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Journal of the American Heart... Jun 2024Cytochrome P450 2C19 (CYP2C19) intermediate and poor metabolizer patients exhibit diminished clopidogrel clinical effectiveness after percutaneous coronary intervention...
BACKGROUND
Cytochrome P450 2C19 (CYP2C19) intermediate and poor metabolizer patients exhibit diminished clopidogrel clinical effectiveness after percutaneous coronary intervention (PCI). However, outcome studies to date have lacked racial diversity. Thus, the impact of genotype on cardiovascular outcomes in patients treated with clopidogrel who identify as Black or African American remains unclear.
METHODS AND RESULTS
Adults among 5 institutions who self-identified as Black or African American, underwent PCI and clinical genotyping, and were treated with clopidogrel were included. Data were abstracted from health records. Major atherothrombotic (composite of death, myocardial infarction, ischemic stroke, stent thrombosis, or revascularization for unstable angina) and bleeding event rates within 1 year after PCI were compared across CYP2C19 metabolizer groups using multivariable Cox regression adjusted for potential confounders and baseline variables meeting a threshold of <0.10. The population included 567 Black patients treated with clopidogrel (median age, 62 years; 46% women; 70% with an acute coronary syndrome indication for PCI). Major atherothrombotic events rates were significantly higher among clopidogrel-treated intermediate and poor metabolizers (24 of 125 [19.2%]) versus patients treated with clopidogrel without a no function allele (43 of 442 [9.7%]; 35.1 versus 15.9 events per 100 person-years; adjusted hazard ratio, 2.00 [95% CI, 1.20-3.33], =0.008). Bleeding event rates were low overall (23 of 567 [4.1%]) and did not differ among the metabolizer groups.
CONCLUSIONS
Black patients with CYP2C19 intermediate and poor metabolizer phenotypes who are treated with clopidogrel exhibit increased risk of adverse cardiovascular outcomes after PCI in a real-world clinical setting. Bleeding outcomes should be interpreted cautiously. Prospective studies are needed to determine whether genotype-guided use of prasugrel or ticagrelor in intermediate and poor metabolizers improves outcomes in Black patients undergoing PCI.
Topics: Aged; Female; Humans; Male; Middle Aged; Acute Coronary Syndrome; Black or African American; Clopidogrel; Coronary Artery Disease; Cytochrome P-450 CYP2C19; Genotype; Hemorrhage; Percutaneous Coronary Intervention; Pharmacogenomic Variants; Platelet Aggregation Inhibitors; Retrospective Studies; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 38874073
DOI: 10.1161/JAHA.123.033791 -
Journal of Vascular Surgery Cases and... Aug 2024We present a rare case of eosinophilic granulomatosis with polyangiitis (EGPA), involving a 26-year-old woman with a history of asthma and nasal polyps. The patient...
We present a rare case of eosinophilic granulomatosis with polyangiitis (EGPA), involving a 26-year-old woman with a history of asthma and nasal polyps. The patient presented with acute aortoiliac thrombosis and mitral insufficiency, which was successfully treated with thrombolysis, aortic thromboendarterectomy, and valve replacement. Peripheral hypereosinophilia with eosinophilic infiltration of the heart led to the diagnosis of antineutrophilic cytoplasmic antibody-negative EGPA. Treatment with prednisone and mepolizumab was started, resulting in a positive outcome. This case showcases an unusual manifestation of EGPA with large size vessel involvement and requiring surgical and pharmacological treatment. It also highlights the importance of early detection for timely intervention and an improved prognosis.
PubMed: 38873328
DOI: 10.1016/j.jvscit.2024.101515 -
Frontiers in Cardiovascular Medicine 2024
PubMed: 38873268
DOI: 10.3389/fcvm.2024.1432580 -
Frontiers in Cardiovascular Medicine 2024The left subclavian artery (LSA) can be intentionally covered by a stent graft to acquire adequate landing zones for a proximal entry tear near the LSA during thoracic...
BACKGROUND
The left subclavian artery (LSA) can be intentionally covered by a stent graft to acquire adequate landing zones for a proximal entry tear near the LSA during thoracic endovascular aortic repair (TEVAR). The Castor single-branched stent graft is designed to treat type B aortic dissection (TBAD) to retain the LSA during TEVAR. This study investigates clinical outcomes, aortic remodeling, and abdominal aortic perfusion patterns after TEVAR with the novel Castor device.
METHODS
From November 2020 to June 2023, 29 patients with TBAD involving the LSA were treated with the Castor single-branched stent graft. In-hospital clinical outcome and aortic computed tomography angiography (CTA) data were analyzed. CTA was performed preoperatively and at follow-up to observe stent morphology; branch patency; endoleak; change in true lumen (TL), false lumen (FL), and transaortic diameters; and abdominal aortic branch perfusion pattern.
RESULTS
The technical success rate was 96.6%. One failure was that the branch section did not completely enter the LSA and the main body migrated distally. No in-hospital mortality, paraplegia, or stroke occurred. During follow-up, one type Ib endoleak, four distal new entry tears, and one recurrent type A dissection arose from a new entry tear at the ascending aorta, no stent migration was observed, and the branch patency rate was 100%. At the thoracic aorta, TL diameters significantly increased, FL diameters markedly decreased, and FL was partially or completely thrombosed in most patients at follow-up. At the abdominal aorta, we observed 33.3% of TL growth and 66.7% of TL stabilization or shrinkage. The initial TL ratio at iliac bifurcation negatively predicted abdominal TL growth after TEVAR with a cutoff of 21.0%. Of the 102 abdominal aortic branches, 94.1% of the branches showed no change in perfusion pattern, 3.9% of the branches had an increased TL perfusion, and 2.0% of the branches had an increased FL contribution.
CONCLUSION
The Castor unibody single-branched stent graft offers an efficient endovascular treatment for TBAD involving the LSA. TEVAR with the Castor device effectively induced thoracic FL thrombosis and thoracic TL enlargement and resulted in abdominal TL growth when the initial TL ratio at iliac bifurcation is less than 21.0%. Abdominal aortic branch perfusion patterns remain relatively stable after TEVAR with the Castor stent graft.
PubMed: 38873267
DOI: 10.3389/fcvm.2024.1370908 -
Frontiers in Cardiovascular Medicine 2024
PubMed: 38873263
DOI: 10.3389/fcvm.2024.1433858 -
Journal of Neuroinflammation Jun 2024Activation of the kallikrein-kinin system promotes vascular leakage, inflammation, and neurodegeneration in ischemic stroke. Inhibition of plasma kallikrein (PK) - a key...
Activation of the kallikrein-kinin system promotes vascular leakage, inflammation, and neurodegeneration in ischemic stroke. Inhibition of plasma kallikrein (PK) - a key component of the KKS - in the acute phase of ischemic stroke has been reported to reduce thrombosis, inflammation, and damage to the blood-brain barrier. However, the role of PK during the recovery phase after cerebral ischemia is unknown. To this end, we evaluated the effect of subacute PK inhibition starting from day 3 on the recovery process after transient middle artery occlusion (tMCAO). Our study demonstrated a protective effect of PK inhibition by reducing infarct volume and improving functional outcome at day 7 after tMCAO. In addition, we observed reduced thrombus formation in cerebral microvessels, fewer infiltrated immune cells, and an improvement in blood-brain barrier integrity. This protective effect was facilitated by promoting tight junction reintegration, reducing detrimental matrix metalloproteinases, and upregulating regenerative angiogenic markers. Our findings suggest that PK inhibition in the subacute phase might be a promising approach to accelerate the post-stroke recovery process.
Topics: Animals; Recovery of Function; Male; Plasma Kallikrein; Mice; Mice, Inbred C57BL; Infarction, Middle Cerebral Artery; Blood-Brain Barrier; Stroke; Thrombosis; Ischemic Stroke; Inflammation
PubMed: 38872149
DOI: 10.1186/s12974-024-03149-w -
Tuberkuloz Ve Toraks Jun 2024This study explores the impact of vascular diameters on mortality risk in Coronavirus disease-2019 (COVID-19) patients. COVID-19, caused by severe acute respiratory...
INTRODUCTION
This study explores the impact of vascular diameters on mortality risk in Coronavirus disease-2019 (COVID-19) patients. COVID-19, caused by severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2), presents diverse clinical manifestations and is associated with thrombosis.
MATERIALS AND METHODS
In this study, we retrospectively examined the data of patients who were hospitalized and treated in our hospital between September 1, 2020, and November 30, 2020, and whose COVID-19 diagnosis was confirmed by reverse transcriptase polymerase chain reaction (RT-PCR). The diameters of the ascending aorta, main pulmonary artery, and right and left pulmonary arteries were measured from the chest computed tomography (CT) scans taken at the time of admission. The aim of the study was to investigate the impact of vascular diameters on the course of the disease.
RESULT
Of 1.705 patients, 840 were eligible for the study. We concluded that 36 of the patients (4.3%) died, and among the non-survivors patients, 12 (33.3%) were females, and 24 (66.7%) were males. Hospitalization duration was 7.1 ± 3.1 vs. 6.1 ± 2 days (p= 0.004) in surviving and non-surviving patients respectively. On the other hand, we found the mean diameters of the right pulmonary artery in the chest CT of patients to be 2.17 ± 0.35 vs. 2.44 ± 0.29 cm in survivors and non-survivors, respectively (p< 0.001). In addition, we found the mean diameters of the left pulmonary artery 2.12 ± 0.32 vs. 2.34 ± 0.28 cm in survivors and non-survivors, respectively (p< 0.001). Mean diameters of the ascending aorta were 3.53 ± 0.46 vs. 3.72 ± 0.34 cm in survivors and non-survivors, respectively (p= 0.017).
CONCLUSIONS
The study underscores the potential prognostic value of vascular diameters, especially in the ascending aorta and main pulmonary artery, as indicators of mortality risk in COVID-19 patients. The association between vascular dilation and severity of COVID-19, coupled with elevated D-dimer levels, suggests a link between thrombosis and vascular involvement.
Topics: Humans; COVID-19; Male; Female; Pulmonary Artery; Retrospective Studies; Middle Aged; Aorta; Aged; SARS-CoV-2; Length of Stay; Tomography, X-Ray Computed; Hospitalization; Turkey; Adult
PubMed: 38869206
DOI: 10.5578/tt.202402930 -
BMJ Open Jun 2024Hepatic artery complications (HACs), such as a thrombosis or stenosis, are serious causes of morbidity and mortality after paediatric liver transplantation (LT). This... (Observational Study)
Observational Study
Incidence, management and outcomes in hepatic artery complications after paediatric liver transplantation: protocol of the retrospective, international, multicentre HEPATIC Registry.
INTRODUCTION
Hepatic artery complications (HACs), such as a thrombosis or stenosis, are serious causes of morbidity and mortality after paediatric liver transplantation (LT). This study will investigate the incidence, current management practices and outcomes in paediatric patients with HAC after LT, including early and late complications.
METHODS AND ANALYSIS
The HEPatic Artery stenosis and Thrombosis after liver transplantation In Children (HEPATIC) Registry is an international, retrospective, multicentre, observational study. Any paediatric patient diagnosed with HAC and treated for HAC (at age <18 years) after paediatric LT within a 20-year time period will be included. The primary outcomes are graft and patient survivals. The secondary outcomes are technical success of the intervention, primary and secondary patency after HAC intervention, intraprocedural and postprocedural complications, description of current management practices, and incidence of HAC.
ETHICS AND DISSEMINATION
All participating sites will obtain local ethical approval and (waiver of) informed consent following the regulations on the conduct of observational clinical studies. The results will be disseminated through scientific presentations at conferences and through publication in peer-reviewed journals.
TRIAL REGISTRATION NUMBER
The HEPATIC registry is registered at the ClinicalTrials.gov website; Registry Identifier: NCT05818644.
Topics: Humans; Hepatic Artery; Liver Transplantation; Registries; Retrospective Studies; Child; Incidence; Postoperative Complications; Thrombosis; Adolescent; Child, Preschool; Female; Male; Constriction, Pathologic; Infant; Multicenter Studies as Topic
PubMed: 38866577
DOI: 10.1136/bmjopen-2023-081933 -
Journal of Atherosclerosis and... Jun 2024Evidence regarding the association between various tumor necrosis factor-α (TNF-α) inhibitors and cardiovascular adverse events (AEs) is both limited and contradictory.
AIM
Evidence regarding the association between various tumor necrosis factor-α (TNF-α) inhibitors and cardiovascular adverse events (AEs) is both limited and contradictory.
METHODS
A retrospective pharmacovigilance study was conducted using the FDA Adverse Event Reporting System (FAERS) database. Cardiovascular AEs associated with TNF-α inhibitors (adalimumab, infliximab, etanercept, golimumab, and certolizumab) were evaluated using a disproportionality analysis. To reduce potential confounders, adjusted ROR and subgroup analyses were performed.
RESULTS
After excluding duplicates, 9,817 cardiovascular reports were associated with the five TNF-α inhibitors. Only adalimumab had positive signals for myocardial infarction (ROR=1.58, 95%CI=1.51-1.64) and arterial thrombosis (ROR=1.54, 95%CI=1.49-1.58). The remaining four TNF-α inhibitors did not show a risk association with any type of cardiovascular event. Further analyses of specific indication subgroups and after adjusting for any confounding factors demonstrated that adalimumab was still significantly associated with cardiovascular events, especially in patients with psoriasis (adjusted ROR=2.16, 95%CI=1.95-2.39).
CONCLUSIONS
This study revealed that adalimumab was the only TNF-α inhibitor associated with an elevated risk of thrombotic cardiovascular AEs, whereas the other four TNF-α inhibitors did not show any risk effect. However, given the limitations of such pharmacovigilance studies, it is necessary to validate these findings in prospective studies in the future.
PubMed: 38866553
DOI: 10.5551/jat.64767 -
Kidney & Blood Pressure Research Jun 2024Patients with idiopathic membranous nephropathy (IMN) are particularly susceptible to thromboembolism (TE). The phospholipase A2 receptor (PLA2R) antibody (Ab) has been...
INTRODUCTION
Patients with idiopathic membranous nephropathy (IMN) are particularly susceptible to thromboembolism (TE). The phospholipase A2 receptor (PLA2R) antibody (Ab) has been indicated to work as an independent risk predictor for venous TE in IMN. This study aims to further explore the predictive value of PLA2R Ab for both venous and arterial TE in IMN patients.
METHODS
A total of 91 IMN patients were retrospectively selected and divided into anti-PLA2R-positive or -negative groups according to the anti-PLA2R Ab titer (cutoff: 20 RU/mL). Serum PLA2R Abs were estimated using ELISA. Anti-PLA2R-positive IMN patients were further assigned into two groups based on the presence or absence of TE.
RESULTS
Twelve (18.18%) IMN patients with anti-PLA2R positivity had TE, including both venous and arterial TE. No TE occurred in the anti-PLA2R-negative group. IMN patients in the anti-PLA2R-positive group had significantly higher levels of total cholesterol and low-density lipoprotein than those in the anti-PLA2R-negative group. No significant difference was observed in the anti-PLA2R Ab titer between patients with and without TE. Patients with TE were significantly older than those without TE.
CONCLUSION
This study demonstrates that the positive status of anti-PLA2R Abs contributes to thrombosis formation in IMN.
PubMed: 38865986
DOI: 10.1159/000539437