The effect of direct oral anticoagulants on blood protein C activity

[Aim] In this study, the effect of direct oral anticoagulants (DOACs) on protein C (PC) activity was examined using several measuring reagents. [Materials and Methods] In total, 90 patients (60 male and ３0 female) with nonvalvular atrial fibrillation or venous thromboembolism (VTE) who were on anticoagulation therapy with DOACs (rivaroxaban, apixaban, or edoxaban) were studied. The plasma levels of PC activity were measured by means of a clotting assay and chromogenic substrate assay, using three reagents for each type of assay. [Result] Prothrombin time (PT) and activated partial thromboplastin time (APTT) were significantly prolonged in a dose-dependent manner in patients who were taking rivaroxaban or edoxaban. PC activity, as measured by all three reagents using the clotting assay, was influenced only by rivaroxaban, indicating an increase in PC activity in a dose-dependent manner. Apixaban did not have any influence on the measurements made using all three reagents in the clotting assay. On the other hand, none of the three FXa inhibitors had any influence on PC activity when it was measured using the three reagents in the chromogenic substrate assay. Plasma samples were collected before, as well as two and four to eight weeks after rivaroxaban administration in seven patients with AF or VTE sequentially. In all three regents using the clotting assay, plasma levels of PC activity had increased after the administration of rivaroxaban. On the other hand, all three regents using the chromogenic assay had very little influence on PC activity after the administration of rivaroxaban. [Conclusion] The inhibitory effects of the different types of DOACs on clotting activity interfere with clotting test measurement systems in patients receiving DOAC therapy. When measuring PC activity while the patient is taking rivaroxaban or edoxaban, it is necessary to use the chromogenic substrate assay to avoid false highs. Moreover, collecting specimens when blood levels of drugs are low, e.g. during the trough phase, whenever possible, would be one way to minimize interference

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Inflation Pressure in Side Branch during Modified Jailed Balloon Technique Does Not Affect Side Branch Outcomes

Objectives. This study aimed to investigate the optimal jailed balloon inflation in the side branch during the modified jailed balloon technique for bifurcated lesions. Background. The modified jailed balloon technique is one of the effective techniques to minimize the emergence of side branch (SB) compromise by preventing plaque or carina shifting during a single stent strategy in the main vessel with provisional SB treatment. However, there are no detailed studies on the method of optimal jailed balloon inflation. Methods. We analyzed 51 consecutive patients who underwent percutaneous coronary intervention (PCI) for bifurcated lesions with a modified jailed balloon technique between September 2018 and December 2020. These 51 patients were divided into two groups according to the magnitude of inflation pressure of the jailed balloon: a higher pressure (HP) group and lower pressure (LP) group. Results. No significant differences in procedural outcomes were observed between the two groups. The findings of SB compromise were relatively common with our procedure (30.0% in the HP group; 33.3% in the LP group). The patterns of SB compromise such as dissection or stenosis increase were observed at similar frequencies between them. In particular, SB dissection was noted in the SB lesion with some plaque burden, irrespective of the magnitude of the jailed balloon inflation pressure. Univariate analysis showed that calcification in the main vessel and SB lesion length was significantly associated with SB compromise. Finally, all PCI procedures were successfully completed without any provisional stent deployment in SB. Conclusions. We speculate that lesion characteristics rather than the PCI procedural factors may be critical determinants to cause SB compromise

Percutaneous Closure Based on Physiological Assessment of an Arteriovenous Fistula in a Patient With Chronic Limb Threatening Ischaemia

Introduction: An arteriovenous fistula (AVF) is a potential complication of endovascular therapy (EVT). Arteriovenous fistula steal syndrome sometimes leads to severe limb ischaemia; however, assessment of peripheral perfusion in AVF has not yet been established. Report: A 90 year old woman diagnosed with chronic limb threatening ischaemia underwent EVT. However, subintimal angioplasty of infrapopliteal lesions resulted in AVF formation in the posterior tibial artery (PTA). Revascularisation of the anterior tibial artery and PTA was performed, but severe AVF steal syndrome persisted and wound healing was delayed. An attempt to physiologically assess the effects of AVF closure and perform an AVF closing manoeuvre, if necessary, was performed. The physiological assessment was performed by laser Doppler flowmetry (LDF) and blood flow was temporarily blocked via the AVF at the distal PTA using a 6 F guiding extension catheter. A significant increase in blood flow was observed in the perfused area of the plantar artery. Coil embolisation and covered stent implantation in the PTA completely closed the AVF. During the procedure, peripheral perfusion with LDF gradually increased in the heel and fifth toe. After AVF closure, the skin perfusion pressure values increased significantly, wound healing was accelerated, and complete healing was achieved. Discussion: Laser Doppler flowmetry measurements under simulated AVF closure using a guiding extension catheter may be useful for the physiological assessment of peripheral perfusion before percutaneous AVF closure

Emphysematous changes as red flag signs preceding rapidly progressive infectious aortic disease: two case reports

Abstract Background Infectious aortic disease is a rare and fatal disease, that requires the appropriate intervention. An accurate diagnosis should be promptly established. However, this is difficult because the clinical manifestations of this disease vary and are non-specific. Case presentation (CASE 1) An 87-year-old male, presenting with generalized malaise and weight loss, was admitted for further examination. A chest computed tomography (CT) showed mediastinal emphysema. Empirical intravenous antibiotics were administered to address the non-specific infectious findings in the laboratory data. The treatment was effective, and the patient fully recovered. However, he was in shock due to aortic rupture and marked pseudo aneurysmal formation around the aortic arch day 25 of hospitalization. An emergency total aortic arch replacement was performed, and the patient was discharged. (CASE 2) An 82-year-old male who had undergone Y-graft replacement in the abdominal aorta 15 years previously was admitted due to general malaise and anorexia. Abdominal CT revealed emphysematous changes adjacent to the abdominal aorta. The patient responded favorably to empirical treatment with intravenous antibiotics and was discharged 19 days after admission. Four days after discharge, the patient went into cardiac arrest after an episode of hematemesis. Abdominal CT revealed an enlarged stomach and duodenum, filled with massive high-density contents proximal to the abdominal aorta. He died of hemorrhagic shock despite cardiopulmonary resuscitation. Conclusions Although emphysematous changes are rare, they are red flag signs during the early stage of infectious aortic disease. Thus, physicians should remain vigilant for this kind of critical sign