A Novel Multiple Risk Score Model for Prediction of Long-Term Ischemic Risk in Patients With Coronary Artery Disease Undergoing Percutaneous Coronary Intervention: Insights From the I-LOVE-IT 2 Trial

Backgrounds: A plug-and-play standardized algorithm to identify the ischemic risk in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) could play a valuable step to help a wide spectrum of clinic workers. This study intended to investigate the ability to use the accumulation of multiple clinical routine risk scores to predict long-term ischemic events in patients with CAD undergoing PCI.Methods: This was a secondary analysis of the I-LOVE-IT 2 (Evaluate Safety and Effectiveness of the Tivoli drug-eluting stent (DES) and the Firebird DES for Treatment of Coronary Revascularization) trial, which was a prospective, multicenter, and randomized study. The Global Registry for Acute Coronary Events (GRACE), baseline Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX), residual SYNTAX, and age, creatinine, and ejection fraction (ACEF) score were calculated in all patients. Risk stratification was based on the number of these four scores that met the established thresholds for the ischemic risk. The primary end point was ischemic events at 48 months, defined as the composite of cardiac death, nonfatal myocardial infarction, stroke, or definite/probable stent thrombosis (ST).Results: The 48-month ischemic events had a significant trend for higher event rates (from 6.61 to 16.93%) with an incremental number of risk scores presenting the higher ischemic risk from 0 to ≥3 (p trend < 0.001). In addition, the categories were associated with increased risk for all components of ischemic events, including cardiac death (from 1.36 to 3.15%), myocardial infarction (MI) (from 3.31 to 9.84%), stroke (3.31 to 6.10%), definite/probable ST (from 0.58 to 1.97%), and all-cause mortality (from 2.14 to 6.30%) (all p trend < 0.05). The net reclassification index after combined with four risk scores was 12.5% (5.3–20.0%), 9.4% (2.0–16.8%), 12.1% (4.5–19.7%), and 10.7% (3.3–18.1%), which offered statistically significant improvement in the performance, compared with SYNTAX, residual SYNTAX, ACEF, and GRACE score, respectively.Conclusion: The novel multiple risk score model was significantly associated with the risk of long-term ischemic events in these patients with an increment of scores. A meaningful improvement to predict adverse outcomes when multiple risk scores were applied to risk stratification.

Balloon expandable Stent utility for early Secondary Prevention of new Cerebral Ischemic events Caused by Intracranial Atherosclerotic Stenosis. Technical Nuances

Objective: Recurrent cerebral ischemic events are estimated to appear in between 12-15% of symptomatic intracranial atherosclerotic disease (ICAD), regardless of the use of leading pharmacological therapies. Balloon expandable stent (balloon mounted coronary stent) could represent a feasible alternative in this disease’s treatment. This study pretends to report the balloon-expandable placement experience in our center. Materials and Methods: A unicentric retrospective study dated between September 2009 and March 2018 was conducted. Patients previously diagnosed with ICAD and symptomatic stenosis treated with balloon-expandable stent were included. Clinical features, morbidity, mortality, short and long-term evolution, and pre-and post-treatment angiographic features were analyzed, as well as a mean 8 years-period follow-up. Data are presented as means, frequencies, and percentages for categorical variables, and ranks for continuous variables. Statistical analysis was carried by IBM SPSS Statistics Base V22.0 (IBM Corporation, Mexico). A Wilcoxon Signed-rank test statistical analysis was performed. Statistical significance was considered when a p-value lesser than 0.05 was measured for every result. Results: A total of 6 patients with 7 affected vessels were treated, with an average age of 62.7 years. Affected and treated vessels were located in the Internal Carotid Artery (ICA) segment in 42.9%, Vertebral Artery (VA) V4 segment in 14.3%, Middle Cerebral Artery (MCA) M1 segment in 28.5%, and Posterior Cerebral Artery (PCA) P1 segment in 14.3%. The incidence of peri-operatory thrombotic events was 0%. Intracranial hemorrhage presented in 0% of cases. Recurrent ischemic or thrombotic events were not reported in a 97-months mean follow-up. 71.4% of patients scored ≤2 in the modified Rankin Score (mRS) pre-treatment, in a 90 day and 12-month follow-up. 100% presented a favorable evolution with mRS ≤2. Restenosis cases were not reported in radiologic control and retreatment was not needed in a 97-month mean follow-up. Conclusions: This study suggests that balloon-expandable stent therapy with some technical endovascular variants for its navigation and placement could be a safe and effective alternative in the treatment of ICAD as a means of cerebral ischemic event early secondary prevention. We propose to consider not to limit endovascular treatment exclusively to those symptomatic ICAD patients refractory to medical-exclusive treatment, as a means to reduce the risk of presenting a new neurological deficit. Further expanded clinical trials are needed to confirm these findings and the advantage of this kind of stents against other kinds reported in the literature.

Anti-apoptotic effects of 2-pyrrolidone derivatives in cerebral ischemia

INTRODUCTION: Uncontrolled course of apoptosis reactions underlies a wide range of pathological processes, including ischemic events. AIM: To evaluate the anti-apoptotic properties of some racetams in experimental brain ischemia in rats. MATERIALS AND METHODS: Cerebral ischemia was modeled in Wistar rats by irreversible occlusion of the middle cerebral artery. The test-compounds and the reference drug piracetam were administered per os at a dose of 250 mg/kg. After 72 hours of the ischemic period, the activity of apoptotic systems in the brain tissue was evaluated by determining the concentration of the apoptotic-inducing factor (AIF), caspase-3, ionized calcium, the latent opening time of the mitochondrial transition permeability pore and the zone of brain necrosis. RESULTS: The study showed that the use of the studied compounds contributed to a decrease in the intensity of reactions, both caspase-dependent and caspase-independent apoptosis, which was reflected in a decrease in the concentration of AIF and caspase-3 by 32.4% (p < 0.05); 34.6% (p < 0.05); 31.1% (p < 0.05), and 41.9% (p < 0.05); 39.1% (p < 0.05); 34.5% (p < 0.05) when PirPr, PirAc and PirBut were administered, respectively. Also, the use of the studied substances led to an increase in the latent period of opening the mitochondrial transition permeability pore, a decrease in the concentration of intracellular calcium and the zone of brain necrosis. At the same time, the pharmacological effect of the administration of the compound PirAc exceeded the effect of piracetam and other test substances. CONCLUSIONS: Based on the results obtained, it can be assumed that the studied racetams have neuroprotective action, realized through suppression of the reactions of apoptosis.

Neutrophils and Platelets: Immune Soldiers Fighting Together in Stroke Pathophysiology

Neutrophils and platelets exhibit a diverse repertoire of functions in thromboinflammatory conditions such as stroke. Most cerebral ischemic events result from longstanding chronic inflammation secondary to underlying pathogenic conditions, e.g., hypertension, diabetes mellitus, obstructive sleep apnea, coronary artery disease, atrial fibrillation, morbid obesity, dyslipidemia, and sickle cell disease. Neutrophils can enable, as well as resolve, cerebrovascular inflammation via many effector functions including neutrophil extracellular traps, serine proteases and reactive oxygen species, and pro-resolving endogenous molecules such as Annexin A1. Like neutrophils, platelets also engage in pro- as well as anti-inflammatory roles in regulating cerebrovascular inflammation. These anucleated cells are at the core of stroke pathogenesis and can trigger an ischemic event via adherence to the hypoxic cerebral endothelial cells culminating in aggregation and clot formation. In this article, we review and highlight the evolving role of neutrophils and platelets in ischemic stroke and discuss ongoing preclinical and clinical strategies that may produce viable therapeutics for prevention and management of stroke.

Ischemic Events Occur Early in Patients Undergoing Percutaneous Coronary Intervention and Are Reduced With Cangrelor: Findings From CHAMPION PHOENIX

Background: Thrombotic events are reduced with cangrelor, an intravenous P2Y 12 inhibitor. We sought to characterize the timing, number, and type of early events (within 2 hours of randomization) in CHAMPION PHOENIX (A Clinical Trial Comparing Cangrelor to Clopidogrel Standard of Care Therapy in Subjects Who Require Percutaneous Coronary Intervention). Methods: CHAMPION PHOENIX was a double-blind, placebo-controlled trial that randomized patients undergoing percutaneous coronary intervention to cangrelor or clopidogrel. For this analysis, we evaluated the efficacy of cangrelor in the first 2 hours postrandomization with regards to the primary end point (death, myocardial infarction, ischemia-driven revascularization, or stent thrombosis). Sensitivity analyses were performed evaluating a secondary, post hoc end point (death, Society of Coronary Angiography and Intervention myocardial infarction, ischemia-driven revascularization, or Academic Research Consortium definite stent thrombosis). Results: The majority of events (63%) that occurred in the trial occurred within 2 hours of randomization. The most common early event was myocardial infarction; next were stent thrombosis, ischemia driven revascularization, and death. In the first 2 hours after randomization, cangrelor significantly decreased the primary composite end point compared with clopidogrel (4.1% versus 5.4%; hazard ratio, 0.76 [95% CI, 0.64–0.90], P =0.002). Similar findings were seen for the composite end point of death, Society of Coronary Angiography and Intervention myocardial infarction, ischemia-driven revascularization, or Academic Research Consortium stent thrombosis at 2 hours (0.9% versus 1.6%; hazard ratio, 0.57 [95% CI, 0.40–0.80], P =0.001). Between 2 and 48 hours, there was no difference in the primary composite end point (0.6% versus 0.5%; odds ratio, 1.17 [95% CI, 0.71–1.93]; P =0.53). Early (≤2 hours of randomization) GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) moderate or severe bleeding events were infrequent, and there was no significant difference with cangrelor compared with clopidogrel (0.2% [n=10] versus 0.1% [n=4]; adjusted odds ratio, 1.41 [95% CI, 0.37–5.40]; P =0.62). Conclusions: The reductions in ischemic events and overall efficacy seen with cangrelor in CHAMPION PHOENIX occurred early and during the period of time in which patients were being actively treated with cangrelor. These findings provide evidence that supports the importance of potent platelet inhibition during percutaneous coronary intervention. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01156571.

Pipeline for the treatment of distal cerebral circulation aneurysms: A multicenter study focusing on periprocedural Complications

Background and Aim Distal cerebral circulation aneurysms (DCCAs) remain treatment challenges for neurointervention. The off-label use of the pipeline embolization device (PED) for these aneurysms remains controversial. This study aimed to evaluate the safety and efficacy of PED for DCCAs in a multicenter cohort of patients. Methods Between March 2016 and June 2021, we retrospectively analyzed the neurointerventional data on the clinical and radiological records of all patients undergoing PED treatment of DCCAs at three medical centers. Results A total of 53 consecutive patients with 53 DCCAs were treated with PED. The mean aneurysm size was 12.3 ± 5.7 mm. In total, 75.4% (40/53) were fusiform and 24.5% (13/53) were saccular. Of these, 17.0% (9/53) were recurrent aneurysms that were previously treated with endovascular or microsurgical approaches. The technical success rate was 100%, among which 81.1% (43/53) procedures were completed with a single PED, and the rest (10/53, 18.8%) required telescoping with two devices. Angiographic follow-up data were available for 51 patients, with a median follow-up time of 12 months. At the latest follow-up, 46/51 (90.2%) aneurysms showed complete obliteration, and 4/51 (7.8%) showed reduced filling. Periprocedural complications such as hemorrhage were observed in two patients with MCA aneurysms (3.8%, 2/53), and ischemic events occurred in six patients (11.3%, 6/53). The overall mortality and morbidity rates were 7% (4/53). Conclusions PED is a viable option for treating DCCAs, especially for recurrent aneurysms. Coverage of bifurcation branches and perforator may increase the risk of complications.

Comparison of Carotid Atherosclerotic Plaque Characteristics between Symptomatic Patients with Transient Ischemic Attack and Stroke using High-Resolution Magnetic Resonance Imaging

Background:This study aimed to compare the characteristics of carotid plaques between patients with transient ischemic attack (TIA) and ischemic stroke using magnetic resonance (MR) imaging.Methods：Patients with a recent ischemic stroke or TIA who exhibited atherosclerotic plaques of carotid arteries in the symptomatic sides determined by MR vessel wall imaging were recruited. The plaque morphology and compositions including intraplaque hemorrhage (IPH), lipid-rich necrotic-core (LRNC) and calcification were compared between TIA and stroke patients. Logistic regression was performed to relate the plaque characteristics to the types of ischemic events.Results:A total of 270 patients with TIA or ischemic stroke were recruited. Stroke patients had significantly higher prevalence of diabetes (42.2% vs. 28.2%, p=0.021), greater mean wall area (35.1 ± 10.1 mm2 vs. 32.0 ± 7.7 mm2, p = 0.004), mean wall thickness (1.3 ± 0.2 mm vs. 1.2 ± 0.2 mm, p=0.001), maximum normalized wall index (NWI)(63.9% ± 6.0% vs. 62.2% ± 5.9%, p=0.023) and %volume of LRNC (9.7%± 8.2% vs. 7.4% ±7.9%, p=0.025) in carotid arteries compared to those with TIA. After adjusted for clinical factors, above characteristics of carotid arteries were significantly associated with the type of ischemic events. After further adjusted for maximum NWI, this association remained statistically significant (OR, 1.41; CI, 1.01-1.96; p=0.041).Conclusions:Ischemic stroke patients had larger plaque burden and greater proportion of LRNC in carotid plaques compared to those with TIA. This study suggests that ischemic stroke patients had more vulnerable plaques compared to those with TIA.

Multifocal atherosclerosis: focus on the prevention of ischemic events

In patients with atherosclerotic lesions of two or more systems or multifocal atherosclerosis (MFA), the risks of ischemic events are extremely high. MFA leads not only to cardiovascular outcomes, but also to a decrease in the patient’s quality of life, life expectancy, and in most cases to disability. The prevalence of this pathology and the importance of preventing adverse outcomes are often underestimated. This literature review examines the problem of MFA in the context of key studies on the prevalence, course of multivessel disease and the reduction of the risk of cardiovascular events in this group of patients, with an emphasis on antiplatelet and anticoagulant therapy.