -3.80 (95% CI: -6.60 to -1.00) for left ventricular end-diastolic dimension and -1.16 (95% CI: -1.98 to -0.35) for E/E' ratio. Regarding adverse events, pooled RR was 1.55 (95% CI: 1.31-1.85) for symptomatic hypotension, 0.93 (95% CI: 0.78-1.11) for worsening renal function, 1.09 (95% CI: 0.94-1.26) for hyperkalaemia and 1.29 (95% CI: 0.67-2.50) for angioedema. ARNIs had beneficial efficacy and safety profile on the management of heart failure especially patients with reduced ejection fraction.

ATP-induced cardioprotection against myocardial ischemia/reperfusion injury is mediated through the RISK pathway.

The aim of the present study was to examine the post-infarct acute effect of adenosine-5'-triphosphate (ATP) on myocardial infarction (MI) size as well as its precise molecular mechanism. Sixty New Zealand white male rabbits were exposed to 40 min of ischemia followed by 180 min of reperfusion. The rabbits were intravenously administered 3 mg/kg of ATP (ATP group) or saline (control group) immediately after reperfusion and maintained throughout the first 30 min. The wortmannin+ATP, PD-98059+ATP, and 5-hydroxydecanoic acid (5-HD) sodium salt+ATP groups were separately injected with wortmannin (0.6 mg/kg), PD-98059 (0.3 mg/kg), and 5-HD (5 mg/kg) 5 min prior to ATP administration. MI size was calculated as the percentage of the risk area in the left ventricle. Myocardial apoptosis was determined using a TUNEL assay. Western blot analysis was performed to examine the levels of protein kinase B (Akt)/p-Akt and extracellular signal-regulated kinase (ERK)/p-ERK in the ischemic myocardium, 180 min after reperfusion. The infarct size was significantly smaller in the ATP group than in the control group (p<0.05). The infarct size-reducing effect of ATP was completely blocked by wortmannin, PD-98059 and 5-HD. Compared with the control group, cardiomyocyte apoptosis was significantly reduced in the ATP group, while this did not occur in the wortmannin+ATP, PD-98059+ATP and 5-HD+ATP groups. Western blot analysis revealed a higher myocardial expression of p-Akt and p-ERK 180 min following reperfusion in the ATP versus the control group. In conclusion, cardioprotection by postischemic ATP administration is mediated through activation of the reperfusion injury salvage kinase (RISK) pathway and opening of the mitochondrial ATP-dependent potassium channels.

Rutin alleviates diabetic cardiomyopathy in a rat model of type 2 diabetes.

Diabetic cardiomyopathy (DCM), an independent coronary heart disease that develops in diabetic individuals, is characterized by changes in the myocardial structure and function. The aim of the present study was to investigate the protective effect of rutin on DCM in a streptozotocin-induced diabetic rat model. Rutin was orally administrated at a dose of 8 mg/kg body weight. Metabolic profiles, myocardial enzymes and oxidative stress were examined by biochemical tests. The expression levels of cellular proteins associated with apoptosis were measured by western blot analysis, while the levels of inflammatory factors were assessed by immunohistochemical analyses. Rats with DCM exhibited an abnormal metabolic profile, aberrant myocardial enzymes, elevation of oxidative stress markers, increased levels of inflammatory factors and enhanced apoptotic cell death. Notably, rutin was shown to protect and improve myocardial dysfunction, oxidative stress, apoptosis and inflammation in the hearts of the diabetic rats. In conclusion, these results indicated that rutin may have great therapeutic potential in the treatment of DCM, and possibly other cardiovascular disorders, by preventing oxidative stress, inflammation and cell death. However, further detailed studies are required to reveal the exact mechanisms underlying the protective effect of rutin.

Elevated lipoprotein-associated phospholipase A2 is associated with progression of nonculprit lesions after percutaneous coronary intervention.

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an enzyme that hydrolyzes oxidized phospholipids to generate bioactive proatherogenic products. Nonculprit lesions have been assumed to contribute to the pathogenesis of recurrent acute coronary syndrome (ACS). The role of LP-PLA2 in the progression of nonculprit coronary lesions after successful percutaneous coronary intervention (PCI) remains unclear. Our study included 123 patients with ACS who underwent initial PCI and a long-term follow-up (mean interval, one year) with coronary angiography. Among them, 19 patients were diagnosed as the progression of nonculprit lesions, based on the presence of at least one of the following factors: (1) ≥ 10% reduction in the diameter of a preexisting ≥ 50% stenosis; (2) ≥ 30% reduction in the diameter of a < 50% stenosis; and (3) early-onset stenosis with ≥ 30% reduction in the diameter of a segment that was normal on the primary angiogram. Blood sampling was drawn from all patients at 12-14 hours after PCI. The ACS patients with progression had higher total cholesterol (4.47 ± 1.02 mmol/L vs. 3.59 ± 0.57 mmol/L, P < 0.05), higher levels of Lp-PLA2 activity (14.39 ± 6.13 nmol/min/ml vs. 8.86 ± 3.14 nmol/min/ml, P < 0.001) and a higher proportion of multi-vessel disease than those without progression. Multivariate logistic regression analysis showed that Lp-PLA2 activity (ß = 0.024, P = 0.005) was an independent predictor for rapid progression of nonculprit coronary lesions. In conclusion, elevated Lp-PLA2 activity is associated with rapid progression of nonculprit coronary lesions in ACS patients who underwent PCI.

[Effects of salvianolic acid B on cardiovascular endothelial cells and platelet activation in a rabbit model of ischemia-reperfusion].

OBJECTIVE: To investigate the effects of salvianolic acid B (SA-B) on cardiovascular endothelial cell function and platelet activation during myocardial ischemia-reperfusion in rabbits. METHODS: A total of 24 New Zealand white rabbits were randomly divided into sham-operated group, ischemia-reperfusion group (untreated group) and SA-B group. The hearts of rabbits in untreated group and SA-B group underwent half an hour of left anterior descending coronary artery (LADCA) occlusion via ligation technology, which was followed by 4 hours of reperfusion to prepared ischemia-reperfusion injury model in vivo. For sham-operated group, the animals were not subjected to occlusion of LADCA. In SA-B treatment group the rabbits were intravenously administered SA-B immediately after LADCA occlusion, and the other two groups were given normal saline in the same way instead of SA-B. The jugular vein bloods of animals were collected before LADCA ligation, half an hour after ligation and after 1-, 4-hour reperfusion, respectively. The content of plasma nitric oxide (NO) was determined by nitrate reductase process. Radioimmunoassay was applied to detect the endothelin (ET) content in plasma and the count of alpha-granule membrane protein-140 (GMP-140) on platelet surface to identify the activation of the platelet. RESULTS: No significant difference was observed before and after sham LADCA occlusion in sham-operated group in the contents of NO and ET in plasma (P>0.05), neither was the count of GMP-140 on platelet surface (P>0.05). The content of NO in plasma detected 0.5 h after LADCA occlusion was significantly decreased in untreated group compared with the sham-operated group at the corresponding time, and they were also much lower than that before LADCA occlusion in the sham-operated group (P<0.05). The plasma content of NO in untreated group showed a progressive decrease in response to the myocardial reperfusion. However, the content of ET in plasma and the count of GMP-140 on platelet surface were remarkably increased after myocardial ischemia as compared with those before LADCA ligation and those detected in sham-operated group (P<0.05). The content of ET and the count of GMP-140 in the untreated group were further increased corresponding to the aggressive reperfusion. The content of NO was significantly increased while the content of ET and the count of GMP-140 were both significantly decreased in SA-B group as compared with untreated group after 1- and 4-hour myocardial reperfusion, respectively (P<0.01). CONCLUSION: The results show that endothelial dysfunction and platelet activation occur during ischemia-reperfusion in rabbit hearts in vivo and SA-B protects cardiovascular endothelium cells against ischemia-reperfusion injury and inhibits the activation of platelet during myocardial ischemia and reperfusion.

Intracoronary thrombosis treated with stent and abciximab in patient with membranous glomerulonephritis

The association of nephrotic syndrome with a hypercoagulable state and vascular thrombosis is well recognized. In all adult series of nephrotics, venous thrombosis are much more common than arterial thrombosis, which has been mainly reported in children. Intracoronary thrombus is among the rarest arterial thromboses. We present a case of acute myocardial infarction in a 39-year-old women with nephrotic syndrome secondary to membranous glomeluronephritis, in which subsequent coronary angiography showed no evidence of atherosclerotic change and thrombotic occlusion in the left main coronary artery which was successfully treated with intracoronary stent and intravenous abciximab.