Intravenous Thrombolysis in Acute Ischemic Stroke After Idarucizumab Reversal of Dabigatran Effect: Analysis of the Cases From Taiwan.

BACKGROUND: Asians with atrial fibrillation carry a higher risk of ischemic stroke than non-Asians even under treatment of nonvitamin K antagonist oral anticoagulants. The purpose of the study was to observe the feasibility of intravenous thrombolytic therapy after administering a reversal agent, idarucizumab, in dabigatran-treated patients with acute ischemic stroke in Taiwan. METHODS: Dabigatran-treated patients with acute ischemic stroke who received intravenous recombinant tissue plasminogen activator (rt-PA) after idarucizumab reversal were enrolled in the retrospective nationwide study. The clinical data, treatment course, and outcomes were recorded. Stroke severity was evaluated using the National Institutes of Health Stroke Scale (NIHSS) score. Any intracerebral hemorrhage (ICH) after rt-PA was detected by neuroimaging studies. RESULTS: Ten dabigatran-treated patients (6 men, mean age 71.10 ± 7.96 years) with acute ischemic stroke were included. Before stroke, the mean CHA2DS2-VASc score was 4.50 ± 1.57 and 8 patients (80%) received dabigatran 110 mg twice daily. All patients were treated with 5 g idarucizumab, following which the activated partial thromboplastin time normalized. Intravenous rt-PA (mean dose .78 mg/kg) was initiated a mean time of 11.11 minutes after idarucizumab infusion. The NIHSS score improved significantly after thrombolysis (16.0 ± 6.67 at admission to 9.38 ± 4.75 at discharge, P = .016). ICH developed in 3 patients (30%). Two of them were asymptomatic and 1 patient suffered from symptomatic ICH leading to mortality. CONCLUSION: Our data reconfirmed the feasibility of intravenous rt-PA for Asian stroke patients after reversal of dabigatran effect with idarucizumab.

Electronegative Low-Density Lipoprotein L5 Induces Adipose Tissue Inflammation Associated With Metabolic Syndrome.

Context: Electronegative low-density lipoprotein (LDL) L5 is a naturally occurring, atherogenic entity found at elevated levels in the plasma of patients with metabolic syndrome (MetS) in the absence of elevated plasma LDL levels. Objective: To investigate the role of L5 in the mechanism of adipose tissue inflammation associated with MetS. Patients/Setting: Plasma LDL isolated from patients with MetS (n = 29) and controls (n = 29) with similar plasma LDL levels was separated into five subfractions, L1 to L5, with increasing electronegativity. Design: We examined the invivo effects of L5 on adipose tissue in mice and the in vitro effects of L5 on adipocytokine signaling and monocytes. Results: Tail-vein injection of human L5 but not L1 into C57BL/6 mice induced the accumulation of F4/80+ and CD11c+ M1 macrophages. The effects of L5 were attenuated in mice deficient for L5's receptor, lectin-like oxidized LDL receptor 1 (LOX-1). L5 but not L1 induced human adipocytes to release inflammatory adipocytokines. Incubating human THP-1 monocytes with LDL-free culture media from L5-treated adipocytes enhanced the migration of monocytes by 300-fold (P < 0.001 vs L1-treated adipocyte media)-effects that were attenuated by LOX-1 neutralizing antibody. Migrated cells were positive for mature macrophage marker PM-2K, indicating the transformation of monocytes into macrophages. The infiltration of M1 macrophages in adipose tissue was also observed in a previously established hamster model of endogenously elevated L5. Conclusions: L5 induces adipose inflammation through LOX-1 by promoting macrophage maturation and infiltration into adipose tissue. Elevated plasma L5 levels may be a novel etiology of adipose tissue inflammation in patients with MetS.

Different Mid-Term Prognostic Predictors of Major Adverse Events in Diabetic and Nondiabetic Peripheral Artery Disease Presenting With Critical Limb Ischemia.

We compared midterm prognostic predictors of peripheral artery disease (PAD) with or without diabetes mellitus (DM) presenting with critical lower limb ischemia (CLI). A total of 172 patients with PAD (109 DM; 63 non-DM) were enrolled. The major adverse events (MAEs) were death or amputation. The diabetic group had a higher MAE rate (39% vs 22%, P = .042) with a mean follow-up duration of 30 ± 19 months. In a multivariate binary logistic regression analysis, revascularization (odds ratio = 0.289, P = .006) and higher serum cholesterol (odds ratio=0.988, P = .027) predicted a lower MAE rate in the DM group. In contrast, the presence of severe chronic kidney disease (stage 4 or 5, odds ratio = 5.238, P = .025) was a positive predictor of MAEs in the nondiabetic group. In conclusion, the prognostic predictors of MAE in diabetic and nondiabetic patients with PAD and CLI were different.

Mesenchymal Stem Cell Derived Exosomes: A New Hope for the Treatment of Cardiovascular Disease?

UNLABELLED: Cardiovascular disease is a major target for numerous experimental stem (progenitor) cell-based therapies. Mesenchymal stem cells (MSCs) from different sources confer regenerative effects in animal models of cardiovascular disease. Some of these investigations have proceeded into phase I and II clinical trials for limb ischemia, heart failure, and acute myocardial infarction. The rationale for MSC therapy is increasingly recognized on a secretion (paracrine) rather than differentiation mechanism. Recently, several groups have demonstrated that the "exosome" is a secreted agent mediating MSC therapeutic efficacy. Unlike cell therapy, exosomes have no risk of aneuploidy, and a lower rate of immune rejection following allogeneic administration. In this short review, we will focus on the potential of using this novel therapeutic modality for the treatment of cardiovascular disease, particularly acute myocardial infarction. KEY WORDS: Cardiovascular disease; Exosome; Mesenchymal.

Histamine2-receptor antagonists are an alternative to proton pump inhibitor in patients receiving clopidogrel.

BACKGROUND & AIMS: Previous observational studies reported that concomitant use of clopidogrel and proton pump inhibitors (PPIs) in patients with prior acute coronary syndrome (ACS) was associated with adverse cardiovascular outcomes. We investigated whether H(2)-receptor antagonist (H(2)RA) is an alternative to PPI in patients with ACS. METHODS: We conducted a population-based retrospective cohort study of 6552 patients in Taiwan discharged for ACS between 2002 and 2005. Patients were divided into 5 cohorts: clopidogrel plus H(2)RA (n = 252), clopidogrel plus PPI (n = 311), clopidogrel alone (n = 5551), H(2)RA alone (n = 235), and PPI alone (n = 203). The primary outcome was rehospitalization for ACS or all-cause mortality within 3 month of rehospitalization. RESULTS: The 1-year cumulative incidence of the primary outcome was 26.8% (95% CI: 21.5%-33.0%) in the clopidogrel plus H(2)RA cohort and 33.2% (95% CI: 27.8%-39.4%) in the clopidogrel plus PPI cohort, compared with 11.6% (95% CI: 10.8%-12.5%) in the clopidogrel alone cohort (P < .0001). No significant difference was observed between the PPI alone cohort (11.0%; 95% CI: 7.1%-16.8%), the H(2)RA alone cohort (11.8%; 95% CI: 8.2%-16.8%), and the clopidogrel alone cohort in terms of the primary outcome. The number needed to harm was 7 with concomitant H(2)RA and 5 with concomitant PPI. On multivariate analysis, concomitant H(2)RA and PPI were independent risk factors predicting adverse outcomes (adjusted hazard ratios, 2.48 and 3.20, respectively; P < .0001). CONCLUSIONS: Concomitant use of clopidogrel and H(2)RA or PPI after hospital discharge for ACS is associated with increased risk of adverse outcomes.

Spontaneous remission of ruptured intramyocardial hematoma detected upon serial multidetector computed tomography.

Intramyocardial hematoma is a rare sequela of percutaneous coronary intervention after acute myocardial infarction. Clinical outcomes of intramyocardial hematoma vary from asymptomatic remission to cardiac death. Close follow-up is imperative. Herein, we report the case of a 69-year-old man who had sustained an acute inferior myocardial infarction. During primary percutaneous coronary intervention to the occluded right coronary artery, an intramyocardial hematoma developed and immediately ruptured into the right ventricle. Because the patient remained hemodynamically stable, a conservative approach was taken. Follow-up with serial multidetector computed tomographic imaging elucidated the course and extent of the hematoma and clearly revealed the healing process. After 1 year, this method of imaging showed complete remission of the hematoma. To the best of our knowledge, this is the 1st use of serial multidetector computed tomography to document the remission of an intramyocardial hematoma that ruptured after complicated percutaneous coronary intervention. We believe that multidetector computed tomography is useful in tracing the natural history of intramyocardial hematomas.

Comprehensive evaluation of ischemic heart disease using MDCT.

OBJECTIVE: Recently MDCT has become widely used for the evaluation of ischemic heart disease, but clinically the evaluation is primarily focused on the coronary artery only. We describe why and how to comprehensively evaluate the cardiac CT scan, including myocardium, motion, viability, valve, and perfusion aspects related to ischemic heart disease. CONCLUSION: Radiologists should be familiar with the protocol design and comprehensive interpretation of cardiac MDCT to provide comprehensive treatment suggestions for the patients.

Use of 40-detector row computed tomography before catheter coronary angiography to select early conservative versus early invasive treatment for patients with low-risk acute coronary syndrome.

OBJECTIVE: Using catheter coronary angiography (CAG) as reference standard, we examined the agreement of 40-detector row computed tomography (MDCT) in triaging patients into the 2 controversial strategies of managing low-risk acute coronary syndrome (ACS). METHODS: Seventy-eight patients with low-risk ACS received both MDCT and CAG. Early invasive strategy was assigned for the patient if there was significant stenosis (> or =50% diameter stenosis) in any of the coronary artery segments with diameter larger than 1.5 mm. The results of MDCT were compared with the CAG for agreement. RESULTS: The overall agreement of the early conservative/early invasive strategy assignment was 92.3%, with kappa value of 0.82 between MDCT and CAG. Only 1 patient needing early invasive strategy was missed by MDCT. CONCLUSION: Forty-detector row computed tomography is reliable in triaging patients into the 2 strategies of managing low-risk ACS.

High glucose impairs early and late endothelial progenitor cells by modifying nitric oxide-related but not oxidative stress-mediated mechanisms.

OBJECTIVE: Endothelial progenitor cells (EPCs) are impaired in diabetes. This study aimed to investigate the direct effects of high glucose on EPCs. RESEARCH DESIGN AND METHODS: Mononuclear cells isolated from healthy subjects were incubated with glucose/mannitol or drugs for EPC study. After 4 days of culture, attached early EPCs appeared. The monolayer late EPCs with cobblestone shape appeared at 2-4 weeks. Various immunofluroscence stainings were used to characterize the early and late EPCs. Senescence assay and the activity of endothelial nitric oxide synthase (eNOS) were determined. Migration and tube formation assay were done to evaluate the capacity for vasculogenesis in late EPCs. RESULTS: Chronic incubation with high glucose but not mannitol (osmotic control) dose-dependently reduced the number and proliferation of early and late EPCs, respectively. High glucose enhanced EPC senescence and impaired the migration and tube formation of late EPCs. High glucose also decreased eNOS, FoxO1, and Akt phosphorylation and bioavailable nitric oxide (NO) in both EPCs. The effects of high glucose could be ameliorated by coincubation with NO donor sodium nitroprusside or p38 mitogen-activated protein kinase inhibitor and deteriorated by eNOS inhibitor or PI3K (phosphatidylinositol 3'-kinase) inhibitor. Antioxidants including vitamin C, N-acetylcysteine-and polyethylene glycol (PEG)-conjugated superoxide dismutase, and PEG-catalase had no effects, whereas pyrrolidine dithiocarbamate, diphenyleneiodonium, apocynin, and rotenone even deteriorated the downregulation of both EPCs. CONCLUSIONS: High glucose impaired the proliferation and function of early and late EPCs. NO donor but not antioxidants reversed the impairments, suggesting the role of NO-related rather than oxidative stress-mediated mechanisms in hyperglycemia-caused EPC downregulation.

Intravenous aminophylline provides no additional renal protection in patient with severe atherosclerotic renal artery stenosis treated by delicate percutaneous renal intervention.

BACKGROUND: Clinical trials on contrast-induced nephropathy (CIN) prevention with different approaches generated various results. In this study, we investigated whether intravenous aminophylline preceding percutaneous transluminal renal artery stenting (PTRS) might provide better renal protection. METHODS: Patients with severe atherosclerotic renal artery stenosis and undergoing PTRS were prospectively studied. Intravenous aminophylline 250 mg was administered 30 min before PTRS. RESULTS: The aminophylline group included 15 patients (mean age, 68+/-4 years) and the case-matched control group consisted of another 15 patients (mean age, 71+/-2 years). After a mean follow-up of 5-6 months, both groups showed similar serum creatinine (1.7+/-0.2 vs. 1.6+/-0.1 mg/dl, P=NS), BUN (20.0+/-3.0 vs. 24.0+/-3.0 mg/dl, P=NS), fall in systolic (-15+/-13 vs. -11+/-3 mm Hg, P=NS) and diastolic BP (-2+/-4 vs. -6+/-5 mm Hg, P=NS). The incidence of post-operative renal deterioration was 6.7% in the study group and none in the control group. CONCLUSION: Pre-treatment intravenous aminophylline provides no additional renal protective effect in delicately practiced PTRS.

Delicate percutaneous renal artery stenting minimizes postoperative renal injury and protects kidney in patients with severe atherosclerotic renal artery stenosis and impaired renal function.

Percutaneous transluminal renal artery stenting (PTRAS) is associated with declining renal function in a non-negligible portion of patients and is inflicted by different mechanisms, including atheroembolism. This study investigated whether delicate PTRAS to reduce atheroembolism might minimize postoperative renal injury and better preserve renal function. Patients undergoing PTRAS performed by experienced interventional cardiologists, applying coronary intervention concepts, techniques, devices and delicacy principles whenever possible, were prospectively studied. A total of 34 patients (29 M/5 F) with impaired renal function (group A, creatinine 2.4 +/- 0.1 mg/dL) and another 20 patients (16 M/4 F) with normal serum creatinine (group B, baseline creatinine 1.2 +/- 0.0 mg/dL) were studied. PTRAS was successfully performed in all but one group A patient. During a 6-month follow-up, systolic and diastolic blood pressure (130 +/- 2 versus 148 +/- 4 mmHg, P = 0.001 and 70 +/- 2 versus 78 +/- 3 mmHg, P = 0.006) and serum creatinine (2.1 +/- 0.1 versus 2.4 +/- 0.1 mg/dL, P < 0.001) were all significantly lowered in group A patients. Using a 20% change cut-off value, renal function improved in eight (24%), remained unchanged in 24 patients (73%), and deteriorated in only one patient (3%). The corresponding alterations in blood pressure and renal function were insignificant in group B patients. Patients with bilateral involvement (eleven patients) also had significantly lowered serum creatinine on follow-up. In conclusion, delicately practiced PTRAS can reduce the rate of postprocedural renal deterioration in patients with impaired renal function, and should be adopted in every renal intervention.