Retrospective analysis of arterial occlusive events in the PACE trial by an independent adjudication committee.

BACKGROUND: The phase 2 PACE (Ponatinib Ph+ ALL and CML Evaluation) trial of ponatinib showed robust long-term benefit in relapsed Philadelphia chromosome-positive (Ph+) leukemia; arterial occlusive events (AOEs) occurred in ≥ 25% of patients based on investigator reporting. However, AOE rates vary depending on the definitions and reporting approach used. METHODS: To better understand clinically relevant AOEs with ponatinib, an independent cardiovascular adjudication committee reviewed 5-year AOE data from the PACE trial according to a charter-defined process and standardized event definitions. RESULTS: A total of 449 patients with chronic myeloid leukemia (CML) or Ph+ acute lymphoblastic leukemia (ALL) received ponatinib (median age 59 y; 47% female; 93% ≥ 2 prior tyrosine kinase inhibitors (TKIs); median follow-up, 37.3 months). The adjudicated AOE rate (17%) was lower than the non-adjudicated rate (i.e., rate before adjudication; 25%). The only adjudicated AOE in > 2% of patients was peripheral arterial occlusive disease (4%). Exposure-adjusted incidence of newly occurring adjudicated AOEs decreased over time. Patients with multiple baseline cardiovascular risk factors had higher adjudicated AOE rates than those without risk factors. CONCLUSIONS: This independent adjudication study identified lower AOE rates than previously reported, suggesting earlier overestimation that may inaccurately reflect AOE risk with ponatinib. This trial was registered under ClinicalTrials.gov identifier NCT01207440 on September 23, 2010 ( https://clinicaltrials.gov/ct2/show/NCT01207440 ).

Performance of a clinical/proteomic panel to predict obstructive peripheral artery disease in patients with and without diabetes mellitus.

Background: Patients with diabetes mellitus (DM) are at substantial risk of developing peripheral artery disease (PAD). We recently developed a clinical/proteomic panel to predict obstructive PAD. In this study, we compare the accuracy of this panel for the diagnosis of PAD in patients with and without DM. Methods and results: The HART PAD panel consists of one clinical variable (history of hypertension) and concentrations of six biomarkers (midkine, kidney injury molecule-1, interleukin-23, follicle-stimulating hormone, angiopoietin-1 and eotaxin-1). In a prospective cohort of 354 patients undergoing peripheral and/or coronary angiography, performance of this diagnostic panel to detect ≥50% stenosis in at least one peripheral vessel was assessed in patients with (n=94) and without DM (n=260). The model had an area under the receiver operating characteristic curve (AUC) of 0.85 for obstructive PAD. At optimal cut-off, the model had 84% sensitivity, 75% specificity, positive predictive value (PPV) of 84% and negative predictive value (NPV) of 75% for detection of PAD among patients with DM, similar as in those without DM. In those with DM, partitioning the model into five levels resulted in a PPV of 95% and NPV of 100% in the highest and lowest levels, respectively. Abnormal scores were associated with a shorter time to revascularisation during 4.3 years of follow-up. Conclusion: A clinical/biomarker model can predict with high accuracy the presence of PAD among patients with DM. Trial registration number: NCT00842868.

Blood kidney injury molecule-1 predicts short and longer term kidney outcomes in patients undergoing diagnostic coronary and/or peripheral angiography-Results from the Catheter Sampled Blood Archive in Cardiovascular Diseases (CASABLANCA) study.

BACKGROUND: Kidney injury is common in patients with cardiovascular disease. OBJECTIVES: We determined whether blood measurement of kidney injury molecule-1 (KIM-1), would predict kidney outcomes in patients undergoing angiographic procedures for various indications. METHODS: One thousand two hundred eight patients undergoing coronary and/or peripheral angiography were prospectively enrolled; blood was collected for KIM-1 measurement. Peri-procedural acute kidney injury (AKI) was defined as AKI within 48 hours of contrast exposure. Non-procedural AKI was defined as AKI beyond 48 hours. Development of chronic kidney disease (CKD) was defined as progression to an estimated glomerular filtration rate (eGFR) <60 milliliters/minute/1.73 m2 by study conclusion. Univariate and multivariable Cox proportional hazards models were used to identify predictors of non-procedural AKI, while univariate and multivariable logistic regression analysis was used to evaluate peri-procedural AKI and predictors of progression to CKD. RESULTS: During mean follow up of 4 years, peri-procedural AKI occurred in 5.0%, non-procedural AKI in 27.3%, and 12.4% developed new reduction in eGFR <60 mL/min/1.73 m2. Higher KIM-1 concentrations were associated with prevalent comorbidities associated with risk in cardiovascular disease and worse left ventricular function. In adjusted analyses, elevated pre- and post-procedural KIM-1 concentrations predicted not only peri-procedural AKI (odds ratio [OR] 1.54, 95% confidence interval [CI] 1.09-2·18, P = .01 and OR 1.54, 95% CI 1.10-2.15, P = .01, respectively) and non-procedural AKI (hazard ratio [HR] 1·49, 95% CI 1·24-1·78, P < .001 and HR 1.46, 95% CI 1.23-1.74, P < .001, respectively), but also progression to CKD (OR 1.99, 95% CI 1.32-2.99, P = .001 and OR 2·02, 95% CI 1·35-3·03, P = .001, respectively). CONCLUSIONS: In a typical at-risk population undergoing coronary and/or peripheral angiography, blood concentrations of KIM-1 may predict incident peri-procedural and non-procedural AKI, as well as progression to CKD.

A clinical and proteomics approach to predict the presence of obstructive peripheral arterial disease: From the Catheter Sampled Blood Archive in Cardiovascular Diseases (CASABLANCA) Study.

BACKGROUND: Peripheral arterial disease (PAD) is a global health problem that is frequently underdiagnosed and undertreated. Noninvasive tools to predict the presence and severity of PAD have limitations including inaccuracy, cost, or need for intravenous contrast and ionizing radiation. HYPOTHESIS: A clinical/biomarker score may offer an attractive alternative diagnostic method for PAD. METHODS: In a prospective cohort of 354 patients referred for diagnostic peripheral and/or coronary angiography, predictors of ≥50% stenosis in ≥1 peripheral vessel (carotid/subclavian, renal, or lower extremity arteries) were identified from >50 clinical variables and 109 biomarkers. Machine learning identified variables predictive of obstructive PAD; a score derived from the final model was developed. RESULTS: The score consisted of 1 clinical variable (history of hypertension) and 6 biomarkers (midkine, kidney injury molecule-1, interleukin-23, follicle-stimulating hormone, angiopoietin-1, and eotaxin-1). The model had an in-sample area under the receiver operating characteristic curve of 0.85 for obstructive PAD and a cross-validated area under the curve of 0.84; higher scores were associated with greater severity of angiographic stenosis. At optimal cutoff, the score had 65% sensitivity, 88% specificity, 76% positive predictive value (PPV), and 81% negative predictive value (NPV) for obstructive PAD and performed consistently across vascular territories. Partitioning the score into 5 levels resulted in a PPV of 86% and NPV of 98% in the highest and lowest levels, respectively. Elevated score was associated with shorter time to revascularization during 4.3 years of follow-up. CONCLUSIONS: A clinical/biomarker score demonstrates high accuracy for predicting the presence of PAD.

Carotid artery stenting for recurrent carotid artery restenosis after previous ipsilateral carotid artery endarterectomy or stenting: a report from the National Cardiovascular Data Registry.

OBJECTIVES: The purpose of this study was to evaluate and compare outcomes of patients undergoing carotid artery stenting (CAS) for ipsilateral restenosis, after either previous CAS or carotid artery endarterectomy (CEA) (CAS-R group), with those of patients who had CAS performed for de novo carotid atherosclerotic stenosis (CAS-DN group). BACKGROUND: Therapeutic revascularization strategies to reduce stroke include CAS and CEA. Limited data exist concerning the outcomes of CAS in the setting of previous ipsilateral carotid revascularization. METHODS: Patients enrolled in the CARE (Carotid Artery Revascularization and Endarterectomy) registry who underwent CAS were identified and separated into 2 groups: those undergoing CAS after previous ipsilateral CEA or CAS (CAS-R group, n = 1,996) and those who had CAS performed for de novo atherosclerotic carotid stenosis (CAS-DN group, n = 10,122). We analyzed the clinical and procedural factors associated with CAS-R and CAS-DN between January 1, 2005, and October 8, 2012. Propensity score matching using 19 clinical and 9 procedural characteristics was used, yielding 1,756 patients in each CAS cohort. RESULTS: The primary endpoint composite of in-hospital death or stroke or myocardial infarction (MI) occurred less often in the CAS-R compared with CAS-DN patients (1.9% vs. 3.2%; p = 0.019). In-hospital adverse cerebrovascular events (stroke or transient ischemic attack) occurred less frequently in the CAS-R cohort (2.2% vs. 3.6%; p < 0.001). However, there was no significant difference in the composite of death, stroke, or MI at 30 days between both groups. CONCLUSIONS: Patients who underwent CAS for restenosis after previous ipsilateral revascularization had lower periprocedural adverse event rates and comparable 30-day adverse event rates compared with CAS for de novo carotid artery stenosis.

Acute evaluation of the Mynx vascular closure device during arterial re-puncture in an ovine model.

BACKGROUND: The Mynx vascular closure device (VCD) (AccessClosure, Inc., Mountain View, California) is used for extravascular closure of the common femoral artery (CFA) after diagnostic or interventional endovascular procedures. Although it is common clinical practice to re-puncture a CFA, for some VCDs, acute repuncture is discouraged, while for other VCDs the safety of direct re-puncture through a previously placed VCD is still in question. The objective of this preclinical study was to evaluate the acute performance of the Mynx device where direct re-puncture has occurred through the hydrogel sealant, followed by delivery of a second Mynx device to close the reaccess puncture site. METHODS: Two ovine models with a total of 24 punctures (12 sets of puncture and re-puncture) were used for this study. Success was measured utilizing angiographic and observational endpoints. RESULTS: There was no evidence of hydrogel sealant prolapse into the artery, distal embolization of sealant following repuncture, groin site bleeding or hematoma. Successful hemostasis was achieved in all punctures (mean activated clotting time = 357 secs) with the exception of a minor (non-clinically significant) contrast extravasation in the tissue tract, which resolved with 2 minutes of adjunctive compression. CONCLUSION: Arterial re-puncture in an ovine model directly through a recently placed Mynx closure device and subsequent re-closure with a second Mynx device can be successfully accomplished.

Carotid artery stent migration in a child with Williams syndrome.

We report a case of distal migration of a stent from the brachiocephalic artery to the distal right common carotid artery 7 months after implantation in a 5-year-old child with Williams syndrome. There were no neurological sequelae and the migrated stent remained widely patent 5 years following implantation.

A novel technique for 14 French arteriotomy closure after percutaneous aortic valvuloplasty using two Mynx closure devices.

Management of large bore arterial access sites often represents a challenge during interventional procedures, and usually requires prolonged manual compression, though suture-mediated closure techniques have been described. We report our experience in using the Mynx vascular closure device to close a 14 French femoral arteriotomy in two patients undergoing percutaneous balloon aortic valvuloplasty.

Percutaneous closure after inadvertent subclavian artery cannulation.

Accidental insertion of an arterial sheath is an uncommon but potentially serious complication of jugular venous catheterization. When the subclavian artery is inadvertently cannulated, sheath removal can be complicated by significant hemorrhage due to its incompressible location. We report a case of inadvertent insertion of an 8 French sheath into the subclavian artery, which was successfully removed and the puncture site sealed with a collagen-based vascular closure device (Angio-Seal STS Plus). This averted an otherwise emergent open surgical procedure to remove the sheath and repair the subclavian artery in a high-risk patient.

Novel use of the Amplatzer septal occluder device in the percutaneous closure of ascending aortic pseudoaneurysms: a case series.

Pseudoaneurysms of the ascending aorta are a potentially fatal condition that usually necessitates definitive surgical management. In this series of three cases, we describe the novel use of the Amplatzer septal occluder device in percutaneously managing this problem.

Lower Extremity Arterial Occlusive Disease: Role of Percutaneous Revascularization.

Percutaneous endovascular interventions for peripheral arterial disease are indicated in carefully selected patients with favorable anatomy and associated clinical symptoms. Although endovascular therapy appears to be hemodynamically equivalent to other modalities in isolated iliac disease, this does not appear to be the case for infrainguinal disease, particularly when the disease is diffuse and extensive. Such disease in these beds can often be treated surgically, although there is an increasing role for percutaneous therapies, particularly in patients at higher surgical risk. Catheter-based therapy should be considered an integral part of comprehensive medical therapy in patients with lower extremity peripheral arterial disease. Embarking on an endovascular approach to therapy should involve a frank physician-patient discussion of the risks, benefits, and durability of the proposed procedure tailored to anatomic locale and patient-specific factors.