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Background: Antiplatelet drugs are widely used in the prevention and treatment of arterial thrombotic diseases but are associated with increased risk of bleeding. Alginate oligosaccharide (AOS), a biodegradable polymer extracted from macroalgae, has been shown to inhibit phosphorylation of mitogen-activated protein kinases, which, in turn, are critical for platelet activation. The present study aimed to examine whether AOS possesses antiplatelet and antithrombotic activity, and if so, the underlying mechanisms. Methods: We detected the effects of AOS on human platelet aggregation and adenosine triphosphate (ATP) release induced by thrombin and collagen, as well as platelet clot retraction and spreading. FeCl₃-injured mouse mesenteric arteriole thrombosis was evaluated in adult C57BL/6 mice pretreated with either AOS (200 mg/kg/d through gavage for 7 consecutive days) or clopidogrel (30 mg/kg/d for 2 days). The impact of AOS on bleeding time in comparison to clopidogrel was also analyzed. Results: At a range of 0.1–1.0 mg/mL, AOS concentration dependently inhibited human platelet aggregation and ATP release induced by thrombin and collagen, as well as platelet clot retraction and spreading. The final occlusion time injured by FeCl₃in mice pretreated with AOS was significantly increased (from 11.9 ± 0.9 min in vehicle control to 17.6 ± 1.0 min, P < 0.01), as well as the first occlusion time (from 4.4 ± 0.5 min in vehicle control to 7.6 ± 0.7 min, P < 0.01). Bleeding time on tail snip was 534 ± 62 s in vehicle control, 581 ± 60 s in mice with AOS pretreatment (P = 0.59 vs. control), and 1260 ± 83 s in mice receiving clopidogrel pretreatment (P < 0.01 vs. control). Preliminary mechanistic investigation using human platelets showed a decreased level of phosphorylated MAP kinases (i.e., p38, Erk1/2, and JNK) by AOS. Conclusions: AOS has antiplatelet and antithrombotic activity, with minimal impact on bleeding time.

A 76-year-old woman presented with non-ST-elevation myocardial infarction. Platelet count was 10×10⁹/L. Bone marrow cytology and platelet antibody testing 9 months earlier suggested refractory immune thrombocytopenia (unresponsive to glucocorticoid and γ-globulin). The patient stabilized after treatments that included clopidogrel, statin, nitrate, and conventional anti-heart failure drugs, but heart failure persisted. Nine days later, angiography revealed 90% occlusion in the left anterior descending artery, and the patient received a zotarolimus-eluting stent. Upon discharge from the hospital, the patient started to receive clopidogrel, statin, β-blocker, and spironolactone. The patient remained free from the symptoms and reported no signs of bleeding for the next 8 months until she was readmitted for pneumonia and heart failure. Platelet count at this time was 2×10⁹/L. Clopidogrel was discontinued. Ginkgo leaf tablets (an herbal medication with reported activity against platelet aggregation) were initiated. Subsequent follow-up visits were unremarkable, until 16 months after percutaneous coronary intervention, when platelet count decreased to 1×10⁹/L. Ginkgo leaf tablet was discontinued. In summary, the evidence supporting the efficacy of clopidogrel at shorter than the recommended 12 months is anecdotal, but the need to adjustment dual antiplatelet therapy in patients with very low platelet count is solid.

The early trials of fractional flow reserve (FFR), such as the Deferral versus Performance of Percutaneous Transluminal Coronary Angioplasty in Patients Without Documented Ischaemia, FFR versus angiography for multivessel evaluation (FAME), and FAME 2 trials, established the role of FFR in the practice of interventional cardiology. These trials led proponents of FFR to propose making FFR a routine procedure before percutaneous coronary intervention (PCI) and to give preference to PCI over optimal medical therapy (OMT) in those with FFR-positive coronary stenoses. Follow-up results of these trials have given more insights. Some of the benefits of FFR-guided strategy over angiography-guided strategy disappeared over time, and beyond revascularization, the FFR strategy did not show benefit over OMT when considering death and myocardial infarction as endpoints. The FUnctional Testing Underlying Coronary REvascularization trial did not demonstrate the superiority of the FFR-guided strategy over angiography-guided strategy. The ORBITA and the ISHEMIA trials gave strength to the lifestyle modification and OMT approach in stable ischemic heart disease patients with moderate-to-severe ischemia. The role of FFR has to be defined in light of the evolving clinical advances in medicine and new evidence. An in-depth review of all current evidence provides no compelling evidence for the routine use of FFR in cardiac interventions. However, FFR can play a role in coronary stenoses where there is uncertainty in the hemodynamic impact of the lesions.

Purpose: The purpose of the study was to investigate the diagnostic performance of instantaneous wave-free ratio (iFR) based on coronary computed tomography (CT) angiography (CCTA) (iFRCT) for a myocardial bridge (MB). Materials and Methods: One hundred and fourteen patients with 115 MBs from 9 Chinese medical centers were prospectively included in this study. All patients underwent CCTA and subsequent invasive coronary angiography with fractional flow reserve (FFR). iFRCTs were measured at 2–4 cm distal to the lesions. Diagnostic performance of iFRCT was assessed using Bland–Altman analysis with invasive FFR as the reference in the entire sample, as well as in subgroups based on MB depth and length. Results: iFRCT has 0.90 sensitivity (95% confidence interval: 0.75–0.97), 0.73 specificity (0.62–0.83), and 0.79 accuracy (0.70–0.86) in the overall analysis. None of the three measures (sensitivity, specificity, and accuracy) differed significantly between superficial (≤2 mm) and deep MB, short (≤30 mm) and long MB, or low (<70% diameter occlusion) and high stenosis (P > 0.05 for all). However, positive predictive value was lower in the low stenosis (<70%) group (0.37 [0.20–0.58] vs. 0.90 [0.72–0.97] in the high stenosis group, P < 0.001). Negative predictive value, in contrast, was higher in the low stenosis group (0.98 [0.87–1.00] vs. 0.75 [0.43–0.93], P = 0.024). The Bland–Altman analysis showed a slight difference between iFRCT and invasive FFR (0.04 in the overall analysis and all subgroup analyses, with an exception of 0.05 in the long MB subgroup). Conclusion: iFRCT has a high diagnostic performance in detecting MB related lesion-specific ischemia.

We can use several noninvasive cardiac imaging modalities in the diagnosis of coronary artery disease (CAD), and we have investigated these technologies in many clinical trials. Some have already become regular examinations in the assessment of CAD among large-scale hospitals. We can detect not only coronary artery anatomic stenosis but also functional myocardial ischemia according to the information provided by these methods. Based on the evaluation of versatile noninvasive cardiac imaging modalities, risk stratification and treatment management help improve the prognosis of patients with CAD. In this review, we summarize these techniques in the evaluation of myocardial ischemia in terms of principles, evidence, advantages, and limitations.

Online since 8^th January 2018